1
|
Li S, Liang Q, Qing W, Fang Z, Yuan C, Pan S, Xie H, Li X, Chen M, He Y, Zhou H, Wang Q. Maternal group B Streptococcus decreases infant length and alters the early-life microbiome: a prospective cohort study. Ann Med 2025; 57:2442070. [PMID: 39693119 DOI: 10.1080/07853890.2024.2442070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 06/18/2024] [Accepted: 11/14/2024] [Indexed: 12/19/2024] Open
Abstract
BACKGROUND Maternal colonization with Group B Streptococcus (GBS) disrupts the vaginal microbiota, potentially affecting infant microbiota assembly and growth. While the gut microbiota's importance in infant growth is recognized, the specific effects of maternal GBS on growth remain unclear. This study aimed to explore the effects of maternal vaginal GBS during pregnancy on early infant growth, microbiome, and metabolomics. METHODS We recruited and classified 453 pregnant women from southern China into GBS or healthy groups based on GBS vaginal colonization. Their infants were categorized as GBS-exposed or GBS-unexposed groups. We comprehensively analyzed infant growth, gut microbiota, and metabolites during early life, along with maternal vaginal microbiota during pregnancy, using 16S rDNA sequencing and targeted metabolomics. RESULTS GBS-exposed infants exhibited lower length-for-age z-scores (LAZ) than GBS-unexposed infants, especially at 2 months. Altered gut microbiota and metabolites in GBS-exposed infants correlated with growth, mediating the impact of maternal GBS on infant LAZ. Changes in the vaginal microbiota of the GBS group during the third trimester correlated with infant LAZ. Additionally, differences in neonatal gut microbiota, metabolites, and vaginal microbiota during pregnancy were identified between infants with overall LAZ<-1 within 8 months after birth and their counterparts, enhancing the discriminatory power of fundamental data for predicting the occurrence of LAZ<-1 during the first 8 months of life. CONCLUSIONS GBS exposure is associated with decreased infant length growth, with altered microbiota and metabolites potentially mediating the effects of maternal GBS on offspring length growth, offering potential targets for predicting and addressing growth impairment.
Collapse
Affiliation(s)
- Shanshan Li
- Department of Laboratory Medicine, Microbiome Medicine Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Qijun Liang
- Department of Obstetrics and Gynecology, Boai Hospital of Zhongshan, Zhongshan, Guangdong, China
| | - Wei Qing
- Department of Laboratory Medicine, Microbiome Medicine Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Zhencheng Fang
- Department of Laboratory Medicine, Microbiome Medicine Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Chunlei Yuan
- Department of Laboratory Medicine, Boai Hospital of Zhongshan, Zhongshan, Guangdong, China
| | - Shilei Pan
- Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Hairui Xie
- Department of Paediatrics Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Xiaocong Li
- Shenzhen Stomatology Hospital (Pingshan), Southern Medical University, Guangdong, China
| | - Muxuan Chen
- Department of Laboratory Medicine, Microbiome Medicine Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Yan He
- Department of Laboratory Medicine, Microbiome Medicine Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Hongwei Zhou
- Department of Laboratory Medicine, Microbiome Medicine Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Qian Wang
- Department of Laboratory Medicine, Microbiome Medicine Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| |
Collapse
|
2
|
Metwaly A, Kriaa A, Hassani Z, Carraturo F, Druart C, Arnauts K, Wilmes P, Walter J, Rosshart S, Desai MS, Dore J, Fasano A, Blottiere HM, Maguin E, Haller D. A Consensus Statement on establishing causality, therapeutic applications and the use of preclinical models in microbiome research. Nat Rev Gastroenterol Hepatol 2025; 22:343-356. [PMID: 40033063 DOI: 10.1038/s41575-025-01041-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/17/2025] [Indexed: 03/05/2025]
Abstract
The gut microbiome comprises trillions of microorganisms and profoundly influences human health by modulating metabolism, immune responses and neuronal functions. Disruption in gut microbiome composition is implicated in various inflammatory conditions, metabolic disorders and neurodegenerative diseases. However, determining the underlying mechanisms and establishing cause and effect is extremely difficult. Preclinical models offer crucial insights into the role of the gut microbiome in diseases and help identify potential therapeutic interventions. The Human Microbiome Action Consortium initiated a Delphi survey to assess the utility of preclinical models, including animal and cell-based models, in elucidating the causal role of the gut microbiome in these diseases. The Delphi survey aimed to address the complexity of selecting appropriate preclinical models to investigate disease causality and to study host-microbiome interactions effectively. We adopted a structured approach encompassing a literature review, expert workshops and the Delphi questionnaire to gather insights from a diverse range of stakeholders. Experts were requested to evaluate the strengths, limitations, and suitability of these models in addressing the causal relationship between the gut microbiome and disease pathogenesis. The resulting consensus statements and recommendations provide valuable insights for selecting preclinical models in future studies of gut microbiome-related diseases.
Collapse
Affiliation(s)
- Amira Metwaly
- Chair of Nutrition and Immunology, TUM School of Life Sciences, Technical University Munich, Freising, Germany
- ZIEL Institute for Food & Health, Technical University Munich, Freising, Germany
| | - Aicha Kriaa
- Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France
| | | | - Federica Carraturo
- European Biomedical Research Institute of Salerno (EBRIS), Salerno, Italy
| | | | - Kaline Arnauts
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - Paul Wilmes
- Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
- Department of Life Sciences and Medicine, Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
| | - Jens Walter
- APC Microbiome Ireland, School of Microbiology, and Department of Medicine, University College Cork, Cork, Ireland
| | - Stephan Rosshart
- Department of Microbiome Research, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany
- Department of Medicine II, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany
| | - Mahesh S Desai
- Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
| | - Joel Dore
- Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France
- Université Paris-Saclay, INRAE, MetaGenoPolis, Jouy-en-Josas, France
| | - Alessio Fasano
- European Biomedical Research Institute of Salerno (EBRIS), Salerno, Italy
- Department of Paediatric Gastroenterology and Nutrition, Mucosal Immunology and Biology Research Center,Massachusetts General Hospital Brigham, Harvard Medical School, Boston, MA, USA
| | - Hervé M Blottiere
- Université Paris-Saclay, INRAE, MetaGenoPolis, Jouy-en-Josas, France
- Nantes Université, INRAE, UMR1280, PhAN, Nantes, France
| | - Emmanuelle Maguin
- Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France.
| | - Dirk Haller
- Chair of Nutrition and Immunology, TUM School of Life Sciences, Technical University Munich, Freising, Germany.
- ZIEL Institute for Food & Health, Technical University Munich, Freising, Germany.
| |
Collapse
|
3
|
Liu C, Wong PY, Barua N, Li B, Wong HY, Zhang N, Chow SKH, Wong SH, Yu J, Ip M, Cheung WH, Duque G, Brochhausen C, Sung JJY, Wong RMY. From Clinical to Benchside: Lacticaseibacillus and Faecalibacterium Are Positively Associated With Muscle Health and Alleviate Age-Related Muscle Disorder. Aging Cell 2025; 24:e14485. [PMID: 39829204 PMCID: PMC12073917 DOI: 10.1111/acel.14485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 12/23/2024] [Accepted: 12/27/2024] [Indexed: 01/22/2025] Open
Abstract
Sarcopenia is an age-related muscle disorder that increases risks of adverse clinical outcomes, but its treatments are still limited. Gut microbiota is potentially associated with sarcopenia, and its role is still unclear. To investigate the role of gut microbiota in sarcopenia, we first compared gut microbiota and metabolites composition in old participants with or without sarcopenia. Fecal microbiota transplantation (FMT) from human donors to antibiotic-treated recipient mice was then performed. Specific probiotics and their mechanisms to treat aged mice were identified. Old people with sarcopenia had different microbial composition and metabolites, including Paraprevotella, Lachnospira, short-chain fatty acids, and purine. After FMT, mice receiving microbes from people with sarcopenia displayed lower muscle mass and strength compared with those receiving microbes from non-sarcopenic donors. Lacticaseibacillus rhamnosus (LR) and Faecalibacterium prausnitzii (FP) were positively related to muscle health of old people, and enhanced muscle mass and function of aged mice. Transcriptomics showed that genes related to tricarboxylic acid cycle (TCA) were enriched after treatments. Metabolic analysis showed increased substrates of TCA cycle in both LR and FP supernatants. Muscle mitochondria density, ATP content, NAD+/NADH, mitochondrial dynamics and biogenesis proteins, as well as colon tight junction proteins of aged mice were improved by both probiotics. LR and the combination of two probiotics also benefit intestinal immune health by reducing CD8+ IFNγ+ T cells. Gut microbiota dysbiosis is a pathogenesis of sarcopenia, and muscle-related probiotics could alleviate age-related muscle disorders mainly through mitochondria improvement. Further clinical translation is warranted.
Collapse
Affiliation(s)
- Chaoran Liu
- Department of Orthopaedics & TraumatologyThe Chinese University of Hong KongHong Kong SARChina
| | - Pui Yan Wong
- Department of Orthopaedics & TraumatologyThe Chinese University of Hong KongHong Kong SARChina
| | - Nilakshi Barua
- Department of MicrobiologyThe Chinese University of Hong KongHong Kong SARChina
| | - Baoqi Li
- Department of Orthopaedics & TraumatologyThe Chinese University of Hong KongHong Kong SARChina
| | - Hei Yuet Wong
- Department of Orthopaedics & TraumatologyThe Chinese University of Hong KongHong Kong SARChina
| | - Ning Zhang
- Department of Orthopaedics & TraumatologyThe Chinese University of Hong KongHong Kong SARChina
| | - Simon Kwoon Ho Chow
- Department of Orthopaedic SurgeryStanford University School of MedicinePalo AltoCaliforniaUSA
| | - Sunny Hei Wong
- Lee Kong Chian School of MedicineNanyang Technological UniversitySingaporeSingapore
- Department of Medicine and TherapeuticsThe Chinese University of Hong KongHong Kong SARChina
| | - Jun Yu
- Department of Medicine and TherapeuticsThe Chinese University of Hong KongHong Kong SARChina
| | - Margaret Ip
- Department of MicrobiologyThe Chinese University of Hong KongHong Kong SARChina
| | - Wing Hoi Cheung
- Department of Orthopaedics & TraumatologyThe Chinese University of Hong KongHong Kong SARChina
| | - Gustavo Duque
- Bone, Muscle & Geroscience Research GroupResearch Institute of the McGill University Health CentreMontrealQuebecCanada
| | - Christoph Brochhausen
- Institute of Pathology, University Medical Center Mannheim, Heidelberg UniversityMannheimGermany
| | - Joseph Jao Yiu Sung
- Lee Kong Chian School of MedicineNanyang Technological UniversitySingaporeSingapore
- Department of Medicine and TherapeuticsThe Chinese University of Hong KongHong Kong SARChina
| | - Ronald Man Yeung Wong
- Department of Orthopaedics & TraumatologyThe Chinese University of Hong KongHong Kong SARChina
| |
Collapse
|
4
|
Hog L, Fundin BT, Everett Palm E, Billger A, Bulik CM, Abbaspour A, Dinkler L. ARFID InitiativE Sweden (ARIES): study protocol for a large-scale genetic and registry-linked cohort study on avoidant/restrictive food intake disorder. BMJ Open 2025; 15:e095559. [PMID: 40246566 PMCID: PMC12007039 DOI: 10.1136/bmjopen-2024-095559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Accepted: 03/19/2025] [Indexed: 04/19/2025] Open
Abstract
INTRODUCTION The ARFID InitiativE Sweden (ARIES) investigates the genetic and environmental factors contributing to avoidant/restrictive food intake disorder (ARFID) in children and adolescents aged 6-14 years. ARIES will establish a national biobank and research registry. It aims to provide data for immediate research and track ARFID outcomes and clarify genetic links between ARFID and other conditions and analyse the gut microbiome to guide nutrition interventions. METHODS AND ANALYSIS The study will involve 1500 Swedish children and adolescents with ARFID and a control group of 500 Swedish children and adolescents without ARFID. Parents/guardians and their children will complete online questionnaires assessing ARFID and other eating disorder (ED) pathology, co-occurring conditions, quality of life and parental stress and ED pathology. All participants will provide a saliva sample for comprehensive genetic analyses. Additionally, a subset of participants will provide a stool sample to investigate the gut microbiome in ARFID. ETHICS AND DISSEMINATION ARIES was approved by the Swedish Ethical Review Authority (Dnr 2023-04638). All participants will give assent and their parents will complete informed consent. Data will be made available by the authors on reasonable request. Findings will be published in scientific journals and shared with the public and stakeholders in accessible ways, for example, via social media.
Collapse
Affiliation(s)
- Liv Hog
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
| | - Bengt T Fundin
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
| | - Erik Everett Palm
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
| | - Annelie Billger
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
| | - Cynthia M Bulik
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
- Department of Psychiatry, The University of North Carolina, Chapel Hill, North Carolina, USA
- Department of Nutrition, The University of North Carolina, Chapel Hill, North Carolina, USA
| | - Afrouz Abbaspour
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
| | - Lisa Dinkler
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
| |
Collapse
|
5
|
Dasari MR, Roche KE, Jansen D, Anderson J, Alberts SC, Tung J, Gilbert JA, Blekhman R, Mukherjee S, Archie EA. Social and environmental predictors of gut microbiome age in wild baboons. eLife 2025; 13:RP102166. [PMID: 40244653 PMCID: PMC12005720 DOI: 10.7554/elife.102166] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/18/2025] Open
Abstract
Mammalian gut microbiomes are highly dynamic communities that shape and are shaped by host aging, including age-related changes to host immunity, metabolism, and behavior. As such, gut microbial composition may provide valuable information on host biological age. Here, we test this idea by creating a microbiome-based age predictor using 13,563 gut microbial profiles from 479 wild baboons collected over 14 years. The resulting 'microbiome clock' predicts host chronological age. Deviations from the clock's predictions are linked to some demographic and socio-environmental factors that predict baboon health and survival: animals who appear old-for-age tend to be male, sampled in the dry season (for females), and have high social status (both sexes). However, an individual's 'microbiome age' does not predict the attainment of developmental milestones or lifespan. Hence, in our host population, gut microbiome age largely reflects current, as opposed to past, social and environmental conditions, and does not predict the pace of host development or host mortality risk. We add to a growing understanding of how age is reflected in different host phenotypes and what forces modify biological age in primates.
Collapse
Affiliation(s)
- Mauna R Dasari
- Department of Biological Sciences, University of Notre DameNotre DameUnited States
- Department of Biological Sciences, University of PittsburghPittsburghUnited States
- California Academy of SciencesSan FranciscoUnited States
| | - Kimberly E Roche
- Program in Computational Biology and Bioinformatics, Duke UniversityDurhamUnited States
| | - David Jansen
- Department of Biological Sciences, University of Notre DameNotre DameUnited States
| | - Jordan Anderson
- Department of Evolutionary Anthropology, Duke UniversityDurhamUnited States
| | - Susan C Alberts
- Department of Evolutionary Anthropology, Duke UniversityDurhamUnited States
- Department of Biology, Duke UniversityDurhamUnited States
- Duke University Population Research Institute, Duke UniversityDurhamUnited States
| | - Jenny Tung
- Department of Evolutionary Anthropology, Duke UniversityDurhamUnited States
- Department of Biology, Duke UniversityDurhamUnited States
- Duke University Population Research Institute, Duke UniversityDurhamUnited States
- Department of Primate Behavior and Evolution, Max Planck Institute for Evolutionary AnthropologyLeipzigGermany
- Canadian Institute for Advanced ResearchTorontoCanada
- Faculty of Life Sciences, Institute of Biology, Leipzig UniversityLeipzigGermany
| | - Jack A Gilbert
- Department of Pediatrics and the Scripps Institution of Oceanography, University of California, San DiegoSan DiegoUnited States
| | - Ran Blekhman
- Section of Genetic Medicine, Department of Medicine, University of ChicagoChicagoUnited States
| | - Sayan Mukherjee
- Departments of Statistical Science, Mathematics, Computer Science, and Bioinformatics and Biostatistics, Duke UniversityDurhamUnited States
- Center for Scalable Data Analytics and Artificial Intelligence, University of LeipzigLeipzigGermany
- Max Planck Institute for Mathematics in the Natural SciencesLeipzigGermany
| | - Elizabeth A Archie
- Department of Biological Sciences, University of Notre DameNotre DameUnited States
| |
Collapse
|
6
|
Lu W, Li ZL, Xu DY, Yu GP. Analysis of intestinal microbiota diversity in children with non-organic anorexia. Rev Argent Microbiol 2025:S0325-7541(25)00028-8. [PMID: 40210583 DOI: 10.1016/j.ram.2025.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Revised: 01/29/2025] [Accepted: 02/06/2025] [Indexed: 04/12/2025] Open
Abstract
The pathogenesis of non-organic anorexia in children is not clear. This study intends to analyze intestinal bacteria to provide a relevant theoretical basis for the clinical rational selection of microecological agents. In the present study, children with non-organic anorexia were included in the anorexia group and normal healthy children in the control group. Stool samples were collected for the bioinformatics analysis after PCR and high-throughput sequencing. The results showed that the Ace, Chao, and Shannon indexes in the anorexia group were higher than those in the control group, while the Simpson index in the control group was lower than in the anorexia group. There were 14 taxa in the anorexia group and 11 taxa in the healthy control group at the phylum level, and 193 taxa in the anorexia group and 180 in the control group at the genus level. The dominant bacteria at the phylum level of the two groups were the same, while there were 16 dominant bacteria taxa in the anorexia group and 17 in the control group at the genus level. The ratio of percentage abundance of Bacteroidetes to that of Firmicutes (the B/F index) in the anorexia group was higher than in the control group. The abundance of Bacteroidetes in the anorexia group was higher than that in the control group, and the abundance of Actinomycetes in the control group was higher than that in the anorexia group. There were significant differences in 14 dominant genera between the two groups at the genus classification level. The LEfSe multilevel species difference analysis showed that at the phylum level, the significant influential bacterial taxa in the anorexia group were Bacteroidetes and Actinobacteria in the control group. At the genus level, the significant influential bacterial taxa in the anorexia group were Bacteroides, Faecalibacterium, and Subdoligranulum, and Bifidobacterium, Blautia, Streptococcus, Lachnoclostridium, and Erysipelatoclostridium in the control group. We conclude that the increase in Bacteroides abundance or in the B/F index and the reduction in Bifidobacterium abundance were related to the pathogenesis of anorexia.
Collapse
Affiliation(s)
- Wei Lu
- Department of Pediatrics, Affiliated Hospital of Zunyi Medical University/Guizhou Children's Hospital, Zun Yi Gui Zhou 563099, China.
| | - Zong-Long Li
- Department of Pediatrics, Affiliated Hospital of Zunyi Medical University/Guizhou Children's Hospital, Zun Yi Gui Zhou 563099, China
| | - De-Yong Xu
- Department of Pediatrics, Affiliated Hospital of Zunyi Medical University/Guizhou Children's Hospital, Zun Yi Gui Zhou 563099, China
| | - Guo-Ping Yu
- Department of Pediatrics, Affiliated Hospital of Zunyi Medical University/Guizhou Children's Hospital, Zun Yi Gui Zhou 563099, China
| |
Collapse
|
7
|
Ayayee P, Custer G, Clayton JB, Price J, Ramer-Tait A, Larsen T. Assessing gut microbial provisioning of essential amino acids to host in a murine model with reconstituted gut microbiomes. RESEARCH SQUARE 2025:rs.3.rs-6255159. [PMID: 40195995 PMCID: PMC11975013 DOI: 10.21203/rs.3.rs-6255159/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/09/2025]
Abstract
Gut microbial essential amino acid (EAA) provisioning to mammalian hosts remains a critical yet poorly understood aspect of host-microbe nutritional interactions, with significant implications for human and animal health. To investigate microbial EAA contributions in mice with reconstituted gut microbiomes, we analyzed stable carbon isotopes (13C) of six EAAs across multiple organs. Germ-free (GF) mice fed a high-protein diet (18%) were compared to conventionalized (CVZ) mice fed a low-protein diet (10%) following fecal microbiota transplantation 30 days prior and a 20-day dietary intervention. We found no evidence for microbial EAA contributions to host tissues, with 13C-EAA fingerprinting revealing nearly identical patterns between GF and CVZ organs. Both groups maintained their expected microbiome statuses, with CVZ gut microbiota dominated by Firmicutes and Bacteroidetes phyla. These findings raise important questions about the functional capacities of reconstituted gut microbiomes. Future studies should investigate longer adaptation periods, varied dietary protein levels, and complementary analytical techniques to better understand the context-dependent nature of microbial EAA provisioning in mammalian hosts.
Collapse
Affiliation(s)
- Paul Ayayee
- Department of Biology, University of Nebraska at Omaha, Omaha, NE, USA
| | - Gordon Custer
- Department of Natural Sciences, University of Maryland Eastern Shore, Princess Anne, MD, USA
| | - Jonathan B. Clayton
- Department of Biology, University of Nebraska at Omaha, Omaha, NE, USA
- Nebraska Food for Health Center, University of Nebraska-Lincoln, Lincoln, NE, USA
| | - Jeff Price
- Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE, USA
- Nebraska Food for Health Center, University of Nebraska-Lincoln, Lincoln, NE, USA
| | - Amanda Ramer-Tait
- Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE, USA
- Nebraska Food for Health Center, University of Nebraska-Lincoln, Lincoln, NE, USA
| | - Thomas Larsen
- Max Planck Institute of Geoanthropology, Jena, Germany
- Institute for Prehistoric and Protohistoric Archaeology, University of Kiel, Kiel, Germany
| |
Collapse
|
8
|
Verster AJ, Salerno P, Valls R, Barrack K, Price CE, McClure EA, Madan JC, O’Toole GA, Sanville JL, Ross BD. Persistent delay in maturation of the developing gut microbiota in infants with cystic fibrosis. mBio 2025; 16:e0342024. [PMID: 39945545 PMCID: PMC11898760 DOI: 10.1128/mbio.03420-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Accepted: 01/23/2025] [Indexed: 02/19/2025] Open
Abstract
The healthy human infant gut microbiome undergoes stereotypical changes in taxonomic composition between birth and maturation to an adult-like stable state. During this time, extensive communication between microbiota and the host immune system contributes to health status later in life. Although there are many reported associations between microbiota compositional alterations and disease in adults, less is known about how microbiome development is altered in pediatric diseases. One pediatric disease linked to altered gut microbiota composition is cystic fibrosis (CF), a multi-organ genetic disease involving impaired chloride secretion across epithelia and heightened inflammation both in the gut and at other body sites. Here, we use shotgun metagenomics to profile the strain-level composition and developmental dynamics of the infant fecal microbiota from several CF and non-CF longitudinal cohorts spanning from birth to greater than 36 months of life. We identify a set of keystone species that define microbiota development in early life in non-CF infants but are missing or decreased in relative abundance in infants with CF, resulting in a delayed pattern of microbiota maturation, persistent entrenchment in a transitional developmental phase, and subsequent failure to attain an adult-like stable microbiota. Delayed maturation is strongly associated with cumulative antibiotic treatments, and we also detect the increased relative abundance of oral-derived bacteria and higher levels of fungi in infants with CF, features that are associated with decreased gut bacterial density. These findings suggest the potential for future directed therapies targeted at overcoming developmental delays in microbiota maturation for infants with CF.IMPORTANCEThe human gastrointestinal tract harbors a diversity of microbes that colonize upon birth and collectively contribute to host health throughout life. Infants with the disease cystic fibrosis (CF) harbor altered gut microbiota compared to non-CF counterparts, with lower levels of beneficial bacteria. How this altered population is established in infants with CF and how it develops over the first years of life is not well understood. By leveraging multiple large non-CF infant fecal metagenomic data sets and samples from a CF cohort collected prior to highly effective modulator therapy, we define microbiome maturation in infants up to 3 years of age. Our findings identify conserved age-diagnostic species in the non-CF infant microbiome that are diminished in abundance in CF counterparts that instead exhibit an enrichment of oral-derived bacteria and fungi associated with antibiotic exposure. Together, our study builds toward microbiota-targeted therapy to restore healthy microbiota dynamics in infants with CF.
Collapse
Affiliation(s)
- Adrian J. Verster
- Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, USA
| | - Paige Salerno
- Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, USA
| | - Rebecca Valls
- Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, USA
| | - Kaitlyn Barrack
- Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, USA
| | - Courtney E. Price
- Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, USA
| | - Emily A. McClure
- Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, USA
| | - Juliette C. Madan
- Department of Pediatrics, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, USA
- Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, USA
| | - George A. O’Toole
- Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, USA
| | - Julie L. Sanville
- Department of Pediatrics, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, USA
| | - Benjamin D. Ross
- Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, USA
| |
Collapse
|
9
|
Fang Y, Tian Z, Li W, Li D, Li J, Hu Z, Qiu Y, Zhu Z, Liu Z. Gut microbiota alterations in adolescent idiopathic scoliosis: a comparison study with healthy control and congenital scoliosis. Spine Deform 2025; 13:497-507. [PMID: 39438431 DOI: 10.1007/s43390-024-00988-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Accepted: 10/06/2024] [Indexed: 10/25/2024]
Abstract
PURPOSE This study aims to compare the composition of GM isolated from individuals with AIS or congenital scoliosis (CS) and age-matched control (Ctr). METHODS A total of 48 patients with AIS, 24 patients with CS, and 31 healthy individuals were recruited as the discovery cohort, and 9 pairs of siblings where one was affected by AIS were recruited as the validation cohort. The GM profile was determined with 16S rRNA sequencing, and the alpha-diversity and beta-diversity metrics were performed with Mothur. Linear discriminant analysis (LDA) analysis was performed to identify the enriched species. RESULTS The α diversity (Chao1 index) was significantly lower in AIS patients with low BMI (< 18.5) than those with normal BMI. The PcoA analysis showed a trend of clustering of GM in AIS compared to that in Ctr and CS groups (r2 = 0.0553, p = 0.001). METASTAT analysis showed Cellulomonadaceae was significantly enriched in AIS groups compared to CS and Ctr. LDA analysis showed 9 enriched species in AIS patients. Compared to Ctr, two species including Hungatella genus and Bacteroides fragilis were significantly enriched, while the Firmicutes versus Bacteroidetes (F/B) ratio and the Ruminococcus genus were significantly decreased in AIS but not CS groups. The significantly reduced F/B ratio and Ruminococcus genus in AIS were replicated in the validation cohort. CONCLUSIONS Our study elucidated an association between low BMI and GM diversity in AIS patients. The reduced F/B ratio and Ruminococcus genus in AIS patients were identified and validated in 9 pairs of AIS patients and their unaffected siblings. Our pilot results may help understand the anthropometric discrepancy in these patients and support a possible role of GM in the pathogenesis of AIS.
Collapse
Affiliation(s)
- Yinyu Fang
- Division of Spine Surgery, Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Zhongshan Road 321, Nanjing, 210008, China
| | - Zhen Tian
- Division of Spine Surgery, Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China
| | - Weibiao Li
- Division of Spine Surgery, Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Zhongshan Road 321, Nanjing, 210008, China
| | - Dongyue Li
- Division of Spine Surgery, Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China
| | - Jie Li
- Division of Spine Surgery, Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Zhongshan Road 321, Nanjing, 210008, China
| | - Zongshan Hu
- Division of Spine Surgery, Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Zhongshan Road 321, Nanjing, 210008, China
| | - Yong Qiu
- Division of Spine Surgery, Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Zhongshan Road 321, Nanjing, 210008, China
- Division of Spine Surgery, Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China
- Division of Spine Surgery, Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China
| | - Zezhang Zhu
- Division of Spine Surgery, Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Zhongshan Road 321, Nanjing, 210008, China
- Division of Spine Surgery, Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China
- Division of Spine Surgery, Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China
| | - Zhen Liu
- Division of Spine Surgery, Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Zhongshan Road 321, Nanjing, 210008, China.
- Division of Spine Surgery, Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China.
- Division of Spine Surgery, Department of Orthopaedic Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China.
| |
Collapse
|
10
|
Meadows V, Antonio JM, Ferraris RP, Gao N. Ruminococcus gnavus in the gut: driver, contributor, or innocent bystander in steatotic liver disease? FEBS J 2025; 292:1252-1264. [PMID: 39589934 PMCID: PMC11927045 DOI: 10.1111/febs.17327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 07/29/2024] [Accepted: 11/11/2024] [Indexed: 11/28/2024]
Abstract
The human gut microbiome plays a crucial role in regulating intestinal and systemic health, impacting host immune response and metabolic function. Dysbiosis of the gut microbiome is linked to various diseases, including steatotic liver diseases. Metabolic dysfunction-associated steatotic liver disease (MASLD), a chronic liver disease characterized by excess hepatic lipid content and impaired metabolism, is the leading cause of liver disease worldwide. Among the gut microbes, Ruminococcus gnavus (R. gnavus) has garnered attention for its association with inflammatory and metabolic diseases. While R. gnavus abundance correlates to liver fat accumulation, further research is needed to identify a causal role or therapeutic intervention in steatotic liver disease. This review surveys our current understanding of R. gnavus in the development and progression of steatotic liver diseases, highlighting its potential mechanisms through metabolite secretion, and emphasizes the need for comprehensive microbiome analyses and longitudinal studies to better understand R. gnavus' impact on liver health. This knowledge could pave the way for targeted interventions aimed at modulating gut microbiota to treat and prevent MASLD and its comorbidities.
Collapse
Affiliation(s)
- Vik Meadows
- Department of Biological Sciences, School of Arts & SciencesRutgers UniversityNewarkNJUSA
- Department of Pharmacology, Physiology, and Neuroscience, New Jersey Medical SchoolRutgers UniversityNewarkNJUSA
| | - Jayson M. Antonio
- Department of Pharmacology, Physiology, and Neuroscience, New Jersey Medical SchoolRutgers UniversityNewarkNJUSA
| | - Ronaldo P. Ferraris
- Department of Pharmacology, Physiology, and Neuroscience, New Jersey Medical SchoolRutgers UniversityNewarkNJUSA
| | - Nan Gao
- Department of Biological Sciences, School of Arts & SciencesRutgers UniversityNewarkNJUSA
- Department of Pharmacology, Physiology, and Neuroscience, New Jersey Medical SchoolRutgers UniversityNewarkNJUSA
| |
Collapse
|
11
|
Chacon J, Faizuddin F, McKee JC, Sheikh A, Vasquez VM, Gadad SS, Mayer G, Siby S, McCabe M, Dhandayuthapani S. Unlocking the Microbial Symphony: The Interplay of Human Microbiota in Cancer Immunotherapy Response. Cancers (Basel) 2025; 17:813. [PMID: 40075661 PMCID: PMC11899421 DOI: 10.3390/cancers17050813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2025] [Revised: 02/13/2025] [Accepted: 02/21/2025] [Indexed: 03/14/2025] Open
Abstract
INTRODUCTION The emergence of cancer immunotherapy has revolutionized cancer treatment, offering remarkable outcomes for patients across various malignancies. However, the heterogeneous response to immunotherapy underscores the necessity of understanding additional factors influencing treatment efficacy. Among these factors, the human microbiota has garnered significant attention for its potential role in modulating immune response. Body: This review explores the intricate relationship between the human microbiota and cancer immunotherapy, highlighting recent advances and potential mechanisms underlying microbial influence on treatment outcomes. CONCLUSION Insights into the microbiome's impact on immunotherapy response not only deepen our understanding of cancer pathogenesis but also hold promise for personalized therapeutic strategies aimed at optimizing patient outcomes.
Collapse
Affiliation(s)
- Jessica Chacon
- Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (F.F.); (J.C.M.); (A.S.); (S.S.G.); (G.M.); (S.S.); (M.M.); (S.D.)
| | - Farah Faizuddin
- Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (F.F.); (J.C.M.); (A.S.); (S.S.G.); (G.M.); (S.S.); (M.M.); (S.D.)
| | - Jack C. McKee
- Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (F.F.); (J.C.M.); (A.S.); (S.S.G.); (G.M.); (S.S.); (M.M.); (S.D.)
| | - Aadil Sheikh
- Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (F.F.); (J.C.M.); (A.S.); (S.S.G.); (G.M.); (S.S.); (M.M.); (S.D.)
| | - Victor M. Vasquez
- Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (F.F.); (J.C.M.); (A.S.); (S.S.G.); (G.M.); (S.S.); (M.M.); (S.D.)
| | - Shrikanth S. Gadad
- Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (F.F.); (J.C.M.); (A.S.); (S.S.G.); (G.M.); (S.S.); (M.M.); (S.D.)
- L. Frederick Francis Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA
- Center of Emphasis in Cancer, Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA
| | - Ghislaine Mayer
- Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (F.F.); (J.C.M.); (A.S.); (S.S.G.); (G.M.); (S.S.); (M.M.); (S.D.)
| | - Sharon Siby
- Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (F.F.); (J.C.M.); (A.S.); (S.S.G.); (G.M.); (S.S.); (M.M.); (S.D.)
| | - Molly McCabe
- Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (F.F.); (J.C.M.); (A.S.); (S.S.G.); (G.M.); (S.S.); (M.M.); (S.D.)
| | - Subramanian Dhandayuthapani
- Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA; (F.F.); (J.C.M.); (A.S.); (S.S.G.); (G.M.); (S.S.); (M.M.); (S.D.)
- L. Frederick Francis Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA
- Center of Emphasis in Infectious Diseases, Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA
| |
Collapse
|
12
|
Noles DL, Matzeller KL, Frank DN, Krebs NF, Tang M. Complementary Feeding and Infant Gut Microbiota: A Narrative Review. Nutrients 2025; 17:743. [PMID: 40077613 PMCID: PMC11901692 DOI: 10.3390/nu17050743] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2025] [Revised: 02/16/2025] [Accepted: 02/17/2025] [Indexed: 03/14/2025] Open
Abstract
Background: The complementary feeding period, spanning from 6 to 24 months of age, marks the transition from an exclusive liquid diet in infants to a dietary pattern requiring the introduction of solid foods to meet nutritional demands. Complementary feeding coincides with other critical development windows, including the maturation of the gut microbiome. However, the effects of specific solid foods on gut microbiota and the subsequent influence on health outcomes require further investigation. Methods: This narrative review analyzes published research from January 2004 to October 2024 and aims to summarize the current evidence of the effects of complementary feeding on the infant gut microbiota. Results: A total of 43 studies were included in this review. Overall, multiple studies reported an increase in alpha-diversity after solid food introduction. Bifidobacteriaceae is the predominant bacterial family during the first 6 months of life, shifting to Lachnospiraceae, Ruminococcaceae, and Clostridium spp. after the introduction of solid foods. The timing of solid food introduction may also influence gut microbiota, though results were inconclusive. The effect of individual dietary components on the gut microbiota was conflicting, with limited evidence to make inferences. Conclusions: Because of variations in study design, dietary intake quantification, and minimal follow-up, a lack of conclusive evidence exists describing the relationship between complementary feeding and gut microbiota outcomes in infants. Future research to describe these relationships should focus on the impact of individual foods on microbial diversity and maturation, as well as the relationship between microbiota and infant health outcomes.
Collapse
Affiliation(s)
- Danielle L. Noles
- Department of Pediatrics, Sections of Gastroenterology, Hepatology, and Nutrition, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA;
| | - Kinzie L. Matzeller
- Department of Pediatrics, Section of Nutrition, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; (K.L.M.)
- Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, CO 80526, USA
| | - Daniel N. Frank
- Department of Medicine, Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
| | - Nancy F. Krebs
- Department of Pediatrics, Section of Nutrition, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; (K.L.M.)
| | - Minghua Tang
- Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, CO 80526, USA
| |
Collapse
|
13
|
Robinson JF, Das S, Khan W, Khanam R, Price JT, Rahman A, Ahmed S, Ali SM, Deb S, Deveale B, Dutta A, Gormley M, Hall SC, Hasan ASMT, Hotwani A, Juma MH, Kasaro MP, Khalid J, Kshetrapal P, McMaster MT, Mehmood U, Nisar I, Pervin J, Rahman S, Raqib R, San A, Sarker P, Tuomivaara ST, Zhang G, Zhou Y, Aktar S, Baqui AH, Jehan F, Sazawal S, Stringer JSA, Fisher SJ. High rates of placental inflammation among samples collected by the Multi-Omics for Mothers and Infants consortium. Am J Obstet Gynecol 2025; 232:230.e1-230.e19. [PMID: 38697337 PMCID: PMC11790342 DOI: 10.1016/j.ajog.2024.04.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 04/18/2024] [Accepted: 04/24/2024] [Indexed: 05/04/2024]
Abstract
BACKGROUND The Multi-Omics for Mothers and Infants consortium aims to improve birth outcomes. Preterm birth is a major obstetrical complication globally and causes significant infant and childhood morbidity and mortality. OBJECTIVE We analyzed placental samples (basal plate, placenta or chorionic villi, and the chorionic plate) collected by the 5 Multi-Omics for Mothers and Infants sites, namely The Alliance for Maternal and Newborn Health Improvement Bangladesh, The Alliance for Maternal and Newborn Health Improvement Pakistan, The Alliance for Maternal and Newborn Health Improvement Tanzania, The Global Alliance to Prevent Prematurity and Stillbirth Bangladesh, and The Global Alliance to Prevent Prematurity and Stillbirth Zambia. The goal was to analyze the morphology and gene expression of samples collected from preterm and uncomplicated term births. STUDY DESIGN The teams provided biopsies from 166 singleton preterm (<37 weeks' gestation) and 175 term (≥37 weeks' gestation) deliveries. The samples were fixed in formalin and paraffin embedded. Tissue sections from these samples were stained with hematoxylin and eosin and subjected to morphologic analyses. Other placental biopsies (n=35 preterm, 21 term) were flash frozen, which enabled RNA purification for bulk transcriptomics. RESULTS The morphologic analyses revealed a surprisingly high rate of inflammation that involved the basal plate, placenta or chorionic villi, and the chorionic plate. The rate of inflammation in chorionic villus samples, likely attributable to chronic villitis, ranged from 25% (Pakistan site) to 60% (Zambia site) of cases. Leukocyte infiltration in this location vs in the basal plate or chorionic plate correlated with preterm birth. Our transcriptomic analyses identified 267 genes that were differentially expressed between placentas from preterm vs those from term births (123 upregulated, 144 downregulated). Mapping the differentially expressed genes onto single-cell RNA sequencing data from human placentas suggested that all the component cell types, either singly or in subsets, contributed to the observed dysregulation. Consistent with the histopathologic findings, gene ontology analyses highlighted the presence of leukocyte infiltration or activation and inflammatory responses in both the fetal and maternal compartments. CONCLUSION The relationship between placental inflammation and preterm birth is appreciated in developed countries. In this study, we showed that this link also exists in developing geographies. In addition, among the participating sites, we found geographic- and population-based differences in placental inflammation and preterm birth, suggesting the importance of local factors.
Collapse
Affiliation(s)
- Joshua F Robinson
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA
| | - Sayan Das
- Public Health Laboratory Ivo de Carneri, Wawi, Chake, Pemba, Zanzibar, Tanzania
| | - Waqasuddin Khan
- Biorepository and Omics Research Group, Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, Karachi, Pakistan; Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, Karachi, Pakistan
| | - Rasheda Khanam
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - Joan T Price
- UNC Global Projects - Zambia, Lusaka, Zambia; Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Anisur Rahman
- Maternal and Child Health Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh
| | | | - Said Mohammed Ali
- Public Health Laboratory Ivo de Carneri, Wawi, Chake, Pemba, Zanzibar, Tanzania
| | - Saikat Deb
- Public Health Laboratory Ivo de Carneri, Wawi, Chake, Pemba, Zanzibar, Tanzania; Center for Public Health Kinetics, Vinoba Puri, Lajpatnagar II, New Delhi, India
| | - Brian Deveale
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA; Department of Urology, University of California, San Francisco, San Francisco, CA
| | - Arup Dutta
- Center for Public Health Kinetics, Vinoba Puri, Lajpatnagar II, New Delhi, India
| | - Matthew Gormley
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA; Sandler-Moore Mass Spectrometry Core Facility, University of California, San Francisco, San Francisco, CA
| | - Steven C Hall
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA; Sandler-Moore Mass Spectrometry Core Facility, University of California, San Francisco, San Francisco, CA
| | - A S M Tarik Hasan
- Maternal and Child Health Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh
| | - Aneeta Hotwani
- Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, Karachi, Pakistan
| | - Mohamed Hamid Juma
- Public Health Laboratory Ivo de Carneri, Wawi, Chake, Pemba, Zanzibar, Tanzania
| | - Margaret P Kasaro
- UNC Global Projects - Zambia, Lusaka, Zambia; Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, NC; Department of Gynaecology and Obstetrics, University of Zambia School of Medicine, Lusaka, Zambia
| | - Javairia Khalid
- Biorepository and Omics Research Group, Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, Karachi, Pakistan; Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, Karachi, Pakistan
| | - Pallavi Kshetrapal
- Maternal and Child Health, Translational Health Science and Technology Institute, Faridabad, India
| | - Michael T McMaster
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA; Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA
| | - Usma Mehmood
- Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, Karachi, Pakistan
| | - Imran Nisar
- Biorepository and Omics Research Group, Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, Karachi, Pakistan; Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, Karachi, Pakistan
| | - Jesmin Pervin
- Maternal and Child Health Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh
| | - Sayedur Rahman
- Maternal and Child Health Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh; Projahnmo Research Foundation, Dhaka, Bangladesh
| | - Rubhana Raqib
- International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh
| | - Ali San
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA
| | - Protim Sarker
- Nutrition and Clinical Services Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh
| | - Sami T Tuomivaara
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA; Sandler-Moore Mass Spectrometry Core Facility, University of California, San Francisco, San Francisco, CA
| | - Ge Zhang
- Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH; Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; March of Dimes Prematurity Research Center Ohio Collaborative, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Yan Zhou
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA
| | - Shaki Aktar
- Maternal and Child Health Division, International Centre for Diarrhoeal Disease Research Bangladesh, Dhaka, Bangladesh
| | - Abdullah H Baqui
- Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - Fyezah Jehan
- Biorepository and Omics Research Group, Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, Karachi, Pakistan; Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, The Aga Khan University, Stadium Road, Karachi, Pakistan
| | - Sunil Sazawal
- Center for Public Health Kinetics, Vinoba Puri, Lajpatnagar II, New Delhi, India
| | - Jeffrey S A Stringer
- Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Susan J Fisher
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA; Sandler-Moore Mass Spectrometry Core Facility, University of California, San Francisco, San Francisco, CA.
| |
Collapse
|
14
|
Marconi S, Sinha B, Apte A, Sasikumar M, Aggarwal G, Chabukswar R, Vasudevan A, Miyandad Z, Pandian S, Shambharkar P, Bhardwaj H, Dayma G, Agarwal D, Taneja S, Mohan VR. Acceptability of Microbiota-Directed Complementary Foods in Treating Indian Children with Moderate Acute Malnutrition: eACT-MAM Pre-Proof-of-Concept Study. J Nutr 2025; 155:612-620. [PMID: 39510507 DOI: 10.1016/j.tjnut.2024.11.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 10/23/2024] [Accepted: 11/01/2024] [Indexed: 11/15/2024] Open
Abstract
BACKGROUND In India, currently, there are no standard guidelines for the management of moderate acute malnutrition (MAM). Previous research in Bangladesh has shown that children with MAM have impaired gut microbiota development, and microbiota-directed complementary foods (MDCF) can potentially repair their gut microbiota. OBJECTIVES The objectives of this study were to evaluate the acceptability and safety of supplementing shelf-stable formulation of MDCF in Indian children with MAM as compared with a locally prepared ready-to-use supplementary food (RUSF) in 3 geographically distinct Indian populations and to establish and pilot systems of intervention delivery, collection, transport, and storage of stool samples using stringent protocols. METHODS This pre-proof-of-concept (prePOC), multicentric, open-labeled, age-stratified, randomized controlled trial was done in children aged 6-18 mo with MAM. After a run-in period of 2 wk, the participants were supplemented with MDCF or RUSF for 4 wk through direct observation and followed up for another 2 wk post intervention. Maternal responses to the acceptability of the organoleptic properties of supplements were recorded weekly during the intervention phase of 4 wk. Compliance was reported based on the amount of supplement consumed by the children. Feasibility of weekly stool sample collection (except 7th week) within 30 min of passage was recorded. Anthropometric measurements were done at baseline and endline. Monitoring for adverse events was done throughout the course of the study. RESULTS A total of 240 children with MAM were randomly selected to receive either MDCF or RUSF, of which 221 (92.1%) completed follow-up. The overall acceptability for >80% of the maternal responses was reported as good or very good for all organoleptic properties in both MDCF and RUSF arms. MDCF and RUSF interventions had good-to-high compliance in 83.0% and 79.8% of participants, respectively. At the end of the intervention phase, 53.2% (58/109) of children in MDCF arm against 42.0% (47/112) in RUSF arm had weight-for-length Z score >-2. The overall incidence of acute gastroenteritis reported was low; higher in MDCF compared with RUSF but not statistically significant. CONCLUSION The prePOC study demonstrates good acceptability and safety of MDCF among Indian children with MAM including the age group of 6-12 mo of age. The study demonstrates the feasibility of conducting a long-term supplementation study in this population. The study was registered at the clinical trial registry of India as CTRI/2023/01/048716.
Collapse
Affiliation(s)
- Sam Marconi
- Community Health Department, Christian Medical College Vellore, Vellore, Tamil Nadu, India.
| | - Bireshwar Sinha
- The Centre for Research and Development, Society for Applied Studies, New Delhi, India; The Centre for Research and Development, DBT/Wellcome India Alliance, India
| | - Aditi Apte
- KEM Hospital Research Centre-Community Health Research Unit, Manchar, Pune, Maharashtra, India
| | - Midhun Sasikumar
- Community Health Department, Christian Medical College Vellore, Vellore, Tamil Nadu, India; International Doctoral Programme in Epidemiology and Public Health, University of Tampere, Tampere, Finland
| | - Gunjan Aggarwal
- The Centre for Research and Development, Society for Applied Studies, New Delhi, India
| | - Rashmi Chabukswar
- KEM Hospital Research Centre-Community Health Research Unit, Manchar, Pune, Maharashtra, India
| | - Akshaya Vasudevan
- Community Health Department, Christian Medical College Vellore, Vellore, Tamil Nadu, India
| | - Zavid Miyandad
- Community Health Department, Christian Medical College Vellore, Vellore, Tamil Nadu, India
| | - Sowndharya Pandian
- Community Health Department, Christian Medical College Vellore, Vellore, Tamil Nadu, India
| | - Pranita Shambharkar
- KEM Hospital Research Centre-Community Health Research Unit, Manchar, Pune, Maharashtra, India
| | - Himani Bhardwaj
- The Centre for Research and Development, Society for Applied Studies, New Delhi, India
| | - Girish Dayma
- KEM Hospital Research Centre-Community Health Research Unit, Manchar, Pune, Maharashtra, India
| | - Dhiraj Agarwal
- KEM Hospital Research Centre-Community Health Research Unit, Manchar, Pune, Maharashtra, India
| | - Sunita Taneja
- The Centre for Research and Development, Society for Applied Studies, New Delhi, India
| | - Venkata Raghava Mohan
- Community Health Department, Christian Medical College Vellore, Vellore, Tamil Nadu, India
| |
Collapse
|
15
|
Panwar D, Briggs J, Fraser ASC, Stewart WA, Brumer H. Transcriptional delineation of polysaccharide utilization loci in the human gut commensal Segatella copri DSM18205 and co-culture with exemplar Bacteroides species on dietary plant glycans. Appl Environ Microbiol 2025; 91:e0175924. [PMID: 39636128 PMCID: PMC11784079 DOI: 10.1128/aem.01759-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Accepted: 11/10/2024] [Indexed: 12/07/2024] Open
Abstract
There is growing interest in members of the genus Segatella (family Prevotellaceae) as members of a well-balanced human gut microbiota (HGM). Segatella are particularly associated with the consumption of a diet rich in plant polysaccharides comprising dietary fiber. However, understanding of the molecular basis of complex carbohydrate utilization in Segatella species is currently incomplete. Here, we used RNA sequencing (RNA-seq) of the type strain Segatella copri DSM 18205 (previously Prevotella copri CB7) to define precisely individual polysaccharide utilization loci (PULs) and associated carbohydrate-active enzymes (CAZymes) that are implicated in the catabolism of common fruit, vegetable, and grain polysaccharides (viz. mixed-linkage β-glucans, xyloglucans, xylans, pectins, and inulin). Although many commonalities were observed, several of these systems exhibited significant compositional and organizational differences vis-à-vis homologs in the better-studied Bacteroides (sister family Bacteroidaceae), which predominate in post-industrial HGM. Growth on β-mannans, β(1, 3)-galactans, and microbial β(1, 3)-glucans was not observed, due to an apparent lack of cognate PULs. Most notably, S. copri is unable to grow on starch, due to an incomplete starch utilization system (Sus). Subsequent transcriptional profiling of bellwether Ton-B-dependent transporter-encoding genes revealed that PUL upregulation is rapid and general upon transfer from glucose to plant polysaccharides, reflective of de-repression enabling substrate sensing. Distinct from previous observations of Bacteroides species, we were unable to observe clearly delineated substrate prioritization on a polysaccharide mixture designed to mimic in vitro diverse plant cell wall digesta. Finally, co-culture experiments generally indicated stable co-existence and lack of exclusive competition between S. copri and representative HGM Bacteroides species (Bacteroides thetaiotaomicron and Bacteroides ovatus) on individual polysaccharides, except in cases where corresponding PULs were obviously lacking. IMPORTANCE There is currently a great level of interest in improving the composition and function of the human gut microbiota (HGM) to improve health. The bacterium Segatella copri is prevalent in people who eat plant-rich diets and is therefore associated with a healthy lifestyle. On one hand, our study reveals the specific molecular systems that enable S. copri to proliferate on individual plant polysaccharides. On the other, a growing body of data suggests that the inability of S. copri to grow on starch and animal glycans, which dominate in post-industrial diets, as well as host mucin, contributes strongly to its displacement from the HGM by Bacteroides species, in the absence of direct antagonism.
Collapse
Affiliation(s)
- Deepesh Panwar
- Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, Canada
| | - Jonathon Briggs
- Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, Canada
| | - Alexander S. C. Fraser
- Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, Canada
| | - William A. Stewart
- Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, Canada
| | - Harry Brumer
- Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia, Canada
- Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, British Columbia, Canada
- Department of Chemistry, The University of British Columbia, Vancouver, British Columbia, Canada
- Department of Botany, The University of British Columbia, Vancouver, British Columbia, Canada
| |
Collapse
|
16
|
Indrio F, Salatto A. Gut Microbiota-Bone Axis. ANNALS OF NUTRITION & METABOLISM 2025:1-10. [PMID: 39848230 DOI: 10.1159/000541999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 10/11/2024] [Indexed: 01/25/2025]
Abstract
BACKGROUND Knowledge of the complex interplay between gut microbiota and human health is gradually increasing as it has just recently been a field of such great interest. SUMMARY Recent studies have reported that communities of microorganisms inhabiting the gut influence the immune system through cellular responses and shape many physiological and pathophysiological aspects of the body, including muscle and bone metabolism (formation and resorption). Specifically, the gut microbiota affects skeletal homeostasis through changes in host metabolism, the immune system, hormone secretion, and the gut-brain axis. The major role on gut-bone axis is due to short-chain fatty acids (SCFAs). They have the ability to influence regulatory T-cell (Tregs) development and activate bone metabolism through the action of Wnt10. SCFA production may be a mechanism by which the microbial community, by increasing the serum level of insulin-like growth factor 1 (IGF-1), leads to the growth and regulation of bone homeostasis. A specific SCFA, butyrate, diffuses into the bone marrow where it expands Tregs. The Tregs induce production of the Wnt ligand Wnt10b by CD8+ T cells, leading to activation of Wnt signaling and stimulation of bone formation. At the hormonal level, the effect of the gut microbiota on bone homeostasis is expressed through the biphasic action of serotonin. Some microbiota, such as spore-forming microbes, regulate the level of serotonin in the gut, serum, and feces. Another group of bacterial species (Lactococcus, Mucispirillum, Lactobacillus, and Bifidobacterium) can increase the level of peripheral/vascular leptin, which in turn manages bone homeostasis through the action of brain serotonin.
Collapse
Affiliation(s)
- Flavia Indrio
- Department of Experimental Medicine, University of Salento, Lecce, Italy
| | - Alessia Salatto
- Department of Translational Medical Science, University of Naples Federico II, Napoli, Italy
| |
Collapse
|
17
|
Park H, Kim SH, Lee KA. Protective effects of Lactobacillus plantarum strain against protein malnutrition-induced muscle atrophy and bone loss in juvenile mice. PLoS One 2025; 20:e0317197. [PMID: 39820793 PMCID: PMC11737667 DOI: 10.1371/journal.pone.0317197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Accepted: 12/23/2024] [Indexed: 01/19/2025] Open
Abstract
Early-life malnutrition adversely affects nearly all organ systems, resulting in multiple physiological adaptations, including growth restriction and muscle and bone loss. Although there is growing evidence that probiotics effectively improve systemic growth under malnourished conditions in different animal models, our knowledge of the beneficial effects of probiotics on various organs is limited. Here, we show that Lactobacillus plantarum strain WJL (LpWJL) can mitigate skeletal muscle and bone loss in protein-malnourished juvenile mice. Mice on prenatal day 21 were fed a protein-malnourished (P-MAL) diet with or without LpWJL supplementation for six weeks. Compared to mice on the P-MAL diet alone, LpWJL supplementation significantly increased muscle mass and size, resulting in enhanced muscle strength and endurance capacity. Furthermore, LpWJL supplementation induced the expression of the key growth factor IGF-1 while decreasing muscle atrophy markers such as Atrogin-1 and MuRF-1, indicating potential mechanisms by which protein malnutrition-induced muscle wasting is counteracted. Additionally, LpWJL supplementation alleviated the reduction in cortical bone thickness and the deterioration of trabecular bone microstructure in the femur. Taken together, these results indicate that LpWJL can protect against skeletal muscle atrophy and compromised bone microarchitecture caused by protein malnutrition, providing novel insights into the potential therapeutic applications of probiotics for treating malnutrition-related disorders.
Collapse
Affiliation(s)
- Hyerim Park
- School of Biological Sciences, Seoul National University, Seoul, South Korea
| | - Sung-Hee Kim
- School of Biological Sciences, Seoul National University, Seoul, South Korea
| | - Kyung-Ah Lee
- School of Biological Sciences, Seoul National University, Seoul, South Korea
| |
Collapse
|
18
|
Qu Z, Zhang B, Lin G, Guo M, Tian P, Wang L, Chen W, Zhang H, Wang G. Dietary nucleotides drive changes in infant fecal microbiota in vitro and gut microbiota-gut-brain development in neonatal rats: A potential "nitrogen source" for early microbiota growth. Food Chem 2025; 463:141333. [PMID: 39340921 DOI: 10.1016/j.foodchem.2024.141333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 08/14/2024] [Accepted: 09/15/2024] [Indexed: 09/30/2024]
Abstract
Various dietary factors in human milk are important nutrients for the formation of the infant gut microbiota (GM). While promoting the growth of the GM, some human milk components that are difficult to absorb and utilize will be broken down by the GM, and converted into nutrients that the baby can use, such as breast milk oligosaccharides-the 'carbon source' for infant GM. This study reveals that nucleotides (NTs), significant non-protein nitrogen sources in human milk, can enhance the abundance of beneficial microbial genera such as g_Bifidobacterium, g_Bacteroides, and g_Blautia in in vitro fecal fermentation fluids of infants at low doses (2 mg/mL). Conversely, high doses of NTs (20 mg/mL) increased the abundance of g_Escherichia-Shigella. Furthermore, low-dose NTs fermentation broth significantly enhanced the expression of neurodevelopmental marker genes such as Tuj1, Sox2, Dcx, and NeuN in NE-4C neural stem cells, whereas a single NTs digestion broth did not exhibit significant activity. However, in vivo studies using neonatal rats as a model demonstrated that both low-dose NTs fermentation broth and NTs digestive juices promoted behavioral development in neonatal rats (PND 20) and neuron maturation in the prefrontal cortex and hippocampus. Non-targeted metabolomics results indicate that low-dose dietary NTs promote the production of certain neuroregulatory metabolites in infant fecal fermentation, such as uridine, L-tyrosine, L-glutamic acid, and succinic acid. These findings suggest that NTs may serve as an important "nitrogen source" during GM formation in early life and have a dose effect in driving the development of the microbiota-gut-brain axis in early life.
Collapse
Affiliation(s)
- Zhihao Qu
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Bo Zhang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Guopeng Lin
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Min Guo
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China; National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Peijun Tian
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China; National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu 214122, China; (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
| | - Linlin Wang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China; National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu 214122, China; (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
| | - Wei Chen
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China; National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Heng Zhang
- Department of Child Health Care, Wuxi Maternity and Child Health Care Hospital, Women's Hospital of Jiangnan University, Jiangnan University, Wuxi, Jiangsu 214002, China
| | - Gang Wang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China; National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu 214122, China; (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China.
| |
Collapse
|
19
|
Merle L, Rastelli M, Datiche F, Véjux A, Jacquin-Piques A, Bouret SG, Benani A. Maternal Diet and Vulnerability to Cognitive Impairment in Adulthood: Possible Link with Alzheimer's Disease? Neuroendocrinology 2025; 115:242-266. [PMID: 39799941 DOI: 10.1159/000543499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Accepted: 12/15/2024] [Indexed: 01/15/2025]
Abstract
BACKGROUND Aging is the main risk factor for developing cognitive impairments and associated neurodegenerative diseases. However, environmental factors, including nutritional health, are likely to promote or reduce cognitive impairments and neurodegenerative pathologies. An intricate relationship exists between maternal nutrition and adult eating behavior, metabolic phenotype, and cognitive abilities. SUMMARY The objective of the present review was to collect available data, suggesting a link between maternal overnutrition and the latter impairment of cognitive functions in the progeny, and to relate this relationship with Alzheimer's disease (AD). Indeed, cognitive impairments are major behavioral signs of AD. We first reviewed studies showing an association between unbalanced maternal diet and cognitive impairments in the progeny in humans and rodent models. Then we looked for cellular and molecular hallmarks which could constitute a breeding ground for AD in those models. With this end, we focused on synaptic dysfunction, altered neurogenesis, neuroinflammation, oxidative stress, and pathological protein aggregation. Finally, we proposed an indirect mechanism linking maternal unbalanced diet and progeny's vulnerability to cognitive impairments and neurodegeneration through promoting metabolic diseases. We also discussed the involvement of progeny's gut microbiota in the maternal diet-induced vulnerability to metabolic and neurodegenerative diseases. KEY MESSAGES Further investigations are needed to fully decipher how maternal diet programs the fetus and infant brain. Addressing this knowledge gap would pave the way to precise nutrition and personalized medicine to better handle cognitive impairments in adulthood.
Collapse
Affiliation(s)
- Laetitia Merle
- Centre des Sciences du Goût et de l'Alimentation, CNRS, INRAE, Institut Agro, Université de Bourgogne, Dijon, France
| | - Marialetizia Rastelli
- Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience and Cognition, Inserm UMR-S1172, CHU Lille, University of Lille, Lille, France
| | - Frédérique Datiche
- Centre des Sciences du Goût et de l'Alimentation, CNRS, INRAE, Institut Agro, Université de Bourgogne, Dijon, France
| | - Anne Véjux
- Centre des Sciences du Goût et de l'Alimentation, CNRS, INRAE, Institut Agro, Université de Bourgogne, Dijon, France
| | - Agnès Jacquin-Piques
- Centre des Sciences du Goût et de l'Alimentation, CNRS, Department of Clinical Neurophysiology, INRAE, Institut Agro, Université de Bourgogne, CHU Dijon, Dijon, France
| | - Sébastien G Bouret
- Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience and Cognition, Inserm UMR-S1172, CHU Lille, University of Lille, Lille, France
| | - Alexandre Benani
- Centre des Sciences du Goût et de l'Alimentation, CNRS, INRAE, Institut Agro, Université de Bourgogne, Dijon, France
| |
Collapse
|
20
|
Rakhshandehroo M, Harvey L, de Bruin A, Timmer E, Lohr J, Tims S, Schipper L. Maternal exposure to purified versus grain-based diet during early lactation in mice affects offspring growth and reduces responsivity to Western-style diet challenge in adulthood. J Dev Orig Health Dis 2025; 16:e3. [PMID: 39780545 DOI: 10.1017/s2040174424000436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
The nutritional environment during fetal and early postnatal life has a long-term impact on growth, development, and metabolic health of the offspring, a process termed "nutritional programming." Rodent models studying programming effects of nutritional interventions use either purified or grain-based rodent diets as background diets. However, the impact of these diets on phenotypic outcomes in these models has not been comprehensively investigated. We used a previously validated (C57BL/6J) mouse model to investigate the effects of infant milk formula (IMF) interventions on nutritional programming. Specifically, we investigated the effects of maternal diet type (i.e., grain-based vs purified) during early lactation and prior to the intervention on offspring growth, metabolic phenotype, and gut microbiota profile. Maternal exposure to purified diet led to an increased post-weaning growth velocity in the offspring and reduced adult diet-induced obesity. Further, maternal exposure to purified diet reduced the offspring gut microbiota diversity and modified its composition post-weaning. These data not only reinforce the notion that maternal nutrition significantly influences the programming of offspring vulnerability to an obesogenic diet in adulthood but emphasizes the importance of careful selection of standard background diet type when designing any preclinical study with (early life) nutritional interventions.
Collapse
Affiliation(s)
| | - L Harvey
- Danone Research & Innovation Center, Utrecht, The Netherlands
| | - A de Bruin
- Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
| | - E Timmer
- Danone Research & Innovation Center, Utrecht, The Netherlands
| | - J Lohr
- Danone Research & Innovation Center, Utrecht, The Netherlands
| | - S Tims
- Danone Research & Innovation Center, Utrecht, The Netherlands
| | - L Schipper
- Danone Research & Innovation Center, Utrecht, The Netherlands
| |
Collapse
|
21
|
Portlock T, Shama T, Kakon SH, Hartjen B, Pook C, Wilson BC, Bhuttor A, Ho D, Shennon I, Engelstad AM, Di Lorenzo R, Greaves G, Rahman N, Kelsey C, Gluckman PD, O'Sullivan JM, Haque R, Forrester T, Nelson CA. Interconnected pathways link faecal microbiota plasma lipids and brain activity to childhood malnutrition related cognition. Nat Commun 2025; 16:473. [PMID: 39773949 PMCID: PMC11707170 DOI: 10.1038/s41467-024-55798-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Accepted: 12/23/2024] [Indexed: 01/11/2025] Open
Abstract
Malnutrition affects over 30 million children annually and has profound immediate and enduring repercussions. Survivors often suffer lasting neurocognitive consequences that impact academic performance and socioeconomic outcomes. Mechanistic understanding of the emergence of these consequences is poorly understood. Using multi-system SHAP interpreted random forest models and network analysis, we show that Moderate Acute Malnutrition (MAM) associates with enrichment of faecal Rothia mucilaginosa, Streptococcus salivarius and depletion of Bacteroides fragilis in a cohort of one-year-old children in Dhaka, Bangladesh. These microbiome changes form interconnected pathways that involve reduced plasma odd-chain fatty acid levels, decreased gamma and beta electroencephalogram power in temporal and frontal brain regions, and reduced vocalization. These findings support the hypothesis that prolonged colonization by oral commensal species delay gut microbiome and brain development. While causal links require empirical validation, this study provides insights to improve interventions targeting MAM-associated neurodevelopmental deficits.
Collapse
Affiliation(s)
- T Portlock
- The Liggins Institute, University of Auckland, Auckland, New Zealand
| | - T Shama
- Infectious Diseases Division, International Centre for Diarrheal Disease Research, Dhaka, Bangladesh
| | - S H Kakon
- Infectious Diseases Division, International Centre for Diarrheal Disease Research, Dhaka, Bangladesh
| | - B Hartjen
- Division of Developmental Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA
- Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| | - C Pook
- The Liggins Institute, University of Auckland, Auckland, New Zealand
| | - B C Wilson
- The Liggins Institute, University of Auckland, Auckland, New Zealand
| | - A Bhuttor
- Division of Developmental Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA
| | - D Ho
- The Liggins Institute, University of Auckland, Auckland, New Zealand
| | - I Shennon
- The Liggins Institute, University of Auckland, Auckland, New Zealand
| | - A M Engelstad
- Division of Developmental Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA
- Harvard Graduate School of Education, Cambridge, MA, USA
| | - R Di Lorenzo
- Division of Developmental Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA
- Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| | - G Greaves
- Division of Developmental Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA
| | - N Rahman
- Division of Developmental Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA
| | - C Kelsey
- Division of Developmental Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA
- Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| | - P D Gluckman
- The Liggins Institute, University of Auckland, Auckland, New Zealand
- Department of Pediatrics, Harvard Medical School, Boston, MA, USA
| | - J M O'Sullivan
- The Liggins Institute, University of Auckland, Auckland, New Zealand.
- Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore, Singapore.
- The Maurice Wilkins Centre, The University of Auckland, Auckland, New Zealand.
- MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
| | - R Haque
- Infectious Diseases Division, International Centre for Diarrheal Disease Research, Dhaka, Bangladesh
- Division of Developmental Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA
| | - T Forrester
- Faculty of Medical Sciences, University of the West Indies (UWI), Kingston, Jamaica
| | - C A Nelson
- Division of Developmental Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA.
- Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
- Harvard Graduate School of Education, Cambridge, MA, USA.
| |
Collapse
|
22
|
Fang Q, Qiu T, Chen F, Tian X, Feng Z, Cao Y, Bai J, Huang J, Liu Y. The relationship between prenatal drought exposure and the diversity and composition of gut microbiome in pregnant women and neonates. Sci Rep 2025; 15:296. [PMID: 39747960 PMCID: PMC11695601 DOI: 10.1038/s41598-024-82148-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 12/03/2024] [Indexed: 01/04/2025] Open
Abstract
Drought induced by climate change poses a serious threat to human health. The gut microbiome also plays a critical role in human health. However, no studies have explored the effect of drought on the human gut microbiome. Therefore, our study aimed to investigate the relationship between drought and gut microbiome. Our study included 59 mothers and 38 neonates in our study. 16S rRNA V3-V4 sequencing was used to profile the gut microbiome. The Standardized Precipitation Evapotranspiration Index (SPEI) was used to represent drought characteristics. KEGG pathway level 3 was employed for functional analysis. Generalized linear models were used to explore the effect of drought on the gut microbiome. Mothers and neonates were divided into the LSPEI (Lower SPEI) group or HSPEI (Higher SPEI) group by calculating the average levels of prenatal SPEI levels. The maternal and neonatal gut microbiome exhibited similar diversities in terms of alpha and beta diversity between the LSPEI and HSPEI groups. However, notable differences were observed in their composition. We found that in the neonatal gut microbiome, Sediminibacterium and Thermovirga were positively associated with SPEI after controlling for PM2.5 in linear regression models. Additionally, SPEI was significantly associated with phenylpropanoid biosynthesis and cyanoamino acid metabolism in neonates. This study identified that prenatal SPEI levels were correlated with specific maternal and neonatal gut microbial taxa, as well as neonatal gut microbial functional pathways. Future studies should further investigate the mechanisms by which drought exposure influences maternal and neonatal gut microbial diversities, composition, and functional pathways.
Collapse
Affiliation(s)
- Qingbo Fang
- Center for Women's and Children's Health Research, Wuhan University School of Nursing, Wuhan University, 169 Donghu Road, Wuhan, 430071, China
| | - Tianlai Qiu
- Center for Women's and Children's Health Research, Wuhan University School of Nursing, Wuhan University, 169 Donghu Road, Wuhan, 430071, China
| | - Fenglan Chen
- Center for Women's and Children's Health Research, Wuhan University School of Nursing, Wuhan University, 169 Donghu Road, Wuhan, 430071, China
- Department of Pediatrics, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China
| | - Xuqi Tian
- Center for Women's and Children's Health Research, Wuhan University School of Nursing, Wuhan University, 169 Donghu Road, Wuhan, 430071, China
| | - Zijun Feng
- Center for Women's and Children's Health Research, Wuhan University School of Nursing, Wuhan University, 169 Donghu Road, Wuhan, 430071, China
| | - Yanan Cao
- Center for Women's and Children's Health Research, Wuhan University School of Nursing, Wuhan University, 169 Donghu Road, Wuhan, 430071, China
| | - Jinbing Bai
- Emory University Nell Hodgson Woodruff School of Nursing, 1520 Clifton Road, Atlanta, GA, 30322, USA
| | - Jing Huang
- Department of Occupational and Environmental Health Sciences, Peking University School of Public Health, Beijing, 100191, China
- Institute for Global Health and Development, Peking University, Beijing, China
| | - Yanqun Liu
- Center for Women's and Children's Health Research, Wuhan University School of Nursing, Wuhan University, 169 Donghu Road, Wuhan, 430071, China.
- Center for Women's and Children's Health Research, Wuhan University School of Nursing, Research Center for Lifespan Health, Wuhan University, 169 Donghu Road, Wuhan, 430071, China.
| |
Collapse
|
23
|
Basharat Z, Foster LJ, Abbas S, Yasmin A. Comparative Proteomics of Bacteria Under Stress Conditions. Methods Mol Biol 2025; 2859:129-162. [PMID: 39436600 DOI: 10.1007/978-1-0716-4152-1_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2024]
Abstract
Bacteria are unicellular organisms with the ability to exist in the harshest of climate and cope with sub-optimal fluctuating environmental conditions. They accomplish this by modification of their internal cellular environment. When external conditions are varied, change in the cell is triggered at the transcriptional level, which usually leads to proteolysis and rewiring of the proteome. Changes in cellular homeostasis, modifications in proteome, and dynamics of such survival mechanisms can be studied using various scientific techniques. Our focus in this chapter would be on comparative proteomics of bacteria under stress conditions using approaches like 2D electrophoresis accompanied by N-terminal sequencing and recently, mass spectrometry. More than 170 such studies on bacteria have been accomplished till to date and involve analysis of whole cells as well as that of cellular fractions, i.e., outer membrane, inner membrane, cell envelope, cytoplasm, thylakoid, lipid bodies, etc. Similar studies conducted on gram-negative and gram-positive model organism, i.e., Escherichia coli and Bacillus subtilis, respectively, have been summarized. Vital information, hypothesis about conservation of stress-specific proteome, and conclusions are also presented in the light of research conducted over the last decades.
Collapse
Affiliation(s)
| | - Leonard J Foster
- Department of Biochemistry and Molecular Biology, Michael Smith Labs, University of British Columbia, Vancouver, BC, Canada
| | - Sidra Abbas
- Department of Biotechnology, Fatima Jinnah Women University, Rawalpindi, Pakistan
| | - Azra Yasmin
- Microbiology & Biotechnology Research Lab, Department of Environmental Sciences, Fatima Jinnah Women University, Rawalpindi, Pakistan.
| |
Collapse
|
24
|
Lalli MK, Salo TE, Hakola L, Knip M, Virtanen SM, Vatanen T. Associations between dietary fibers and gut microbiome composition in the EDIA longitudinal infant cohort. Am J Clin Nutr 2025; 121:83-99. [PMID: 39551356 PMCID: PMC11747200 DOI: 10.1016/j.ajcnut.2024.11.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 10/31/2024] [Accepted: 11/12/2024] [Indexed: 11/19/2024] Open
Abstract
BACKGROUND The infant gut microbiome undergoes rapid changes in the first year of life, supporting normal development and long-term health. Although diet shapes this process, the role of fibers in complementary foods on gut microbiome maturation is poorly understood. OBJECTIVES We explored how the transition from human milk to fibers in complementary foods shapes the taxonomic and functional maturation of the gut microbiome within the first year of life. METHODS We assessed the longitudinal and cross-sectional development of infant gut microbiomes (N = 68 infants) and metabolomes (N = 33 infants) using linear mixed models to uncover their associations to dietary fibers and their food sources. Fiber intakes were assessed with 3-d food records (months 3, 6, 9, and 12) relying on CODEX-compliant fiber fraction values, and questionnaires tracked the overall complementary food introduction. Bacterial species were identified and quantified via MetaPhlAn2 from metagenomic data, and metabolomic profiles were obtained using 4 LC-MS methods. RESULTS We identified 176 complementary food fiber-bacterial species associations. First plant-based fibers associated with microbiota compositions similar to breastfeeding, and further associated with aromatic amino acid-derived metabolites, including 5-hydroxyindoleacetic acid (total dietary fiber - complementary foods (g) - β = 3.50, CI: 2.48, 4.52, P = 6.53 × 10-5). Distinct fibers from different food categories showed unique associations with specific bacterial taxa. Key species, such as Faecalibacterium prausnitznii, associated with oat fibers (g/MJ, β = 2.18, confidence interval: 1.36, 2.84, P = 6.12 × 10-6), reflective of maturing microbial communities. Fiber intake during weaning associated with shifts in metabolite profiles, including immunomodulatory metabolites, with fiber effects observed in a source- and timing-dependent manner, implicated in gradual microbiome diversification. CONCLUSIONS Introducing complementary dietary fibers during the weaning period supports gut microbiome diversification and stabilization. Even minor dietary variations shows significant associations with microbial taxa and functions from the onset of weaning, highlighting the importance of infant dietary recommendations that support the gut microbiome maturation during early life. This trial was registered at clinicaltrials.gov as registration number NCT01735123.
Collapse
Affiliation(s)
- Marianne K Lalli
- Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland
| | - Tuuli Ei Salo
- Department of Public Health, Finnish Institute for Health and Welfare, Helsinki, Finland; Unit of Health Sciences, Faculty of Social Sciences, Tampere University, Tampere, Finland
| | - Leena Hakola
- Department of Public Health, Finnish Institute for Health and Welfare, Helsinki, Finland; Unit of Health Sciences, Faculty of Social Sciences, Tampere University, Tampere, Finland; Tampere University Hospital, Wellbeing Services County of Pirkanmaa, Tampere, Finland
| | - Mikael Knip
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; New Children's Hospital, Helsinki University Hospital, Helsinki, Finland; Center for Child Health Research, Tampere University and Tampere University Hospital, Tampere, Finland
| | - Suvi M Virtanen
- Department of Public Health, Finnish Institute for Health and Welfare, Helsinki, Finland; Unit of Health Sciences, Faculty of Social Sciences, Tampere University, Tampere, Finland; Tampere University Hospital, Wellbeing Services County of Pirkanmaa, Tampere, Finland; Center for Child Health Research, Tampere University and Tampere University Hospital, Tampere, Finland
| | - Tommi Vatanen
- Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland; Department of Microbiology, Faculty of Agriculture and Forestry, University of Helsinki, Helsinki, Finland; Broad Institute of MIT and Harvard, Cambridge, MA, United States; Liggins Institute, University of Auckland, Auckland, New Zealand.
| |
Collapse
|
25
|
Dasari MR, Roche KE, Jansen D, Anderson J, Alberts SC, Tung J, Gilbert JA, Blekhman R, Mukherjee S, Archie EA. Social and environmental predictors of gut microbiome age in wild baboons. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.08.02.605707. [PMID: 39131274 PMCID: PMC11312535 DOI: 10.1101/2024.08.02.605707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 08/13/2024]
Abstract
Mammalian gut microbiomes are highly dynamic communities that shape and are shaped by host aging, including age-related changes to host immunity, metabolism, and behavior. As such, gut microbial composition may provide valuable information on host biological age. Here we test this idea by creating a microbiome-based age predictor using 13,563 gut microbial profiles from 479 wild baboons collected over 14 years. The resulting "microbiome clock" predicts host chronological age. Deviations from the clock's predictions are linked to some demographic and socio-environmental factors that predict baboon health and survival: animals who appear old-for-age tend to be male, sampled in the dry season (for females), and have high social status (both sexes). However, an individual's "microbiome age" does not predict the attainment of developmental milestones or lifespan. Hence, in our host population, gut microbiome age largely reflects current, as opposed to past, social and environmental conditions, and does not predict the pace of host development or host mortality risk. We add to a growing understanding of how age is reflected in different host phenotypes and what forces modify biological age in primates.
Collapse
Affiliation(s)
- Mauna R. Dasari
- Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA
- Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA
- California Academy of Sciences, San Francisco, CA, USA
| | - Kimberly E. Roche
- Program in Computational Biology and Bioinformatics, Duke University, Durham, NC, USA
| | - David Jansen
- Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA
| | - Jordan Anderson
- Department of Evolutionary Anthropology, Duke University, Durham, NC, USA
| | - Susan C. Alberts
- Department of Evolutionary Anthropology, Duke University, Durham, NC, USA
- Department of Biology, Duke University, Durham, NC, USA
- Duke University Population Research Institute, Duke University, Durham, NC, USA
| | - Jenny Tung
- Department of Evolutionary Anthropology, Duke University, Durham, NC, USA
- Department of Biology, Duke University, Durham, NC, USA
- Duke University Population Research Institute, Duke University, Durham, NC, USA
- Department of Primate Behavior and Evolution, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany
- Canadian Institute for Advanced Research, Toronto, Ontario, Canada
- Faculty of Life Sciences, Institute of Biology, Leipzig University, Leipzig, Germany
| | - Jack A. Gilbert
- Department of Pediatrics and the Scripps Institution of Oceanography, University of California, San Diego, San Diego, CA, USA
| | - Ran Blekhman
- Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA
| | - Sayan Mukherjee
- Departments of Statistical Science, Mathematics, Computer Science, and Bioinformatics & Biostatistics, Duke University, Durham, NC, USA
- Center for Scalable Data Analytics and Artificial Intelligence, University of Leipzig, Leipzig Germany
- Max Planck Institute for Mathematics in the Natural Sciences, Leipzig, Germany
| | - Elizabeth A. Archie
- Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA
| |
Collapse
|
26
|
Miao Y, Xie L, Chen S, Zhang X, Liu W, Xie P. Ketogenic diet in treating sepsis-related acquired weakness: is it friend or foe? Front Nutr 2024; 11:1484856. [PMID: 39668897 PMCID: PMC11636000 DOI: 10.3389/fnut.2024.1484856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Accepted: 11/05/2024] [Indexed: 12/14/2024] Open
Abstract
Background Sepsis is the body's extreme response to an infection leading to organ dysfunction. Sepsis-related acquired weakness (SAW), a critical illness closely related to metabolic disorders, is characterized by generalized sepsis-induced skeletal muscle weakness, mainly manifesting as symmetrical atrophy of respiratory and limb muscles. Muscle accounts for 40% of the body's total mass and is one of the major sites of glucose and energy absorption. Diet affects skeletal muscle metabolism, which further impacts physiology and signaling pathways. The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that has shown benefits in patients with a variety of neuromuscular disorders. Patients with SAW are in a hypermetabolic state and can consume approximately 1% of total body muscle mass in a day. Due to the decreased total body energy expenditure secondary to starvation, skeletal muscles enter a low metabolic state, with reduced gluconeogenesis and protein consumption and elevated levels of ketone bodies. The latest research suggests that KD may be a new strategy for SAW prevention and treatment, but its mechanism is still unclear. Objective Our article aims to explore the effect and mechanism of KD on SAW. And we hope that our review will inspire further research on the KD and foster the exploration of novel strategies for combating SAW. Methods Search medical databases and related academic websites, using keywords such as "Sepsis-related acquired weakness," "ketogenic diet," and "skeletal muscle," and select representative literature. Using the method of induction and summary, analyze the effect and mechanism of KD on SAW. Results Compared with early nutrition, KD has a more protective effect on SAW, but its mechanism is complex. Firstly, KD can alter energy metabolism substrates to affect SAW's energy metabolism; Secondly, KD can directly act as a signaling molecule to improve mitochondrial function in skeletal muscle and stimulate skeletal muscle regeneration signaling molecules; Thirdly, KD can affect the gut microbiota to exert anti-inflammatory effects, enhance immunity, and thus protect SAW. Conclusion KD has a protective effect on SAW, which includes improving energy metabolism, stimulating muscle regeneration signals, optimizing gut microbiota composition, and reducing inflammation and oxidative stress.
Collapse
Affiliation(s)
- Yanmei Miao
- Department of Critical Care Medicine of the Third Affiliated Hospital (The First People's Hospital of Zunyi), Zunyi Medical University, Zunyi, China
| | - Leiyu Xie
- Department of Critical Care Medicine of the Third Affiliated Hospital (The First People's Hospital of Zunyi), Zunyi Medical University, Zunyi, China
| | - Shaolin Chen
- Department of Nursing of Affiliated Hospital, Zunyi Medical University, Zunyi, China
| | - Xiaoming Zhang
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, United States
| | - Wenjie Liu
- Department of Anesthesiology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Peng Xie
- Department of Critical Care Medicine of the Third Affiliated Hospital (The First People's Hospital of Zunyi), Zunyi Medical University, Zunyi, China
- Department of Critical Care Medicine, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
| |
Collapse
|
27
|
Saleem J, Zakar R, Iqbal S, Arshad M, Shahzad R, Batool M, Nawaz M, Butt MS, Fischer F. Effects of prebiotics on microbial diversity and abundance in young children with acute malnutrition: study protocol for a multi-centered, double-blinded randomized controlled trial. Trials 2024; 25:798. [PMID: 39593072 PMCID: PMC11590257 DOI: 10.1186/s13063-024-08647-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Accepted: 11/21/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND The anti-inflammatory and antimicrobial benefits of prebiotics may present an affordable and cost-effective strategy for not only the prevention but also treatment of malnutrition. Therefore, the present trial has been designed with the aim to evaluate the role of prebiotics on the gut microbiome of severe acute malnourished (SAM) children. METHODS The study is designed as a prospective, double-blinded, triple-armed, multi-centered randomized controlled trial, with 6-59 months old uncomplicated SAM children recruited to the experimental group receiving ready-to-use therapeutic food (RUTF) plus prebiotics and the active comparator group receiving RUTF plus starch for 2 months duration (8 weeks). Healthy children with matching age and gender will be recruited to placebo comparator group and will receive starch as a placebo during the study period. A total of 58 participants will be recruited to each arm with 1:1:1 allocation ratio following a pre-defined inclusion and exclusion criteria. The results of the gut microbiome diversity will serve as the primary outcome, while weight-for-height/length z-score, mid-upper-arm circumference, neurodevelopment assessment, and body mass accumulation will serve as the secondary outcome. Data collection and evaluations will be conducted at baseline and at the end of the trial (week 8), while the safety monitoring will be conducted at every second week. For analysis, the principles of intention-to-treat will be followed. CONCLUSIONS Conclusively, the results of the present trial would provide useful insights and high-quality data for the treatment and management of SAM children by evaluating the effect of RUTF plus prebiotic on the gut microbiome diversity of children, leading to medical evidence for designing the large-scale studies. TRIAL REGISTRATION The present trial is registered at ClinicalTrials.gov with identifier No: NCT06155474 and registration date 4 December 2023.
Collapse
Affiliation(s)
- Javeria Saleem
- Department of Public Health, University of the Punjab, Lahore, Pakistan
| | - Rubeena Zakar
- Department of Public Health, University of the Punjab, Lahore, Pakistan
| | - Sanaullah Iqbal
- Department of Food Science and Human Nutrition, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | - Muhammad Arshad
- Centre for Genomics and Systems Biology, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - Ruhma Shahzad
- Department of Public Health, University of the Punjab, Lahore, Pakistan
| | - Munazza Batool
- Department of Public Health, University of the Punjab, Lahore, Pakistan
| | - Muhammad Nawaz
- Institute of Microbiology, University of Veterinary and Animal Sciences, Lahore, Pakistan
| | | | - Florian Fischer
- Institute of Public Health, Charité - Universitätsmedizin Berlin, Berlin, Germany.
| |
Collapse
|
28
|
Toussaint Nguélé A, Mozzicafreddo M, Carrara C, Piersanti A, Salum SS, Ali SM, Miceli C. Interplay Between Helminth Infections, Malnutrition, and Gut Microbiota in Children and Mothers from Pemba, Tanzania: Potential of Microbiota-Directed Interventions. Nutrients 2024; 16:4023. [PMID: 39683417 DOI: 10.3390/nu16234023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 11/20/2024] [Accepted: 11/21/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND/OBJECTIVES Despite efforts within the framework of the Sustainable Development Goal to end malnutrition by 2030, malnutrition and soil-transmitted helminth infections persist in sub-Saharan Africa. A significant barrier to success is the inadequate understanding of effective intervention methods. Most research on the gut microbiota's role in health has been conducted in developed countries, leaving a critical gap in knowledge regarding low-income populations. This study addresses this gap by expanding research on the gut microbiota of underprivileged populations to help tackle these public health challenges. METHODS We employed 16S rDNA sequencing to assess the bacterial gut microbiota composition of 60 children (mean age: 26.63 ± 6.36 months) and their 58 mothers (mean age: 30.03 ± 6.31 years) in Pemba, with a focus on helminth infection and nutritional status. RESULTS Our differential abundance analysis identified bacterial taxa that were significantly negatively associated with both helminth infections and malnutrition, highlighting the potential for microbiota-directed interventions to address these health issues simultaneously. Notably, we identified Akkermansia, Blautia, Dorea, and Odoribacter as promising probiotic candidates for such interventions. In stunted children, positive co-occurrences were observed between Lactobacillus, Prevotella, and Bacteroides, while Escherichia/Shigella displayed negative co-abundance relationships with short-chain fatty acid (SCFA) producers in the gut microbiota. These findings suggest that administering Lactobacillus and SCFA-producing probiotics to children may foster the growth of beneficial bacteria like Prevotella and Bacteroides while reducing the relative abundance of Escherichia/Shigella, potentially enhancing overall health. CONCLUSIONS This study underscores the importance of microbiota-directed interventions in children and women of reproductive age as promising strategies, alongside established approaches, for combating helminth infections and malnutrition in vulnerable populations.
Collapse
Affiliation(s)
- Aristide Toussaint Nguélé
- School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy
- Institut Supérieur des Sciences de la Santé, Université Adventiste Cosendai, Nanga Eboko 04, Cameroon
| | - Matteo Mozzicafreddo
- Department of Clinical and Molecular Sciences, Marche Polytechnic University, 60126 Ancona, Italy
| | - Chiara Carrara
- School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy
| | - Angela Piersanti
- School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy
- Department of Biology, University of Padova, 35121 Padova, Italy
| | - Salum Seif Salum
- School of Health and Medical Sciences, State University of Zanzibar, Zanzibar City 146, Tanzania
| | - Said M Ali
- Public Health Laboratory Ivo de Carneri, Chake Chake 122, Tanzania
| | - Cristina Miceli
- School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy
| |
Collapse
|
29
|
Ma N, Wang H, Li Q, Chang M, Zhu J, Nan S, Zhang Q, Li Q, Yang D, Ming K, Zhuang S, Guo P, Yin R, Sun J, Wang H, Lei Q, Liu Z, Ding M, Zhou X, Ding Y. Gut-derived IL-13 contributes to growth via promoting hepatic IGF-1 production. MICROBIOME 2024; 12:248. [PMID: 39580435 PMCID: PMC11585157 DOI: 10.1186/s40168-024-01929-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 09/10/2024] [Indexed: 11/25/2024]
Abstract
BACKGROUND The gut microbiota has a profound effect on immunity and metabolic status of the host, which has increasingly attracted research communities. However, the intrinsic mechanism underlying the interplay among these three aspects remains unclear. RESULTS Different immune states were established via shaping the population structure of gut microbiota with antibacterial agents. The gut microbiota population structures altered with the subtherapeutic level of antibacterial agents facilitated growth phenotype in both piglets and infant mice. Notably, increased colonization of Prevotella copri was observed in the intestinal microbiota, which shifted the immune balance from a CD4+ T cell-dominated population toward a T helper 2 cell (Th2) phenotype, accompanied by a significant elevation of interleukin-13 (IL-13) levels in the portal vein, which was found to display a strong positive correlation with hepatic insulin-like growth factor-1 (IGF-1) levels. Subsequent investigations unveiled that gut-derived IL-13 stimulated the production of hepatic IGF-1 by activating the IL-13R/Jak2/Stat6 pathway in vitro. The IGF-1 levels were increased in the muscles, leading to an upregulation of and resulted the increased genes associated with related to myofibrillar synthesis and differentiation, which ultimately improving the growth phenotype. CONCLUSIONS Our findings highlight the modification of gut immunity states as a central strategy for increasing anabolism of the host, which has significant implications for addressing human undernutrition/stunting, sarcopenia, obesity and related comorbidities. Video Abstract.
Collapse
Affiliation(s)
- Ning Ma
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China
| | - Haolong Wang
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China
| | - Qiuhua Li
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China
| | - Mengyu Chang
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China
| | - Jiandi Zhu
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China
| | - Sha Nan
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China
| | - Qiulin Zhang
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China
| | - Qiao Li
- College of Veterinary Medicine, Nanjing Agricultural University, Jiangsu, 210095, People's Republic of China
| | - Diqi Yang
- School of Animal Science and Technology, Hainan University, Haikou, 570228, People's Republic of China
| | - Ke Ming
- School of Life Sciences, Hubei University, Wuhan, 430070, People's Republic of China
| | - Shen Zhuang
- College of Animal Science and Technology, Northwest A&F University, Shanxi, 712100, People's Republic of China
| | - Panpan Guo
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China
| | - Ruiling Yin
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China
| | - Jinrui Sun
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China
| | - Huikang Wang
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China
| | - Qianghui Lei
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China
| | - Zhenli Liu
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China
| | - Mingxing Ding
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China
| | - Xiaoshu Zhou
- College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.
| | - Yi Ding
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.
| |
Collapse
|
30
|
Qiu T, Fang Q, Tian X, Cao Y, Fan X, Li Y, Tu Y, Liu L, Chen Z, Wei Y, Bai J, Huang J, Liu Y. Time-varying ambient air pollution exposure is associated with gut microbiome variation in the first 2 years of life. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2024; 360:124705. [PMID: 39134171 DOI: 10.1016/j.envpol.2024.124705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 08/06/2024] [Accepted: 08/07/2024] [Indexed: 08/16/2024]
Abstract
The infant gut microbiome matures greatly in the first year of life. Ambient air pollution (AAP) exposure is associated with the infant gut microbiome. However, whether time-varying AAP influences infant gut microbiome variation is rarely investigated. This study aimed to investigate the effects of PM2.5, PM10, and O3 on infant gut microbiome variation longitudinally. Demographic information, stool samples, and AAP exposure concentrations were collected at 6, 12, 24 months from infants. Gut microbiome was processed and analyzed using 16S rRNA V3-V4 gene regions. AAP exposure concentrations were calculated using the China High Air Pollutants (CHAP) database. Multiple pollutant models were used to assess the mixed effects of PM2.5, PM10, and O3 on infant gut microbiome variation. Infants' gut microbiomes at 6, 12, 24 months old had significant differences in alpha diversity, beta diversity, and community composition. PM2.5 and O3 respectively explained 6.3% and 5.3% of the differences in community composition for 24-month-old infants. Single pollutant exposure and multiple pollutant exposure in different periods were both associated with alpha diversity indices and specific gut microbial phyla and genera. AAP was more associated with infant gut microbial alpha diversity indices, phyla variations, and genera variations at 12-24 months than 6-12 months. Multiple pollutant exposure in 0-2 lag months showed negative correlations with 12-24 months variation in Escherichia-Shigella (β = -0.854, 95%CI: 1.398 to -0.310) and Enterococcus (β = -0.979, 95%CI: 1.429 to -0.530). This study highlighted that time-varying PM2.5, PM10, and O3 synergistically influenced the variation of alpha diversity and abundance of gut microbial taxa in infants. Further research is needed to explore the effects and mechanisms of other environmental exposures on infant gut microbiome variation.
Collapse
Affiliation(s)
- Tianlai Qiu
- Wuhan University School of Nursing, Wuhan University, 169 Donghu Road, Wuhan, 430071, China
| | - Qingbo Fang
- Wuhan University School of Nursing, Wuhan University, 169 Donghu Road, Wuhan, 430071, China
| | - Xuqi Tian
- Wuhan University School of Nursing, Wuhan University, 169 Donghu Road, Wuhan, 430071, China
| | - Yanan Cao
- Wuhan University School of Nursing, Wuhan University, 169 Donghu Road, Wuhan, 430071, China
| | - Xiaoxiao Fan
- Wuhan University School of Nursing, Wuhan University, 169 Donghu Road, Wuhan, 430071, China
| | - Yanting Li
- Wuhan University School of Nursing, Wuhan University, 169 Donghu Road, Wuhan, 430071, China
| | - Yiming Tu
- Wuhan University School of Nursing, Wuhan University, 169 Donghu Road, Wuhan, 430071, China
| | - Linxia Liu
- Wuhan University School of Nursing, Wuhan University, 169 Donghu Road, Wuhan, 430071, China
| | - Zitong Chen
- Wuhan University School of Nursing, Wuhan University, 169 Donghu Road, Wuhan, 430071, China
| | - Yi Wei
- Wuhan University School of Nursing, Wuhan University, 169 Donghu Road, Wuhan, 430071, China
| | - Jinbing Bai
- Emory University Nell Hodgson Woodruff School of Nursing, 1520 Clifton Road, Atlanta, GA, 30322, USA
| | - Jing Huang
- Department of Occupational and Environmental Health Sciences, Peking University School of Public Health, Beijing, 100191, China
| | - Yanqun Liu
- Wuhan University School of Nursing, Wuhan University, 169 Donghu Road, Wuhan, 430071, China; Research Center for Lifespan Health, Wuhan University, 169 Donghu Road, Wuhan, 430071, China.
| |
Collapse
|
31
|
Fundora MP, Calamaro CJ, Wu Y, Brown AM, St John A, Keiffer R, Xiang Y, Liu K, Gillespie S, Denning PW, Sanders-Lewis K, Seitter B, Bai J. Microbiome and Growth in Infants with Congenital Heart Disease. J Pediatr 2024; 274:114169. [PMID: 38944188 DOI: 10.1016/j.jpeds.2024.114169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 06/14/2024] [Accepted: 06/24/2024] [Indexed: 07/01/2024]
Abstract
OBJECTIVE To profile the gut microbiome (GM) in infants with congenital heart disease (CHD) undergoing cardiac surgery compared with matched infants and to investigate the association with growth (weight, length, and head circumference). STUDY DESIGN A prospective study in the cardiac intensive care unit at Children's Healthcare of Atlanta and newborn nursery within the Emory Healthcare system. Characteristics including weight, length, head circumference, and surgical variables were collected. Fecal samples were collected presurgery (T1), postsurgery (T2), and before discharge (T3), and once for controls. 16 small ribosomal RNA subunit V4 gene was sequenced from fecal samples and classified into taxonomy using Silva v138. RESULTS There were 34 children with CHD (cases) and 34 controls. Cases had higher alpha-diversity, and beta-diversity showed significant dissimilarities compared with controls. GM was associated with lower weight and smaller head circumference (z-score < 2). Lower weight was associated with less Acinetobacter, Clostridioides, Parabacteroides, and Escherichia-Shigella. Smaller head circumference with more Veillonella, less Acinetobacter, and less Parabacteroides. CONCLUSIONS Significant differences in GM diversity and abundance were observed between infants with CHD and control infants. Lower weight and smaller head circumference were associated with distinct GM patterns. Further study is needed to understand the longitudinal effect of microbial dysbiosis on growth in children with CHD.
Collapse
Affiliation(s)
- Michael P Fundora
- Children's Healthcare of Atlanta Cardiology, Emory School of Medicine, Emory University, Atlanta, GA
| | - Christina J Calamaro
- Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA; Children's Healthcare of Atlanta, Heart Center, Atlanta, GA
| | - Yuhua Wu
- Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA
| | - Ann-Marie Brown
- Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA; Children's Healthcare of Atlanta, Heart Center, Atlanta, GA; ECU Health, Greenville, NC
| | - Amelia St John
- Children's Healthcare of Atlanta, Heart Center, Atlanta, GA
| | | | - Yijin Xiang
- Children's Healthcare of Atlanta, Emory University School of Medicine, Biostatistics, Atlanta, GA
| | - Katie Liu
- Children's Healthcare of Atlanta, Emory University School of Medicine, Biostatistics, Atlanta, GA
| | - Scott Gillespie
- Children's Healthcare of Atlanta, Emory University School of Medicine, Biostatistics, Atlanta, GA
| | - Patricia Wei Denning
- Children's Healthcare of Atlanta, Neonatology, Emory University School of Medicine, Atlanta, GA
| | - Kolby Sanders-Lewis
- Children's Healthcare of Atlanta, Research Core, Emory University School of Medicine, Atlanta, GA
| | - Brooke Seitter
- Children's Healthcare of Atlanta, Research Core, Emory University School of Medicine, Atlanta, GA
| | - Jinbing Bai
- Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA.
| |
Collapse
|
32
|
Gulliver EL, Di Simone SK, Chonwerawong M, Forster SC. Unlocking the potential for microbiome-based therapeutics to address the sustainable development goal of good health and wellbeing. Microb Biotechnol 2024; 17:e70041. [PMID: 39487814 PMCID: PMC11531172 DOI: 10.1111/1751-7915.70041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 10/17/2024] [Indexed: 11/04/2024] Open
Abstract
Recent years have witnessed major advances and an ever-growing list of healthcare applications for microbiome-based therapeutics. However, these advances have disproportionately targeted diseases common in high-income countries (HICs). Within low- to middle-income countries (LMIC), opportunities for microbiome-based therapeutics include sexual health epidemics, maternal health, early life mortality, malnutrition, vaccine response and infectious diseases. In this review we detail the advances that have been achieved in microbiome-based therapeutics for these areas of healthcare and identify where further work is required. Current efforts to characterise microbiomes from LMICs will aid in targeting and optimisation of therapeutics and preventative strategies specifically suited to the unmet needs within these populations. Once achieved, opportunities from disease treatment and improved treatment efficacy through to disease prevention and vector control can be effectively addressed using probiotics and live biotherapeutics. Together these strategies have the potential to increase individual health, overcome logistical challenges and reduce overall medical, individual, societal and economic costs.
Collapse
Affiliation(s)
- Emily L. Gulliver
- Centre for Innate Immunity and Infectious DiseasesHudson Institute of Medical ResearchClaytonVictoriaAustralia
- Department of Molecular and Translational ScienceMonash UniversityClaytonVictoriaAustralia
| | - Sara K. Di Simone
- Centre for Innate Immunity and Infectious DiseasesHudson Institute of Medical ResearchClaytonVictoriaAustralia
- Ritchie Centre, HudsonInstitute of Medical ResearchMelbourneVictoriaAustralia
- Department of PaediatricsMonash UniversityMelbourneVictoriaAustralia
| | - Michelle Chonwerawong
- Centre for Innate Immunity and Infectious DiseasesHudson Institute of Medical ResearchClaytonVictoriaAustralia
- Department of Molecular and Translational ScienceMonash UniversityClaytonVictoriaAustralia
| | - Samuel C. Forster
- Centre for Innate Immunity and Infectious DiseasesHudson Institute of Medical ResearchClaytonVictoriaAustralia
- Department of Molecular and Translational ScienceMonash UniversityClaytonVictoriaAustralia
| |
Collapse
|
33
|
Cheng J, Venkatesh S, Ke K, Barratt MJ, Gordon JI. A human gut Faecalibacterium prausnitzii fatty acid amide hydrolase. Science 2024; 386:eado6828. [PMID: 39446943 PMCID: PMC11572954 DOI: 10.1126/science.ado6828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Accepted: 08/14/2024] [Indexed: 10/26/2024]
Abstract
Undernutrition in Bangladeshi children is associated with disruption of postnatal gut microbiota assembly; compared with standard therapy, a microbiota-directed complementary food (MDCF) substantially improved their ponderal and linear growth. Here, we characterize a fatty acid amide hydrolase (FAAH) from a growth-associated intestinal strain of Faecalibacterium prausnitzii cultured from these children. This enzyme, expressed and purified from Escherichia coli, hydrolyzes a variety of N-acylamides, including oleoylethanolamide (OEA), neurotransmitters, and quorum sensing N-acyl homoserine lactones; it also synthesizes a range of N-acylamides, notably N-acyl amino acids. Treating germ-free mice with N-oleoylarginine and N-oleolyhistidine, major products of FAAH OEA metabolism, markedly affected expression of intestinal immune function pathways. Administering MDCF to Bangladeshi children considerably reduced fecal OEA, a satiety factor whose levels were negatively correlated with abundance and expression of their F. prausnitzii FAAH. This enzyme, structurally and catalytically distinct from mammalian FAAH, is positioned to regulate levels of a variety of bioactive molecules.
Collapse
Affiliation(s)
- Jiye Cheng
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA
- The Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA
| | - Siddarth Venkatesh
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA
- The Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA
| | - Ke Ke
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA
- The Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA
| | - Michael J. Barratt
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA
- The Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA
| | - Jeffrey I. Gordon
- The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA
- The Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA
| |
Collapse
|
34
|
Perruzza L, Heckmann J, Rezzonico Jost T, Raneri M, Guglielmetti S, Gargari G, Palatella M, Willers M, Fehlhaber B, Werlein C, Vogl T, Roth J, Grassi F, Viemann D. Postnatal supplementation with alarmins S100a8/a9 ameliorates malnutrition-induced neonate enteropathy in mice. Nat Commun 2024; 15:8623. [PMID: 39366940 PMCID: PMC11452687 DOI: 10.1038/s41467-024-52829-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Accepted: 09/19/2024] [Indexed: 10/06/2024] Open
Abstract
Malnutrition is linked to 45% of global childhood mortality, however, the impact of maternal malnutrition on the child's health remains elusive. Previous studies suggested that maternal malnutrition does not affect breast milk composition. Yet, malnourished children often develop a so-called environmental enteropathy, assumed to be triggered by frequent pathogen uptake and unfavorable gut colonization. Here, we show in a murine model that maternal malnutrition induces a persistent inflammatory gut dysfunction in the offspring that establishes during nursing and does not recover after weaning onto standard diet. Early intestinal influx of neutrophils, impaired postnatal development of gut-regulatory functions, and expansion of Enterobacteriaceae were hallmarks of this enteropathy. This gut phenotype resembled those developing under deficient S100a8/a9-supply via breast milk, which is a known key factor for the postnatal development of gut homeostasis. We could confirm that S100a8/a9 is lacking in the breast milk of malnourished mothers and the offspring's intestine. Nutritional supply of S100a8 to neonates of malnourished mothers abrogated the aberrant development of gut mucosal immunity and microbiota colonization and protected them lifelong against severe enteric infections and non-infectious bowel diseases. S100a8 supplementation after birth might be a promising measure to counteract deleterious imprinting of gut immunity by maternal malnutrition.
Collapse
Affiliation(s)
- Lisa Perruzza
- Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana (USI), Bellinzona, Switzerland.
- Humabs BioMed SA a Subsidiary of Vir Biotechnology Inc., Bellinzona, Switzerland.
| | - Julia Heckmann
- Department of Pediatrics, University Hospital Würzburg, Würzburg, Germany
| | - Tanja Rezzonico Jost
- Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana (USI), Bellinzona, Switzerland
| | - Matteo Raneri
- Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana (USI), Bellinzona, Switzerland
| | - Simone Guglielmetti
- Department of Biotechnology and Biosciences (BtBs), University of Milano-Bicocca, Milan, Italy
- Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy
| | - Giorgio Gargari
- Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy
| | - Martina Palatella
- Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana (USI), Bellinzona, Switzerland
| | - Maike Willers
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany
| | - Beate Fehlhaber
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany
| | | | - Thomas Vogl
- Institute of Immunology, University of Münster, Münster, Germany
| | - Johannes Roth
- Institute of Immunology, University of Münster, Münster, Germany
| | - Fabio Grassi
- Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana (USI), Bellinzona, Switzerland
| | - Dorothee Viemann
- Department of Pediatrics, University Hospital Würzburg, Würzburg, Germany.
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
- Center for Infection Research, University Würzburg, Würzburg, Germany.
- Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany.
| |
Collapse
|
35
|
Hartman SJ, Hibberd MC, Mostafa I, Naila NN, Islam MM, Zaman MU, Huq S, Mahfuz M, Islam MT, Mukherji K, Moghaddam VA, Chen RY, Province MA, Webber DM, Henrissat S, Henrissat B, Terrapon N, Rodionov DA, Osterman AL, Barratt MJ, Ahmed T, Gordon JI. A microbiome-directed therapeutic food for children recovering from severe acute malnutrition. Sci Transl Med 2024; 16:eadn2366. [PMID: 39356745 PMCID: PMC11572952 DOI: 10.1126/scitranslmed.adn2366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Accepted: 07/22/2024] [Indexed: 10/04/2024]
Abstract
Globally, severe acute malnutrition (SAM), defined as a weight-for-length z-score more than three SDs below a reference mean (WLZ < -3), affects 14 million children under 5 years of age. Complete anthropometric recovery after standard, short-term interventions is rare, with children often left with moderate acute malnutrition (MAM; WLZ -2 to -3). We conducted a randomized controlled trial (RCT) involving 12- to 18-month-old Bangladeshi children from urban and rural sites, who, after initial hospital-based treatment for SAM, received a 3-month intervention with a microbiome-directed complementary food (MDCF-2) or a calorically more dense, standard ready-to-use supplementary food (RUSF). The rate of WLZ improvement was significantly greater in MDCF-2-treated children (P = 8.73 × 10-3), similar to our previous RCT of Bangladeshi children with MAM without antecedent SAM (P = 0.032). A correlated meta-analysis of plasma levels of 4520 proteins in both RCTs revealed 215 positively associated with WLZ (largely representing musculoskeletal and central nervous system development) and 44 negatively associated (primarily related to immune activation). Moreover, the positively associated proteins were significantly enriched by MDCF-2 (q = 1.1 × 10-6). Characterizing the abundances of 754 bacterial metagenome-assembled genomes in serially collected fecal samples disclosed the effects of acute rehabilitation for SAM on the microbiome and how, during treatment for MAM, specific strains of Prevotella copri function at the intersection between MDCF-2 glycan metabolism and anthropometric recovery. These results provide a rationale for further testing the generalizability of MDCF efficacy and for identifying biomarkers to define treatment responses.
Collapse
Affiliation(s)
- Steven J. Hartman
- Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA
- Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA
| | - Matthew C. Hibberd
- Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA
- Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110 USA
| | - Ishita Mostafa
- International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, Bangladesh
| | - Nurun N. Naila
- International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, Bangladesh
| | - Md. Munirul Islam
- International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, Bangladesh
| | - Mahabub Uz Zaman
- International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, Bangladesh
| | - Sayeeda Huq
- International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, Bangladesh
| | - Mustafa Mahfuz
- International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, Bangladesh
| | - Md. Tazul Islam
- Terre des Hommes Netherlands - Bangladesh Country Office, Dhaka 1209, Bangladesh
| | - Kallol Mukherji
- Terre des Hommes Netherlands - Bangladesh Country Office, Dhaka 1209, Bangladesh
| | - Vaha Akbary Moghaddam
- Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110 USA
| | - Robert Y. Chen
- Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA
- Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA
| | - Michael A. Province
- Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110 USA
| | - Daniel M. Webber
- Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA
- Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110 USA
| | - Suzanne Henrissat
- Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA
- Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA
| | - Bernard Henrissat
- Department of Biotechnology and Biomedicine (DTU Bioengineering), Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark
- Department of Biological Sciences, King Abdulaziz University, Jeddah, 21589 Saudi Arabia
| | - Nicolas Terrapon
- Architecture et Fonction des Macromolécules Biologiques, CNRS, Aix-Marseille University, F-13288, Marseille, France
| | - Dmitry A. Rodionov
- Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037 USA
| | - Andrei L. Osterman
- Infectious and Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037 USA
| | - Michael J. Barratt
- Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA
- Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110 USA
| | - Tahmeed Ahmed
- International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, Bangladesh
| | - Jeffrey I. Gordon
- Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63110 USA
- Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, MO 63110 USA
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110 USA
| |
Collapse
|
36
|
Gopalakrishnappa C, Li Z, Kuehn S. Environmental modulators of algae-bacteria interactions at scale. Cell Syst 2024; 15:838-853.e13. [PMID: 39236710 PMCID: PMC11412779 DOI: 10.1016/j.cels.2024.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Revised: 11/29/2023] [Accepted: 08/07/2024] [Indexed: 09/07/2024]
Abstract
Interactions between photosynthetic and heterotrophic microbes play a key role in global primary production. Understanding phototroph-heterotroph interactions remains challenging because these microbes reside in chemically complex environments. Here, we leverage a massively parallel droplet microfluidic platform that enables us to interrogate interactions between photosynthetic algae and heterotrophic bacteria in >100,000 communities across ∼525 environmental conditions with varying pH, carbon availability, and phosphorus availability. By developing a statistical framework to dissect interactions in this complex dataset, we reveal that the dependence of algae-bacteria interactions on nutrient availability is strongly modulated by pH and buffering capacity. Furthermore, we show that the chemical identity of the available organic carbon source controls how pH, buffering capacity, and nutrient availability modulate algae-bacteria interactions. Our study reveals the previously underappreciated role of pH in modulating phototroph-heterotroph interactions and provides a framework for thinking about interactions between phototrophs and heterotrophs in more natural contexts.
Collapse
Affiliation(s)
| | - Zeqian Li
- Department of Physics, The University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Center for the Physics of Evolving Systems, The University of Chicago, Chicago, IL 60637, USA; Department of Ecology and Evolution, The University of Chicago, Chicago, IL 60637, USA
| | - Seppe Kuehn
- Center for the Physics of Evolving Systems, The University of Chicago, Chicago, IL 60637, USA; Department of Ecology and Evolution, The University of Chicago, Chicago, IL 60637, USA; National Institute for Theory and Mathematics in Biology, Northwestern University and The University of Chicago, Chicago, IL 60637, USA; Center for Living Systems, The University of Chicago, Chicago, IL 60637, USA.
| |
Collapse
|
37
|
Wang H, Basang W, Pingcuo Z, Jiang N, Sun G, Nawaz S, Cidan Y, Liu Y, Zhu Y, Luosang D. Impact of weight variation on the microbiome of yak dams and calves. Front Microbiol 2024; 15:1465992. [PMID: 39360324 PMCID: PMC11446105 DOI: 10.3389/fmicb.2024.1465992] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 08/26/2024] [Indexed: 10/04/2024] Open
Abstract
Introduction Limited information exists regarding the microbiome composition of yak calves of varying weights. Therefore, this study aimed to investigate the microbiomes of mother-calf pairs with different weight profiles. Methods Fecal and blood samples were collected from both lower-weight (CB) and higher-weight (HB) yak calves, along with their corresponding female yaks (CA, HA). Results The results revealed significantly higher levels of T-AOC (total antioxidant capacity) and GSH-Px (glutathione peroxidase) in HB animals (p < 0.001). Sequencing yielded 652,181 and 643,369 filtered reads in female and calf yaks, respectively. Alpha diversity analysis indicated that Chao1, Faith_pd, and Observed species were significantly higher in CA compared to HA (p < 0.01). Furthermore, nine genera were notably different between HA and CA yaks, including Avispirillum, Fimenecus, CAG-1031, Odoribacter 865974, and Jeotgalicoccus A 310962. Compared to CB yaks, CA animals exhibited significant differences in one phylum and six genera, including CAG-485 (p < 0.05), CAG-83 (p < 0.01), Copromorpha (p < 0.01), Phocaeicola A 858004 (p < 0.05), and UBA2253 (p < 0.05). Conclusion In summary, higher-weight yak calves demonstrated increased oxidative resistance, and weight profiles were linked to the microbiomes of both female yaks and their calves. These findings offer valuable insights for optimizing yak breeding practices in high-altitude regions.
Collapse
Affiliation(s)
- Hongzhuang Wang
- State Key Laboratory of Hulless Barley and Yak Germplasm Resources and Genetic Improvement, Lhasa, China
- Institute of Animal Husbandry and Veterinary Medicine, Tibet Academy of Agriculture and Animal Husbandry Science, Lhasa, China
| | - Wangdui Basang
- State Key Laboratory of Hulless Barley and Yak Germplasm Resources and Genetic Improvement, Lhasa, China
- Institute of Animal Husbandry and Veterinary Medicine, Tibet Academy of Agriculture and Animal Husbandry Science, Lhasa, China
| | - Zhandui Pingcuo
- State Key Laboratory of Hulless Barley and Yak Germplasm Resources and Genetic Improvement, Lhasa, China
- Institute of Animal Husbandry and Veterinary Medicine, Tibet Academy of Agriculture and Animal Husbandry Science, Lhasa, China
| | - Nan Jiang
- State Key Laboratory of Hulless Barley and Yak Germplasm Resources and Genetic Improvement, Lhasa, China
- Institute of Animal Husbandry and Veterinary Medicine, Tibet Academy of Agriculture and Animal Husbandry Science, Lhasa, China
| | - Guangming Sun
- State Key Laboratory of Hulless Barley and Yak Germplasm Resources and Genetic Improvement, Lhasa, China
- Institute of Animal Husbandry and Veterinary Medicine, Tibet Academy of Agriculture and Animal Husbandry Science, Lhasa, China
| | - Shah Nawaz
- Department of Anatomy, Faculty of Veterinary Science, University of Agriculture, Faisalabad, Pakistan
| | - Yangji Cidan
- State Key Laboratory of Hulless Barley and Yak Germplasm Resources and Genetic Improvement, Lhasa, China
- Institute of Animal Husbandry and Veterinary Medicine, Tibet Academy of Agriculture and Animal Husbandry Science, Lhasa, China
| | - Yang Liu
- State Key Laboratory of Hulless Barley and Yak Germplasm Resources and Genetic Improvement, Lhasa, China
- Institute of Animal Husbandry and Veterinary Medicine, Tibet Academy of Agriculture and Animal Husbandry Science, Lhasa, China
| | - Yanbin Zhu
- State Key Laboratory of Hulless Barley and Yak Germplasm Resources and Genetic Improvement, Lhasa, China
- Institute of Animal Husbandry and Veterinary Medicine, Tibet Academy of Agriculture and Animal Husbandry Science, Lhasa, China
| | - Dunzhu Luosang
- State Key Laboratory of Hulless Barley and Yak Germplasm Resources and Genetic Improvement, Lhasa, China
- Institute of Animal Husbandry and Veterinary Medicine, Tibet Academy of Agriculture and Animal Husbandry Science, Lhasa, China
| |
Collapse
|
38
|
Van Hul M, Neyrinck AM, Everard A, Abot A, Bindels LB, Delzenne NM, Knauf C, Cani PD. Role of the intestinal microbiota in contributing to weight disorders and associated comorbidities. Clin Microbiol Rev 2024; 37:e0004523. [PMID: 38940505 PMCID: PMC11391702 DOI: 10.1128/cmr.00045-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/29/2024] Open
Abstract
SUMMARYThe gut microbiota is a major factor contributing to the regulation of energy homeostasis and has been linked to both excessive body weight and accumulation of fat mass (i.e., overweight, obesity) or body weight loss, weakness, muscle atrophy, and fat depletion (i.e., cachexia). These syndromes are characterized by multiple metabolic dysfunctions including abnormal regulation of food reward and intake, energy storage, and low-grade inflammation. Given the increasing worldwide prevalence of obesity, cachexia, and associated metabolic disorders, novel therapeutic strategies are needed. Among the different mechanisms explaining how the gut microbiota is capable of influencing host metabolism and energy balance, numerous studies have investigated the complex interactions existing between nutrition, gut microbes, and their metabolites. In this review, we discuss how gut microbes and different microbiota-derived metabolites regulate host metabolism. We describe the role of the gut barrier function in the onset of inflammation in this context. We explore the importance of the gut-to-brain axis in the regulation of energy homeostasis and glucose metabolism but also the key role played by the liver. Finally, we present specific key examples of how using targeted approaches such as prebiotics and probiotics might affect specific metabolites, their signaling pathways, and their interactions with the host and reflect on the challenges to move from bench to bedside.
Collapse
Affiliation(s)
- Matthias Van Hul
- UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute (LDRI), Metabolism and Nutrition Research Group (MNUT), Brussels, Belgium
- Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), WELBIO department, WEL Research Institute, Wavre, Belgium
- NeuroMicrobiota, International Research Program (IRP) INSERM/UCLouvain, France/Belgium
| | - Audrey M Neyrinck
- UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute (LDRI), Metabolism and Nutrition Research Group (MNUT), Brussels, Belgium
| | - Amandine Everard
- UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute (LDRI), Metabolism and Nutrition Research Group (MNUT), Brussels, Belgium
- Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), WELBIO department, WEL Research Institute, Wavre, Belgium
| | | | - Laure B Bindels
- UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute (LDRI), Metabolism and Nutrition Research Group (MNUT), Brussels, Belgium
- Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), WELBIO department, WEL Research Institute, Wavre, Belgium
| | - Nathalie M Delzenne
- UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute (LDRI), Metabolism and Nutrition Research Group (MNUT), Brussels, Belgium
| | - Claude Knauf
- NeuroMicrobiota, International Research Program (IRP) INSERM/UCLouvain, France/Belgium
- INSERM U1220, Institut de Recherche en Santé Digestive (IRSD), Université Paul Sabatier, Toulouse III, CHU Purpan, Toulouse, France
| | - Patrice D Cani
- UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute (LDRI), Metabolism and Nutrition Research Group (MNUT), Brussels, Belgium
- Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), WELBIO department, WEL Research Institute, Wavre, Belgium
- NeuroMicrobiota, International Research Program (IRP) INSERM/UCLouvain, France/Belgium
- UCLouvain, Université catholique de Louvain, Institute of Experimental and Clinical Research (IREC), Brussels, Belgium
| |
Collapse
|
39
|
Berggren H, Yıldırım Y, Nordahl O, Larsson P, Dopson M, Tibblin P, Lundin D, Pinhassi J, Forsman A. Ecological filtering drives rapid spatiotemporal dynamics in fish skin microbiomes. Mol Ecol 2024; 33:e17496. [PMID: 39161196 DOI: 10.1111/mec.17496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 08/01/2024] [Accepted: 08/05/2024] [Indexed: 08/21/2024]
Abstract
Skin microbiomes provide vital functions, yet knowledge about the drivers and processes structuring their species assemblages is limited-especially for non-model organisms. In this study, fish skin microbiome was assessed by high throughput sequencing of amplicon sequence variants from metabarcoding of V3-V4 regions in the 16S rRNA gene on fish hosts subjected to the following experimental manipulations: (i) translocation between fresh and brackish water habitats to investigate the role of environment; (ii) treatment with an antibacterial disinfectant to reboot the microbiome and investigate community assembly and priority effects; and (iii) maintained alone or in pairs to study the role of social environment and inter-host dispersal of microbes. The results revealed that fish skin microbiomes harbour a highly dynamic microbial composition that was distinct from bacterioplankton communities in the ambient water. Microbiome composition first diverged as an effect of translocation to either the brackish or freshwater habitat. When the freshwater individuals were translocated back to brackish water, their microbiome composition converged towards the fish microbiomes in the brackish habitat. In summary, external environmental conditions and individual-specific factors jointly determined the community composition dynamics, whereas inter-host dispersal had negligible effects. The dynamics of the microbiome composition was seemingly non-affected by reboot treatment, pointing towards high resilience to disturbance. The results emphasised the role of inter-individual variability for the unexplained variation found in many host-microbiome systems, although the mechanistic underpinnings remain to be identified.
Collapse
Affiliation(s)
- Hanna Berggren
- Ecology and Evolution in Microbial Model Systems (EEMiS), Department of Biology and Environmental Science, Linnaeus University, Kalmar, Sweden
| | - Yeşerin Yıldırım
- Department of Ecology and Genetics, Uppsala University, Uppsala, Sweden
| | - Oscar Nordahl
- Ecology and Evolution in Microbial Model Systems (EEMiS), Department of Biology and Environmental Science, Linnaeus University, Kalmar, Sweden
| | - Per Larsson
- Ecology and Evolution in Microbial Model Systems (EEMiS), Department of Biology and Environmental Science, Linnaeus University, Kalmar, Sweden
| | - Mark Dopson
- Ecology and Evolution in Microbial Model Systems (EEMiS), Department of Biology and Environmental Science, Linnaeus University, Kalmar, Sweden
| | - Petter Tibblin
- Ecology and Evolution in Microbial Model Systems (EEMiS), Department of Biology and Environmental Science, Linnaeus University, Kalmar, Sweden
| | - Daniel Lundin
- Ecology and Evolution in Microbial Model Systems (EEMiS), Department of Biology and Environmental Science, Linnaeus University, Kalmar, Sweden
| | - Jarone Pinhassi
- Ecology and Evolution in Microbial Model Systems (EEMiS), Department of Biology and Environmental Science, Linnaeus University, Kalmar, Sweden
| | - Anders Forsman
- Ecology and Evolution in Microbial Model Systems (EEMiS), Department of Biology and Environmental Science, Linnaeus University, Kalmar, Sweden
| |
Collapse
|
40
|
Mertelsmann AM, Bowers SF, Wright D, Maganga JK, Mazigo HD, Ndhlovu LC, Changalucha JM, Downs JA. Effects of Schistosoma haematobium infection and treatment on the systemic and mucosal immune phenotype, gene expression and microbiome: A systematic review. PLoS Negl Trop Dis 2024; 18:e0012456. [PMID: 39250522 PMCID: PMC11412685 DOI: 10.1371/journal.pntd.0012456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 09/19/2024] [Accepted: 08/13/2024] [Indexed: 09/11/2024] Open
Abstract
BACKGROUND Urogenital schistosomiasis caused by Schistosoma haematobium affects approximately 110 million people globally, with the majority of cases in low- and middle-income countries. Schistosome infections have been shown to impact the host immune system, gene expression, and microbiome composition. Studies have demonstrated variations in pathology between schistosome subspecies. In the case of S. haematobium, infection has been associated with HIV acquisition and bladder cancer. However, the underlying pathophysiology has been understudied compared to other schistosome species. This systematic review comprehensively investigates and assimilates the effects of S. haematobium infection on systemic and local host mucosal immunity, cellular gene expression and microbiome. METHODS We conducted a systematic review assessing the reported effects of S. haematobium infections and anthelmintic treatment on the immune system, gene expression and microbiome in humans and animal models. This review followed PRISMA guidelines and was registered prospectively in PROSPERO (CRD42022372607). Randomized clinical trials, cohort, cross-sectional, case-control, experimental ex vivo, and animal studies were included. Two reviewers performed screening independently. RESULTS We screened 3,177 studies and included 94. S. haematobium was reported to lead to: (i) a mixed immune response with a predominant type 2 immune phenotype, increased T and B regulatory cells, and select pro-inflammatory cytokines; (ii) distinct molecular alterations that would compromise epithelial integrity, such as increased metalloproteinase expression, and promote immunological changes and cellular transformation, specifically upregulation of genes p53 and Bcl-2; and (iii) microbiome dysbiosis in the urinary, intestinal, and genital tracts. CONCLUSION S. haematobium induces distinct alterations in the host's immune system, molecular profile, and microbiome. This leads to a diverse range of inflammatory and anti-inflammatory responses and impaired integrity of the local mucosal epithelial barrier, elevating the risks of secondary infections. Further, S. haematobium promotes cellular transformation with oncogenic potential and disrupts the microbiome, further influencing the immune system and genetic makeup. Understanding the pathophysiology of these interactions can improve outcomes for the sequelae of this devastating parasitic infection.
Collapse
Affiliation(s)
- Anna M Mertelsmann
- Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, United States of America
- Center for Global Health, Weill Cornell Medicine, New York, New York, United States of America
| | - Sheridan F Bowers
- Center for Global Health, Weill Cornell Medicine, New York, New York, United States of America
| | - Drew Wright
- Samuel J. Wood Library & C.V. Starr Biomedical Information Center, Weill Cornell Medical College, New York, New York, United States of America
| | - Jane K Maganga
- Mwanza Intervention Trials Unit/National Institute for Medical Research, Mwanza, Tanzania
| | - Humphrey D Mazigo
- Department of Parasitology and Entomology, Catholic University of Health and Allied Sciences, Mwanza, Tanzania
| | - Lishomwa C Ndhlovu
- Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, United States of America
| | - John M Changalucha
- Mwanza Intervention Trials Unit/National Institute for Medical Research, Mwanza, Tanzania
| | - Jennifer A Downs
- Center for Global Health, Weill Cornell Medicine, New York, New York, United States of America
- Mwanza Intervention Trials Unit/National Institute for Medical Research, Mwanza, Tanzania
- Weill Bugando School of Medicine, Mwanza, Tanzania
| |
Collapse
|
41
|
Chen L, Bao Y, Wang D, Tian Y, Zeng T, Gu T, Xu W, Lu L. Integrated omics analysis reveals the differentiation of intestinal microbiota and metabolites between Pekin ducks and Shaoxing ducks. Poult Sci 2024; 103:103976. [PMID: 39024692 PMCID: PMC11315098 DOI: 10.1016/j.psj.2024.103976] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 05/21/2024] [Accepted: 06/10/2024] [Indexed: 07/20/2024] Open
Abstract
Pekin ducks and Shaoxing ducks are 2 Chinese local duck breeds, both domesticated from mallard, but after domestication and long-term artificial selection, the body weight of Pekin ducks is significantly higher than that of Shaoxing ducks. It is no debate that genetic factors are the main factors responsible for this difference, but whether intestinal microbiota contribute to this difference is yet unknown. Thus, we performed comparative intestinal metagenomics and metabolomics analysis between Pekin ducks and Shaoxing ducks. We found obvious differentiation of intestinal metagenome and metabolome between the 2 breeds. Four cecal microbial genera, including Fusobacterium, Methanobrevibacter, Butyricicoccus, and Anaerotignum showed higher abundance in Pekin ducks. Among them, Methanobrevibacter and Butyricicoccus may positively correlate with fat deposition and body weight. A total of 310 metabolites showed difference between the 2 breeds. Functions of these differential metabolites were mainly enriched in amino acid metabolism, including energy metabolism-related histidine metabolism. Integrated omics analysis showed that microbial changes were closely related to altered metabolites. Especially, Butyricicoccus showing higher abundance in Pekin ducks was significantly negatively correlated with D-glucosamine-6-phosphate, which has been reported to prevent body weight gains. These findings may contribute to further understand the difference in body weight between Pekin ducks and Shaoxing ducks.
Collapse
Affiliation(s)
- Li Chen
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Zhejiang-Ukraine Joint Laboratory for Poultry Germplasm Resources Conservation, Exploitation and Utilization, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China; Xianghu Laboratory, Hangzhou, 311231, China
| | - Ying Bao
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Zhejiang-Ukraine Joint Laboratory for Poultry Germplasm Resources Conservation, Exploitation and Utilization, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
| | - Dandan Wang
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Zhejiang-Ukraine Joint Laboratory for Poultry Germplasm Resources Conservation, Exploitation and Utilization, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
| | - Yong Tian
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Zhejiang-Ukraine Joint Laboratory for Poultry Germplasm Resources Conservation, Exploitation and Utilization, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
| | - Tao Zeng
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Zhejiang-Ukraine Joint Laboratory for Poultry Germplasm Resources Conservation, Exploitation and Utilization, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
| | - Tiantian Gu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Zhejiang-Ukraine Joint Laboratory for Poultry Germplasm Resources Conservation, Exploitation and Utilization, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
| | - Wenwu Xu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Zhejiang-Ukraine Joint Laboratory for Poultry Germplasm Resources Conservation, Exploitation and Utilization, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
| | - Lizhi Lu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Zhejiang-Ukraine Joint Laboratory for Poultry Germplasm Resources Conservation, Exploitation and Utilization, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China.
| |
Collapse
|
42
|
Zhen L, Huang Y, Bi X, Gao A, Peng L, Chen Y. Melatonin feeding changed the microbial diversity and metabolism of the broiler cecum. Front Microbiol 2024; 15:1422272. [PMID: 39224220 PMCID: PMC11367786 DOI: 10.3389/fmicb.2024.1422272] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 08/02/2024] [Indexed: 09/04/2024] Open
Abstract
To study the effect of melatonin supplementation on the gut microbes of broilers, 160 healthy 3-week-old Ross 308 broilers with similar body weights were selected and randomly divided into four groups (M0, M20, M40, and M80) supplemented with 0, 20, 40, or 80 mg/kg melatonin. The results showed that the abundance-based coverage estimator (ACE) index of cecum microorganisms was significantly lower in the M80 group. The dominant phyla of intestinal contents in the M0, M20, M40, and M80 groups were Bacteroidetes and Firmicutes. The M40 group showed an increase in the relative abundance of Bacteroidetes spp. in the intestine, while the relative abundance of Ruminococcus spp. in the intestine of the M20, M40, and M80 groups was significantly greater than that of the M0 group. Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses revealed that the supplementation of melatonin increases the expression of genes related to cellular processes (cell motility, cell growth and death, and cellular community-eukaryotes), environmental information processing (membrane transport and signal transduction), and genetic information processing (transport and transcription), and Cluster of Orthologous Groups (COG) of proteins functional analyses revealed that the supplementation of melatonin resulted in a significant increase in cellular processes and signaling (cell motility, signal transduction mechanisms, intracellular trafficking, secretion, and vesicular transport), information storage and processing (RNA processing and modification, chromatin structure and dynamics, translation, ribosomal structure, and biogenesis), metabolism (energy production and conversion, lipid transportation and metabolism, inorganic ion transport and metabolism, secondary metabolite biosynthesis, transport, and catabolism), and poorly characterized (general function prediction only). In summary, supplementation of feed with melatonin can increase the diversity of intestinal microorganisms and the relative abundance of Bacteroides and Firmicutes in the cecum, improve digestive ability and nutrient absorption ability, and positively regulate the metabolic ability of broilers.
Collapse
Affiliation(s)
- Li Zhen
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China
- Key Laboratory of Bovine Disease Control in Northeast China, Ministry of Agriculture and Rural Affairs, Daqing, China
- Heilongjiang Provincial Key Laboratory of Prevention and Control of Bovine Diseases, Daqing, China
| | - Yi Huang
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China
| | - Xuewen Bi
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China
| | - Anyu Gao
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China
| | - Linlin Peng
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China
| | - Yong Chen
- College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, China
| |
Collapse
|
43
|
Liu F, Ye F, Yang Y, Kang Z, Liu Y, Chen W, Wang S, Kou H, Kang L, Sun J. Gut bacteria are essential for development of an invasive bark beetle by regulating glucose transport. Proc Natl Acad Sci U S A 2024; 121:e2410889121. [PMID: 39110737 PMCID: PMC11331112 DOI: 10.1073/pnas.2410889121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 07/09/2024] [Indexed: 08/21/2024] Open
Abstract
Insects and their gut bacteria form a tight and beneficial relationship, especially in utilization of host nutrients. The red turpentine beetle (RTB), a destructive and invasive pine pest, employs mutualistic microbes to facilitate its invasion success. However, the molecular mechanism underlying the utilization of nutrients remains unknown. In this study, we found that gut bacteria are crucial for the utilization of D-glucose, a main carbon source for RTB development. Downstream assays revealed that gut bacteria-induced gut hypoxia and the secretion of riboflavin are responsible for RTB development by regulating D-glucose transport via the activation of a hypoxia-induced transcription factor 1 (Hif-1α). Further functional investigations confirmed that Hif-1α mediates glucose transport by direct upregulation of two glucose transporters (ST10 and ST27), thereby promoting RTB development. Our findings reveal how gut bacteria regulate the development of RTB, and promote our understanding of the mutualistic relationship of animals and their gut bacteria.
Collapse
Affiliation(s)
- Fanghua Liu
- College of Life Sciences/Hebei Basic Science Center for Biotic Interactions, Institute of Life Science and Green Development, Hebei University, Baoding071002, China
| | - Fangyuan Ye
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, Chaoyang District100101, China
| | - Yunwen Yang
- College of Life Sciences/Hebei Basic Science Center for Biotic Interactions, Institute of Life Science and Green Development, Hebei University, Baoding071002, China
| | - Zhiwei Kang
- College of Life Sciences/Hebei Basic Science Center for Biotic Interactions, Institute of Life Science and Green Development, Hebei University, Baoding071002, China
| | - Yang Liu
- State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, Haidian District100193, China
| | - Wei Chen
- College of Life Sciences/Hebei Basic Science Center for Biotic Interactions, Institute of Life Science and Green Development, Hebei University, Baoding071002, China
| | - Saige Wang
- College of Life Sciences/Hebei Basic Science Center for Biotic Interactions, Institute of Life Science and Green Development, Hebei University, Baoding071002, China
| | - Hongru Kou
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, Chaoyang District100101, China
| | - Le Kang
- College of Life Sciences/Hebei Basic Science Center for Biotic Interactions, Institute of Life Science and Green Development, Hebei University, Baoding071002, China
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, Chaoyang District100101, China
| | - Jianghua Sun
- College of Life Sciences/Hebei Basic Science Center for Biotic Interactions, Institute of Life Science and Green Development, Hebei University, Baoding071002, China
- State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing, Chaoyang District100101, China
| |
Collapse
|
44
|
Schweitzer M, Wlasak M, Wassermann B, Marcher F, Poglitsch C, Pirker J, Berg G. 'Tiny Biome Tales': A gamified review about the influence of lifestyle choices on the human microbiome. Microb Biotechnol 2024; 17:e14544. [PMID: 39119866 PMCID: PMC11310763 DOI: 10.1111/1751-7915.14544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Accepted: 07/23/2024] [Indexed: 08/10/2024] Open
Abstract
In the last two decades, new discoveries from microbiome research have changed our understanding of human health. It became evident that daily habits and lifestyle choices shape the human microbiome and ultimately determine health or disease. Therefore, we developed 'Tiny Biome Tales' (https://microbiome.gamelabgraz.at/), a science pedagogy video game designed like a scientific review based exclusively on peer-reviewed articles, to teach about the influence of lifestyle choices on the human microbiome during pregnancy, early and adult life, and related health consequences. Despite the scientific character, it can be played by a broad audience. Here, we also present a scientific assessment and showed that playing the game significantly contributed to knowledge gain. The innovative style of the 'gamified review' represents an ideal platform to disseminate future findings from microbiome research by updating existing and adding new scenes to the game.
Collapse
Affiliation(s)
- Matthias Schweitzer
- Institute of Environmental BiotechnologyGraz University of TechnologyGrazAustria
| | - Maximilian Wlasak
- Institute of Interactive Systems and Data ScienceGraz University of TechnologyGrazAustria
| | - Birgit Wassermann
- Institute of Environmental BiotechnologyGraz University of TechnologyGrazAustria
| | - Florian Marcher
- Institute of Interactive Systems and Data ScienceGraz University of TechnologyGrazAustria
| | - Christian Poglitsch
- Institute of Interactive Systems and Data ScienceGraz University of TechnologyGrazAustria
| | - Johanna Pirker
- Institute of Interactive Systems and Data ScienceGraz University of TechnologyGrazAustria
- Institut für InformatikLudwig‐Maximilians‐UniversitätMunichGermany
| | - Gabriele Berg
- Institute of Environmental BiotechnologyGraz University of TechnologyGrazAustria
- Leibniz Institute for Agricultural Engineering and Bioeconomy (ATB)PotsdamGermany
- Institute for Biochemistry and BiologyUniversity of PotsdamPotsdamGermany
| |
Collapse
|
45
|
da Silva LMAV, Assunção WG, Bento VAA, Sachi VP, Colombo FE, Ique MMA, Faria BMA, Bertoz APDM. Assessment of the gut microbiota of children with obstructive sleep apnea syndrome: A systematic review. Sleep Med 2024; 120:56-64. [PMID: 38878352 DOI: 10.1016/j.sleep.2024.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Revised: 05/30/2024] [Accepted: 06/05/2024] [Indexed: 07/02/2024]
Abstract
Sleep-disordered breathing promotes not only unfavorable craniofacial changes in untreated pediatric patients but also neurocognitive, metabolic, cardiovascular, and even long-term social alterations. This systematic review evaluated whether children diagnosed with obstructive sleep apnea syndrome (OSAS) have different intestinal microbiota constitutions from healthy children and was based on the PRISMA guidelines (PROSPERO: CRD42022360074). A total of 1562 clinical studies published between 2019 and 2023 were selected from the PubMed/MEDLINE, Embase, Web of Science, Scopus, and Cochrane Library databases, of which five were included in the qualitative analysis, three being randomized and two prospective. The methodological quality was assessed (RoB 2.0 and ROBINS-I) and all studies showed a negative effect of intervention. Sleep deprivation and intermittent hypoxia in children with OSAS seem to trigger a cascade of inflammatory pathways that exacerbate the tissue response to the release of reactive oxygen species and the generation of oxidative stress, leading to a reduction in oxygen supply to the intestinal mucosa and the integral destruction of the intestinal barrier. More evidence-based investigations are needed to optimize the identification of possible alterations in the gut microbiota of pediatric patients, given that its composition may be influenced by the patient's sleep quality and, consequently, by OSAS, showing quantitative and qualitative alterations compared to that found in healthy individuals.
Collapse
Affiliation(s)
| | - Wirley Gonçalves Assunção
- Department of Dental Materials and Prosthodontics, São Paulo State University (UNESP), School of Dentistry, Araçatuba, São Paulo, Brazil.
| | - Victor Augusto Alves Bento
- Department of Dental Materials and Prosthodontics, São Paulo State University (UNESP), School of Dentistry, Araçatuba, São Paulo, Brazil.
| | - Victor Perinazzo Sachi
- Department of Preventive and Restorative Dentistry, São Paulo State University (UNESP), School of Dentistry, Araçatuba, São Paulo, Brazil.
| | - Fabio Eduardo Colombo
- Department of Preventive and Restorative Dentistry, São Paulo State University (UNESP), School of Dentistry, Araçatuba, São Paulo, Brazil.
| | - Manuel Martin Adriazola Ique
- Department of Preventive and Restorative Dentistry, São Paulo State University (UNESP), School of Dentistry, Araçatuba, São Paulo, Brazil.
| | - Bianca Martinatti Andrade Faria
- Department of Preventive and Restorative Dentistry, São Paulo State University (UNESP), School of Dentistry, Araçatuba, São Paulo, Brazil.
| | - André Pinheiro de Magalhães Bertoz
- Department of Preventive and Restorative Dentistry, São Paulo State University (UNESP), School of Dentistry, Araçatuba, São Paulo, Brazil.
| |
Collapse
|
46
|
Wang J, Li Y, Mu Y, Huang K, Li D, Lan C, Cui Y, Wang J. Missing microbes in infants and children in the COVID-19 pandemic: a study of 1,126 participants in Beijing, China. SCIENCE CHINA. LIFE SCIENCES 2024; 67:1739-1750. [PMID: 38748355 DOI: 10.1007/s11427-023-2488-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Accepted: 11/16/2023] [Indexed: 08/09/2024]
Abstract
The COVID-19 pandemic has caused many fatalities worldwide and continues to affect the health of the recovered patients in the form of long-COVID. In this study, we compared the gut microbiome of uninfected infants and children before the pandemic began (BEFORE cohort, n=906) to that of after the pandemic (AFTER cohort, n=220) to examine the potential impact of social distancing and life habit changes on infant/children gut microbiome. Based on 16S rRNA sequencing, we found a significant change in microbiome composition after the pandemic, with Bacteroides enterotype increasing to 35.45% from 30.46% before the pandemic. qPCR quantification indicated that the bacterial loads of seven keystone taxa decreased by 91.69%-19.58%. Quantitative microbiome profiling, used to enhance the resolution in detecting microbiome differences, revealed a greater explained variance of pandemic on microbiome compared to gender, as well as a significant decrease in bacterial loads in 15 of the 20 major genera. The random forest age-predictor indicated the gut microbiomes were less mature in the after-pandemic cohort than in the before-pandemic cohort in the children group (3-12 years old) and had features of a significantly younger age (average of 1.86 years). Lastly, body weight and height were significantly lower in the after-pandemic cohort than in the before-pandemic cohort in infants (<1 year of age), which was associated with a decrease in bacterial loads in the fecal microbiome.
Collapse
Affiliation(s)
- Jiejing Wang
- CAS Key Lab for Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Yuejuan Li
- CAS Key Lab for Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China
- University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Yu Mu
- Beijing Dr. CUIYUTAO Clinic, Beijing, 100028, China
| | - Kefei Huang
- Beijing Dr. CUIYUTAO Clinic, Beijing, 100028, China
| | - Danyi Li
- R-Institute Co. Ltd., Beijing, 100011, China
| | - Canhui Lan
- R-Institute Co. Ltd., Beijing, 100011, China
| | - Yutao Cui
- Beijing Dr. CUIYUTAO Clinic, Beijing, 100028, China.
| | - Jun Wang
- CAS Key Lab for Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
- University of Chinese Academy of Sciences, Beijing, 100049, China.
| |
Collapse
|
47
|
Yan L, Ye B, Yang M, Shan Y, Yan D, Fang D, Zhang K, Yu Y. Gut microbiota and metabolic changes in children with idiopathic short stature. BMC Pediatr 2024; 24:468. [PMID: 39039462 PMCID: PMC11265363 DOI: 10.1186/s12887-024-04944-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2023] [Accepted: 07/12/2024] [Indexed: 07/24/2024] Open
Abstract
BACKGROUND Idiopathic short stature (ISS) is characterized by short stature with unknown causes. Recent studies showed different gut microbiota flora and reduced fecal short-chain fatty acids in ISS children. However, the roles of the microbiome and metabolites in the pathogenesis of ISS remains largely unknown. METHODS We recruited 51 Chinese subjects, comprising 26 ISS children and 25 normal-height control individuals. Untargeted metabolomics was performed to explore the fecal metabolic profiles between groups. A shotgun metagenomic sequencing approach was used to investigate the microbiome at the strains level. Mediation analyses were done to reveal correlations between the height standard deviation (SD) value, the gut microbiome and metabolites. RESULTS We detected marked differences in the composition of fecal metabolites in the ISS group, particularly a significant increase in erucic acid and a decrease in spermidine, adenosine and L-5-Hydroxytryptophan, when compared to those of controls. We further identified specific groups of bacterial strains to be associated with the different metabolic profile. Through mediation analysis, 50 linkages were established. KEGG pathway analysis of microbiota and metabolites indicated nutritional disturbances. 13 selected features were able to accurately distinguish the ISS children from the controls (AUC = 0.933 [95%CI, 79.9-100%]) by receiver operating characteristic (ROC) analysis. CONCLUSION Our study suggests that the microbiome and the microbial-derived metabolites play certain roles in children's growth. These findings provide a new research direction for better understanding the mechanism(s) underlying ISS.
Collapse
Affiliation(s)
- Luyan Yan
- Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Bin Ye
- Department of Pediatric Internal Medicine, Taizhou Central Hospital, Taizhou University Hospital, Taizhou, China
| | - Min Yang
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yongsheng Shan
- Department of Pediatrics, Xiaoshan Hospital Affiliated to Hangzhou Normal University, Hangzhou, China
| | - Dan Yan
- Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - DanFeng Fang
- Department of Pediatric Internal Medicine, Taizhou Central Hospital, Taizhou University Hospital, Taizhou, China
| | - Kaichuang Zhang
- Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yongguo Yu
- Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| |
Collapse
|
48
|
Perruzza L, Rezzonico Jost T, Raneri M, Gargari G, Palatella M, De Ponte Conti B, Seehusen F, Heckmann J, Viemann D, Guglielmetti S, Grassi F. Protection from environmental enteric dysfunction and growth improvement in malnourished newborns by amplification of secretory IgA. Cell Rep Med 2024; 5:101639. [PMID: 38959887 PMCID: PMC11293325 DOI: 10.1016/j.xcrm.2024.101639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Revised: 04/04/2024] [Accepted: 06/11/2024] [Indexed: 07/05/2024]
Abstract
Environmental enteric dysfunction (EED) is a condition associated with malnutrition that can progress to malabsorption and villous atrophy. Severe EED results in linear growth stunting, slowed neurocognitive development, and unresponsiveness to oral vaccines. Prenatal exposure to malnutrition and breast feeding by malnourished mothers replicates EED. Pups are characterized by deprivation of secretory IgA (SIgA) and altered development of the gut immune system and microbiota. Extracellular ATP (eATP) released by microbiota limits T follicular helper (Tfh) cell activity and SIgA generation in Peyer's patches (PPs). Administration of a live biotherapeutic releasing the ATP-degrading enzyme apyrase to malnourished pups restores SIgA levels and ameliorates stunted growth. SIgA is instrumental in improving the growth and intestinal immune competence of mice while they are continuously fed a malnourished diet. The analysis of microbiota composition suggests that amplification of endogenous SIgA may exert a dominant function in correcting malnourishment dysbiosis and its consequences on host organisms, irrespective of the actual microbial ecology.
Collapse
Affiliation(s)
- Lisa Perruzza
- Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland.
| | - Tanja Rezzonico Jost
- Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland
| | - Matteo Raneri
- Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland
| | - Giorgio Gargari
- Division of Food Microbiology and Bioprocesses, Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, 20133 Milan, Italy
| | - Martina Palatella
- Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland
| | - Benedetta De Ponte Conti
- Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland; Graduate School of Cellular and Molecular Sciences, University of Bern, 3012 Bern, Switzerland
| | - Frauke Seehusen
- Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland
| | - Julia Heckmann
- Department of Pediatrics, University Hospital Würzburg, 97080 Würzburg, Germany
| | - Dorothee Viemann
- Department of Pediatrics, University Hospital Würzburg, 97080 Würzburg, Germany; Cluster of Excellence RESIST (EXC 2355), Hannover Medical School, 30625 Hannover, Germany; Center for Infection Research, University Würzburg, 97080 Würzburg, Germany
| | - Simone Guglielmetti
- Department of Biotechnology and Biosciences (BtBs), University of Milano-Bicocca, 20126 Milan, Italy
| | - Fabio Grassi
- Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland.
| |
Collapse
|
49
|
Yu J, Wang J, Cao C, Gong J, Cao J, Yin J, Wu S, Huang P, Tan B, Fan Z. Maternal intervention with a combination of galacto-oligosaccharides and hyocholic acids during late gestation and lactation increased the reproductive performance, colostrum composition, antioxidant and altered intestinal microflora in sows. Front Microbiol 2024; 15:1367877. [PMID: 38933026 PMCID: PMC11199897 DOI: 10.3389/fmicb.2024.1367877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 05/21/2024] [Indexed: 06/28/2024] Open
Abstract
Introduction This study was conducted to evaluate the effects of dietary galacto-oligosaccharides (GOS) and hyocholic acids (HCA) during late gestation and lactation on reproductive performance, colostrum quality, antioxidant capacity and gut microbiota in multiparous sows. Methods A total of 60 healthy multiparous cross-bred sows (Landrace × Yorkshire) were randomly fed 4 groups diets as follows: the basal diets (CTRL group), or the basal diets containing only 600 mg/kg GOS (GOS group), 600 mg/kg GOS + 100 mg/kg HCA (GOS + Low HCA group), and 600 mg/kg + 200 mg/kg HCA (GOS + High HCA group) from d 85 of gestation to weaning. Multiple parameters of sows were determined. Results There was a trend of shortening the labor process of sows (p = 0.07) in the GOS group and GOS + Low/High HCA group. Compared with the CTRL group, the GOS + Low/High HCA group increased the average piglets weight at birth (p < 0.05), and increased the IgA concentration of colostrum (p < 0.05). In addition, serum triglyceride (TG) concentration was lower (p < 0.05), and serum total antioxidant capacity (T-AOC) was higher (p < 0.05) in the GOS and GOS + Low/High HCA groups than in the CTRL group at farrowing. Serum catalase (CAT) activities was higher in the GOS and GOS + High HCA groups than in the CTRL group at farrowing. The 16S rRNA analysis showed that GOS combination with high-dose HCA shaped the composition of gut microbiota in different reproductive stages (d 107 of gestation, G107; d 0 of lactation, L0; d 7 of lactation, L7). At the phylum level, the relative abundance of Bacteroidota and Desulfobacterota in G107, Bacteroidota, and Proteobacteria in L0, and Planctomycetota in L7 was increased in GOS + High HCA group (p < 0.05). Spearman correlation analysis showed that Streptococcus was positively correlated with the serum TG but negatively correlated with the average piglets weight at birth (p < 0.05). Conclusion This investigation demonstrated that the administration of galacto-oligosaccharides (GOS) in conjunction with hyocholic acids (HCA), to sows with nutrient restrictions during late gestation and lactation, further improved their antioxidant capacity and milk quality. The observed beneficial effects of GOS + HCA supplementation could potentially be linked to an improvement in gut microbiota disorders of the sows.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | - Bi’e Tan
- College of Animal Science and Technology, Hunan Agricultural University, Changsha, China
| | - Zhiyong Fan
- College of Animal Science and Technology, Hunan Agricultural University, Changsha, China
| |
Collapse
|
50
|
Yang X, Huang J, Peng J, Wang P, Wong FS, Wang R, Wang D, Wen L. Gut microbiota from B-cell-specific TLR9-deficient NOD mice promote IL-10 + Breg cells and protect against T1D. Front Immunol 2024; 15:1413177. [PMID: 38903498 PMCID: PMC11187306 DOI: 10.3389/fimmu.2024.1413177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Accepted: 05/22/2024] [Indexed: 06/22/2024] Open
Abstract
Introduction Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing β cells. Toll-like receptor 9 (TLR9) plays a role in autoimmune diseases, and B cell-specific TLR9 deficiency delays T1D development. Gut microbiota are implicated in T1D, although the relationship is complex. However, the impact of B cell-specific deficiency of TLR9 on intestinal microbiota and the impact of altered intestinal microbiota on the development of T1D are unclear. Objectives This study investigated how gut microbiota and the intestinal barrier contribute to T1D development in B cell-specific TLR9-deficient NOD mice. Additionally, this study explored the role of microbiota in immune regulation and T1D onset. Methods The study assessed gut permeability, gene expression related to gut barrier integrity, and gut microbiota composition. Antibiotics depleted gut microbiota, and fecal samples were transferred to germ-free mice. The study also examined IL-10 production, Breg cell differentiation, and their impact on T1D development. Results B cell-specific TLR9-deficient NOD mice exhibited increased gut permeability and downregulated gut barrier-related gene expression. Antibiotics restored gut permeability, suggesting microbiota influence. Altered microbiota were enriched in Lachnospiraceae, known for mucin degradation. Transferring this microbiota to germ-free mice increased gut permeability and promoted IL-10-expressing Breg cells. Rag-/- mice transplanted with fecal samples from Tlr9 fl/fl Cd19-Cre+ mice showed delayed diabetes onset, indicating microbiota's impact. Conclusion B cell-specific TLR9 deficiency alters gut microbiota, increasing gut permeability and promoting IL-10-expressing Breg cells, which delay T1D. This study uncovers a link between TLR9, gut microbiota, and immune regulation in T1D, with implications for microbiota-targeted T1D therapies.
Collapse
Affiliation(s)
- Xin Yang
- Department of Food Science and Technology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China
- Section of Endocrinology, Internal Medicine, School of Medicine, Yale University, New Haven, CT, United States
| | - Juan Huang
- Section of Endocrinology, Internal Medicine, School of Medicine, Yale University, New Haven, CT, United States
| | - Jian Peng
- Section of Endocrinology, Internal Medicine, School of Medicine, Yale University, New Haven, CT, United States
| | - Pai Wang
- Section of Endocrinology, Internal Medicine, School of Medicine, Yale University, New Haven, CT, United States
- Department of Gastrocolorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China
| | - F. Susan Wong
- Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
| | - Ruirui Wang
- Shanghai Innovation Center of Traditional Chinese Medicine (TCM) Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Dapeng Wang
- Department of Food Science and Technology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China
| | - Li Wen
- Section of Endocrinology, Internal Medicine, School of Medicine, Yale University, New Haven, CT, United States
| |
Collapse
|