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Guo F, Jing L, Xu Y, Zhang K, Li Y, Sun N, Liu P, Zhang H. Gut microbiota and inflammatory factor characteristics in major depressive disorder patients with anorexia. BMC Psychiatry 2024; 24:334. [PMID: 38698338 PMCID: PMC11067108 DOI: 10.1186/s12888-024-05778-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Accepted: 04/18/2024] [Indexed: 05/05/2024] Open
Abstract
BACKGROUND This study aimed to explore the gut microbiota and inflammatory factor characteristics in major depressive disorder (MDD) patients with anorexia and to analyze the correlation between gut microbiota and inflammatory factors, anorexia, and HAMD scores. METHODS 46 MDD patients and 46 healthy controls (HC) were included in the study. The 46 MDD patients were divided into two groups according to whether they had anorexia:20 MDD without anorexia (MDA0 group) and 26 MDD with anorexia (MDA1 group). We used the Hamilton Depression Scale-24 (HAMD-24) to evaluate the depression status of all participants and 16 S ribosomal RNA (16 S rRNA)sequencing to evaluate the composition of the gut microbiota. Inflammatory factors in peripheral blood such as C-reactive protein (CRP) were detected using enzyme-linked immunosorbent assay (ELISA). Spearman's correlation analysis was used to evaluate the correlation between gut microbiota and inflammatory factors, HAMD scores, and anorexia. RESULTS 1). CRP was significantly higher in the MDA0, MDA1, than HC. 2). An analysis of α-diversity shows: the Simpson and Pielou indices of the HC group are higher than the MDA1 group (P < 0.05). 3). The β-diversity analysis shows differences in the composition of microbial communities between the MDA0, MDA1, and HC group. 4). A correlation analysis showed that Blautia positively correlated with anorexia, HAMD scores, and CRP level, whereas Faecalibacterium, Bacteroides, Roseburia, and Parabacteroides negatively correlated with anorexia, HAMD scores, and CRP level. 5). The receiver operating characteristic (ROC) curve was drawn using the differential bacterial genera between MDD patients with or without anorexia as biomarkers to identify whether MDD patients were accompanied with anorexia, and its area under curve (AUC) was 0.85. The ROC curve was drawn using the differential bacterial genera between MDD patients with anorexia and healthy controls as biomarkers to diagnose MDD patients with anorexia, with its AUC was 0.97. CONCLUSION This study suggested that MDD patients with anorexia had a distinct gut microbiota compared to healthy individuals, with higher level of CRP. Blautia was more abundant in MDD patients with anorexia and positively correlated with CRP, HAMD scores, and anorexia. The gut microbiota might have influenced MDD and anorexia through the inflammatory factor CRP.
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Affiliation(s)
- Fengtao Guo
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, 030001, China
- Shanxi Medical University, Taiyuan, 030001, China
- Yanhu District Branch, The First Hospital of Shanxi Medical University, Yuncheng, 044000, China
| | - Lin Jing
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, 030001, China
- Shanxi Medical University, Taiyuan, 030001, China
| | - Yunfan Xu
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, 030001, China
- Shanxi Medical University, Taiyuan, 030001, China
| | - Kun Zhang
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, 030001, China
- Shanxi Medical University, Taiyuan, 030001, China
| | - Ying Li
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, 030001, China
- Shanxi Medical University, Taiyuan, 030001, China
| | - Ning Sun
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, 030001, China
| | - Penghong Liu
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, 030001, China.
- Shanxi Medical University, Taiyuan, 030001, China.
| | - Huanhu Zhang
- Shanxi Medical University, Taiyuan, 030001, China.
- Shanxi University of Chinese Medicine, Jinzhong, 030619, China.
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Hilliard MA, Sela DA. Transmission and Persistence of Infant Gut-Associated Bifidobacteria. Microorganisms 2024; 12:879. [PMID: 38792709 PMCID: PMC11124121 DOI: 10.3390/microorganisms12050879] [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: 03/22/2024] [Revised: 04/18/2024] [Accepted: 04/25/2024] [Indexed: 05/26/2024] Open
Abstract
Bifidobacterium infantis are the primary colonizers of the infant gut, yet scientific research addressing the transmission of the genus Bifidobacterium to infants remains incomplete. This review examines microbial reservoirs of infant-type Bifidobacterium that potentially contribute to infant gut colonization. Accordingly, strain inheritance from mother to infant via the fecal-oral route is likely contingent on the bifidobacterial strain and phenotype, whereas transmission via the vaginal microbiota may be restricted to Bifidobacterium breve. Additional reservoirs include breastmilk, horizontal transfer from the environment, and potentially in utero transfer. Given that diet is a strong predictor of Bifidobacterium colonization in early life and the absence of Bifidobacterium is observed regardless of breastfeeding, it is likely that additional factors are responsible for bifidobacterial colonization early in life.
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Affiliation(s)
- Margaret A. Hilliard
- Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA;
- Organismic and Evolutionary Biology Graduate Program, University of Massachusetts, Amherst, MA 01003, USA
| | - David A. Sela
- Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA;
- Organismic and Evolutionary Biology Graduate Program, University of Massachusetts, Amherst, MA 01003, USA
- Department of Nutrition, University of Massachusetts, Amherst, MA 01003, USA
- Department of Microbiology, University of Massachusetts, Amherst, MA 01003, USA
- Department of Microbiology & Physiological Systems and Center for Microbiome Research, University of Massachusetts Medical School, Worcester, MA 01605, USA
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Ennis D, Shmorak S, Jantscher-Krenn E, Yassour M. Longitudinal quantification of Bifidobacterium longum subsp. infantis reveals late colonization in the infant gut independent of maternal milk HMO composition. Nat Commun 2024; 15:894. [PMID: 38291346 PMCID: PMC10827747 DOI: 10.1038/s41467-024-45209-y] [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: 07/19/2023] [Accepted: 01/15/2024] [Indexed: 02/01/2024] Open
Abstract
Breast milk contains human milk oligosaccharides (HMOs) that cannot be digested by infants, yet nourish their developing gut microbiome. While Bifidobacterium are the best-known utilizers of individual HMOs, a longitudinal study examining the evolving microbial community at high-resolution coupled with mothers' milk HMO composition is lacking. Here, we developed a high-throughput method to quantify Bifidobacterium longum subsp. infantis (BL. infantis), a proficient HMO-utilizer, and applied it to a longitudinal cohort consisting of 21 mother-infant dyads. We observed substantial changes in the infant gut microbiome over the course of several months, while the HMO composition in mothers' milk remained relatively stable. Although Bifidobacterium species significantly influenced sample variation, no specific HMOs correlated with Bifidobacterium species abundance. Surprisingly, we found that BL. infantis colonization began late in the breastfeeding period both in our cohort and in other geographic locations, highlighting the importance of focusing on BL. infantis dynamics in the infant gut.
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Affiliation(s)
- Dena Ennis
- Microbiology & Molecular Genetics Department, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Shimrit Shmorak
- Microbiology & Molecular Genetics Department, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | | | - Moran Yassour
- Microbiology & Molecular Genetics Department, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
- The Rachel and Selim Benin School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.
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4
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Rios-Carlos M, Cervantes-García D, Córdova-Dávalos LE, Bermúdez-Humarán LG, Salinas E. Unraveling the gut-skin axis in atopic dermatitis: exploiting insights for therapeutic strategies. Gut Microbes 2024; 16:2430420. [PMID: 39601281 PMCID: PMC11610564 DOI: 10.1080/19490976.2024.2430420] [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: 04/11/2024] [Revised: 08/14/2024] [Accepted: 11/12/2024] [Indexed: 11/29/2024] Open
Abstract
Gut microbiota exert functions of high importance in the intestine. Furthermore, there is increasing evidence for its role in immune regulation and maintenance of homeostasis in many physiological processes taking place in distant tissues. In particular, in this review, we explore the impact of metabolites produced by the gut microbiota on the development of atopic dermatitis (AD). Probiotics and prebiotics balance the microbiota and promote the generation of bacterial metabolites, such as short-chain fatty acids and tryptophan derivates, which promote the regulation of the exacerbated AD immune response through regulatory T cells and IL-10 and TGF-β cytokines. Metabolites also have a direct action on keratinocytes once they reach the bloodstream. Besides, probiotics decrease the levels of metabolites associated with AD onset, such as phenols. Understanding all these crosstalk processes between the gut and the skin reveals a number of possibilities, mainly through the manipulation of the gut microbiome, which may represent therapeutic strategies that can contribute to the standard treatments of AD patients to improve their quality of life.
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Affiliation(s)
- Marcela Rios-Carlos
- Department of Microbiology, Universidad Autónoma de Aguascalientes. Av. Universidad 940, Aguascalientes, Mexico
| | - Daniel Cervantes-García
- Department of Microbiology, Universidad Autónoma de Aguascalientes. Av. Universidad 940, Aguascalientes, Mexico
- Consejo Nacional de Humanidades Ciencias y Tecnologías, Ciudad de México, México
| | - Laura E. Córdova-Dávalos
- Department of Microbiology, Universidad Autónoma de Aguascalientes. Av. Universidad 940, Aguascalientes, Mexico
| | | | - Eva Salinas
- Department of Microbiology, Universidad Autónoma de Aguascalientes. Av. Universidad 940, Aguascalientes, Mexico
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Derrien M, Mikulic N, Uyoga MA, Chenoll E, Climent E, Howard-Varona A, Nyilima S, Stoffel NU, Karanja S, Kottler R, Stahl B, Zimmermann MB, Bourdet-Sicard R. Gut microbiome function and composition in infants from rural Kenya and association with human milk oligosaccharides. Gut Microbes 2023; 15:2178793. [PMID: 36794816 PMCID: PMC9980514 DOI: 10.1080/19490976.2023.2178793] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/17/2023] Open
Abstract
The gut microbiota evolves rapidly after birth, responding dynamically to environmental factors and playing a key role in short- and long-term health. Lifestyle and rurality have been shown to contribute to differences in the gut microbiome, including Bifidobacterium levels, between infants. We studied the composition, function and variability of the gut microbiomes of 6- to 11-month-old Kenyan infants (n = 105). Shotgun metagenomics showed Bifidobacterium longum to be the dominant species. A pangenomic analysis of B. longum in gut metagenomes revealed a high prevalence of B. longum subsp. infantis (B. infantis) in Kenyan infants (80%), and possible co-existence of this subspecies with B. longum subsp. longum. Stratification of the gut microbiome into community (GMC) types revealed differences in composition and functional features. GMC types with a higher prevalence of B. infantis and abundance of B. breve also had a lower pH and a lower abundance of genes encoding pathogenic features. An analysis of human milk oligosaccharides (HMOs) classified the human milk (HM) samples into four groups defined on the basis of secretor and Lewis polymorphisms revealed a higher prevalence of HM group III (Se+, Le-) (22%) than in most previously studied populations, with an enrichment in 2'-fucosyllactose. Our results show that the gut microbiome of partially breastfed Kenyan infants over the age of six months is enriched in bacteria from the Bifidobacterium community, including B. infantis, and that the high prevalence of a specific HM group may indicate a specific HMO-gut microbiome association. This study sheds light on gut microbiome variation in an understudied population with limited exposure to modern microbiome-altering factors.
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Affiliation(s)
- Muriel Derrien
- Advanced Health & Science, Danone Nutricia Research, Palaiseau, France,CONTACT Muriel Derrien Advanced Health & Science, Danone Nutricia Research, Palaiseau, France
| | - Nadja Mikulic
- Laboratory of Human Nutrition, Department of Health Sciences and Technology, ETH Zurich, Switzerland
| | - Mary A Uyoga
- Laboratory of Human Nutrition, Department of Health Sciences and Technology, ETH Zurich, Switzerland
| | - Empar Chenoll
- ADM-Biopolis, ADM, Parc Cientific Universitat de Valencia, Paterna, Valencia, Spain
| | - Eric Climent
- ADM-Biopolis, ADM, Parc Cientific Universitat de Valencia, Paterna, Valencia, Spain
| | - Adrian Howard-Varona
- ADM-Biopolis, ADM, Parc Cientific Universitat de Valencia, Paterna, Valencia, Spain
| | - Suzane Nyilima
- Public and Community Health Department, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya
| | - Nicole U Stoffel
- Laboratory of Human Nutrition, Department of Health Sciences and Technology, ETH Zurich, Switzerland
| | - Simon Karanja
- Public and Community Health Department, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya
| | | | - Bernd Stahl
- Advanced Health & Science, Danone Nutricia Research, Utrecht, The Netherlands,Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
| | - Michael B Zimmermann
- Laboratory of Human Nutrition, Department of Health Sciences and Technology, ETH Zurich, Switzerland
| | - Raphaëlle Bourdet-Sicard
- Advanced Health & Science, Danone Nutricia Research, Palaiseau, France,Raphaëlle Bourdet-Sicard Advanced Health & Science, Danone Nutricia Research, Palaiseau, France
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Mills DA, German JB, Lebrilla CB, Underwood MA. Translating neonatal microbiome science into commercial innovation: metabolism of human milk oligosaccharides as a basis for probiotic efficacy in breast-fed infants. Gut Microbes 2023; 15:2192458. [PMID: 37013357 PMCID: PMC10075334 DOI: 10.1080/19490976.2023.2192458] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Accepted: 03/13/2023] [Indexed: 04/05/2023] Open
Abstract
For over a century, physicians have witnessed a common enrichment of bifidobacteria in the feces of breast-fed infants that was readily associated with infant health status. Recent advances in bacterial genomics, metagenomics, and glycomics have helped explain the nature of this unique enrichment and enabled the tailored use of probiotic supplementation to restore missing bifidobacterial functions in at-risk infants. This review documents a 20-year span of discoveries that set the stage for the current use of human milk oligosaccharide-consuming bifidobacteria to beneficially colonize, modulate, and protect the intestines of at-risk, human milk-fed, neonates. This review also presents a model for probiotic applications wherein bifidobacterial functions, in the form of colonization and HMO-related catabolic activity in situ, represent measurable metabolic outcomes by which probiotic efficacy can be scored toward improving infant health.
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Affiliation(s)
- David A. Mills
- Department of Food Science and Technology, University of California-Davis, Davis, CA, United States
- Department of Viticulture and Enology, University of California-Davis, Davis, CA, United States
- Foods for Health Institute, University of California-Davis, Davis, CA, United States
| | - J. Bruce German
- Department of Food Science and Technology, University of California-Davis, Davis, CA, United States
- Foods for Health Institute, University of California-Davis, Davis, CA, United States
| | - Carlito B. Lebrilla
- Foods for Health Institute, University of California-Davis, Davis, CA, United States
- Department of Chemistry, University of California-Davis, Davis, CA, United States
- Department of Biochemistry and Molecular Medicine, University of California-Davis, Davis, CA, United States
| | - Mark A. Underwood
- Foods for Health Institute, University of California-Davis, Davis, CA, United States
- Division of Neonatology, Department of Pediatrics, University of California-Davis, Sacramento, CA, United States
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7
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Lacticaseibacillus casei Strain Shirota Modulates Macrophage-Intestinal Epithelial Cell Co-Culture Barrier Integrity, Bacterial Sensing and Inflammatory Cytokines. Microorganisms 2022; 10:microorganisms10102087. [PMID: 36296363 PMCID: PMC9607601 DOI: 10.3390/microorganisms10102087] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 10/03/2022] [Accepted: 10/06/2022] [Indexed: 11/06/2022] Open
Abstract
Probiotic bacteria modulate macrophage immune inflammatory responses, with functional cytokine responses determined by macrophage subset polarisation, stimulation and probiotic strain. Mucosal macrophages exhibit subset functional heterogeneity but are organised in a 3-dimensional tissue, over-laid by barrier epithelial cells. This study aimed to investigate the effects of the probiotic Lacticaseibacillus casei strain Shirota (LcS) on macrophage-epithelial cell cytokine responses, pattern recognition receptor (PRR) expression and LPS responses and the impacts on barrier integrity. THP-1-derived M1 and M2 subset macrophages were co-cultured in a transwell system with differentiated Caco-2 epithelial cells in the presence or absence of enteropathogenic LPS. Both Caco-2 cells in monoculture and macrophage co-culture were assayed for cytokines, PRR expression and barrier integrity (TEER and ZO-1) by RT-PCR, ELISA, IHC and electrical resistance. Caco-2 monocultures expressed distinct cytokine profiles (IL-6, IL-8, TNFα, endogenous IL-10), PRRs and barrier integrity, determined by inflammatory context (TNFα or IL-1β). In co-culture, LcS rescued ZO-1 and TEER in M2/Caco-2, but not M1/Caco-2. LcS suppressed TLR2, TLR4, MD2 expression in both co-cultures and differentially regulated NOD2, TLR9, Tollip and cytokine secretion. In conclusion, LcS selectively modulates epithelial barrier integrity, pathogen sensing and inflammatory cytokine profile; determined by macrophage subset and activation status.
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8
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Abuaish S, Al-Otaibi NM, Aabed K, Abujamel TS, Alzahrani SA, Alotaibi SM, Bhat RS, Arzoo S, Algahtani N, Moubayed NM, El-Ansary A. The Efficacy of Fecal Transplantation and Bifidobacterium Supplementation in Ameliorating Propionic Acid-Induced Behavioral and Biochemical Autistic Features in Juvenile Male Rats. J Mol Neurosci 2022; 72:372-381. [PMID: 35094316 DOI: 10.1007/s12031-021-01959-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 12/16/2021] [Indexed: 02/06/2023]
Abstract
Gut microbiota plays a major role in neurological disorders, including autism. Modulation of the gut microbiota through fecal microbiota transplantation (FMT) or probiotic administration, such as Bifidobacteria, is suggested to alleviate autistic symptoms; however, their effects on the brain are not fully examined. We tested both approaches in a propionic acid (PPA) rodent model of autism as treatment strategies. Autism was induced in Sprague-Dawley rats by administering PPA orally (250 mg/kg) for 3 days. Animals were later treated with either saline, FMT, or Bifidobacteria for 22 days. Control animals were treated with saline throughout the study. Social behavior and selected brain biochemical markers related to stress hormones, inflammation, and oxidative stress were assessed. PPA treatment induced social impairments, which was rescued by the treatments. In the brain, Bifidobacteria treatment increased oxytocin relative to control and PPA groups. Moreover, Bifidobacteria treatment rescued the PPA-induced increase in IFN-γ levels. Both treatments increased GST levels, which was diminished by the PPA treatment. These findings indicate the potential of gut microbiota-targeted therapeutics in ameliorating behavioral deficit and underlying neural biochemistry.
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Affiliation(s)
- Sameera Abuaish
- Department of Basic Sciences, College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Norah M Al-Otaibi
- Department of Biology, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Kawther Aabed
- Department of Biology, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Turki S Abujamel
- Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.,Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
| | - Saleha Ahmad Alzahrani
- Department of Biology, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Sohailah Masoud Alotaibi
- Department of Biology, College of Science, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Ramesa Shafi Bhat
- Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Shaista Arzoo
- Department of Food Science and Nutrition, King Saud University, Riyadh, Saudi Arabia
| | - Norah Algahtani
- Central Research Laboratory, King Saud University Female Campus, P O Box 22452, Prince Turki Road, Riyadh, 22452, Saudi Arabia
| | - Nadine Ms Moubayed
- Botany and Microbiology Department, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Afaf El-Ansary
- Central Research Laboratory, King Saud University Female Campus, P O Box 22452, Prince Turki Road, Riyadh, 22452, Saudi Arabia.
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Duboux S, Ngom-Bru C, De Bruyn F, Bogicevic B. Phylogenetic, Functional and Safety Features of 1950s B. infantis Strains. Microorganisms 2022; 10:microorganisms10020203. [PMID: 35208658 PMCID: PMC8879182 DOI: 10.3390/microorganisms10020203] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 01/04/2022] [Accepted: 01/06/2022] [Indexed: 02/05/2023] Open
Abstract
Strains of Bifidobacterium longum subsp. infantis (B. infantis) are amongst the first to colonize the infant gut, partly due to their capacity to metabolize complex human milk oligosaccharides (HMO), and are proposed to play a key role in the development of the infant gut. Since early life, B. infantis supplementation is of high interest, and detailed phylogenetic, functional and safety characterization of the selected strains should be pursued. Using a combination of long and short-read sequencing technologies, we first decipher the genetic distance between different isolates of the same B. infantis strain. Using the same approach, we show that several publicly available genomes recapitulate this strain-level distance as compared to two of the first strains obtained in the 1950s. Furthermore, we demonstrate that the two 1950s B. infantis strains display different functional and safety attributes, as ATCC 15697 is resistant to streptomycin and shows a preference towards lacto-N-tetraose LNT and sialylated HMOs, while LMG 11588 is sensitive to all tested antibiotics and shows a preference towards fucosylated HMOs. Overall, our work highlights that the current diversity observed in B. infantis is likely underestimated and that strain selection within this subspecies must be the subject of scientific pursuit and associated evaluation.
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Affiliation(s)
- Stéphane Duboux
- Société des Produits Nestlé SA, Nestlé Research, Route du Jorat 57, CH-1000 Lausanne 26, Switzerland; (C.N.-B.); (B.B.)
- Correspondence:
| | - Catherine Ngom-Bru
- Société des Produits Nestlé SA, Nestlé Research, Route du Jorat 57, CH-1000 Lausanne 26, Switzerland; (C.N.-B.); (B.B.)
| | - Florac De Bruyn
- Société des Produits Nestlé SA, Nestlé Research & Development, Nestléstrasse 3, CH-3510 Konolfingen, Switzerland;
| | - Biljana Bogicevic
- Société des Produits Nestlé SA, Nestlé Research, Route du Jorat 57, CH-1000 Lausanne 26, Switzerland; (C.N.-B.); (B.B.)
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10
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Abstract
The neonatal body provides a range of potential habitats, such as the gut, for microbes. These sites eventually harbor microbial communities (microbiotas). A "complete" (adult) gut microbiota is not acquired by the neonate immediately after birth. Rather, the exclusive, milk-based nutrition of the infant encourages the assemblage of a gut microbiota of low diversity, usually dominated by bifidobacterial species. The maternal fecal microbiota is an important source of bacterial species that colonize the gut of infants, at least in the short-term. However, development of the microbiota is influenced by the use of human milk (breast feeding), infant formula, preterm delivery of infants, caesarean delivery, antibiotic administration, family details and other environmental factors. Following the introduction of weaning (complementary) foods, the gut microbiota develops in complexity due to the availability of a diversity of plant glycans in fruits and vegetables. These glycans provide growth substrates for the bacterial families (such as members of the Ruminococcaceae and Lachnospiraceae) that, in due course, will dominate the gut microbiota of the adult. Although current data are often fragmentary and observational, it can be concluded that the nutrition that a child receives in early life is likely to impinge not only on the development of the microbiota at that time but also on the subsequent lifelong, functional relationships between the microbiota and the human host. The purpose of this review, therefore, is to discuss the importance of promoting the assemblage of functionally robust gut microbiotas at appropriate times in early life.
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Affiliation(s)
- Gerald W. Tannock
- Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
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11
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Bardanzellu F, Puddu M, Fanos V. Breast Milk and COVID-19: From Conventional Data to "Omics" Technologies to Investigate Changes Occurring in SARS-CoV-2 Positive Mothers. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:5668. [PMID: 34070662 PMCID: PMC8199242 DOI: 10.3390/ijerph18115668] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 05/19/2021] [Accepted: 05/22/2021] [Indexed: 12/18/2022]
Abstract
In this context of COVID-19 pandemic, great interest has been aroused by the potential maternal transmission of SARS-CoV-2 by transplacental route, during delivery, and, subsequently, through breastfeeding. Some open questions still remain, especially regarding the possibility of finding viable SARS-CoV-2 in breast milk (BM), although this is not considered a worrying route of transmission. However, in BM, it was pointed out the presence of antibodies against SARS-CoV-2 and other bioactive components that could protect the infant from infection. The aim of our narrative review is to report and discuss the available literature on the detection of anti-SARS-CoV-2 antibodies in BM of COVID-19 positive mothers, and we discussed the unique existing study investigating BM of SARS-CoV-2 positive mothers through metabolomics, and the evidence regarding microbiomics BM variation in COVID-19. Moreover, we tried to correlate metabolomics and microbiomics findings in BM of positive mothers with potential effects on breastfed infants metabolism and health. To our knowledge, this is the first review summarizing the current knowledge on SARS-CoV-2 effects on BM, resuming both "conventional data" (antibodies) and "omics technologies" (metabolomics and microbiomics).
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Affiliation(s)
- Flaminia Bardanzellu
- Neonatal Intensive Care Unit, Department of Surgical Sciences, AOU and University of Cagliari, SS 554 km 4500, 09042 Monserrato, Italy; (M.P.); (V.F.)
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12
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Lai WT, Deng WF, Xu SX, Zhao J, Xu D, Liu YH, Guo YY, Wang MB, He FS, Ye SW, Yang QF, Liu TB, Zhang YL, Wang S, Li MZ, Yang YJ, Xie XH, Rong H. Shotgun metagenomics reveals both taxonomic and tryptophan pathway differences of gut microbiota in major depressive disorder patients. Psychol Med 2021; 51:90-101. [PMID: 31685046 DOI: 10.1017/s0033291719003027] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND The microbiota-gut-brain axis, especially the microbial tryptophan (Trp) biosynthesis and metabolism pathway (MiTBamp), may play a critical role in the pathogenesis of major depressive disorder (MDD). However, studies on the MiTBamp in MDD are lacking. The aim of the present study was to analyze the gut microbiota composition and the MiTBamp in MDD patients. METHODS We performed shotgun metagenomic sequencing of stool samples from 26 MDD patients and 29 healthy controls (HCs). In addition to the microbiota community and the MiTBamp analyses, we also built a classification based on the Random Forests (RF) and Boruta algorithm to identify the gut microbiota as biomarkers for MDD. RESULTS The Bacteroidetes abundance was strongly reduced whereas that of Actinobacteria was significantly increased in the MDD patients compared with the abundance in the HCs. Most noteworthy, the MDD patients had increased levels of Bifidobacterium, which is commonly used as a probiotic. Four Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) (K01817, K11358, K01626, K01667) abundances in the MiTBamp were significantly lower in the MDD group. Furthermore, we found a negative correlation between the K01626 abundance and the HAMD scores in the MDD group. Finally, RF classification at the genus level can achieve an area under the receiver operating characteristic curve of 0.890. CONCLUSIONS The present findings enabled a better understanding of the changes in gut microbiota and the related Trp pathway in MDD. Alterations of the gut microbiota may have the potential as biomarkers for distinguishing MDD patients form HCs.
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Affiliation(s)
- Wen-Tao Lai
- Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
| | - Wen-Feng Deng
- Laboratory of Brain Stimulation and Biological Psychiatry, Brain Function and Psychosomatic Medicine Institute, Second People's Hospital of Huizhou, Huizhou, Guangdong, China
| | - Shu-Xian Xu
- Laboratory of Brain Stimulation and Biological Psychiatry, Brain Function and Psychosomatic Medicine Institute, Second People's Hospital of Huizhou, Huizhou, Guangdong, China
| | - Jie Zhao
- Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
| | - Dan Xu
- Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
| | - Yang-Hui Liu
- Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
| | - Yuan-Yuan Guo
- Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
| | - Ming-Bang Wang
- Xiamen Branch, Shanghai Key Laboratory of Birth Defects, Division of Neonatology, Children's Hospital of Fudan University, National Center for Children's Health, Shanghai, China
| | | | - Shu-Wei Ye
- Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
| | - Qi-Fan Yang
- Laboratory of Brain Stimulation and Biological Psychiatry, Brain Function and Psychosomatic Medicine Institute, Second People's Hospital of Huizhou, Huizhou, Guangdong, China
| | - Tie-Bang Liu
- Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
| | - Ying-Li Zhang
- Department of Depression, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
| | - Sheng Wang
- Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
| | - Min-Zhi Li
- Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
| | - Ying-Jia Yang
- Department of Depression, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
| | - Xin-Hui Xie
- Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
- Laboratory of Brain Stimulation and Biological Psychiatry, Brain Function and Psychosomatic Medicine Institute, Second People's Hospital of Huizhou, Huizhou, Guangdong, China
- Center of Acute Psychiatry Service, Second People's Hospital of Huizhou, Huizhou, Guangdong, China
| | - Han Rong
- Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong, China
- Affiliated Shenzhen Clinical College of Psychiatry, Jining Medical University, Jining, Shandong, China
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13
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Duar RM, Casaburi G, Mitchell RD, Scofield LN, Ortega Ramirez CA, Barile D, Henrick BM, Frese SA. Comparative Genome Analysis of Bifidobacterium longum subsp. infantis Strains Reveals Variation in Human Milk Oligosaccharide Utilization Genes among Commercial Probiotics. Nutrients 2020; 12:nu12113247. [PMID: 33114073 PMCID: PMC7690671 DOI: 10.3390/nu12113247] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 10/16/2020] [Accepted: 10/19/2020] [Indexed: 12/23/2022] Open
Abstract
Dysbiosis is associated with acute and long-term consequences for neonates. Probiotics can be effective in limiting the growth of bacteria associated with dysbiosis and promoting the healthy development of the infant microbiome. Given its adaptation to the infant gut, and promising data from animal and in vitro models, Bifidobacterium longum subsp. infantis is an attractive candidate for use in infant probiotics. However, strain-level differences in the ability of commercialized strains to utilize human milk oligosaccharides (HMOs) may have implications in the performance of strains in the infant gut. In this study, we characterized twelve B. infantis probiotic strains and identified two main variants in one of the HMO utilization gene clusters. Some strains possessed the full repertoire of HMO utilization genes (H5-positive strains), while H5-negative strains lack an ABC-type transporter known to bind core HMO structures. H5-positive strains achieved significantly superior growth on lacto-N-tetraose and lacto-N-neotetraose. In vitro, H5-positive strains had a significant fitness advantage over H5-negative strains, which was also observed in vivo in breastfed infants. This work provides evidence of the functional implications of genetic differences among B. infantis strains and highlights that genotype and HMO utilization phenotype should be considered when selecting a strain for probiotic use in infants.
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Affiliation(s)
- Rebbeca M. Duar
- Evolve BioSystems, Inc., Davis, CA 95618, USA; (R.M.D.); (G.C.); (R.D.M.); (L.N.C.S.); (C.A.O.R.); (B.M.H.)
| | - Giorgio Casaburi
- Evolve BioSystems, Inc., Davis, CA 95618, USA; (R.M.D.); (G.C.); (R.D.M.); (L.N.C.S.); (C.A.O.R.); (B.M.H.)
| | - Ryan D. Mitchell
- Evolve BioSystems, Inc., Davis, CA 95618, USA; (R.M.D.); (G.C.); (R.D.M.); (L.N.C.S.); (C.A.O.R.); (B.M.H.)
| | - Lindsey N.C. Scofield
- Evolve BioSystems, Inc., Davis, CA 95618, USA; (R.M.D.); (G.C.); (R.D.M.); (L.N.C.S.); (C.A.O.R.); (B.M.H.)
| | - Camila A. Ortega Ramirez
- Evolve BioSystems, Inc., Davis, CA 95618, USA; (R.M.D.); (G.C.); (R.D.M.); (L.N.C.S.); (C.A.O.R.); (B.M.H.)
| | - Daniela Barile
- Foods for Health Institute, University of California at Davis, Davis, CA 95616, USA;
- Department of Food Science and Technology, University of California at Davis, Davis, CA 95616, USA
| | - Bethany M. Henrick
- Evolve BioSystems, Inc., Davis, CA 95618, USA; (R.M.D.); (G.C.); (R.D.M.); (L.N.C.S.); (C.A.O.R.); (B.M.H.)
- Department of Food Science and Technology, University of Nebraska, Lincoln, NE 68588, USA
| | - Steven A. Frese
- Evolve BioSystems, Inc., Davis, CA 95618, USA; (R.M.D.); (G.C.); (R.D.M.); (L.N.C.S.); (C.A.O.R.); (B.M.H.)
- Department of Food Science and Technology, University of Nebraska, Lincoln, NE 68588, USA
- Correspondence: ; Tel.: +1-530-747-2045
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14
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Hughes RL, Arnold CD, Young RR, Ashorn P, Maleta K, Fan YM, Ashorn U, Chaima D, Malamba-Banda C, Kable ME, Dewey KG. Infant gut microbiota characteristics generally do not modify effects of lipid-based nutrient supplementation on growth or inflammation: secondary analysis of a randomized controlled trial in Malawi. Sci Rep 2020; 10:14861. [PMID: 32908192 PMCID: PMC7481312 DOI: 10.1038/s41598-020-71922-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Accepted: 08/21/2020] [Indexed: 12/22/2022] Open
Abstract
An unhealthy gut microbial community may act as a barrier to improvement in growth and health outcomes in response to nutritional interventions. The objective of this analysis was to determine whether the infant microbiota modified the effects of a randomized controlled trial of lipid-based nutrient supplements (LNS) in Malawi on growth and inflammation at 12 and 18 months, respectively. We characterized baseline microbiota composition of fecal samples at 6 months of age (n = 506, prior to infant supplementation, which extended to 18 months) using 16S rRNA gene sequencing of the V4 region. Features of the gut microbiota previously identified as being involved in fatty acid or micronutrient metabolism or in outcomes relating to growth and inflammation, especially in children, were investigated. Prior to correction for multiple hypothesis testing, the effects of LNS on growth appeared to be modified by Clostridium (p-for-interaction = 0.02), Ruminococcus (p-for-interaction = 0.007), and Firmicutes (p-for-interaction = 0.04) and effects on inflammation appeared to be modified by Faecalibacterium (p-for-interaction = 0.03) and Streptococcus (p-for-interaction = 0.004). However, after correction for multiple hypothesis testing these findings were not statistically significant, suggesting that the gut microbiota did not alter the effect of LNS on infant growth and inflammation in this cohort.
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Affiliation(s)
- Riley L Hughes
- Department of Nutrition, University of California, Davis, CA, USA
| | - Charles D Arnold
- Department of Nutrition, University of California, Davis, CA, USA
| | - Rebecca R Young
- Department of Nutrition, University of California, Davis, CA, USA
| | - Per Ashorn
- Center for Child Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Pediatrics, Tampere University Hospital, Tampere, Finland
| | - Ken Maleta
- College of Medicine, University of Malawi, Blantyre 3, Malawi
| | - Yue-Mei Fan
- Center for Child Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Ulla Ashorn
- Center for Child Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - David Chaima
- School of Public Health and Family Medicine, University of Malawi College of Medicine, Blantyre, Malawi
| | - Chikondi Malamba-Banda
- School of Public Health and Family Medicine, University of Malawi College of Medicine, Blantyre, Malawi
| | - Mary E Kable
- Immunity and Disease Prevention, Western Human Nutrition Research Center, Agricultural Research Service, USDA, Davis, CA, USA
| | - Kathryn G Dewey
- Department of Nutrition, University of California, Davis, CA, USA.
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15
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Manasian P, Bustos AS, Pålsson B, Håkansson A, Peñarrieta JM, Nilsson L, Linares-Pastén JA. First Evidence of Acyl-Hydrolase/Lipase Activity From Human Probiotic Bacteria: Lactobacillus rhamnosus GG and Bifidobacterium longum NCC 2705. Front Microbiol 2020; 11:1534. [PMID: 32793131 PMCID: PMC7393678 DOI: 10.3389/fmicb.2020.01534] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Accepted: 06/12/2020] [Indexed: 01/23/2023] Open
Abstract
Lactobacillus rhamnosus GG (ATCC 53103) and Bifidobacterium longum NCC 2705 are among the most studied probiotics. However, the first evidence of acyl hydrolase/lipase of two annotated proteins, one in each genome of these strains, is reported in this work. Signal peptide analysis has predicted that these proteins are exported to the extracellular medium. Both proteins were produced in Escherichia coli, purified and characterized. Molecular masses (without signal peptides) were 27 and 52.3 kDa for the proteins of L. rhamnosus and B. longum, respectively. Asymmetrical flow field-flow fractionation analysis has shown that both proteins are present as monomers in their native forms at pH 7. Both have shown enzymatic activity on pNP-laurate at pH 7 and 37°C. The enzyme from L. rhamnosus was characterized deeper, showing preference on pNP-esters with short chain fatty acids. In addition, a computational model of the 3D structure has allowed the prediction of the catalytic amino acids. The enzymatic activities using synthetic substrates were very low for both enzymes. The investigation of natural substrates and biological functions of these enzymes is still open.
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Affiliation(s)
- Panagiotis Manasian
- Biotechnology, Faculty of Engineering, Lunds Tekniska Högskola (LTH), Lund University, Lund, Sweden.,Food Technology, Faculty of Engineering, Lunds Tekniska Högskola (LTH), Lund University, Lund, Sweden
| | - Atma-Sol Bustos
- Food Technology, Faculty of Engineering, Lunds Tekniska Högskola (LTH), Lund University, Lund, Sweden.,Faculty of Pure and Natural Sciences, School of Chemistry, Universidad Mayor de San Andrés, La Paz, Bolivia
| | - Björn Pålsson
- Biotechnology, Faculty of Engineering, Lunds Tekniska Högskola (LTH), Lund University, Lund, Sweden
| | - Andreas Håkansson
- Food Technology, Faculty of Engineering, Lunds Tekniska Högskola (LTH), Lund University, Lund, Sweden
| | - J Mauricio Peñarrieta
- Faculty of Pure and Natural Sciences, School of Chemistry, Universidad Mayor de San Andrés, La Paz, Bolivia
| | - Lars Nilsson
- Food Technology, Faculty of Engineering, Lunds Tekniska Högskola (LTH), Lund University, Lund, Sweden
| | - Javier A Linares-Pastén
- Biotechnology, Faculty of Engineering, Lunds Tekniska Högskola (LTH), Lund University, Lund, Sweden
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16
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Wang X, Chen J, Zhang R, Liu L, Ma G, Zhu H. Interleukin-6 in Siberian sturgeon (Acipenser baeri): Molecular characterization and immune functional activity. FISH & SHELLFISH IMMUNOLOGY 2020; 102:296-306. [PMID: 32184192 DOI: 10.1016/j.fsi.2020.03.023] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/17/2019] [Revised: 02/19/2020] [Accepted: 03/11/2020] [Indexed: 06/10/2023]
Abstract
Interleukin-6 (IL-6) is a pleiotropic cytokine with crucial immunoregulatory functions in both innate and adaptive immune responses. However, the IL-6 sequence and function remain unknown in sturgeon, one chondrostean fish. In the present study, we identified an interleukin-6 homolog from Siberian sturgeon (Acipenser baeri), named AbIL-6. Its open reading frame (ORF) was 657 nucleotides in length, encoding a polypeptide of 218 amino acids, which contains a signal peptide and the IL-6 family domain. Phylogenetic analysis showed that sturgeon IL-6 had close relationship with both teleost and chondrichthyes IL-6s. Abil-6 mRNA was highly expressed in spleen, brain and liver tissues of healthy sturgeon, and significantly up-regulated in the spleen, head kidney and liver by A.hydrophila (A.h) challenge. Heat-killed A.h and LPS effectively stimulated Abil-6 transcripts in primary spleen cells in vitro. In order to understand the bioactivity and influence of AbIL-6 on immune responses, recombinant AbIL-6 (rAbIL-6) was synthesized by prokaryotes and demonstrated to promote the proliferation of spleen cells and head kidney cells in vitro. Additionally, intraperitoneal injection of rAbIL-6 induced significantly higher expression of four immuno-related genes including il-1β, cxcl10, mhcIIβ and igm. rAbIL-6 improved the survival rate and reduced the tissue bacterial load after A.h infection. Taken together, these results suggest that AbIL-6 plays an important role in inflammatory responses and immune defense against bacterial infection of sturgeon.
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Affiliation(s)
- Xiaowen Wang
- Beijing Fisheries Research Institute & Beijing Key Laboratory of Fishery Biotechnology, Beijing, 100068, People's Republic of China; National Freshwater Fisheries Engineering Technology Research Center, Beijing, 100068, People's Republic of China
| | - Jingyi Chen
- Beijing Fisheries Research Institute & Beijing Key Laboratory of Fishery Biotechnology, Beijing, 100068, People's Republic of China; National Freshwater Fisheries Engineering Technology Research Center, Beijing, 100068, People's Republic of China
| | - Rong Zhang
- Beijing Fisheries Research Institute & Beijing Key Laboratory of Fishery Biotechnology, Beijing, 100068, People's Republic of China; National Freshwater Fisheries Engineering Technology Research Center, Beijing, 100068, People's Republic of China
| | - Lili Liu
- Beijing Fisheries Research Institute & Beijing Key Laboratory of Fishery Biotechnology, Beijing, 100068, People's Republic of China; National Freshwater Fisheries Engineering Technology Research Center, Beijing, 100068, People's Republic of China
| | - Guoqing Ma
- Beijing Fisheries Research Institute & Beijing Key Laboratory of Fishery Biotechnology, Beijing, 100068, People's Republic of China; National Freshwater Fisheries Engineering Technology Research Center, Beijing, 100068, People's Republic of China
| | - Hua Zhu
- Beijing Fisheries Research Institute & Beijing Key Laboratory of Fishery Biotechnology, Beijing, 100068, People's Republic of China; National Freshwater Fisheries Engineering Technology Research Center, Beijing, 100068, People's Republic of China.
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17
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Galacto- and Fructo-oligosaccharides Utilized for Growth by Cocultures of Bifidobacterial Species Characteristic of the Infant Gut. Appl Environ Microbiol 2020; 86:AEM.00214-20. [PMID: 32220841 DOI: 10.1128/aem.00214-20] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Accepted: 03/25/2020] [Indexed: 02/06/2023] Open
Abstract
Bifidobacterial species are common inhabitants of the gut of human infants during the period when milk is a major component of the diet. Bifidobacterium breve, Bifidobacterium bifidum, Bifidobacterium longum subspecies longum, and B. longum subspecies infantis have been detected frequently in infant feces, but B. longum subsp. infantis may be disadvantaged numerically in the gut of infants in westernized countries. This may be due to the different durations of breast milk feeding in different countries. Supplementation of the infant diet or replacement of breast milk using formula feeds is common in Western countries. Formula milks often contain galacto- and/or fructo-oligosaccharides (GOS and FOS, respectively) as additives to augment the concentration of oligosaccharides in ruminant milks, but the ability of B. longum subsp. infantis to utilize these potential growth substrates when they are in competition with other bifidobacterial species is unknown. We compared the growth and oligosaccharide utilization of GOS and FOS by bifidobacterial species in pure culture and coculture. Short-chain GOS and FOS (degrees of polymerization [DP] 2 and 3) were favored growth substrates for strains of B. bifidum and B. longum subsp. longum, whereas both B. breve and B. longum subsp. infantis had the ability to utilize both short- and longer-chain GOS and FOS (DP 2 to 6). B. breve was nevertheless numerically dominant over B. longum subsp. infantis in cocultures. This was probably related to the slower use of GOS of DP 3 by B. longum subsp. infantis, indicating that the kinetics of substrate utilization is an important ecological factor in the assemblage of gut communities.IMPORTANCE The kinds of bacteria that form the collection of microbes (the microbiota) in the gut of human infants may influence health and well-being. Knowledge of how the composition of the infant diet influences the assemblage of the bacterial collection is therefore important because dietary interventions may offer opportunities to alter the microbiota with the aim of improving health. Bifidobacterium longum subspecies infantis is a well-known bacterial species, but under modern child-rearing conditions it may be disadvantaged in the gut. Modern formula milks often contain particular oligosaccharide additives that are generally considered to support bifidobacterial growth. However, studies of the ability of various bifidobacterial species to grow together in the presence of these oligosaccharides have not been conducted. These kinds of studies are essential for developing concepts of microbial ecology related to the influence of human nutrition on the development of the gut microbiota.
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18
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Oral and nasal probiotic administration for the prevention and alleviation of allergic diseases, asthma and chronic obstructive pulmonary disease. Nutr Res Rev 2020; 34:1-16. [PMID: 32281536 DOI: 10.1017/s0954422420000116] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Interaction between a healthy microbiome and the immune system leads to body homeostasis, as dysbiosis in microbiome content and loss of diversity may result in disease development. Due to the ability of probiotics to help and modify microbiome constitution, probiotics are now widely used for the prevention and treatment of different gastrointestinal, inflammatory, and, more recently, respiratory diseases. In this regard, chronic respiratory diseases including chronic obstructive pulmonary disease (COPD), asthma and allergic rhinitis are among the most common and complicated respiratory diseases with no specific treatment until now. Accordingly, many studies have evaluated the therapeutic efficacy of probiotic administration (mostly via the oral route and much lesser nasal route) on chronic respiratory diseases. We tried to summarise and evaluate these studies to give a perspective of probiotic therapy via both the oral and nasal routes for respiratory infections (in general) and chronic respiratory diseases (specifically). We finally concluded that probiotics might be useful for allergic diseases. For asthmatic patients, probiotics can modulate serum cytokines and IgE and decrease eosinophilia, but with no significant reduction in clinical symptoms. For COPD, only limited studies were found with uncertain clinical efficacy. For intranasal administration, although some studies propose more efficiency than the oral route, more clinical evaluations are warranted.
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19
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20
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Colonization Resistance in the Infant Gut: The Role of B. infantis in Reducing pH and Preventing Pathogen Growth. High Throughput 2020; 9:ht9020007. [PMID: 32230716 PMCID: PMC7349288 DOI: 10.3390/ht9020007] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 03/20/2020] [Accepted: 03/25/2020] [Indexed: 12/17/2022] Open
Abstract
Over the past century, there has been a steady increase in the stool pH of infants from industrialized countries. Analysis of historical data revealed a strong association between abundance of Bifidobacterium in the gut microbiome of breasted infants and stool pH, suggesting that this taxon plays a key role in determining the pH in the gut. Bifidobacterium longum subsp. infantis is uniquely equipped to metabolize human milk oligosaccharides (HMO) from breastmilk into acidic end products, mainly lactate and acetate. The presence of these acidic compounds in the infant gut is linked to a lower stool pH. Conversely, infants lacking B. infantis have a significantly higher stool pH, carry a higher abundance of potential pathogens and mucus-eroding bacteria in their gut microbiomes, and have signs of chronic enteric inflammation. This suggests the presence of B. infantis and low intestinal pH may be critical to maintaining a protective environment in the infant gut. Here, we summarize recent studies demonstrating that feeding B. infantis EVC001 to breastfed infants results in significantly lower fecal pH compared to controls and propose that low pH is one critical factor in preventing the invasion and overgrowth of harmful bacteria in the infant gut, a process known as colonization resistance.
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21
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Bukharin OV, Andryuschenko SV, Perunova NB, Ivanova EV, Chainikova IN, Zdvizhkova IA. Genome sequence data announcement of Bifidobacterium bifidum strain ICIS-202 isolated from a healthy human intestine stimulating active nitrogen oxide production in macrophages. Data Brief 2019; 27:104761. [PMID: 31799343 PMCID: PMC6883332 DOI: 10.1016/j.dib.2019.104761] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Revised: 10/22/2019] [Accepted: 10/30/2019] [Indexed: 01/15/2023] Open
Abstract
This report presents the data on the draft genome sequence of Bifidobacterium bifidum strain ICIS-202. The strain, isolated from the intestine of a young healthy woman, was deposited in the State Collection of Microorganisms of Normal Microbiota in Gabrichevsky Institute of Epidemiology and Microbiology, Moscow, Russian Federation as a prospective candidate for probiotic development. The size of the genome was 2,265,060 bp (62,4% G + C content). The annotation revealed 1771 coding sequences, including 1771 proteins, 5 rRNA, 52 tRNA, and 3 ncRNA genes. The draft genome sequence data of B. bifidum strain ICIS-202 is available in DBJ/EMBL/GenBank under the accession nos. SSMS00000000.1, PRJNA412271 and SAMN07709009 for Genome, Bioproject and Biosample databases, respectively.
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22
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Lawley B, Otal A, Moloney-Geany K, Diana A, Houghton L, Heath ALM, Taylor RW, Tannock GW. Fecal Microbiotas of Indonesian and New Zealand Children Differ in Complexity and Bifidobacterial Taxa during the First Year of Life. Appl Environ Microbiol 2019; 85:e01105-19. [PMID: 31375480 PMCID: PMC6752005 DOI: 10.1128/aem.01105-19] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Accepted: 07/22/2019] [Indexed: 02/07/2023] Open
Abstract
The biological succession that occurs during the first year of life in the gut of infants in Western countries is broadly predictable in terms of the increasing complexity of the composition of microbiotas. Less information is available about microbiotas in Asian countries, where environmental, nutritional, and cultural influences may differentially affect the composition and development of the microbial community. We compared the fecal microbiotas of Indonesian (n = 204) and New Zealand (NZ) (n = 74) infants 6 to 7 months and 12 months of age. Comparisons were made by analysis of 16S rRNA gene sequences and derivation of community diversity metrics, relative abundances of bacterial families, enterotypes, and cooccurrence correlation networks. Abundances of Bifidobacterium longum subsp. infantis and B. longum subsp. longum were determined by quantitative PCR. All observations supported the view that the Indonesian and NZ infant microbiotas developed in complexity over time, but the changes were much greater for NZ infants. B. longum subsp. infantis dominated the microbiotas of Indonesian children, whereas B. longum subsp. longum was dominant in NZ children. Network analysis showed that the niche model (in which trophic adaptation results in preferential colonization) of the assemblage of microbiotas was supported in Indonesian infants, whereas the neutral (stochastic) model was supported by the development of the microbiotas of NZ infants. The results of the study show that the development of the fecal microbiota is not the same for infants in all countries, and they point to the necessity of obtaining a better understanding of the factors that control the colonization of the gut in early life.IMPORTANCE This study addresses the microbiology of a natural ecosystem (the infant bowel) for children in a rural setting in Indonesia and in an urban environment in New Zealand. Analysis of DNA sequences generated from the microbial community (microbiota) in the feces of the infants during the first year of life showed marked differences in the composition and complexity of the bacterial collections. The differences were most likely due to differences in the prevalence and duration of breastfeeding of infants in the two countries. These kinds of studies are essential for developing concepts of microbial ecology related to the influence of nutrition and environment on the development of the gut microbiota and for determining the long-term effects of microbiological events in early life on human health and well-being.
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Affiliation(s)
- Blair Lawley
- Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
| | - Anna Otal
- Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
| | - Kit Moloney-Geany
- Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
| | - Aly Diana
- Department of Human Nutrition, University of Otago, Dunedin, New Zealand
| | - Lisa Houghton
- Department of Human Nutrition, University of Otago, Dunedin, New Zealand
- Microbiome Otago, University of Otago, Dunedin, New Zealand
| | - Anne-Louise M Heath
- Department of Human Nutrition, University of Otago, Dunedin, New Zealand
- Microbiome Otago, University of Otago, Dunedin, New Zealand
| | - Rachael W Taylor
- Microbiome Otago, University of Otago, Dunedin, New Zealand
- Department of Medicine, University of Otago, Dunedin, New Zealand
| | - Gerald W Tannock
- Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
- Microbiome Otago, University of Otago, Dunedin, New Zealand
- Riddet Centre of Research Excellence, Massey University, Palmerston North, New Zealand
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Casaburi G, Duar RM, Vance DP, Mitchell R, Contreras L, Frese SA, Smilowitz JT, Underwood MA. Early-life gut microbiome modulation reduces the abundance of antibiotic-resistant bacteria. Antimicrob Resist Infect Control 2019; 8:131. [PMID: 31423298 PMCID: PMC6693174 DOI: 10.1186/s13756-019-0583-6] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Accepted: 07/22/2019] [Indexed: 01/21/2023] Open
Abstract
Background Antibiotic-resistant (AR) bacteria are a global threat. AR bacteria can be acquired in early life and have long-term sequelae. Limiting the spread of antibiotic resistance without triggering the development of additional resistance mechanisms is of immense clinical value. Here, we show how the infant gut microbiome can be modified, resulting in a significant reduction of AR genes (ARGs) and the potentially pathogenic bacteria that harbor them. Methods The gut microbiome was characterized using shotgun metagenomics of fecal samples from two groups of healthy, term breastfed infants. One group was fed B. infantis EVC001 in addition to receiving lactation support (n = 29, EVC001-fed), while the other received lactation support alone (n = 31, controls). Coliforms were isolated from fecal samples and genome sequenced, as well as tested for minimal inhibitory concentrations against clinically relevant antibiotics. Results Infants fed B. infantis EVC001 exhibited a change to the gut microbiome, resulting in a 90% lower level of ARGs compared to controls. ARGs that differed significantly between groups were predicted to confer resistance to beta lactams, fluoroquinolones, or multiple drug classes, the majority of which belonged to Escherichia, Clostridium, and Staphylococcus. Minimal inhibitory concentration assays confirmed the resistance phenotypes among isolates with these genes. Notably, we found extended-spectrum beta lactamases among healthy, vaginally delivered breastfed infants who had never been exposed to antibiotics. Conclusions Colonization of the gut of breastfed infants by a single strain of B. longum subsp. infantis had a profound impact on the fecal metagenome, including a reduction in ARGs. This highlights the importance of developing novel approaches to limit the spread of these genes among clinically relevant bacteria. Future studies are needed to determine whether colonization with B. infantis EVC001 decreases the incidence of AR infections in breastfed infants. Trial registration This clinical trial was registered at ClinicalTrials.gov, NCT02457338.
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Affiliation(s)
| | | | | | | | | | - Steven A. Frese
- Evolve Biosystems, Inc, Davis, CA 95618 USA
- Department of Food Science and Technology, University of Nebraska, Lincoln, NE 68588 USA
| | - Jennifer T. Smilowitz
- Department of Food Science and Technology, University of California, Davis, CA 95616 USA
- Foods for Health Institute, University of California, Davis, CA 95616 USA
| | - Mark A. Underwood
- Foods for Health Institute, University of California, Davis, CA 95616 USA
- Department of Pediatrics, UC Davis Children’s Hospital, Sacramento, CA 95817 USA
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24
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Insel R, Knip M. Prospects for primary prevention of type 1 diabetes by restoring a disappearing microbe. Pediatr Diabetes 2018; 19:1400-1406. [PMID: 30136344 DOI: 10.1111/pedi.12756] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Revised: 08/14/2018] [Accepted: 08/14/2018] [Indexed: 12/18/2022] Open
Abstract
Prevention of childhood-onset type 1 diabetes has become more urgent with its marked increased incidence in recent decades in the modern world. Temporally associated with the rising incidence of type 1 diabetes, as well as other autoimmune and allergic diseases in childhood in modern times, is the disappearance of Bifidobacterium and specifically Bifidobacterium longum subsp. infantis (B. infantis) predominance in the intestinal microbiota of breastfed, vaginally-delivered infants. B. infantis efficiently metabolizes human milk oligosaccharides (HMOs) without cross-feeding free sugar monomers to other commensals or pathogens and thereby dominates the intestinal microbiota of breastfed infants. Increased levels of short-chain fatty acids (SCFA), which stimulate both immunoregulation and healthy intestinal and pancreatic β-cell function, are generated by B. infantis. Based on recent observations of the intestinal microbiota in early life in young children who develop type 1 diabetes and demonstration of the robust preventive effects of SCFA in animal models of autoimmune diabetes, we hypothesize that restoring a B. infantis-dominant microbiota early in infancy will prevent islet autoimmunity and childhood-onset type 1 diabetes.
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Affiliation(s)
| | - Mikael Knip
- Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.,Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland.,Folkhälsan Research Center, Helsinki, Finland
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25
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Vitetta L, Vitetta G, Hall S. Immunological Tolerance and Function: Associations Between Intestinal Bacteria, Probiotics, Prebiotics, and Phages. Front Immunol 2018; 9:2240. [PMID: 30356736 PMCID: PMC6189397 DOI: 10.3389/fimmu.2018.02240] [Citation(s) in RCA: 80] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Accepted: 09/10/2018] [Indexed: 12/12/2022] Open
Abstract
Post-birth there is a bacterial assault on all mucosal surfaces. The intestinal microbiome is an important participant in health and disease. The pattern of composition and concentration of the intestinal microbiome varies greatly. Therefore, achieving immunological tolerance in the first 3-4 years of life is critical for maintaining health throughout a lifetime. Probiotic bacteria are organisms that afford beneficial health effects to the host and in certain instances may protect against the development of disease. The potential benefits of modifying the composition of the intestinal microbial cohort for therapeutic benefit is evident in the use in high risks groups such as premature infants, children receiving antibiotics, rotavirus infections in non-vaccinated children and traveler's diarrhea in adults. Probiotics and prebiotics are postulated to have immunomodulating capabilities by influencing the intestinal microbial cohort and dampening the activity of pathobiont intestinal microbes, such as Klebsiella pneumonia and Clostridia perfringens. Lactobacilli and Bifidobacteria are examples of probiotics found in the large intestine and so far, the benefits afforded to probiotics have varied in efficacy. Most likely the efficacy of probiotic bacteria has a multifactorial dependency, namely on a number of factors that include agents used, the dose, the pattern of dosing, and the characteristics of the host and the underlying luminal microbial environment and the activity of bacteriophages. Bacteriophages, are small viruses that infect and lyse intestinal bacteria. As such it can be posited that these viruses display an effective local protective control mechanism for the intestinal barrier against commensal pathobionts that indirectly may assist the host in controlling bacterial concentrations in the gut. A co-operative activity may be envisaged between the intestinal epithelia, mucosal immunity and the activity of bacteriophages to eliminate pathobiots, highlighting the potential role of bacteriophages in assisting with maintaining intestinal homeostasis. Hence bacteriophage local control of inflammation and immune responses may be an additional immunological defense mechanism that exploits bacteriophage-mucin glycoprotein interactions that controls bacterial diversity and abundance in the mucin layers of the gut. Moreover, and importantly the efficacy of probiotics may be dependent on the symbiotic incorporation of prebiotics, and the abundance and diversity of the intestinal microbiome encountered. The virome may be an important factor that determines the efficacy of some probiotic formulations.
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Affiliation(s)
- Luis Vitetta
- Discipline of Pharmacology, Faculty of Medicine and Health, School of Medicine, The University of Sydney, Camperdown, NSW, Australia
- Medlab Clinical Ltd., Sydney, NSW, Australia
| | | | - Sean Hall
- Medlab Clinical Ltd., Sydney, NSW, Australia
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26
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Wang ML, Shen X, Ge L, He M, Li M, Yao JR, He F. [A preliminary study of the difference in composition of intestinal bifidobacteria between healthy infants and infants with allergic diseases]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2018; 20:746-752. [PMID: 30210028 PMCID: PMC7389175 DOI: 10.7499/j.issn.1008-8830.2018.09.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Accepted: 08/14/2018] [Indexed: 06/08/2023]
Abstract
OBJECTIVE To investigate the association between intestinal bifidobacteria and allergic diseases in infants by comparing the composition of intestinal bifidobacteria between healthy infants and infants with allergic diseases. METHODS A total of 48 infants were enrolled, and fecal samples were collected on days 0, 2, 7, and 15 and at months 1, 6, and 12 after birth. Among these infants, 22 who experienced allergic diseases before the age of 1 year were enrolled as allergic group and 26 healthy infants were enrolled as healthy group. Quantitative real-time PCR was used for the qualitative and quantitative analyses of Bifidobacterium and 8 species of bifidobacteria in fecal samples. RESULTS There was a difference in the composition of intestinal bifidobacteria between the two groups within 1 month after birth: the healthy group showed a reduction in bifidobacteria on day 2, while this feature was not observed in the allergic group. Compared with the healthy group, the allergic group had a significantly lower detection count of Bifidobacterium at month 1 (P<0.05) and a significantly lower detection rate of B.breve on day 15 (P<0.05), with delayed colonization of B.infantis. CONCLUSIONS Intestinal bifidobacteria and their composition within 1 month after birth may be associated with the development of allergic diseases, and this period of time may be a critical period for the prevention and treatment of allergic diseases in infants.
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Affiliation(s)
- Mao-Lin Wang
- Department of Nutrition, Food Safety and Toxicology, West China School of Public Health, Sichuan University, Chengdu 610041, China.
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27
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tuf Gene Sequence Variation in Bifidobacterium longum subsp. infantis Detected in the Fecal Microbiota of Chinese Infants. Appl Environ Microbiol 2018; 84:AEM.00336-18. [PMID: 29703739 DOI: 10.1128/aem.00336-18] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Accepted: 04/20/2018] [Indexed: 12/12/2022] Open
Abstract
Members of the bacterial genus Bifidobacterium generally dominate the fecal microbiota of infants. The species Bifidobacterium longum is prevalent, but the B. longum subsp. longum and B. longum subsp. infantis strains that are known to colonize the infant bowel are not usually differentiated in microbiota investigations. These subspecies differ in their capacities to metabolize human milk oligosaccharides (HMO) and may have different ecological and symbiotic roles in humans. Quantitative PCR provides a quick analytical method by which to accurately ascertain the abundances of target species in microbiotas and microcosms. However, amplification targets in DNA extracted from samples need to be dependably differential. We evaluated the tuf gene sequence as a molecular target for quantitative PCR measurements of the abundances of B. longum subsp. infantis and B. longum subsp. longum in fecal microbiotas. This approach resulted in the detection of a tuf gene variant (operational taxonomic unit 49 [OTU49]) in Chinese infants that has sequence similarities to both B. longum subsp. infantis and B. longum subsp. longum We compared the genome sequence and growth and transcriptional characteristics of an OTU49 isolate cultured in HMO medium to those of other B. longum subsp. infantis cultures. We concluded from these studies that OTU49 belongs to B. longum subsp. infantis, that dependable quantitative PCR (qPCR) differentiation between the B. longum subspecies cannot be achieved by targeting tuf gene sequences, and that functional genes involved in carbohydrate metabolism might be better targets because they delineate ecological functions.IMPORTANCE High-throughput DNA sequencing methods and advanced bioinformatics analysis have revealed the composition and biochemical capacities of microbial communities (microbiota and microbiome), including those that inhabit the gut of human infants. However, the microbiology and function of natural ecosystems have received little attention in recent decades, so an appreciation of the dynamics of gut microbiota interactions is lacking. With respect to infants, rapid methodologies, such as quantitative PCR, are needed to determine the prevalences and proportions of different bifidobacterial species in observational and microcosm studies in order to obtain a better understanding of the dynamics of bifidobacterial nutrition and syntrophy, knowledge that might be used to manipulate the microbiota and perhaps ensure the better health of infants.
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Abstract
Although immunotherapy has been remarkably effective across multiple cancer types, there continues to be a significant number of non-responding patients. A possible factor proposed to influence the efficacy of immunotherapies is the gut microbiome. We discuss the results and implications of recent research on the relationship between the gut microbiome, our immune systems, and immune checkpoint inhibitor therapies including anti-CTLA-4 Ab and anti-PD-1 Ab. While the investigations all exhibit interesting results and conclusions, we find little congruence in the specific bacteria that were found favorable for antitumor responses. It is unclear whether the inconsistencies are due to differential approaches in study design (pre-clinical or clinical subjects, anti-CTLA-4 Ab or anti-PD-1 Ab), experimental methods and measurements (metagenomics sequencing and clustering variations) or subject population dynamics (differential cancer types and baseline characteristics). Moreover, we note studies regarding particular bacterial commensals and autoimmune diseases, which challenge findings from these investigations. We conclude that with the current research, clinical investigators can appreciate the critical role of gut microbiota in mediating immunostimulant response. However, prospective research exploring the biochemical mechanisms which commensal bacteria communicate with each other and the immune system is imperative to understand how they can be adjusted properly for higher immunotherapy response.
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Affiliation(s)
- Audrey Humphries
- a Department of Medicine , Division of Hematology/Oncology, University of California San Francisco , San Francisco , CA , USA
| | - Adil Daud
- a Department of Medicine , Division of Hematology/Oncology, University of California San Francisco , San Francisco , CA , USA
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29
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Adachi K, Tamada K. Microbial biomarkers for immune checkpoint blockade therapy against cancer. J Gastroenterol 2018; 53:999-1005. [PMID: 30003334 PMCID: PMC6132931 DOI: 10.1007/s00535-018-1492-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Accepted: 06/29/2018] [Indexed: 02/04/2023]
Abstract
Three major standard treatments, i.e., surgery, chemotherapy, and radiotherapy, were traditionally applied to the treatment of cancer and saved many patients. Meanwhile, clinical studies as well as basic research of immunotherapy are being actively conducted for intractable or advanced malignancies that cannot be cured by the conventional standard treatments. Remarkable therapeutic efficacies have been recently reported in clinical trials on some cancer types, and immunotherapy is now being recognized as the "fourth" standard therapy against cancer. In particular, immune checkpoint inhibitor therapy (ICI) has demonstrated the effectiveness of immunotherapy through large-scale randomized clinical trials, leading to the paradigm-shift in cancer treatment. Immune checkpoint molecules transduce co-inhibitory signals to immunocompetent cells including T cells, and crucially contribute to the formation of an immunosuppressive microenvironment in tumor tissues, which intrinsically confers the treatment resistance. Programmed death-1 (PD-1, CD279) is one of the typical immune checkpoint molecules. Anti-tumor therapies targeting PD-1 and its ligands had been developed and approved in many countries, and various studies utilizing clinical specimens are currently progressing. In this review, we provide an overview of the biomarkers based on the analysis of enteric microbiota that correlate with the clinical efficacy/inefficacy of PD-1-based therapy.
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Affiliation(s)
- Keishi Adachi
- 0000 0001 0660 7960grid.268397.1Department of Immunology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505 Japan
| | - Koji Tamada
- 0000 0001 0660 7960grid.268397.1Department of Immunology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505 Japan
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30
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Milani C, Duranti S, Bottacini F, Casey E, Turroni F, Mahony J, Belzer C, Delgado Palacio S, Arboleya Montes S, Mancabelli L, Lugli GA, Rodriguez JM, Bode L, de Vos W, Gueimonde M, Margolles A, van Sinderen D, Ventura M. The First Microbial Colonizers of the Human Gut: Composition, Activities, and Health Implications of the Infant Gut Microbiota. Microbiol Mol Biol Rev 2017; 81:e00036-17. [PMID: 29118049 PMCID: PMC5706746 DOI: 10.1128/mmbr.00036-17] [Citation(s) in RCA: 1121] [Impact Index Per Article: 140.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The human gut microbiota is engaged in multiple interactions affecting host health during the host's entire life span. Microbes colonize the neonatal gut immediately following birth. The establishment and interactive development of this early gut microbiota are believed to be (at least partially) driven and modulated by specific compounds present in human milk. It has been shown that certain genomes of infant gut commensals, in particular those of bifidobacterial species, are genetically adapted to utilize specific glycans of this human secretory fluid, thus representing a very intriguing example of host-microbe coevolution, where both partners are believed to benefit. In recent years, various metagenomic studies have tried to dissect the composition and functionality of the infant gut microbiome and to explore the distribution across the different ecological niches of the infant gut biogeography of the corresponding microbial consortia, including those corresponding to bacteria and viruses, in healthy and ill subjects. Such analyses have linked certain features of the microbiota/microbiome, such as reduced diversity or aberrant composition, to intestinal illnesses in infants or disease states that are manifested at later stages of life, including asthma, inflammatory bowel disease, and metabolic disorders. Thus, a growing number of studies have reported on how the early human gut microbiota composition/development may affect risk factors related to adult health conditions. This concept has fueled the development of strategies to shape the infant microbiota composition based on various functional food products. In this review, we describe the infant microbiota, the mechanisms that drive its establishment and composition, and how microbial consortia may be molded by natural or artificial interventions. Finally, we discuss the relevance of key microbial players of the infant gut microbiota, in particular bifidobacteria, with respect to their role in health and disease.
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Affiliation(s)
- Christian Milani
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy
| | - Sabrina Duranti
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy
| | - Francesca Bottacini
- APC Microbiome Institute and School of Microbiology, National University of Ireland, Cork, Ireland
| | - Eoghan Casey
- APC Microbiome Institute and School of Microbiology, National University of Ireland, Cork, Ireland
| | - Francesca Turroni
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy
- Microbiome Research Hub, University of Parma, Parma, Italy
| | - Jennifer Mahony
- APC Microbiome Institute and School of Microbiology, National University of Ireland, Cork, Ireland
| | - Clara Belzer
- Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
| | - Susana Delgado Palacio
- Departamento de Microbiologia y Bioquimica de Productos Lacteos, IPLA-CSIC, Villaviciosa, Asturias, Spain
| | - Silvia Arboleya Montes
- Departamento de Microbiologia y Bioquimica de Productos Lacteos, IPLA-CSIC, Villaviciosa, Asturias, Spain
| | - Leonardo Mancabelli
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy
| | - Gabriele Andrea Lugli
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy
| | - Juan Miguel Rodriguez
- Department of Nutrition, Food Science and Food Technology, Complutense University of Madrid, Madrid, Spain
| | - Lars Bode
- Department of Pediatrics and Larsson-Rosenquist Foundation Mother-Milk-Infant Center of Research Excellence, University of California-San Diego, La Jolla, California, USA
| | - Willem de Vos
- Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
- Department of Bacteriology & Immunology, RPU Immunobiology, University of Helsinki, Helsinki, Finland
| | - Miguel Gueimonde
- Departamento de Microbiologia y Bioquimica de Productos Lacteos, IPLA-CSIC, Villaviciosa, Asturias, Spain
| | - Abelardo Margolles
- Departamento de Microbiologia y Bioquimica de Productos Lacteos, IPLA-CSIC, Villaviciosa, Asturias, Spain
| | - Douwe van Sinderen
- APC Microbiome Institute and School of Microbiology, National University of Ireland, Cork, Ireland
| | - Marco Ventura
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy
- Microbiome Research Hub, University of Parma, Parma, Italy
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31
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Oh S, Yap GC, Hong PY, Huang CH, Aw MM, Shek LPC, Liu WT, Lee BW. Immune-modulatory genomic properties differentiate gut microbiota of infants with and without eczema. PLoS One 2017; 12:e0184955. [PMID: 29049378 PMCID: PMC5648123 DOI: 10.1371/journal.pone.0184955] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2016] [Accepted: 08/28/2017] [Indexed: 12/13/2022] Open
Abstract
Gut microbiota play an important role in human immunological processes, potentially affecting allergic diseases such as eczema. The diversity and structure of gut microbiota in infants with eczema have been previously documented. This study aims to evaluate by comparative metagenomics differences in genetic content in gut microbiota of infants with eczema and their matched controls. Stools were collected at the age of one month old from twelve infants from an at risk birth cohort in a case control manner. Clinical follow up for atopic outcomes were carried out at the age of 12 and 24 months. Microbial genomic DNA were extracted from stool samples and used for shotgun sequencing. Comparative metagenomic analysis showed that immune-regulatory TCAAGCTTGA motifs were significantly enriched in the six healthy controls (C) communities compared to the six eczema subjects (E), with many encoded by Bifidobacterium (38% of the total motifs in the C communities). Draft genomes of five Bifidobacterium species populations (B. longum, B. bifidum, B. breve, B. dentium, and B. pseudocatenulatum) were recovered from metagenomic datasets. The B. longum BFN-121-2 genome encoded more TCAAGCTTGA motifs (4.2 copies per one million genome sequence) than other Bifidobacterium genomes. Additionally, the communities in the stool of controls (C) were also significantly enriched in functions associated with tetrapyrrole biosynthesis compared to those of eczema (E). Our results show distinct immune-modulatory genomic properties of gut microbiota in infants associated with eczema and provide new insights into potential role of gut microbiota in affecting human immune homeostasis.
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Affiliation(s)
- Seungdae Oh
- Department of Civil Engineering, Kyung Hee University, Yongin-si, Gyeonggi-do, Republic of Korea
- Department of Civil and Environmental Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States of America
| | - Gaik Chin Yap
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Pei-Ying Hong
- Division of Biological and Environmental Science and Engineering, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia
- Water Desalination and Reuse Center, Division of Biological and Environmental Science and Engineering, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia
| | - Chiung-Hui Huang
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Marion M. Aw
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Paediatrics, Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore, Singapore
| | - Lynette Pei-Chi Shek
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Paediatrics, Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore, Singapore
| | - Wen-Tso Liu
- Department of Civil and Environmental Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States of America
| | - Bee Wah Lee
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Paediatrics, Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore, Singapore
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32
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Nagpal R, Kurakawa T, Tsuji H, Takahashi T, Kawashima K, Nagata S, Nomoto K, Yamashiro Y. Evolution of gut Bifidobacterium population in healthy Japanese infants over the first three years of life: a quantitative assessment. Sci Rep 2017; 7:10097. [PMID: 28855672 PMCID: PMC5577255 DOI: 10.1038/s41598-017-10711-5] [Citation(s) in RCA: 70] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Accepted: 08/15/2017] [Indexed: 01/05/2023] Open
Abstract
Bifidobacteria are important members of human gut microbiota; however, quantitative data on their early-life dynamics is limited. Here, using a sensitive reverse transcription-qPCR approach, we demonstrate the carriage of eight signature infant-associated Bifidobacterium species (B. longum, B. breve, B. bifidum, B. catenulatum group, B. infantis, B. adolescentis, B. angulatum and B. dentium) in 76 healthy full-term vaginally-born infants from first day to three years of life. About 21% babies carry bifidobacteria at first day of life (6.2 ± 1.9 log10 cells/g feces); and this carriage increases to 64% (8.0 ± 2.2), 79% (8.5 ± 2.1), 97% (9.3 ± 1.8), 99% (9.6 ± 1.6), and 100% (9.7 ± 0.9) at age 7 days, 1, 3 and 6 months, and 3 years, respectively. B. longum, B. breve, B. catenulatum group and B. bifidum are among the earliest and abundant bifidobacterial clades. Interestingly, infants starting formula-feed as early as first week of life have higher bifidobacterial carriage compared to exclusively breast-fed counterparts. Bifidobacteria demonstrate an antagonistic correlation with enterobacteria and enterococci. Further analyses also reveal a relatively lower/ delayed bifidobacterial carriage in cesarean-born babies. The study presents a quantitative perspective of the early-life gut Bifidobacterium colonization and shows how factors such as birth and feeding modes could influence this acquisition even in healthy infants.
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Affiliation(s)
- Ravinder Nagpal
- Probiotics Research Laboratory, Juntendo University Graduate School of Medicine, Hongo 2-9-8-3F, Bunkyo-ku, Tokyo, 113-0033, Japan. .,Gut Microbiome and Metabolic Diseases, Center for Diabetes, Obesity and Metabolism, Wake Forest School of Medicine, Biotech Place, Winston-Salem, NC, 27101, USA.
| | | | | | | | | | - Satoru Nagata
- Department of Pediatrics, School of Medicine, Tokyo Women's Medical University, Shinjuku, Tokyo, Japan
| | - Koji Nomoto
- Yakult Central Institute, Kunitachi-shi, Tokyo, Japan
| | - Yuichiro Yamashiro
- Probiotics Research Laboratory, Juntendo University Graduate School of Medicine, Hongo 2-9-8-3F, Bunkyo-ku, Tokyo, 113-0033, Japan
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Wen C, Zheng Z, Shao T, Liu L, Xie Z, Le Chatelier E, He Z, Zhong W, Fan Y, Zhang L, Li H, Wu C, Hu C, Xu Q, Zhou J, Cai S, Wang D, Huang Y, Breban M, Qin N, Ehrlich SD. Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis. Genome Biol 2017; 18:142. [PMID: 28750650 PMCID: PMC5530561 DOI: 10.1186/s13059-017-1271-6] [Citation(s) in RCA: 238] [Impact Index Per Article: 29.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Accepted: 06/27/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The assessment and characterization of the gut microbiome has become a focus of research in the area of human autoimmune diseases. Ankylosing spondylitis is an inflammatory autoimmune disease and evidence showed that ankylosing spondylitis may be a microbiome-driven disease. RESULTS To investigate the relationship between the gut microbiome and ankylosing spondylitis, a quantitative metagenomics study based on deep shotgun sequencing was performed, using gut microbial DNA from 211 Chinese individuals. A total of 23,709 genes and 12 metagenomic species were shown to be differentially abundant between ankylosing spondylitis patients and healthy controls. Patients were characterized by a form of gut microbial dysbiosis that is more prominent than previously reported cases with inflammatory bowel disease. Specifically, the ankylosing spondylitis patients demonstrated increases in the abundance of Prevotella melaninogenica, Prevotella copri, and Prevotella sp. C561 and decreases in Bacteroides spp. It is noteworthy that the Bifidobacterium genus, which is commonly used in probiotics, accumulated in the ankylosing spondylitis patients. Diagnostic algorithms were established using a subset of these gut microbial biomarkers. CONCLUSIONS Alterations of the gut microbiome are associated with development of ankylosing spondylitis. Our data suggest biomarkers identified in this study might participate in the pathogenesis or development process of ankylosing spondylitis, providing new leads for the development of new diagnostic tools and potential treatments.
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Affiliation(s)
- Chengping Wen
- Institute of Basic Research in Clinical Medicine, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
| | - Zhijun Zheng
- Realbio Genomics Institute, Shanghai, 200123, China
| | - Tiejuan Shao
- Institute of Basic Research in Clinical Medicine, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Lin Liu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, the First Affiliated College of Medicine, Zhejiang University, Hangzhou, 310003, China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, 310003, China
| | - Zhijun Xie
- Institute of Basic Research in Clinical Medicine, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Emmanuelle Le Chatelier
- INRA, Institut National de la Recherche Agronomique, Metagenopolis, Jouy en Josas, 78350, France
| | - Zhixing He
- Institute of Basic Research in Clinical Medicine, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Wendi Zhong
- Realbio Genomics Institute, Shanghai, 200123, China
| | - Yongsheng Fan
- Institute of Basic Research in Clinical Medicine, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | | | - Haichang Li
- Institute of Basic Research in Clinical Medicine, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Chunyan Wu
- Realbio Genomics Institute, Shanghai, 200123, China
| | - Changfeng Hu
- Institute of Basic Research in Clinical Medicine, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Qian Xu
- Realbio Genomics Institute, Shanghai, 200123, China
| | - Jia Zhou
- Institute of Basic Research in Clinical Medicine, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Shunfeng Cai
- Realbio Genomics Institute, Shanghai, 200123, China
| | - Dawei Wang
- Institute of Basic Research in Clinical Medicine, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Yun Huang
- Realbio Genomics Institute, Shanghai, 200123, China
| | - Maxime Breban
- Rheumatology Division, Ambroise-Paré Hospital, AP-HP, 9, avenue Charles-de-Gaulle, 92100, Boulogne-Billancourt, France
| | - Nan Qin
- Realbio Genomics Institute, Shanghai, 200123, China. .,State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, the First Affiliated College of Medicine, Zhejiang University, Hangzhou, 310003, China. .,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, 310003, China.
| | - Stanislav Dusko Ehrlich
- INRA, Institut National de la Recherche Agronomique, Metagenopolis, Jouy en Josas, 78350, France. .,King's College London, Centre for Host-Microbiome Interactions, Dental Institute Central Office, Guy's Hospital, London Bridge, London, SE1 9RT, UK.
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Lawley B, Munro K, Hughes A, Hodgkinson AJ, Prosser CG, Lowry D, Zhou SJ, Makrides M, Gibson RA, Lay C, Chew C, Lee PS, Wong KH, Tannock GW. Differentiation of Bifidobacterium longum subspecies longum and infantis by quantitative PCR using functional gene targets. PeerJ 2017; 5:e3375. [PMID: 28560114 PMCID: PMC5446769 DOI: 10.7717/peerj.3375] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Accepted: 05/04/2017] [Indexed: 01/16/2023] Open
Abstract
Background Members of the genus Bifidobacterium are abundant in the feces of babies during the exclusively-milk-diet period of life. Bifidobacterium longum is reported to be a common member of the infant fecal microbiota. However, B. longum is composed of three subspecies, two of which are represented in the bowel microbiota (B. longum subsp. longum; B. longum subsp. infantis). B. longum subspecies are not differentiated in many studies, so that their prevalence and relative abundances are not accurately known. This may largely be due to difficulty in assigning subspecies identity using DNA sequences of 16S rRNA or tuf genes that are commonly used in bacterial taxonomy. Methods We developed a qPCR method targeting the sialidase gene (subsp. infantis) and sugar kinase gene (subsp. longum) to differentiate the subspecies using specific primers and probes. Specificity of the primers/probes was tested by in silico, pangenomic search, and using DNA from standard cultures of bifidobacterial species. The utility of the method was further examined using DNA from feces that had been collected from infants inhabiting various geographical regions. Results A pangenomic search of the NCBI genomic database showed that the PCR primers/probes targeted only the respective genes of the two subspecies. The primers/probes showed total specificity when tested against DNA extracted from the gold standard strains (type cultures) of bifidobacterial species detected in infant feces. Use of the qPCR method with DNA extracted from the feces of infants of different ages, delivery method and nutrition, showed that subsp. infantis was detectable (0–32.4% prevalence) in the feces of Australian (n = 90), South-East Asian (n = 24), and Chinese babies (n = 91), but in all cases at low abundance (<0.01–4.6%) compared to subsp. longum (0.1–33.7% abundance; 21.4–100% prevalence). Discussion Our qPCR method differentiates B. longum subspecies longum and infantis using characteristic functional genes. It can be used as an identification aid for isolates of bifidobacteria, as well as in determining prevalence and abundance of the subspecies in feces. The method should thus be useful in ecological studies of the infant gut microbiota during early life where an understanding of the ecology of bifidobacterial species may be important in developing interventions to promote infant health.
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Affiliation(s)
- Blair Lawley
- Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
| | - Karen Munro
- Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
| | - Alan Hughes
- Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
| | | | | | - Dianne Lowry
- Dairy Goat Cooperative (NZ) Ltd., Hamilton, New Zealand
| | - Shao J Zhou
- Women's and Children's Health Research Institute, Adelaide, Australia.,School of Agriculture, Food and Wine, University of Adelaide, Adelaide, Australia
| | - Maria Makrides
- Healthy Mothers, Babies and Children, South Australian Health and Medical Research Institute, Adelaide, Australia
| | - Robert A Gibson
- School of Agriculture, Food and Wine, University of Adelaide, Adelaide, Australia
| | | | | | | | | | - Gerald W Tannock
- Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.,Riddet Institute Centre of Research Excellence, Palmerston North, New Zealand.,Microbiome Otago, University of Otago, Dunedin, New Zealand
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35
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Lewis ZT, Mills DA. Differential Establishment of Bifidobacteria in the Breastfed Infant Gut. NESTLE NUTRITION INSTITUTE WORKSHOP SERIES 2017; 88:149-159. [PMID: 28346936 DOI: 10.1159/000455399] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
The composition of an infant's gut microbiome can impact their immediate and long-term health. Bifdobacteria play a major role in structuring the gut microbiome of breastfed infants due to their ability to consume oligosaccharides found in human milk. However, recent studies have revealed that bifidobacteria are often absent in the gut microbiome of breastfed infants in some locations. This lack of colonization may be due either to differences in the environmental conditions in the gastrointestinal tract of uncolonized infants which prohibit the growth of bifidobacteria or a dearth of sources from which infants may acquire these specialized bacterial species. Potential mechanisms by which these broad factors may lead to lower colonization of infants by bifidobacteria are discussed herein. Environmental conditions which may select against bifidobacteria include low rates/duration of breastfeeding, milk glycan composition, and antimicrobial use. Routes of colonization by bifidobacteria which may be disrupted include maternal transfer via vaginal birth, fecal-oral routes, or via breast milk itself. A careful contemplation of the conditions experienced by bifidobacteria over human evolutionary history may lead to further hypotheses as to the causative factors of the differential colonization by this foundation genus in some contemporary locations.
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36
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Searching for the Perfect Homeostasis: Five Strains of Bifidobacterium longum From Centenarians Have a Similar Behavior in the Production of Cytokines. J Clin Gastroenterol 2016; 50 Suppl 2, Proceedings from the 8th Probiotics, Prebiotics & New Foods for Microbiota and Human Health meeting held in Rome, Italy on September 13-15, 2015:S126-S130. [PMID: 27741155 DOI: 10.1097/mcg.0000000000000678] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
GOALS To investigate the modulation of human cytokines by Bifidobacterium longum strains isolated from Centenarians. In particular, we measured the production of interleukin (IL)-12p70, interferon-γ, IL-17A, and IL-4 from human peripheral blood mononuclear cells after stimulation with live bacteria. BACKGROUND Probiotics may inhibit pathogens and modulate the immune system, bringing a beneficial effect on human health. Among the probiotic strains, bifidobacteria play a key role in the maturation of the host's immune system. At present, only a few comparative data are available on the effects of bifidobacteria associations on cytokine production. STUDY Peripheral blood mononuclear cells were isolated, cultured, and stimulated (ratio 1:1) with B. longum DLBL07, B. longum DLBL08, B. longum DLBL09, B. longum DLBL10, or B. longum DLBL11, either alone or in association. Cytokine production was determined by an enzyme-linked immunosorbent assay. RESULTS Both the B. longum DLBL mixture and the individual B. longum DLBL strains induced similar levels of IL-4, interferon-γ, and IL-17A. Under all conditions tested, no IL-12p70 release was detected. CONCLUSIONS The fact that B. longum strains were obtained from Centenarians suggests a perfect homeostasis between this specific species and the host. Moreover all the B. longum strains from Centenarians used in our study share some biological similarities.
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37
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GAO JISHENG, WU HONGWEI, LIU JINFENG. Importance of gut microbiota in health and diseases of new born infants. Exp Ther Med 2016; 12:28-32. [PMID: 27347013 PMCID: PMC4906629 DOI: 10.3892/etm.2016.3253] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2015] [Accepted: 04/11/2016] [Indexed: 12/21/2022] Open
Abstract
The multifarious assortment of microorganisms present in gut of humans is termed as gut microbiota. These include 1,000 species accompanied by approximately 2 million genes in an individual adult. The gut microbiota has multifactorial protective roles against allergic reactions, inflammation, cardiac pathological states and even in the state of malignant carcinogenesis existing in humans. By contrast, adverse alterations in the microbiota result in chronic pathological states, including autoimmune diseases, cancer and circulatory system obstructions. Gut bacteria also maintain sensitivity towards nutritional changes as well as antibiotics. The present review article focused on the importance of gut bacteria in newborn infants with special reference to their protective role in various pediatric pathological states linked with gut bacteria. In addition, the importance of probiotics in relation to gut microbiota are to be discussed.
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Affiliation(s)
- JISHENG GAO
- Department of Neonatology, Xuzhou Chlidren's Hospital, Xuzhou, Jiangsu 221002, P.R. China
| | - HONGWEI WU
- Department of Neonatology, Xuzhou Chlidren's Hospital, Xuzhou, Jiangsu 221002, P.R. China
| | - JINFENG LIU
- Department of Neonatology, Xuzhou Chlidren's Hospital, Xuzhou, Jiangsu 221002, P.R. China
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38
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Tannock GW, Lee PS, Wong KH, Lawley B. Why Don't All Infants Have Bifidobacteria in Their Stool? Front Microbiol 2016; 7:834. [PMID: 27303402 PMCID: PMC4886621 DOI: 10.3389/fmicb.2016.00834] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2016] [Accepted: 05/17/2016] [Indexed: 01/03/2023] Open
Affiliation(s)
- Gerald W Tannock
- Department of Microbiology and Immunology, University of OtagoDunedin, New Zealand; Riddet Centre for Research Excellence, Massey UniversityPalmerston North, New Zealand
| | - Pheng Soon Lee
- Mead Johnson NutritionSingapore, Singapore; Department of Human Nutrition, University of OtagoDunedin, New Zealand
| | | | - Blair Lawley
- Department of Microbiology and Immunology, University of Otago Dunedin, New Zealand
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39
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Szilagyi A. Adaptation to Lactose in Lactase Non Persistent People: Effects on Intolerance and the Relationship between Dairy Food Consumption and Evalution of Diseases. Nutrients 2015; 7:6751-79. [PMID: 26287234 PMCID: PMC4555148 DOI: 10.3390/nu7085309] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 07/29/2015] [Accepted: 08/03/2015] [Indexed: 02/07/2023] Open
Abstract
Dairy foods contain complex nutrients which interact with the host. Yet, evolution of lactase persistence has divided the human species into those that can or cannot digest lactose in adulthood. Such a ubiquitous trait has differential effects on humanity. The literature is reviewed to explore how the divide affects lactose handling by lactase non persistent persons. There are two basic differences in digesters. Firstly, maldigesters consume less dairy foods, and secondly, excess lactose is digested by colonic microflora. Lactose intolerance in maldigesters may occur with random lactose ingestion. However, lactose intolerance without maldigestion tends to detract from gaining a clear understanding of the mechanisms of symptoms formation and leads to confusion with regards to dairy food consumption. The main consequence of intolerance is withholding dairy foods. However, regular dairy food consumption by lactase non persistent people could lead to colonic adaptation by the microbiome. This process may mimic a prebiotic effect and allows lactase non persistent people to consume more dairy foods enhancing a favorable microbiome. This process then could lead to alterations in outcome of diseases in response to dairy foods in lactose maldigesters. The evidence that lactose is a selective human prebiotic is reviewed and current links between dairy foods and some diseases are discussed within this context. Colonic adaptation has not been adequately studied, especially with modern microbiological techniques.
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Affiliation(s)
- Andrew Szilagyi
- Division of Gastroenterology, Department of Medicine, Jewish General Hospital, McGill University School of Medicine; 3755, Chemin de la Cote-Ste-Catherine Rd, Rm E110, Montreal H3T 1E2, QC, Canada.
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40
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Habil N, Abate W, Beal J, Foey AD. Heat-killed probiotic bacteria differentially regulate colonic epithelial cell production of human β-defensin-2: dependence on inflammatory cytokines. Benef Microbes 2015; 5:483-95. [PMID: 25116382 DOI: 10.3920/bm2013.0061] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
The inducible antimicrobial peptide human β-defensin-2 (hBD-2) stimulated by pro-inflammatory cytokines and bacterial products is essential to antipathogen responses of gut epithelial cells. Commensal and probiotic bacteria can augment such mucosal defences. Probiotic use in the treatment of inflammatory bowel disease, however, may have adverse effects, boosting inflammatory responses. The aim of this investigation was to determine the effect of selected probiotic strains on hBD-2 production by epithelial cells induced by pathologically relevant pro-inflammatory cytokines and the role of cytokine modulators in controlling hBD-2. Caco-2 colonic intestinal epithelial cells were pre-incubated with heat-killed probiotics, i.e. Lactobacillus casei strain Shirota (LcS) or Lactobacillus fermentum strain MS15 (LF), followed by stimulation of hBD-2 by interleukin (IL)-1β and tumour necrosis factor alpha (TNF-α) in the absence or presence of exogenous IL-10 or anti-IL-10 neutralising antibody. Cytokines and hBD-2 mRNA and protein were analysed by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. LcS augmented IL-1β-induced hBD-2, whereas LF enhanced TNF-α- and suppressed IL-1β-induced hBD-2. LF enhanced TNF-α-induced TNF-α and suppressed IL-10, whereas augmented IL-1β-induced IL-10. LcS upregulated IL-1β-induced TNF-α mRNA and suppressed IL-10. Endogenous IL-10 differentially regulated hBD-2; neutralisation of IL-10 augmented TNF-α- and suppressed IL-1β-induced hBD-2. Exogenous IL-10, however, suppressed both TNF-α- and IL-1β-induced hBD-2; LcS partially rescued suppression in TNF-α- and IL-1β-stimulation, whereas LF further suppressed IL-1β-induced hBD-2. It can be concluded that probiotic strains differentially regulate hBD-2 mRNA expression and protein secretion, modulation being dictated by inflammatory stimulus and resulting cytokine environment.
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Affiliation(s)
- N Habil
- School of Biomedical & Healthcare Sciences, University of Plymouth, Drake Circus, Plymouth PL4 8AA, United Kingdom Foundation of Technical Education (FTE), Alnakabat Street, 55555 Baghdad, Iraq
| | - W Abate
- School of Biomedical & Healthcare Sciences, University of Plymouth, Drake Circus, Plymouth PL4 8AA, United Kingdom
| | - J Beal
- School of Biomedical & Healthcare Sciences, University of Plymouth, Drake Circus, Plymouth PL4 8AA, United Kingdom
| | - A D Foey
- School of Biomedical & Healthcare Sciences, University of Plymouth, Drake Circus, Plymouth PL4 8AA, United Kingdom
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41
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Lin RJ, Qiu LH, Guan RZ, Hu SJ, Liu YY, Wang GJ. Protective effect of probiotics in the treatment of infantile eczema. Exp Ther Med 2015; 9:1593-1596. [PMID: 26136864 DOI: 10.3892/etm.2015.2299] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2014] [Accepted: 12/18/2014] [Indexed: 02/04/2023] Open
Abstract
The aim of the present study was to provide evidence for the application of probiotics in the prevention and treatment of infantile eczema by exploring changes in the intestinal Bifidobacteria levels and the Scoring Atopic Dermatitis (SCORAD) index prior and subsequent to treatment with probiotics in infants with eczema. A total of 40 infants with eczema were randomly divided into treatment and control groups. Prior and subsequent to the treatment, the SCORAD index was evaluated and the content of Bifidobacterium bifidum in the stool of each infant in the two groups was quantified using 16S rRNA/DNA quantitative polymerase chain reaction analysis. After four weeks of treatment with B. bifidum triple viable capsules, the levels of B. bifidum increased sharply (P<0.05) and the SCORAD index was notably reduced (P<0.05) as compared with the values prior to treatment. By contrast, neither the content of B. bifidum nor the SCORAD index changed significantly in the control group after four weeks (P>0.05). Following treatment, the levels of B. bifidum in the stools of the treatment group were significantly higher than those in the stools of the control group (P<0.05), and the SCORAD index was significantly lower than that of the control group (P<0.05). In conclusion, probiotic supplementation has a positive effect on the prevention and treatment of infantile eczema.
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Affiliation(s)
- Rong-Jun Lin
- Department of Pediatrics, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266071, P.R. China
| | - Li-Hua Qiu
- Department of Pediatrics, The Maternal-Child Healthcare Center of Qingdao, Qingdao, Shandong 266035, P.R. China
| | - Ren-Zheng Guan
- Department of Pediatrics, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266071, P.R. China
| | - Su-Juan Hu
- Department of Pediatrics, The Maternal-Child Healthcare Center of Qingdao, Qingdao, Shandong 266035, P.R. China
| | - Ying-Ying Liu
- Department of Pediatrics, The Maternal-Child Healthcare Center of Qingdao, Qingdao, Shandong 266035, P.R. China
| | - Guang-Jun Wang
- Department of Pediatrics, Shandong Traffic hospital, Jinan, Shandong 250031, P.R. China
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Scuotto A, Djorie S, Colavizza M, Romond PC, Romond MB. Bifidobacterium breve C50 secretes lipoprotein with CHAP domain recognized in aggregated form by TLR2. Biochimie 2014; 107 Pt B:367-75. [PMID: 25457102 DOI: 10.1016/j.biochi.2014.10.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2014] [Accepted: 10/10/2014] [Indexed: 10/24/2022]
Abstract
Extracellular components secreted by Bifidobacterium breve C50 can induce maturation, high IL-10 production and prolonged survival of dendritic cells via a TLR2 pathway. In this study, the components were isolated from the supernatant by gel filtration chromatography. Antibodies raised against the major compounds with molecular weight above 600 kDa (Bb C50BC) also recognized compounds of lower molecular weight (200–600 kDa). TLR2 and TLR6 bound to the components already recognized by the antibodies. Trypsin digestion of Bb C50BC released three major peptides whose sequences displayed close similarities to a putative secreted protein with a CHAP amidase domain from B. breve. The 1300-bp genomic region corresponding to the hypothetical protein was amplified by PCR. The deduced polypeptide started with an N-terminal signal sequence of 45 amino acids, containing the lipobox motif (LAAC) with the cysteine in position 25, and 2 positively charged residues within the first 14 residues of the signal sequence. Lipid detection in Bb C50BC by GC/MS further supported the implication of a lipoprotein. Sugars were also detected in Bb C50BC. Close similarity with the glucan-binding protein B from Bifidobacterium animalis of two released peptides from Bb C50BC protein suggested that glucose moieties, possibly in glucan form, could be bound to the lipoprotein. Finally, heating at 100 °C for 5 min led to the breakdown of Bb C50BC in compounds of molecular weight below 67 kDa, which suggested that Bb C50BC was an aggregate. One might assume that a basic unit was formed by the lipoprotein bound putatively to glucan. Besides the other sugars and hexosamines recognized by galectin 1 were localized at the surface of the Bb C50BC aggregate. In conclusion, the extracellular components secreted by B. breve C50 were constituted of a lipoprotein putatively associated with glucose moieties and acting in an aggregating form as an agonist of TLR2/TLR6.
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43
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Ha CWY, Lam YY, Holmes AJ. Mechanistic links between gut microbial community dynamics, microbial functions and metabolic health. World J Gastroenterol 2014; 20:16498-16517. [PMID: 25469018 PMCID: PMC4248193 DOI: 10.3748/wjg.v20.i44.16498] [Citation(s) in RCA: 84] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2014] [Revised: 06/26/2014] [Accepted: 08/28/2014] [Indexed: 02/06/2023] Open
Abstract
Gut microbes comprise a high density, biologically active community that lies at the interface of an animal with its nutritional environment. Consequently their activity profoundly influences many aspects of the physiology and metabolism of the host animal. A range of microbial structural components and metabolites directly interact with host intestinal cells and tissues to influence nutrient uptake and epithelial health. Endocrine, neuronal and lymphoid cells in the gut also integrate signals from these microbial factors to influence systemic responses. Dysregulation of these host-microbe interactions is now recognised as a major risk factor in the development of metabolic dysfunction. This is a two-way process and understanding the factors that tip host-microbiome homeostasis over to dysbiosis requires greater appreciation of the host feedbacks that contribute to regulation of microbial community composition. To date, numerous studies have employed taxonomic profiling approaches to explore the links between microbial composition and host outcomes (especially obesity and its comorbidities), but inconsistent host-microbe associations have been reported. Available data indicates multiple factors have contributed to discrepancies between studies. These include the high level of functional redundancy in host-microbiome interactions combined with individual variation in microbiome composition; differences in study design, diet composition and host system between studies; and inherent limitations to the resolution of rRNA-based community profiling. Accounting for these factors allows for recognition of the common microbial and host factors driving community composition and development of dysbiosis on high fat diets. New therapeutic intervention options are now emerging.
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44
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Akay HK, Bahar Tokman H, Hatipoglu N, Hatipoglu H, Siraneci R, Demirci M, Borsa BA, Yuksel P, Karakullukcu A, Kangaba AA, Sirekbasan S, Aka S, Mamal Torun M, Kocazeybek BS. The relationship between bifidobacteria and allergic asthma and/or allergic dermatitis: a prospective study of 0-3 years-old children in Turkey. Anaerobe 2014; 28:98-103. [PMID: 24878320 DOI: 10.1016/j.anaerobe.2014.05.006] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2013] [Revised: 03/25/2014] [Accepted: 05/19/2014] [Indexed: 12/17/2022]
Abstract
Bifidobacteria are beneficial bacteria for humans. These bacteria are particularly effective at protecting against infectious diseases and modulating the immune response. It was shown that in newborns, the fecal distribution of the colonizing Bifidobacterium species influences the prevalence of allergic diseases. This study aimed to compare the faecal Bifidobacterium species of allergic children to those of healthy children to detect species level differences in faecal distribution. Stool samples were obtained from 99 children between 0 and 3 years of age whose clinical symptoms and laboratory reports were compatible with atopic dermatitis and allergic asthma. Samples were also obtained from 102 healthy children who were similar to the case group with respect to age and sex. Bifidobacteria were isolated by culture and identified at the genus level by API 20 A. In addition, 7 unique species-specific primers were used for the molecular characterization of bifidobacteria. The McNemar test was used for statistical analyses, and p < 0.05 was accepted as significant. Bifidobacterium longum was detected in 11 (11.1%) of the allergic children and in 31 (30.3%) of the healthy children. Statistical analysis revealed a significant difference in the prevalence of B. longum between these two groups (X(2): 11.2, p < 0.001). However, no significant differences in the prevalence of other Bifidobacterium species were found between faecal samples from healthy and allergic children. (p > 0.05). The significant difference in the isolation of B. longum from our study groups suggests that this species favors the host by preventing the development of asthma and allergic dermatitis. Based on these results, we propose that the production of probiotics in accordance with country-specific Bifidobacterium species densities would improve public health. Thus, country-specific prospective case-control studies that collect broad data sets are needed.
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Affiliation(s)
- Hatice Kubra Akay
- Istanbul University, Cerrahpasa School of Medicine, Department of Medical Microbiology, Istanbul, Turkey.
| | - Hrisi Bahar Tokman
- Istanbul University, Cerrahpasa School of Medicine, Department of Medical Microbiology, Istanbul, Turkey.
| | - Nevin Hatipoglu
- Kanuni Sultan Suleyman Education and Research Hospital, Department of Pediatric Infectious Diseases, Allergy and Immunology, Istanbul, Turkey.
| | - Huseyin Hatipoglu
- Kanuni Sultan Suleyman Education and Research Hospital, Department of Pediatric Infectious Diseases, Allergy and Immunology, Istanbul, Turkey.
| | - Rengin Siraneci
- Kanuni Sultan Suleyman Education and Research Hospital, Department of Pediatric Infectious Diseases, Allergy and Immunology, Istanbul, Turkey.
| | - Mehmet Demirci
- Istanbul University, Cerrahpasa School of Medicine, Department of Medical Microbiology, Istanbul, Turkey.
| | - Baris Ata Borsa
- Kemerburgaz University, Medical Faculty, Department of Medical Microbiology, Istanbul, Turkey.
| | - Pelin Yuksel
- Istanbul University, Cerrahpasa School of Medicine, Department of Medical Microbiology, Istanbul, Turkey.
| | - Asiye Karakullukcu
- Istanbul University, Cerrahpasa School of Medicine, Department of Medical Microbiology, Istanbul, Turkey.
| | - Achille Aime Kangaba
- Istanbul University, Cerrahpasa School of Medicine, Department of Medical Microbiology, Istanbul, Turkey.
| | - Serhat Sirekbasan
- Istanbul University, Cerrahpasa School of Medicine, Department of Medical Microbiology, Istanbul, Turkey.
| | - Sibel Aka
- Acıbadem University School of Medicine, Department of Children Health and Disease, Istanbul, Turkey.
| | - Muzeyyen Mamal Torun
- Istanbul University, Cerrahpasa School of Medicine, Department of Medical Microbiology, Istanbul, Turkey.
| | - Bekir S Kocazeybek
- Istanbul University, Cerrahpasa School of Medicine, Department of Medical Microbiology, Istanbul, Turkey.
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Moratalla A, Gómez-Hurtado I, Santacruz A, Moya Á, Peiró G, Zapater P, González-Navajas JM, Giménez P, Such J, Sanz Y, Francés R. Protective effect of Bifidobacterium pseudocatenulatum CECT7765 against induced bacterial antigen translocation in experimental cirrhosis. Liver Int 2014; 34:850-8. [PMID: 24267920 DOI: 10.1111/liv.12380] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2013] [Accepted: 10/31/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Intervention in the gut ecosystem is considered as a potential strategy to treat liver diseases and their complications. We have evaluated the effects of Bifidobacterium pseudocatenulatum CECT7765 on bacterial translocation and the liver status in experimental cirrhosis. ANIMALS & METHODS Liver damage was induced in Balb/c mice by weight-controlled oral administration of carbon tetrachloride. Laparotomies were performed at week 12. One week prior to laparotomy, animals received B. pseudocatenulatum CECT7765 (10(9) cfu/daily) or placebo intragastrically. All animals received Escherichia coli (10(7) cfu/single dose) intragastrically 24 hours before laparotomy. A group of naïve non-treated animals was included as control. Liver tissue specimens, mesenteric lymph nodes, intestinal content and blood were collected. Liver histology, profibrogenic genes expression, bacterial DNA translocation, serum endotoxaemia and liver cytokine levels were measured. RESULTS Bifidobacterium pseudocatenulatum CECT7765 showed no significant effect on structural liver damage, as determined by histological evaluation, alpha-smooth muscle actin distribution, profibrogenic gene expression levels, total hydroxyproline levels and malon dialdehyde production compared with mice receiving placebo. Interestingly, bacterial DNA translocation and serum endotoxin levels were significantly decreased in mice receiving the Bifidobacterium strain compared with placebo. Gut barrier integrity markers were up-regulated in mice receiving B. pseudocatenulatum CECT7765 and quantitatively correlated with intestinal gene copy numbers of the bifidobacterial strain. Gene expression levels of several anti-inflammatory mediators were also increased in mice receiving B. pseudocatenulatum CECT7765 compared with placebo. CONCLUSION Oral administration of B. pseudocatenulatum CECT7765 is associated with improved gut barrier integrity and shows a beneficial effect against induced bacterial antigen translocation in the CCl4 -model of cirrhosis.
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Affiliation(s)
- Alba Moratalla
- CIBERehd, Instituto de Salud Carlos III, Madrid, Spain; Unidad Hepática, Consejo Superior de Investigaciones Científicas (IATA-CSIC), Valencia, Spain
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TgaA, a VirB1-like component belonging to a putative type IV secretion system of Bifidobacterium bifidum MIMBb75. Appl Environ Microbiol 2014; 80:5161-9. [PMID: 24951779 DOI: 10.1128/aem.01413-14] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Bifidobacterium bifidum MIMBb75 is a human intestinal isolate demonstrated to be interactive with the host and efficacious as a probiotic. However, the molecular biology of this microorganism is yet largely unknown. For this reason, we undertook whole-genome sequencing of B. bifidum MIMBb75 to identify potential genetic factors that would explain the metabolic and probiotic attributes of this bacterium. Comparative genomic analysis revealed a 45-kb chromosomal region that comprises 19 putative genes coding for a potential type IV secretion system (T4SS). Thus, we undertook the initial characterization of this genetic region by studying the putative virB1-like gene, named tgaA. Gene tgaA encodes a peptidoglycan lytic enzyme containing two active domains: lytic murein transglycosylase (LT, cd00254.3) and cysteine- and histidine-dependent amidohydrolase/peptidase (CHAP, pfam05257.4). By means of several in vitro assays, we experimentally confirmed that protein TgaA, consistent with its computationally assigned role, has peptidoglycan lytic activity, which is principally associated to the LT domain. Furthermore, immunofluorescence and immunogold labeling showed that the protein TgaA is abundantly expressed on the cell surface of B. bifidum MIMBb75. According to the literature, the T4SSs, which have not been characterized before in bifidobacteria, can have important implications for bacterial cell-to-cell communication as well as cross talk with host cells, justifying the interest for further studies aimed at the investigation of this genetic region.
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Murein lytic enzyme TgaA of Bifidobacterium bifidum MIMBb75 modulates dendritic cell maturation through its cysteine- and histidine-dependent amidohydrolase/peptidase (CHAP) amidase domain. Appl Environ Microbiol 2014; 80:5170-7. [PMID: 24814791 DOI: 10.1128/aem.00761-14] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Bifidobacteria are Gram-positive inhabitants of the human gastrointestinal tract that have evolved close interaction with their host and especially with the host's immune system. The molecular mechanisms underlying such interactions, however, are largely unidentified. In this study, we investigated the immunomodulatory potential of Bifidobacterium bifidum MIMBb75, a bacterium of human intestinal origin commercially used as a probiotic. Particularly, we focused our attention on TgaA, a protein expressed on the outer surface of MIMBb75's cells and homologous to other known bacterial immunoactive proteins. TgaA is a peptidoglycan lytic enzyme containing two active domains: lytic murein transglycosylase (LT) and cysteine- and histidine-dependent amidohydrolase/peptidase (CHAP). We ran immunological experiments stimulating dendritic cells (DCs) with the B. bifidum MIMBb75 and TgaA, with the result that both the bacterium and the protein activated DCs and triggered interleukin-2 (IL-2) production. In addition, we observed that the heterologous expression of TgaA in Bifidobacterium longum transferred to the bacterium the ability to induce IL-2. Subsequently, immunological experiments performed using two purified recombinant proteins corresponding to the single domains LT and CHAP demonstrated that the CHAP domain is the immune-reactive region of TgaA. Finally, we also showed that TgaA-dependent activation of DCs requires the protein CD14, marginally involves TRIF, and is independent of Toll-like receptor 4 (TLR4) and MyD88. In conclusion, our study suggests that the bacterial CHAP domain is a novel microbe-associated molecular pattern actively participating in the cross talk mechanisms between bifidobacteria and the host's immune system.
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Taverniti V, Scabiosi C, Arioli S, Mora D, Guglielmetti S. Short-term daily intake of 6 billion live probiotic cells can be insufficient in healthy adults to modulate the intestinal bifidobacteria and lactobacilli. J Funct Foods 2014. [DOI: 10.1016/j.jff.2013.11.014] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
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Di Gioia D, Aloisio I, Mazzola G, Biavati B. Bifidobacteria: their impact on gut microbiota composition and their applications as probiotics in infants. Appl Microbiol Biotechnol 2013; 98:563-77. [PMID: 24287935 DOI: 10.1007/s00253-013-5405-9] [Citation(s) in RCA: 138] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2013] [Revised: 11/11/2013] [Accepted: 11/12/2013] [Indexed: 01/05/2023]
Abstract
This review is aimed at describing the most recent advances in the gut microbiota composition of newborns and infants with a particular emphasis on bifidobacteria. The newborn gut microbiota is quite unstable, whereas after weaning, it becomes more stable and gets closer to the typical adult microbiota. The newborn and infant gut microbiota composition is impaired in several enteric and non-enteric pathologies. The core of this review is the description of the most recent documented applications of bifidobacteria to newborns and infants for their prevention and treatment. Acute diarrhea is the most studied disease for which bifidobacteria are applied with great success, Bifidobacterium longum and Bifidobacterium breve being the most applied species. Moreover, the most recent updates in the use of bifidobacteria for the prevention and treatment of pathologies typical of newborns, such as necrotizing enterocolitis, colics, and streptococcal infections, are presented. In addition, a number of not strictly enteric pathologies have in recent years evidenced a strict correlation with an aberrant gut microbiota in infants, in particular showing a reduced level of bifidobacteria. These diseases represent new potential opportunities for probiotic applications. Among them, allergic diseases, celiac disease, obesity, and neurologic diseases are described in this review. The preliminary use of bifidobacteria in in vitro systems and animal models is summarized as well as preliminary in vivo studies. Only after validation of the results via human clinical trials will the potentiality of bifidobacteria in the prevention and cure of these pathologies be definitely assessed.
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Affiliation(s)
- Diana Di Gioia
- Department of Agricultural Science, University of Bologna, viale Fanin 44, 40127, Bologna, Italy,
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50
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You J, Dong H, Mann ER, Knight SC, Yaqoob P. Probiotic modulation of dendritic cell function is influenced by ageing. Immunobiology 2013; 219:138-48. [PMID: 24094416 PMCID: PMC4064698 DOI: 10.1016/j.imbio.2013.08.012] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2013] [Revised: 07/30/2013] [Accepted: 08/27/2013] [Indexed: 12/23/2022]
Abstract
Dendritic cells (DCs) are critical for the generation of T-cell responses. DC function may be modulated by probiotics, which confer health benefits in immunocompromised individuals, such as the elderly. This study investigated the effects of four probiotics, Bifidobacterium longum bv. infantis CCUG 52486, B. longum SP 07/3, Lactobacillus rhamnosus GG (L.GG) and L. casei Shirota (LcS), on DC function in an allogeneic mixed leucocyte reaction (MLR) model, using DCs and T-cells from young and older donors in different combinations. All four probiotics enhanced expression of CD40, CD80 and CCR7 on both young and older DCs, but enhanced cytokine production (TGF-β, TNF-α) by old DCs only. LcS induced IL-12 and IFNγ production by DC to a greater degree than other strains, while B. longum bv. infantis CCUG 52486 favoured IL-10 production. Stimulation of young T cells in an allogeneic MLR with DC was enhanced by probiotic pretreatment of old DCs, which demonstrated greater activation (CD25) than untreated controls. However, pretreatment of young or old DCs with LPS or probiotics failed to enhance the proliferation of T-cells derived from older donors. In conclusion, this study demonstrates that ageing increases the responsiveness of DCs to probiotics, but this is not sufficient to overcome the impact of immunosenescence in the MLR.
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Affiliation(s)
- Jialu You
- Department of Food and Nutritional Sciences, The University of Reading, Reading, UK
| | - Honglin Dong
- Department of Food and Nutritional Sciences, The University of Reading, Reading, UK
| | - Elizabeth R Mann
- Antigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark's Campus, Harrow, HA1 3UJ, UK
| | - Stella C Knight
- Antigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark's Campus, Harrow, HA1 3UJ, UK
| | - Parveen Yaqoob
- Department of Food and Nutritional Sciences, The University of Reading, Reading, UK.
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