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Nunez H, Nieto PA, Mars RA, Ghavami M, Sew Hoy C, Sukhum K. Early life gut microbiome and its impact on childhood health and chronic conditions. Gut Microbes 2025; 17:2463567. [PMID: 39916516 PMCID: PMC11810090 DOI: 10.1080/19490976.2025.2463567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 12/20/2024] [Accepted: 02/02/2025] [Indexed: 02/12/2025] Open
Abstract
The development of the gut microbiome is crucial to human health, particularly during the first three years of life. Given its role in immune development, disturbances in the establishment process of the gut microbiome may have long term consequences. This review summarizes evidence for these claims, highlighting compositional changes of the gut microbiome during this critical period of life as well as factors that affect gut microbiome development. Based on human and animal data, we conclude that the early-life microbiome is a determinant of long-term health, impacting physiological, metabolic, and immune processes. The early-life gut microbiome field faces challenges. Some of these challenges are technical, such as lack of standardized stool collection protocols, inconsistent DNA extraction methods, and outdated sequencing technologies. Other challenges are methodological: small sample sizes, lack of longitudinal studies, and poor control of confounding variables. To address these limitations, we advocate for more robust research methodologies to better understand the microbiome's role in health and disease. Improved methods will lead to more reliable microbiome studies and a deeper understanding of its impact on health outcomes.
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Affiliation(s)
- Harold Nunez
- Seeding Inc, DBA Tiny Health, Austin, Texas, USA
| | | | - Ruben A. Mars
- Seeding Inc, DBA Tiny Health, Austin, Texas, USA
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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2
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Kennedy KM, Plagemann A, Sommer J, Hofmann M, Henrich W, Surette MG, Braun T, Sloboda DM. Delivery mode, birth order, and sex impact neonatal microbial colonization. Gut Microbes 2025; 17:2491667. [PMID: 40251947 PMCID: PMC12013413 DOI: 10.1080/19490976.2025.2491667] [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: 12/10/2024] [Revised: 04/02/2025] [Accepted: 04/05/2025] [Indexed: 04/21/2025] Open
Abstract
The initial microbial colonization of the infant gut during birth plays a critical role in shaping both immediate and long-term health outcomes. While mode of delivery is a known determinant of this colonization process, the potential impacts of infant sex and birth order remain underexplored. This study investigates the influence of delivery mode, infant sex, and birth order (maternal parity) on the microbial communities in first-pass meconium samples from neonates, using 16S rRNA gene sequencing. We found that delivery mode impacted the presence of detectable microbial communities. Specifically, only 17% of samples from neonates delivered by elective Cesarean section showed any microbial presence, compared to approximately two-thirds of samples from neonates exposed to maternal vaginal microbes (emergency C-section or vaginal delivery). Among vaginally delivered neonates without antibiotic exposure, birth order was associated with taxonomic shifts. Neonates born to primiparous mothers had a lower abundance of Bifidobacterium, a keystone species in the infant gut microbiome. Unexpectedly, the gut microbiota differed by infant sex, with males having lower alpha diversity and shifts in microbial community composition (PERMANOVA p = 0.008), characterized by elevated levels of Enterobacteriales, which was both less prevalent and less abundant in female neonates. These findings highlight the intricate interplay between delivery mode, infant sex, and birth order in shaping the early gut microbiome.
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Affiliation(s)
- Katherine M. Kennedy
- Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada
- Department of Obstetrics and Gynecology, McMaster University, Hamilton, Canada
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
- McMaster Immunology Research Centre, McMaster University, Hamilton, Canada
- M.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Canada
| | - Andreas Plagemann
- Department of Obstetrics and Department of ‘Experimental Obstetrics’, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Julia Sommer
- Department of Obstetrics and Department of ‘Experimental Obstetrics’, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Marie Hofmann
- Department of Obstetrics and Department of ‘Experimental Obstetrics’, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Wolfgang Henrich
- Department of Obstetrics and Department of ‘Experimental Obstetrics’, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Michael G. Surette
- Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
- Department of Medicine, McMaster University, Hamilton, Canada
| | - Thorsten Braun
- Department of Obstetrics and Department of ‘Experimental Obstetrics’, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Deborah M. Sloboda
- Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada
- Department of Obstetrics and Gynecology, McMaster University, Hamilton, Canada
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
- Department of Medicine, McMaster University, Hamilton, Canada
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3
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Wang S, Zheng C, Bu C, Guo D, Zhang C, Xie Q, Pan J, Sun J, Chen W, Jiang S, Zhai Q. Role of sn-2 palmitate on the development of the infant gut microbiome: A metagenomic insight. Food Res Int 2025; 211:116488. [PMID: 40356145 DOI: 10.1016/j.foodres.2025.116488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2025] [Revised: 02/26/2025] [Accepted: 04/15/2025] [Indexed: 05/15/2025]
Abstract
The infant gut microbiome, which develops from birth, has profound and lasting effects on human health. Its establishment in early life is influenced by events such as delivery mode and feeding type. This study examined the effects of formula milk enriched with sn-2 palmitate on the gut microbiota of healthy term infants. We conducted a 16-week comparative analysis of three feeding groups: infants receiving high sn-2 palmitate formula (n = 30), regular vegetable oil formula (n = 32), and breast milk (n = 30). Using shotgun metagenomic sequencing of fecal samples, we performed a comprehensive assessment of the gut microbiota. While overall microbial composition and diversity were comparable across groups, the functional profile of the microbiome in infants receiving sn-2 palmitate-enriched formula more closely resembled that of breastfed infants compared to the control formula group. This similarity extended to microbial species interactions, virulence gene abundance, and metabolic pathway expression patterns. In addition, sn-2 palmitate promoted the proliferation of Bifidobacterium breve and enhanced the robustness of the gut microbial ecology. Notably, the phylogenetic analysis of B. breve strains in the sn-2 palmitate group showed closer alignment with the breastfed group compared to the control group. These findings suggest that sn-2 palmitate-enriched formula may confer gut microbiota functional benefits that more closely resemble those of breast milk compared to control formula milk. This study provides scientific evidence for the development of future functional infant formulas.
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Affiliation(s)
- Shumin Wang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Chengdong Zheng
- Heilongjiang Feihe Dairy Co., Ltd., C-16, 10A Jiuxianqiao Rd., Chaoyang, Beijing 100015, China; PKUHSC-China Feihe Joint Research Institute of Nutrition and Healthy Lifespan Development, Xueyuan Road 38, Haidian, Beijing 100083, China
| | - Chaozhi Bu
- Wuxi Maternity and Child Health Care Hospital, Affiliated Women's Hospital of Jiangnan University, Wuxi, Jiangsu 214002, China
| | - Danying Guo
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Chengcheng Zhang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Qinggang Xie
- Heilongjiang Feihe Dairy Co., Ltd., C-16, 10A Jiuxianqiao Rd., Chaoyang, Beijing 100015, China; PKUHSC-China Feihe Joint Research Institute of Nutrition and Healthy Lifespan Development, Xueyuan Road 38, Haidian, Beijing 100083, China
| | - Jiancun Pan
- Heilongjiang Feihe Dairy Co., Ltd., C-16, 10A Jiuxianqiao Rd., Chaoyang, Beijing 100015, China; PKUHSC-China Feihe Joint Research Institute of Nutrition and Healthy Lifespan Development, Xueyuan Road 38, Haidian, Beijing 100083, China
| | - Jianguo Sun
- Heilongjiang Feihe Dairy Co., Ltd., C-16, 10A Jiuxianqiao Rd., Chaoyang, Beijing 100015, China; PKUHSC-China Feihe Joint Research Institute of Nutrition and Healthy Lifespan Development, Xueyuan Road 38, Haidian, Beijing 100083, China
| | - Wei Chen
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China; National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, Jiangsu 214122, China
| | - Shilong Jiang
- Heilongjiang Feihe Dairy Co., Ltd., C-16, 10A Jiuxianqiao Rd., Chaoyang, Beijing 100015, China; PKUHSC-China Feihe Joint Research Institute of Nutrition and Healthy Lifespan Development, Xueyuan Road 38, Haidian, Beijing 100083, China.
| | - Qixiao Zhai
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China.
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Ni X, Li J, Xiong H, Deng Z, Sun Y. Influence of fatty acid distribution on lipid metabolism and cognitive development in first-weaned mice. Food Res Int 2025; 209:116292. [PMID: 40253195 DOI: 10.1016/j.foodres.2025.116292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 02/18/2025] [Accepted: 03/13/2025] [Indexed: 04/21/2025]
Abstract
There are significant structural differences between breast milk fat and the fat found in existing infant formulas, and these differences may partly explain the observed variations in growth and development between breastfed and formula-fed infants. This study used mice compared three groups: a control group (mixed vegetable oil), an OPO group (vegetable oil added with OPO), and a human milk fat substitute (HMFS) group formulated to match the fatty acid composition of breast milk. Compared to the control group and OPO group, HMFS-fed mice exhibited reduced body fat content and improved cognitive abilities. Lipidomics studies revealed that these differences in HMFS mice were associated with downregulation of hepatic glycerolipids and upregulation of glycerophospholipids and sphingolipids, facilitating the delivery of long-chain polyunsaturated fatty acids to the brain. Molecular investigations confirmed that HMFS reduces body fat accumulation by inhibiting endogenous fatty acid synthesis and promoting fatty acid β-oxidation, while changes in hepatic lipid profiles result from lipid molecule synthesis and interconversion. Metataxonomic studies demonstrated that HMFS reshaped the gut microbiota, including upregulating Akkermansia and downregulating Desulfovibrio and the Firmicutes/Bacteroidetes ratio, with strong correlations observed between the change of gut microbiota and responded lipids in liver. Overall, the breast milk's unique fatty acid distribution promotes organismal growth by modulating hepatic lipid metabolism, systemic lipid circulation, and gut microbiota. These findings underscore the nutritional benefits of breast milk fat structure and provide insights for the development of next-generation infant formulas.
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Affiliation(s)
- Xinggang Ni
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, Jiangxi 330047, China
| | - Jing Li
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, Jiangxi 330047, China
| | - Hua Xiong
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, Jiangxi 330047, China
| | - Zeyuan Deng
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, Jiangxi 330047, China
| | - Yong Sun
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, Jiangxi 330047, China.
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Wu F, Liu Y, Zhang M, Yuan X, Jin Y, Li Y, Wang R, Hao Y, Fang B. Effects of 1,3-Dioleoyl-2-palmitoylglycerol on Intestine Structural and Functional Development in Early Life. Mol Nutr Food Res 2025; 69:e70051. [PMID: 40129020 DOI: 10.1002/mnfr.70051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 03/03/2025] [Accepted: 03/12/2025] [Indexed: 03/26/2025]
Abstract
1,3-Dioleoyl-2-palmitoyl-glycerol (OPO) is a specific triglyceride in human breast milk, and it has been added to infant formula to mimic human breast milk fat. Existing studies only focused on its effects on fatty acid and calcium absorption, as well as the intestinal microbial composition; however, effects of OPO on the early-life development of intestine were still unclear. Our study explored the effects of OPO on intestinal epithelial structure and barrier construction in neonatal mice and the involvement of intestinal microorganisms. OPO supplementation significantly increased the number of intestinal stem cells, which in turn promoted villus and crypt, and promoted goblet cell and Paneth cell differentiation. OPO also promotes epithelial barrier integrity by increasing the expression of mucin 2, lysozyme 1, and tight junction proteins. Furthermore, the benefits of OPO were associated with the higher abundance of beneficial bacteria (unclassified_f_Muribaculaceae, Akkermansia, Bifidobacterium, and Blautia) and elevated butyrate levels. This study demonstrates the efficacy of OPO on intestinal health in neonatal mice beyond defecation, expands the understanding of the biological functions of OPO, and expands its application in intestinal health products targeting special populations, such as the elderly or individuals with intestinal fragility or injury.
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Affiliation(s)
- Fang Wu
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China
| | - Yaqiong Liu
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China
| | - Ming Zhang
- School of Food Science and Chemical Engineering, Beijing Technology and Business University, Beijing, China
| | - Xinlei Yuan
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China
- College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin, China
| | - Yutong Jin
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China
| | - Yixuan Li
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China
| | - Ran Wang
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China
| | - Yanling Hao
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China
| | - Bing Fang
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China
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Abavisani M, Tafti P, Khoshroo N, Ebadpour N, Khoshrou A, Kesharwani P, Sahebkar A. The heart of the matter: How gut microbiota-targeted interventions influence cardiovascular diseases. Pathol Res Pract 2025; 269:155931. [PMID: 40174272 DOI: 10.1016/j.prp.2025.155931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 03/10/2025] [Accepted: 03/26/2025] [Indexed: 04/04/2025]
Abstract
The human body is habitat to a wide spectrum of microbial populations known as microbiota, which play an important role in overall health. The considerable research has mostly focused on the gut microbiota due to its potential to impact numerous physiological functions and its correlation with a variety of disorders, such as cardiovascular diseases (CVDs). Imbalances in the gut microbiota, known as dysbiosis, have been linked to the development and progression of CVDs through various processes, including the generation of metabolites like trimethylamine-N-oxide and short-chain fatty acids. Studies have also looked at the idea of using therapeutic interventions, like changing your diet, taking probiotics or prebiotics, or even fecal microbiota transplantation (FMT), to change the gut microbiota's make-up and how it works in order to prevent or treat CVDs. Exploring the cause-and-effect connection between the gut microbiota and CVDs offers a hopeful path for creating innovative microbiome-centered strategies to prevent and cure CVDs. This review presents an in-depth review of the correlation between the gut microbiota and CVDs, as well as potential therapeutic approaches for manipulating the gut microbiota to enhance cardiovascular health.
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Affiliation(s)
- Mohammad Abavisani
- Student research committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Pourya Tafti
- Student research committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Niloofar Khoshroo
- Student research committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Negar Ebadpour
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Alireza Khoshrou
- Student research committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Prashant Kesharwani
- Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya, Sagar, Madhya Pardesh, India; University Institute of Pharma Sciences, Chandigarh University, Mohali, Punjab, India.
| | - Amirhossein Sahebkar
- Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
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7
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Petitclerc I, Perron J, Dugas C, Mayer T, Raymond F, Di Marzo V, Veilleux A, Robitaille J. Association between gestational diabetes mellitus, maternal health and diet, and gut microbiota in mother-infant dyads. BMC Pregnancy Childbirth 2025; 25:486. [PMID: 40275186 PMCID: PMC12023395 DOI: 10.1186/s12884-025-07584-2] [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: 01/08/2025] [Accepted: 04/08/2025] [Indexed: 04/26/2025] Open
Abstract
BACKGROUND Gestational diabetes mellitus (GDM) increasingly affects women and predisposes both mothers and their infants to short- and long-term health consequences. Emerging research links GDM to maternal gut microbiota dysbiosis. However, the impact of GDM on the infant gut microbiota remains unclear. This cross-sectional study aims to explore potential associations between GDM and the gut microbiota in mothers and their infants, as well as correlations between maternal diet, cardiometabolic profile, and gut microbiota composition. METHODS Gut microbiota taxonomic composition was characterized by 16S rRNA gene sequencing on fecal samples collected at 2 months postpartum from 28 mothers, including 17 with (GDM+) and 11 without (GDM-) GDM, as well as 30 infants, 17 GDM + and 13 GDM-. Variations in overall composition and specific taxa between GDM + and GDM- were assessed. Correlations between maternal cardiometabolic profile, dietary intakes, and taxa were performed. RESULTS GDM was associated with the overall composition of gut microbiota between GDM + and GDM- in the maternal group, but not in infants. No statistically significant difference in alpha diversity between groups was found in either mothers or infants. However, 14 taxa showed significantly different abundance between GDM + and GDM- mothers, and 4 taxa differed in infants. Specific taxa at the family rank were correlated with maternal dietary and cardiometabolic variables in both mothers and infants. CONCLUSIONS GDM exposition was associated with gut microbiota composition in both mothers and infants at two months postpartum. This study enhances our understanding of how maternal health could be linked with the gut microbiota of mothers and their infants. TRIAL REGISTRATION NCT02872402 (2016-08-04, https://clinicaltrials.gov/study/NCT02872402?term=NCT02872402&rank=1 ) and NCT04263675 (2020-02-07, https://clinicaltrials.gov/study/NCT04263675?term=NCT04263675&rank=1 ).
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Affiliation(s)
- Isabelle Petitclerc
- Centre de recherche Nutrition, Santé et Société (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Université Laval, Quebec City, QC, G1V 0A6, Canada
- School of Nutrition, Université Laval, Quebec City, QC, G1V 0A6, Canada
| | - Julie Perron
- Centre de recherche Nutrition, Santé et Société (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Université Laval, Quebec City, QC, G1V 0A6, Canada
| | - Camille Dugas
- Centre de recherche Nutrition, Santé et Société (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Université Laval, Quebec City, QC, G1V 0A6, Canada
| | - Thomas Mayer
- Centre de recherche Nutrition, Santé et Société (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Université Laval, Quebec City, QC, G1V 0A6, Canada
- Canada Research Excellence Chair in the Microbiome-Endocannabinoidome Axis in Metabolic Health (CERC-MEND), Université Laval, Quebec City, QC, G1V 0A6, Canada
| | - Frédéric Raymond
- Centre de recherche Nutrition, Santé et Société (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Université Laval, Quebec City, QC, G1V 0A6, Canada
- School of Nutrition, Université Laval, Quebec City, QC, G1V 0A6, Canada
- Canada Research Excellence Chair in the Microbiome-Endocannabinoidome Axis in Metabolic Health (CERC-MEND), Université Laval, Quebec City, QC, G1V 0A6, Canada
| | - Vincenzo Di Marzo
- Centre de recherche Nutrition, Santé et Société (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Université Laval, Quebec City, QC, G1V 0A6, Canada
- School of Nutrition, Université Laval, Quebec City, QC, G1V 0A6, Canada
- Canada Research Excellence Chair in the Microbiome-Endocannabinoidome Axis in Metabolic Health (CERC-MEND), Université Laval, Quebec City, QC, G1V 0A6, Canada
- Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ), Université Laval, Quebec City, QC, G1V 4G5, Canada
| | - Alain Veilleux
- Centre de recherche Nutrition, Santé et Société (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Université Laval, Quebec City, QC, G1V 0A6, Canada
- School of Nutrition, Université Laval, Quebec City, QC, G1V 0A6, Canada
- Canada Research Excellence Chair in the Microbiome-Endocannabinoidome Axis in Metabolic Health (CERC-MEND), Université Laval, Quebec City, QC, G1V 0A6, Canada
| | - Julie Robitaille
- Centre de recherche Nutrition, Santé et Société (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Université Laval, Quebec City, QC, G1V 0A6, Canada.
- School of Nutrition, Université Laval, Quebec City, QC, G1V 0A6, Canada.
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Keshet A, Hochwald O, Lavon A, Borenstein-Levin L, Shoer S, Godneva A, Glantz-Gashai Y, Cohen-Dolev N, Timstut F, Lotan-Pompan M, Solt I, Weinberger A, Segal E, Shilo S. Development of antibiotic resistome in premature infants. Cell Rep 2025; 44:115515. [PMID: 40198224 DOI: 10.1016/j.celrep.2025.115515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 12/17/2024] [Accepted: 03/14/2025] [Indexed: 04/10/2025] Open
Abstract
Preterm birth is a major concern in neonatal care, significantly impacting infant survival and long-term health. The gut microbiome, essential for infant development, often becomes imbalanced in preterm infants, making it crucial to understand the effects of antibiotics on its development. Our study analyzed weekly, 6-month, and 1-year stool samples from 100 preterm infants, correlating clinical data on antibiotic use and feeding patterns. Comparing infants who received no antibiotics with those given empirical post-birth treatment, we observed notable alterations in the gut microbiome's composition and an increase in antibiotic resistance gene abundance early in life. Although these effects diminished over time, their long-term clinical impacts remain unclear. Human milk feeding was associated with beneficial microbiota like Actinobacteriota and reduced antibiotic resistance genes, underscoring its protective role. This highlights the importance of judicious antibiotic use and promoting human milk to foster a healthy gut microbiome in preterm infants.
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Affiliation(s)
- Ayya Keshet
- Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
| | - Ori Hochwald
- Neonatal Intensive Care Unit, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel; Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Amit Lavon
- Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
| | - Liron Borenstein-Levin
- Neonatal Intensive Care Unit, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel; Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Saar Shoer
- Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
| | - Anastasia Godneva
- Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
| | - Yitav Glantz-Gashai
- Neonatal Intensive Care Unit, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Noa Cohen-Dolev
- Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
| | - Fanny Timstut
- Neonatal Intensive Care Unit, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel
| | - Maya Lotan-Pompan
- Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
| | - Ido Solt
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Department of Obstetrics and Gynecology, Rambam Health Care Campus, Haifa, Israel
| | - Adina Weinberger
- Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
| | - Eran Segal
- Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
| | - Smadar Shilo
- Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel; The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children's Medical Center of Israel, Petah Tikva, Israel; Faculty of Medical and Health Sciences, Tel Aviv University, Tel-Aviv, Israel.
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Anil H, Nimbalkar SM, Joshi C, Kunjadiya A, Patel A, Pujara R, Raval K, Shekh S, Dalwadi P, Patel DV. Characterising the Human Milk Microbiota of Indian Mothers: Prospects for Probiotic Discoveries and Antimicrobial Peptides. Int J Pediatr 2025; 2025:4819511. [PMID: 40276127 PMCID: PMC12021482 DOI: 10.1155/ijpe/4819511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 03/22/2025] [Indexed: 04/26/2025] Open
Abstract
Background: The human milk microbiome is vital in the formation of the newborn microbiome and affects various health outcomes. Probiotics prevent severe necrotizing enterocolitis in neonates, but uncertainty about their safety is the obstacle to their use. Probiotic organisms and antimicrobial peptides derived from probiotic strains in human milk can offer safer options. Aim: This study is aimed at determining the probiotic properties in the human breastmilk microbiome and their potential antimicrobial activity. Methods: Study Design: We conducted a prospective longitudinal study. Participants: The study included 30 mothers, equally divided among gestational ages of < 32 weeks, 32-36 6/7 weeks, and above 37 weeks at the time of delivery. Milk samples were collected and analyzed at three different time points, that is, colostrum, transition milk (7-9 days), and mature milk (after 14 days). Outcome: The microbiome isolated was tested for probiotic and antimicrobial properties. Results: Three hundred and eighty-one bacterial colonies were isolated, of which 38 different species were identified. Of these, Gemella haemolysans, Micrococcus luteus and lylae, and Staphylococcus hominis and warneri were selected. Few showed bile salt, phenol, and NaCl tolerance, but none showed tolerance to pH. Antimicrobial activity was not seen when isolates or protein extracts were tested against the pathogen. Enhancement in the zone of clearance was seen when a combination of protein and antimicrobial agents was tested compared to antimicrobial alone. The zone of clearance was seen even at one-tenth of the standard concentration of amphotericin B when combined with protein extract. Conclusion: The non-Lactobacillus strains tested showed few probiotic properties. Though the isolates did not exhibit antimicrobial properties, the protein extracted from them enhanced the potency of antimicrobial agents.
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Affiliation(s)
- H. Anil
- Department of Neonatology, Pramukhswami Medical College, Bhaikaka University, Anand, Gujarat, India
| | - Somashekhar M. Nimbalkar
- Department of Neonatology, Pramukhswami Medical College, Bhaikaka University, Anand, Gujarat, India
| | - Chaitanya Joshi
- Department of Science and Technology, Gujarat Biotechnology Research Center, Gandhinagar, Gujarat, India
| | - Anju Kunjadiya
- Postgraduate Department of Applied and Interdisciplinary Sciences (IICISST), Sardar Patel University, Anand, Gujarat, India
| | - Axil Patel
- Central Research Services, Bhaikaka University, Anand, Gujarat, India
| | - Reshma Pujara
- Department of Neonatology, Pramukhswami Medical College, Bhaikaka University, Anand, Gujarat, India
| | - Krutarth Raval
- Department of Science and Technology, Gujarat Biotechnology Research Center, Gandhinagar, Gujarat, India
| | - Satyamitra Shekh
- Department of Science and Technology, Gujarat Biotechnology Research Center, Gandhinagar, Gujarat, India
| | - Priyanka Dalwadi
- Postgraduate Department of Applied and Interdisciplinary Sciences (IICISST), Sardar Patel University, Anand, Gujarat, India
| | - Dipen V. Patel
- Department of Neonatology, Pramukhswami Medical College, Bhaikaka University, Anand, Gujarat, India
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10
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Hamouda AG, Abd-Allah ER, Mahmoud AA. Linezolid administration to lactating Wistar rats affects the health of their offspring. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-04060-8. [PMID: 40220029 DOI: 10.1007/s00210-025-04060-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/31/2025] [Accepted: 03/13/2025] [Indexed: 04/14/2025]
Abstract
Lactational exposure to antibacterial medications may affect the normal development of newborns during this crucial stage and later in adult life. Linezolid (LNZ) is an oxazolidinone antibacterial drug that is effective against drug-resistant Gram-positive bacteria and multidrug-resistant Mycobacterium tuberculosis. Although it is relatively toxic, there is insufficient data about LNZ use during lactation. This study aimed to elucidate the impact of linezolid administration during lactation on Wistar rats' offspring. Eighteen lactating Wistar female rats were separated into three groups (n = 6): control, therapeutic, and low dose groups. The therapeutic dose group received 61.66 mg/kg of LNZ (equivalent to the human dose), while the low dose group received 15.41 mg/kg of LNZ (1/4 of the human therapeutic dose) by gavage twice daily. All lactating dams and their offspring died four days after receiving a therapeutic dose. In the low dose group, LNZ significantly reduced the body weight of lactating females and their pups. The liver tissue of the pups showed a considerable increase in malondialdehyde levels, along with a decrease in the catalase, glutathione, and superoxide dismutase activities accompanied by moderate histological alterations like congestion, and infiltration, and DNA fragmentation as indicated by comet assay. Microscopic examination of renal tissue revealed glomeruli deterioration, cellular infiltration, and intratubular protein deposits. In conclusion, this study highlights the potential risks linezolid may pose to infants during postpartum. Therefore, there is a need for preweaning monitoring and caution should be taken during breastfeeding.
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Affiliation(s)
- Aya G Hamouda
- Zoology Department, Faculty of Science, Cairo University, Giza, Egypt
| | - Entsar R Abd-Allah
- Zoology Department, Faculty of Science, Al-Azhar University, Nasr City, Egypt
| | - Aya A Mahmoud
- Zoology Department, Faculty of Science, Cairo University, Giza, Egypt.
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11
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Kalkan AE, BinMowyna MN, Raposo A, Ahmad MF, Ahmed F, Otayf AY, Carrascosa C, Saraiva A, Karav S. Beyond the Gut: Unveiling Butyrate's Global Health Impact Through Gut Health and Dysbiosis-Related Conditions: A Narrative Review. Nutrients 2025; 17:1305. [PMID: 40284169 PMCID: PMC12029953 DOI: 10.3390/nu17081305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 04/03/2025] [Accepted: 04/07/2025] [Indexed: 04/29/2025] Open
Abstract
Short-chain fatty acids (SCFAs), mainly produced by gut microbiota through the fermentation process of dietary fibers and proteins, are crucial to human health, with butyrate, a famous four-carbon SCFA, standing out for its inevitably regulatory impact on both gut and immune functions. Within this narrative review, the vital physiological functions of SCFAs were examined, with emphasis on butyrate's role as an energy source for colonocytes and its ability to enhance the gut barrier while exhibiting anti-inflammatory effects. Knowledge of butyrate synthesis, primarily generated by Firmicutes bacteria, can be influenced by diets with specifically high contents of resistant starches and fiber. Butyrate can inhibit histone deacetylase, modulate gene expression, influence immune functionality, and regulate tight junction integrity, supporting the idea of its role in gut barrier preservation. Butyrate possesses systemic anti-inflammatory properties, particularly, its capacity to reduce pro-inflammatory cytokines and maintain immune homeostasis, highlighting its therapeutic potential in managing dysbiosis and inflammatory diseases. Although butyrate absorption into circulation is typically minimal, its broader health implications are substantial, especially regarding obesity and type 2 diabetes through its influence on metabolic regulation and inflammation. Furthermore, this narrative review thoroughly examines butyrate's growing recognition as a modulator of neurological health via its interaction with the gut-brain axis. Additionally, butyrate's neuroprotective effects are mediated through activation of specific G-protein-coupled receptors, such as FFAR3 and GPR109a, and inhibition of histone deacetylases (HDACs). Research indicates that butyrate can alleviate neurological disorders, including Alzheimer's, Parkinson's, autism spectrum disorder, and Huntington's disease, by reducing neuroinflammation, enhancing neurotransmitter modulation, and improving histone acetylation. This focus will help unlock its full therapeutic potential for metabolic and neurological health, rather than exclusively on its well-known benefits for gut health, as these are often interconnected.
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Affiliation(s)
- Arda Erkan Kalkan
- Department of Molecular Biology and Genetics, Çanakkale Onsekiz Mart University, Çanakkale 17100, Turkey;
| | - Mona N. BinMowyna
- College of Education, Shaqra University, Shaqra 11911, Saudi Arabia;
| | - António Raposo
- CBIOS (Research Center for Biosciences and Health Technologies), Universidade Lusófona de Humanidades e Tecnologias, Campo Grande 376, 1749-024 Lisboa, Portugal
| | - Md Faruque Ahmad
- Department of Clinical Nutrition, College of Nursing and Health Sciences, Jazan University, Jazan 45142, Saudi Arabia; (M.F.A.); (A.Y.O.)
| | - Faiyaz Ahmed
- Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, P.O. Box 6666, Buraydah 51452, Saudi Arabia;
| | - Abdullah Y. Otayf
- Department of Clinical Nutrition, College of Nursing and Health Sciences, Jazan University, Jazan 45142, Saudi Arabia; (M.F.A.); (A.Y.O.)
| | - Conrado Carrascosa
- Department of Animal Pathology and Production, Bromatology and Food Technology, Faculty of Veterinary, Universidad de Las Palmas de Gran Canaria, Trasmontaña s/n, 35413 Arucas, Spain;
| | - Ariana Saraiva
- Research in Veterinary Medicine (I-MVET), Faculty of Veterinary Medicine, Lisbon University Centre, Lusófona University, Campo Grande 376, 1749-024 Lisboa, Portugal;
- Veterinary and Animal Research Centre (CECAV), Faculty of Veterinary Medicine, Lisbon University Centre, Lusófona University, Campo Grande 376, 1749-024 Lisboa, Portugal
| | - Sercan Karav
- Department of Molecular Biology and Genetics, Çanakkale Onsekiz Mart University, Çanakkale 17100, Turkey;
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12
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Tafesse Y, Köhler A, Sanchez Sanchez G, Rodrigues PB, Verce M, Vitsos P, Verdebout I, Rezwani M, Papadopoulou M, Everard A, Flamand V, Vermijlen D. Maternal Administration of Probiotics Augments IL17-Committed γδ T Cells in the Newborn Lung. Eur J Immunol 2025; 55:e202451051. [PMID: 40259457 DOI: 10.1002/eji.202451051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 03/25/2025] [Accepted: 03/27/2025] [Indexed: 04/23/2025]
Abstract
The early life period is increasingly being recognized as a window of opportunity to shape immunity, where microbiota and related probiotics have an important impact. Innate γδ T cells are the first T cells generated in utero, populating epithelial tissues such as the lung and contributing to tissue protection through, for example, IL17 production. Here, we studied the influence of maternal microbiota and probiotic supplementation during pregnancy on innate γδ T cells in the lung and thymus of newborn mice. Detailed time-kinetic experiments showed that at birth, the murine lung T cell population was specifically dominated by IL17-committed γδ T cells expressing an invariant Vγ6Vδ1 TCR. Single-cell RNA-sequencing showed that the biased IL17-commitment of perinatal lung γδT cells is highly conserved between mice and humans. While maternal microbiota depletion with antibiotics tended to decrease the frequency of the lung Vγ6 T cells of the offspring at birth, the maternal administration of Lacticaseibacillus rhamnosus (L.rhm.), but not of Bifidobacterium animalis subsp. lactis (B.lac.), increased significantly their frequency, resulting in the augmentation of the IL17-commitment of the mouse lung T cell compartment. Altogether, our data indicate that the maternal microbiota contributes to the shaping of IL17-committed γδT cells in the lungs of newborns and that maternal administration of specific probiotic strains can enhance this process.
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Affiliation(s)
- Yohannes Tafesse
- Department of Pharmacotherapy and Pharmaceutics, Université Libre de Bruxelles (ULB), Brussels, Belgium
- Institute for Medical Immunology (IMI), Université Libre de Bruxelles (ULB), Gosselies, Belgium
- ULB Center for Research in Immunology (U-CRI), Belgium
- WELBIO Department, WEL Research Institute, Wavre, Belgium
| | - Arnaud Köhler
- Institute for Medical Immunology (IMI), Université Libre de Bruxelles (ULB), Gosselies, Belgium
- ULB Center for Research in Immunology (U-CRI), Belgium
| | - Guillem Sanchez Sanchez
- Department of Pharmacotherapy and Pharmaceutics, Université Libre de Bruxelles (ULB), Brussels, Belgium
- Institute for Medical Immunology (IMI), Université Libre de Bruxelles (ULB), Gosselies, Belgium
- ULB Center for Research in Immunology (U-CRI), Belgium
- WELBIO Department, WEL Research Institute, Wavre, Belgium
| | - Patricia Brito Rodrigues
- WELBIO Department, WEL Research Institute, Wavre, Belgium
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique De Louvain, Brussels, Belgium
| | - Marko Verce
- WELBIO Department, WEL Research Institute, Wavre, Belgium
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique De Louvain, Brussels, Belgium
| | - Panagiotis Vitsos
- Department of Pharmacotherapy and Pharmaceutics, Université Libre de Bruxelles (ULB), Brussels, Belgium
- Institute for Medical Immunology (IMI), Université Libre de Bruxelles (ULB), Gosselies, Belgium
- ULB Center for Research in Immunology (U-CRI), Belgium
- WELBIO Department, WEL Research Institute, Wavre, Belgium
| | - Isoline Verdebout
- Department of Pharmacotherapy and Pharmaceutics, Université Libre de Bruxelles (ULB), Brussels, Belgium
- Institute for Medical Immunology (IMI), Université Libre de Bruxelles (ULB), Gosselies, Belgium
- ULB Center for Research in Immunology (U-CRI), Belgium
- WELBIO Department, WEL Research Institute, Wavre, Belgium
| | - Moosa Rezwani
- Department of Pharmacotherapy and Pharmaceutics, Université Libre de Bruxelles (ULB), Brussels, Belgium
- Institute for Medical Immunology (IMI), Université Libre de Bruxelles (ULB), Gosselies, Belgium
- ULB Center for Research in Immunology (U-CRI), Belgium
- WELBIO Department, WEL Research Institute, Wavre, Belgium
| | - Maria Papadopoulou
- Department of Pharmacotherapy and Pharmaceutics, Université Libre de Bruxelles (ULB), Brussels, Belgium
- Institute for Medical Immunology (IMI), Université Libre de Bruxelles (ULB), Gosselies, Belgium
- ULB Center for Research in Immunology (U-CRI), Belgium
- WELBIO Department, WEL Research Institute, Wavre, Belgium
| | - Amandine Everard
- WELBIO Department, WEL Research Institute, Wavre, Belgium
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique De Louvain, Brussels, Belgium
| | - Véronique Flamand
- Institute for Medical Immunology (IMI), Université Libre de Bruxelles (ULB), Gosselies, Belgium
- ULB Center for Research in Immunology (U-CRI), Belgium
| | - David Vermijlen
- Department of Pharmacotherapy and Pharmaceutics, Université Libre de Bruxelles (ULB), Brussels, Belgium
- Institute for Medical Immunology (IMI), Université Libre de Bruxelles (ULB), Gosselies, Belgium
- ULB Center for Research in Immunology (U-CRI), Belgium
- WELBIO Department, WEL Research Institute, Wavre, Belgium
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13
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Toubon G, Patin C, Delannoy J, Rozé JC, Barbut F, Ancel PY, Charles MA, Butel MJ, Lepage P, Aires J. Very preterm gut microbiota development from the first week of life to 3.5 years of age: a prospective longitudinal multicenter study. Microbiol Spectr 2025; 13:e0163624. [PMID: 39969235 PMCID: PMC11960047 DOI: 10.1128/spectrum.01636-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Accepted: 01/18/2025] [Indexed: 02/20/2025] Open
Abstract
This study analyzed the longitudinal evolution of intestinal microbiota in very preterm neonates (PN) during and after their hospitalization. The bacterial 16S rRNA gene sequencing approach was applied for the analysis of fecal samples (n = 1,307) from 596 PN. Samples were collected at one week after birth, at one month, at the neonatal intensive care unit discharge, and at 3.5 years of age. Over time, the intestinal microbiota of the infants matured progressively, with increasing alpha diversity and decreasing beta diversity. Based on a Dirichlet multinomial mixture clustering approach (DMM), during hospitalization, infants progressed among ten different clusters. At 3.5 years of age, only three clusters were identified. The influence of the gestational age, the neonatal antibiotic administration, and the maternal antibiotic therapy during delivery on the gut microbiota varied over time and depended on the sampling period. Preconceptional maternal body mass index (BMI) was associated with the gut microbiota of infants during the hospitalization period and at 3.5 years of age. Infants with a lower gestational age or those born by Cesarean section shifted between clusters more frequently. Using PICRUSt2, the inferred metabolic pathways revealed a change in the functional capacities of the intestinal microbiota over time. We found that preconceptional maternal BMI was the only consistent perinatal factor influencing the development of the gut microbiota over time. After hospital discharge, infants exhibited a transition toward a microbiota community similar to that of adults by 3.5 years of age, in accordance with the functional metabolic pathways of the gut microbiota.IMPORTANCEThis study is among the very few reports analyzing the gut microbiota development in very preterm infants over time in a large, multicenter population of 596 children from a well-described nationwide birth cohort, with a follow-up until the age of 3.5 years. The maturation of the intestinal microbiota was confirmed to occur over time, with increased alpha diversity and decreased beta diversity. Specifically, 13 microbiota clusters were identified during the hospitalization period, while and only three clusters were observed at 3.5 years. Infants born prematurely or via Cesarean section exhibited a less stable microbiota, frequently shifting clusters. A number of perinatal factors were identified as influencing the development of the microbiota. Among these, the preconceptional maternal BMI emerged as the only consistent factor up to 3.5 years. The metabolic pathways of the microbiota evolved over time, in accordance with the maturation of the gut microbiota.
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Affiliation(s)
- Gaël Toubon
- INSERM, UMR1153 Centre de Recherche Épidémiologie et StatistiqueS (CRESS), Université Paris Cité, Paris, France
- INSERM, UMR-S 1139, Physiopathologie et Pharmacotoxicologie Placentaire Humaine Microbiote Pré & Postnatal, Université Paris Cité,, Paris, France
- FHU PREMA, “Fighting Prematurity”, Paris, France
| | - Constance Patin
- INRAE, UMR 1319, AgrosParisTech, Institut Micalis, Université Paris-Saclay, Paris, France
| | - Johanne Delannoy
- INSERM, UMR-S 1139, Physiopathologie et Pharmacotoxicologie Placentaire Humaine Microbiote Pré & Postnatal, Université Paris Cité,, Paris, France
- FHU PREMA, “Fighting Prematurity”, Paris, France
| | - Jean-Christophe Rozé
- INRAE, UMR 1280, Physiologie des Adaptations Nutritionnelles (PhAN), Université Hospitalière de Nantes, Nantes, France
| | - Frédéric Barbut
- INSERM, UMR-S 1139, Physiopathologie et Pharmacotoxicologie Placentaire Humaine Microbiote Pré & Postnatal, Université Paris Cité,, Paris, France
- FHU PREMA, “Fighting Prematurity”, Paris, France
| | - Pierre-Yves Ancel
- INSERM, UMR1153 Centre de Recherche Épidémiologie et StatistiqueS (CRESS), Université Paris Cité, Paris, France
- FHU PREMA, “Fighting Prematurity”, Paris, France
| | - Marie-Aline Charles
- INSERM, UMR1153 Centre de Recherche Épidémiologie et StatistiqueS (CRESS), Université Paris Cité, Paris, France
| | - Marie-José Butel
- INSERM, UMR-S 1139, Physiopathologie et Pharmacotoxicologie Placentaire Humaine Microbiote Pré & Postnatal, Université Paris Cité,, Paris, France
- FHU PREMA, “Fighting Prematurity”, Paris, France
| | - Patricia Lepage
- INRAE, UMR 1319, AgrosParisTech, Institut Micalis, Université Paris-Saclay, Paris, France
| | - Julio Aires
- INSERM, UMR-S 1139, Physiopathologie et Pharmacotoxicologie Placentaire Humaine Microbiote Pré & Postnatal, Université Paris Cité,, Paris, France
- FHU PREMA, “Fighting Prematurity”, Paris, France
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14
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Mackawy AMH, Alharbi BF, Almatroudi A, Huq M, Mohammed AH, Wasti AZ, Elharbi MF, Allemailem KS. The Impact of Maternal Antibiotic Consumption on the Development of Oral Thrush Infection in Breastfeeding Infants: A Quasi-Experimental Study. Breastfeed Med 2025. [PMID: 40160140 DOI: 10.1089/bfm.2024.0209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/02/2025]
Abstract
Background: Oral thrush is a common yeast infection caused by Candida albicans in infants during their first few weeks or months. Infant mothers' antibiotics consumption can contribute to this opportunistic fungal growth due to their weaker immune systems. Objectives: To investigate the relationship between maternal antibiotic consumption and oral thrush infection in breastfeeding infants, this study aims to provide insights for health care professionals regarding antibiotic prescriptions and preventive strategies for managing oral thrush. Methods: A quasi-experimental design with a control group was used. Eighty-two breastfeeding infants were divided into two groups: Group 1 (n = 40) infants of antibiotic-consuming mothers and Group 2 (n = 42) infants of nonantibiotic-consuming mothers. The oral samples were collected using sterile cotton swabs and cultured on Sabouraud's dextrose agar C. albicans, confirmed by simple staining and a germ tube test. Results: Infants aged 1-11 months with a mean ± standard deviation of 4.8 ± 3.51. Within all 82 oral swabs, 42.7% were positive for C. albicans growth and 57.3% were negative. The highest percentage was in 1-month-old infants (n = 9, 25.71%), and the lowest was in 11 months old (n = 2, 5.71%). Group 2 infants had significantly fewer positive C. albicans growth (n = 12, 28.57%) compared with group 1 (n = 23; 57.5%) (χ2 = 7.0, p = 0.007; odds ratio = 3.332, 95% confidence interval = 1.35-8.46). Oral thrush clinical signs were identified in 66.6% and 33.4% of group 1 and 2 infants, respectively, while 31.4% of C. albicans-positive colonization showed no clinical manifestations. Conclusion: Maternal antibiotic consumption for more than 1 week is associated with the occurrence of oral thrush in breastfeeding infants. Differences in clinical signs in two groups of infants indicate the importance of laboratory tests for early oral thrush diagnosis. This can help health care professionals understand oral thrush causes, enable early detection, improve treatment, and enhance appropriate antibiotic use in breastfeeding mothers.
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Affiliation(s)
- Amal M H Mackawy
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
- Faculty of Medicine, Department of Medical Biochemistry and Molecular Biology, Zagazig University, Zagazig, Egypt
| | - Basmah F Alharbi
- Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Ahmad Almatroudi
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Mohsina Huq
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Amal Hussain Mohammed
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
| | - Afshan Zeeshan Wasti
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
- Department of Biochemistry, Jinnah University for Women, Karachi, Pakistan
| | - Manal F Elharbi
- Maternal and Child Health Nursing Department College of Nursing, King Saud University Riyadh, Riyadh, Saudi Arabia
| | - Khaled S Allemailem
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia
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15
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Heidrich V, Valles-Colomer M, Segata N. Human microbiome acquisition and transmission. Nat Rev Microbiol 2025:10.1038/s41579-025-01166-x. [PMID: 40119155 DOI: 10.1038/s41579-025-01166-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/14/2025] [Indexed: 03/24/2025]
Abstract
As humans, we host personal microbiomes intricately connected to our biology and health. Far from being isolated entities, our microbiomes are dynamically shaped by microbial exchange with the surroundings, in lifelong microbiome acquisition and transmission processes. In this Review, we explore recent studies on how our microbiomes are transmitted, beginning at birth and during interactions with other humans and the environment. We also describe the key methodological aspects of transmission inference, based on the uniqueness of the building blocks of the microbiome - single microbial strains. A better understanding of human microbiome transmission will have implications for studies of microbial host regulation, of microbiome-associated diseases, and for effective microbiome-targeting strategies. Besides exchanging strains with other humans, there is also preliminary evidence we acquire microorganisms from animals and food, and thus a complete understanding of microbiome acquisition and transmission can only be attained by adopting a One Health perspective.
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Affiliation(s)
| | | | - Nicola Segata
- Department CIBIO, University of Trento, Trento, Italy.
- Department of Experimental Oncology, IEO European Institute of Oncology IRCCS, Milan, Italy.
- Department of Twins Research and Genetic Epidemiology, King's College London, London, UK.
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16
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Sun Y, Huang S, Li M, Yang Y, Ma J, Xie R, Wang J, Zhao Q, Qin S, He L, Jiang J, Zhao Q, Jin G, Liu X, Huang H, Yang Y, Wei J, Liu W, Wang B, Yang R, Su X, Cao H. Maternal high-fat diet disrupts intestinal mucus barrier of offspring by regulating gut immune receptor LRRC19. Commun Biol 2025; 8:420. [PMID: 40075219 PMCID: PMC11903762 DOI: 10.1038/s42003-025-07836-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2024] [Accepted: 02/26/2025] [Indexed: 03/14/2025] Open
Abstract
Maternal high fat diet (MHFD) increased colitis susceptibility in adulthood. However, the mechanism remains unclear. We sought to explore whether novel gut immune receptor leucine-rich repeat C19 (LRRC19) contributed to the impaired mucus barrier of offspring exposed to MHFD via gut immune response and microbiota. The results showed that MHFD significantly impaired the intestinal mucus barrier of offspring, and up-regulated the expression of LRRC19. Lrrc19 deletion alleviated the mucus barrier disruption. Mechanistically, metagenome sequencing revealed that the MHFD-induced gut microbiota alteration was partly restored in Lrrc19-/- offspring. Muc2-associated bacteria were decreased in the MHFD group, such as Akkermansia_muciniphila_CAG_154, which increased in the Lrrc19-deficient offspring. Moreover, Lrrc19-/- offspring had a higher rate of indole-3-acetic acid (IAA)-producing bacterium, such as Lactobacillus reuteri. A targeted metabolomics analysis revealed that IAA emerged as the top candidate that might mediate the protective effects. IAA was found to improve the mucus barrier function by increasing the ratio of interleukin-22 (IL-22)+ ILC3 cells in an aryl hydrocarbon receptor (AhR)-dependent manner. These results suggest that MHFD disrupts the intestinal mucus barrier of offspring through regulating gut immune receptor LRRC19 and inducing an imbalance of gut microbiota and microbiota-derived metabolites.
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Affiliation(s)
- Yue Sun
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Key Medical Discipline (Specialty), Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, 300052, China
- Department of Endoscopy, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, China
| | - Shumin Huang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Key Medical Discipline (Specialty), Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, 300052, China
| | - Mengfan Li
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Key Medical Discipline (Specialty), Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, 300052, China
| | - Yunwei Yang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Key Medical Discipline (Specialty), Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, 300052, China
| | - Jiahui Ma
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Key Medical Discipline (Specialty), Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, 300052, China
| | - Runxiang Xie
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Key Medical Discipline (Specialty), Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, 300052, China
| | - Jingyi Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Key Medical Discipline (Specialty), Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, 300052, China
| | - Qianjing Zhao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Key Medical Discipline (Specialty), Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, 300052, China
| | - Siqi Qin
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Key Medical Discipline (Specialty), Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, 300052, China
| | - Linlin He
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Key Medical Discipline (Specialty), Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, 300052, China
| | - Jiaying Jiang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Key Medical Discipline (Specialty), Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, 300052, China
| | - Qing Zhao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Key Medical Discipline (Specialty), Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, 300052, China
| | - Ge Jin
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Key Medical Discipline (Specialty), Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, 300052, China
| | - Xiang Liu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Key Medical Discipline (Specialty), Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, 300052, China
| | - Huan Huang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Key Medical Discipline (Specialty), Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, 300052, China
| | - Yazheng Yang
- Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, 300071, China
| | - Jianmei Wei
- Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, 300071, China
| | - Wentian Liu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Key Medical Discipline (Specialty), Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, 300052, China
| | - Bangmao Wang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Key Medical Discipline (Specialty), Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, 300052, China
| | - Rongcun Yang
- Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, 300071, China
| | - Xiaomin Su
- Department of Immunology, Nankai University School of Medicine, Nankai University, Tianjin, 300071, China.
| | - Hailong Cao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Key Medical Discipline (Specialty), Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, 300052, China.
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17
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Zhang Y, Jing Y, He J, Dong R, Li T, Li F, Zheng X, Liu G, Jia R, Xu J, Wu F, Jia C, Song J, Zhang L, Zhou P, Wang H, Yao Z, Liu Q, Yu Y, Zhou J. Bile acid receptor FXR promotes intestinal epithelial ferroptosis and subsequent ILC3 dysfunction in neonatal necrotizing enterocolitis. Immunity 2025; 58:683-700.e10. [PMID: 40023163 DOI: 10.1016/j.immuni.2025.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Revised: 11/14/2024] [Accepted: 02/04/2025] [Indexed: 03/04/2025]
Abstract
Necrotizing enterocolitis (NEC) is a common pediatric emergency primarily afflicting preterm infants, yet its mechanisms remain to be fully understood. Here, we report that plasma fibroblast growth factor (FGF)19, a target of farnesoid X receptor (FXR), was positively correlated with the clinical parameters of NEC. NEC patients and the NEC murine model displayed abundant FXR in intestinal epithelial cells (IECs), which was restricted by microbiota-derived short-chain fatty acids (SCFAs) under homeostasis. Genetic deficiency of FXR in IECs caused remission of NEC. Mechanistically, FXR facilitated ferroptosis of IECs via targeting acyl-coenzyme A synthetase long-chain family member 4 (Acsl4). Lipid peroxides released by ferroptotic IECs suppressed interleukin (IL)-22 secretion from type 3 innate lymphoid cells (ILC3s), thereby exacerbating NEC. Intestinal FXR antagonist, ACSL4 inhibitor, and ferroptosis inhibitor ameliorated murine NEC. Furthermore, the elevated lipid peroxides in NEC patients were positively correlated with FGF19 and disease parameters. These observations demonstrate the therapeutic value of targeting intestinal FXR and ferroptosis in NEC treatment.
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MESH Headings
- Animals
- Ferroptosis/immunology
- Humans
- Enterocolitis, Necrotizing/metabolism
- Enterocolitis, Necrotizing/immunology
- Enterocolitis, Necrotizing/pathology
- Mice
- Receptors, Cytoplasmic and Nuclear/metabolism
- Receptors, Cytoplasmic and Nuclear/genetics
- Intestinal Mucosa/metabolism
- Intestinal Mucosa/immunology
- Intestinal Mucosa/pathology
- Infant, Newborn
- Lymphocytes/immunology
- Lymphocytes/metabolism
- Fibroblast Growth Factors/blood
- Fibroblast Growth Factors/metabolism
- Disease Models, Animal
- Mice, Inbred C57BL
- Coenzyme A Ligases/metabolism
- Mice, Knockout
- Female
- Male
- Immunity, Innate
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Affiliation(s)
- Yuxin Zhang
- Tianjin Institute of Immunology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, International Joint Laboratory of Ocular Diseases (Ministry of Education), State Key Laboratory of Experimental Hematology, Tianjin 300070, China
| | - Yuchao Jing
- Tianjin Institute of Immunology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, International Joint Laboratory of Ocular Diseases (Ministry of Education), State Key Laboratory of Experimental Hematology, Tianjin 300070, China; Department of Immunology, Basic Medical College, Changzhi 046000, China
| | - Juan He
- Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China
| | - Rui Dong
- Tianjin Institute of Immunology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, International Joint Laboratory of Ocular Diseases (Ministry of Education), State Key Laboratory of Experimental Hematology, Tianjin 300070, China
| | - Tongyang Li
- Tianjin Institute of Immunology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, International Joint Laboratory of Ocular Diseases (Ministry of Education), State Key Laboratory of Experimental Hematology, Tianjin 300070, China
| | - Fang Li
- Department of Central Laboratory, Changzhi Medical College, Changzhi 046000, China
| | - Xiaoqing Zheng
- Laboratory of Immunity, Inflammation & Cancer, Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Gaoyu Liu
- Laboratory of Immunity, Inflammation & Cancer, Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Ran Jia
- Department of Clinical Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China
| | - Jin Xu
- Department of Clinical Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China
| | - Fan Wu
- Department of Neonatology, Guangzhou Key Laboratory of Neonatal Intestinal Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, Guangdong, China
| | - Chunhong Jia
- Department of Neonatology, Guangzhou Key Laboratory of Neonatal Intestinal Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, Guangdong, China
| | - Jin Song
- Department of Pediatric Surgery Maternal and Child Health Care of Changzhi, Changzhi 046011, China
| | - Lijuan Zhang
- Tianjin Institute of Immunology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, International Joint Laboratory of Ocular Diseases (Ministry of Education), State Key Laboratory of Experimental Hematology, Tianjin 300070, China
| | - Pan Zhou
- Tianjin Institute of Immunology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, International Joint Laboratory of Ocular Diseases (Ministry of Education), State Key Laboratory of Experimental Hematology, Tianjin 300070, China
| | - Haitao Wang
- Department of Oncology, The Second Hospital of Tianjin Medical University, Tianjin Key Laboratory of Precision Medicine for Sex Hormones and Diseases, Tianjin 300211, China
| | - Zhi Yao
- Tianjin Institute of Immunology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, International Joint Laboratory of Ocular Diseases (Ministry of Education), State Key Laboratory of Experimental Hematology, Tianjin 300070, China
| | - Qiang Liu
- Tianjin Institute of Immunology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, International Joint Laboratory of Ocular Diseases (Ministry of Education), State Key Laboratory of Experimental Hematology, Tianjin 300070, China; Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300050, China
| | - Ying Yu
- Tianjin Institute of Immunology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, International Joint Laboratory of Ocular Diseases (Ministry of Education), State Key Laboratory of Experimental Hematology, Tianjin 300070, China; Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
| | - Jie Zhou
- Tianjin Institute of Immunology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, International Joint Laboratory of Ocular Diseases (Ministry of Education), State Key Laboratory of Experimental Hematology, Tianjin 300070, China; Laboratory of Immunity, Inflammation & Cancer, Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
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18
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Guan S, Cai P, Cai D, Duan S. Analysis of the effect of the Xianglian capsule on patients with diarrhea after cholecystectomy: a protocol for a single-center, randomized controlled trial. BMC Complement Med Ther 2025; 25:96. [PMID: 40057752 PMCID: PMC11889896 DOI: 10.1186/s12906-025-04831-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 02/14/2025] [Indexed: 05/13/2025] Open
Abstract
INTRODUCTION Diarrhea is a common complication in patients after cholecystectomy. In China, tens of millions of patients experience diarrhea every year after cholecystectomy, which results in long-term pain in patients. Traditional Chinese medicine is a national treasure and has made great contributions to human health throughout the long history of the Chinese nation. However, as a classic ready-for-use traditional Chinese medicine, the exact clinical efficacy of the Xianglian preparation needs further observation. This article presents the protocol of a single-center, randomized controlled trial to evaluate the clinical efficacy of Xianglian capsules in patients with diarrhea after cholecystectomy. METHODS AND ANALYSIS This study was conducted in the Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital of Guangdong Medical University, following the recommendations of the current SPIRIT and CONSORT statements. We will recruit 90 patients who have developed diarrhea after cholecystectomy and randomize them 1:1 into the observation and control groups. The control group was given starch placebo capsules, and the observation group was given Xianglian capsules. Patient diarrhea-related indicators were collected at baseline and 5 days postdose. We will also collect patients' intestinal inflammation-related indicators and fecal microbial samples to analyze the possible mechanism of action of drugs. DISCUSSION This study will clarify the clinical effects of the Xianglian preparation on patients with diarrhea after cholecystectomy, provide evidence-based evidence, and promote the development and application of this classic prescription. TRIAL REGISTRATION http://www.chictr.org.cn . TRIAL NUMBER ChiCTR2200061854. Registered on 04 July 2022.
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Affiliation(s)
- Songmei Guan
- The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524003, China
| | - Peiling Cai
- School of Preclinical Medicine, Chengdu University, Chengdu, Sichuan, 610106, China
| | - De Cai
- The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524003, China.
| | - Shigang Duan
- The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524003, China.
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19
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Ehlers G, Tödtmann AM, Holsten L, Willers M, Heckmann J, Schöning J, Richter M, Heinemann AS, Pirr S, Heinz A, Dopfer C, Händler K, Becker M, Büchel J, Wöckel A, von Kaisenberg C, Hansen G, Hiller K, Schultze JL, Härtel C, Kastenmüller W, Vaeth M, Ulas T, Viemann D. Oxidative phosphorylation is a key feature of neonatal monocyte immunometabolism promoting myeloid differentiation after birth. Nat Commun 2025; 16:2239. [PMID: 40050264 PMCID: PMC11885822 DOI: 10.1038/s41467-025-57357-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Accepted: 02/20/2025] [Indexed: 03/09/2025] Open
Abstract
Neonates primarily rely on innate immune defense, yet their inflammatory responses are usually restricted compared to adults. This is controversially interpreted as a sign of immaturity or essential programming, increasing or decreasing the risk of sepsis, respectively. Here, combined transcriptomic, metabolic, and immunological studies in monocytes of healthy individuals reveal an inverse ontogenetic shift in metabolic pathway activities with increasing age. Neonatal monocytes are characterized by enhanced oxidative phosphorylation supporting ongoing myeloid differentiation. This phenotype is gradually replaced during early childhood by increasing glycolytic activity fueling the inflammatory responsiveness. Microbial stimulation shifts neonatal monocytes to an adult-like metabolism, whereas ketogenic diet in adults mimicking neonatal ketosis cannot revive a neonate-like metabolism. Our findings disclose hallmarks of innate immunometabolism during healthy postnatal immune adaptation and suggest that premature activation of glycolysis in neonates might increase their risk of sepsis by impairing myeloid differentiation and promoting hyperinflammation.
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Affiliation(s)
- Greta Ehlers
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany
| | - Annika Marie Tödtmann
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany
| | - Lisa Holsten
- Department of Pediatrics, University Hospital Würzburg, Würzburg, Germany
- Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany
- Systems Medicine, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
- PRECISE Platform for Single Cell Genomics and Epigenomics, DZNE and University of Bonn, Bonn, Germany
| | - Maike Willers
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany
| | - Julia Heckmann
- Department of Pediatrics, University Hospital Würzburg, Würzburg, Germany
| | - Jennifer Schöning
- Department of Pediatrics, University Hospital Würzburg, Würzburg, Germany
| | - Maximilian Richter
- Department of Pediatrics, University Hospital Würzburg, Würzburg, Germany
| | - Anna Sophie Heinemann
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany
| | - Sabine Pirr
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany
| | - Alexander Heinz
- Department for Bioinformatics and Biochemistry, BRICS, Technical University Braunschweig, Braunschweig, Germany
| | - Christian Dopfer
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany
| | - Kristian Händler
- Systems Medicine, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
- Institute of Human Genetics, University of Lübeck, Lübeck, Germany
| | - Matthias Becker
- Systems Medicine, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
- Modular High Performance Computing and Artificial Intelligence, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany
| | - Johanna Büchel
- Department of Gynecology and Obstetrics, University Hospital Würzburg, Würzburg, Germany
| | - Achim Wöckel
- Department of Gynecology and Obstetrics, University Hospital Würzburg, Würzburg, Germany
| | | | - Gesine Hansen
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany
- Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
| | - Karsten Hiller
- Department for Bioinformatics and Biochemistry, BRICS, Technical University Braunschweig, Braunschweig, Germany
| | - Joachim L Schultze
- Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany
- Systems Medicine, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
- PRECISE Platform for Single Cell Genomics and Epigenomics, DZNE and University of Bonn, Bonn, Germany
| | - Christoph Härtel
- Department of Pediatrics, University Hospital Würzburg, Würzburg, Germany
| | - Wolfgang Kastenmüller
- Würzburg Institute of Systems Immunology, Max Planck Research Group, Julius-Maximilians-University Würzburg, Würzburg, Germany
| | - Martin Vaeth
- Würzburg Institute of Systems Immunology, Max Planck Research Group, Julius-Maximilians-University Würzburg, Würzburg, Germany
| | - Thomas Ulas
- Genomics and Immunoregulation, Life & Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany
- Systems Medicine, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
- PRECISE Platform for Single Cell Genomics and Epigenomics, DZNE and University of Bonn, Bonn, Germany
| | - Dorothee Viemann
- Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
- Department of Pediatrics, University Hospital Würzburg, Würzburg, Germany.
- Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany.
- Center for Infection Research, University Würzburg, Würzburg, Germany.
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20
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Wei L, Qi C, Wang T, Jin X, Zhou X, Luo M, Lu M, Chen H, Guo J, Wang H, Xu D. Prenatal amoxicillin exposure induces depressive-like behavior in offspring via gut microbiota and myristic acid-mediated modulation of the STING pathway. JOURNAL OF HAZARDOUS MATERIALS 2025; 485:136750. [PMID: 39672059 DOI: 10.1016/j.jhazmat.2024.136750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 11/20/2024] [Accepted: 12/01/2024] [Indexed: 12/15/2024]
Abstract
Amoxicillin is a widely used antibiotic globally, and its pervasive environmental presence poses significant risks to human health and ecosystems. Notably, prenatal amoxicillin exposure (PAmE) may have long-term neurodevelopmental toxicity for offspring. In this study, we investigated the lasting effects of PAmE on depressive-like behaviors in offspring rats, emphasizing the biological mechanisms mediated by changes in gut microbiota and its metabolite, myristic acid. Our results showed that PAmE significantly disrupted the gut microbiota composition in offspring, particularly through the reduction of Lachnospiraceae, leading to decreased levels of myristic acid. This disruption hindered the N-myristoylation of ADP-ribosylation factor 1 (ARF1), impaired the normal degradation of the stimulator of interferon genes protein, inhibited autophagic processes, and promoted M1 polarization of microglia, ultimately leading to depressive-like behaviors in the offspring. Remarkably, supplementation with Lachnospira or myristic acid effectively reversed the PAmE-induced neurodevelopmental and behavioral abnormalities, alleviating depressive-like symptoms. This study reveals how PAmE affects offspring neurodevelopment and behavior through gut microbiota and myristic acid, highlighting the crucial role of the gut-brain axis in the modulation of depressive symptoms. Supplementing Lachnospira or myristic acid could represent a novel strategy to mitigate PAmE-induced fetal-originated depression, providing new biological evidence and potential therapeutic avenues.
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Affiliation(s)
- Liyi Wei
- Department of Obstetric, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
| | - Cuiping Qi
- Department of Obstetric, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
| | - Tingting Wang
- Department of Obstetric, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
| | - Xiuping Jin
- Department of Obstetric, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
| | - Xinli Zhou
- Department of Pharmacology, Taikang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan 430071, China
| | - Mingcui Luo
- Department of Obstetric, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
| | - Mengxi Lu
- Department of Obstetric, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
| | - Huijun Chen
- Department of Obstetric, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
| | - Juanjuan Guo
- Department of Obstetric, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
| | - Hui Wang
- Department of Pharmacology, Taikang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China
| | - Dan Xu
- Department of Obstetric, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China.
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21
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Kim HS, Lee JY, Whon TW, Bae JW. Assembly and maturation of calf gut microbiome from neonate to post-puberty. Sci Data 2025; 12:376. [PMID: 40038317 PMCID: PMC11880526 DOI: 10.1038/s41597-025-04677-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 02/19/2025] [Indexed: 03/06/2025] Open
Abstract
With the help of rumen bacteria, ruminants can feed on indigestible plant materials and produce over 70% of their energy as fatty acids. However, during lactation, ruminants exhibit characteristics of monogastric animals due to an undeveloped rumen; therefore, understanding gut microbiome changes in growing calves is essential. Our understanding of the gut microbiome in growing calves remains limited in large populations with the same diet, breed, and period. Here, we describe 16S rRNA gene amplicon sequencing data from 420 faecal samples, 20 rumen contents, 17 small intestine contents, and 18 large intestine contents collected from 57 healthy, antibiotic-free Korean beef cattle from neonatal to post-pubertal age. Eight 16S rRNA gene amplicon datasets from the host diet samples were obtained. Approximately 148 million raw reads, averaging 153,352 ± 96,050 (mean ± SD) reads per sample, and 51,596 unique amplicon sequence variants (381-368 per sample) were identified in the 483 samples. These shareable datasets can be reused by researchers to assess gut microbiome-related functions in growing calves and improve ruminant production and health.
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Affiliation(s)
- Hyun Sik Kim
- Department of Biology, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - Jae-Yun Lee
- Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - Tae Woong Whon
- Kimchi Functionality Research Group, World Institute of Kimchi, Gwangju, 61755, Republic of Korea.
| | - Jin-Woo Bae
- Department of Biology, Kyung Hee University, Seoul, 02447, Republic of Korea.
- Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, 02447, Republic of Korea.
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22
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Shukla A, Sharma C, Malik MZ, Singh AK, Aditya AK, Mago P, Shalimar, Ray AK. Deciphering the tripartite interaction of urbanized environment, gut microbiome and cardio-metabolic disease. JOURNAL OF ENVIRONMENTAL MANAGEMENT 2025; 377:124693. [PMID: 40022791 DOI: 10.1016/j.jenvman.2025.124693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 02/13/2025] [Accepted: 02/21/2025] [Indexed: 03/04/2025]
Abstract
The world is experiencing a sudden surge in urban population, especially in developing Asian and African countries. Consequently, the global burden of cardio-metabolic disease (CMD) is also rising owing to gut microbiome dysbiosis due to urbanization factors such as mode of birth, breastfeeding, diet, environmental pollutants, and soil exposure. Dysbiotic gut microbiome indicated by altered Firmicutes to Bacteroides ratio and loss of beneficial short-chain fatty acids-producing bacteria such as Prevotella, and Ruminococcus may disrupt host-intestinal homeostasis by altering host immune response, gut barrier integrity, and microbial metabolism through altered T-regulatory cells/T-helper cells balance, activation of pattern recognition receptors and toll-like receptors, decreased mucus production, elevated level of trimethylamine-oxide and primary bile acids. This leads to a pro-inflammatory gut characterized by increased pro-inflammatory cytokines such as tumour necrosis factor-α, interleukin-2, Interferon-ϒ and elevated levels of metabolites or metabolic endotoxemia due to leaky gut formation. These pathophysiological characteristics are associated with an increased risk of cardio-metabolic disease. This review aims to comprehensively elucidate the effect of urbanization on gut microbiome-driven cardio-metabolic disease. Additionally, it discusses targeting the gut microbiome and its associated pathways via strategies such as diet and lifestyle modulation, probiotics, prebiotics intake, etc., for the prevention and treatment of disease which can potentially be integrated into clinical and professional healthcare settings.
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Affiliation(s)
- Avaneesh Shukla
- Department of Environmental Studies, University of Delhi, New Delhi, India
| | - Chanchal Sharma
- Department of Environmental Studies, University of Delhi, New Delhi, India
| | - Md Zubbair Malik
- Department of Translational Medicine, Dasman Diabetes Institute, Kuwait City, Kuwait
| | - Alok Kumar Singh
- Department of Zoology, Ramjas College, University of Delhi, New Delhi, India
| | - Abhishek Kumar Aditya
- Department of Medicine, K.D. Medical College, Hospital and Research Center, Mathura, India
| | - Payal Mago
- Shaheed Rajguru College of Applied Sciences for Women, University of Delhi, New Delhi, India; Campus of Open Learning, University of Delhi, New Delhi, India
| | - Shalimar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Ashwini Kumar Ray
- Department of Environmental Studies, University of Delhi, New Delhi, India.
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Magalhães MI, Azevedo MJ, Castro F, Oliveira MJ, Costa ÂM, Sampaio Maia B. The link between obesity and the gut microbiota and immune system in early-life. Crit Rev Microbiol 2025; 51:264-284. [PMID: 38651972 DOI: 10.1080/1040841x.2024.2342427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 04/04/2024] [Accepted: 04/06/2024] [Indexed: 04/25/2024]
Abstract
In early-life, the gut microbiota is highly modifiable, being modulated by external factors such as maternal microbiota, mode of delivery, and feeding strategies. The composition of the child's gut microbiota will deeply impact the development and maturation of its immune system, with consequences for future health. As one of the main sources of microorganisms to the child, the mother represents a crucial factor in the establishment of early-life microbiota, impacting the infant's wellbeing. Recent studies have proposed that dysbiotic maternal gut microbiota could be transmitted to the offspring, influencing the development of its immunity, and leading to the development of diseases such as obesity. This paper aims to review recent findings in gut microbiota and immune system interaction in early-life, highlighting the benefits of a balanced gut microbiota in the regulation of the immune system.
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Affiliation(s)
- Maria Inês Magalhães
- Doctoral Program in Biomedical Sciences, ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
- Nephrology and Infectious Diseases R&D group, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- Tumor and Microenvironment Interactions group, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- nBTT, NanoBiomaterials for Targeted Therapies group, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- FMDUP - Faculdade de Medicina Dentária da Universidade do Porto, Porto, Portugal
| | - Maria João Azevedo
- Nephrology and Infectious Diseases R&D group, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- nBTT, NanoBiomaterials for Targeted Therapies group, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- FMDUP - Faculdade de Medicina Dentária da Universidade do Porto, Porto, Portugal
- Academic Center for Dentistry Amsterdam (ACTA), Universiteit van Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Flávia Castro
- Tumor and Microenvironment Interactions group, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
| | - Maria José Oliveira
- Tumor and Microenvironment Interactions group, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
| | - Ângela M Costa
- Tumor and Microenvironment Interactions group, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
| | - Benedita Sampaio Maia
- Nephrology and Infectious Diseases R&D group, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- nBTT, NanoBiomaterials for Targeted Therapies group, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
- FMDUP - Faculdade de Medicina Dentária da Universidade do Porto, Porto, Portugal
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Caesar R. The impact of novel probiotics isolated from the human gut on the gut microbiota and health. Diabetes Obes Metab 2025; 27 Suppl 1:3-14. [PMID: 39726216 PMCID: PMC11894790 DOI: 10.1111/dom.16129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Revised: 12/02/2024] [Accepted: 12/02/2024] [Indexed: 12/28/2024]
Abstract
The gut microbiota plays a pivotal role in influencing the metabolism and immune responses of the body. A balanced microbial composition promotes metabolic health through various mechanisms, including the production of beneficial metabolites, which help regulate inflammation and support immune functions. In contrast, imbalance in the gut microbiota, known as dysbiosis, can disrupt metabolic processes and increase the risk of developing diseases, such as obesity, type 2 diabetes, and inflammatory disorders. The composition of the gut microbiota is dynamic and can be influenced by environmental factors such as diet, medication, and the consumption of live bacteria. Since the early 1900s, bacteria isolated from food and have been used as probiotics. However, the human gut also offers an enormous reservoir of bacterial strains, and recent advances in microbiota research have led to the discovery of strains with probiotic potentials. These strains, derived from a broad spectrum of microbial taxa, differ in their ecological properties and how they interact with their hosts. For most probiotics bacterial structural components and metabolites, such as short-chain fatty acids, contribute to the maintenance of metabolic and immunological homeostasis by regulating inflammation and reinforcing gut barrier integrity. Metabolites produced by probiotic strains can also be used for bacterial cross-feeding to promote a balanced microbiota. Despite the challenges related to safety, stability, and strain-specific properties, several newly identified strains offer great potential for personalized probiotic interventions, allowing for targeted health strategies.
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Affiliation(s)
- Robert Caesar
- The Wallenberg Laboratory, Department of Molecular and Clinical MedicineUniversity of GothenburgGothenburgSweden
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25
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Musallam N, Almog M, Wagner R, Epov L, Dor V, Kessel A. Can exclusive breastfeeding in the first 4 months reduce food allergy?: A retrospective questionnaire study. Ann Allergy Asthma Immunol 2025:S1081-1206(25)00089-4. [PMID: 39993473 DOI: 10.1016/j.anai.2025.02.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 02/12/2025] [Accepted: 02/12/2025] [Indexed: 02/26/2025]
Abstract
BACKGROUND IgE-mediated food allergy (FA) is a major global health concern. Although the early introduction of allergenic foods and breastfeeding are potential preventive strategies, the role of breast milk in reducing the incidence of FAs remains inconclusive. OBJECTIVE To investigate the impact of exclusive breastfeeding for the first 4 months compared with partial breastfeeding or cow's milk formula (CMF) on the development of IgE-mediated FAs in an Israeli cohort. METHODS A cross-sectional online survey in 3030 mothers with infants aged 6 to 24 months collected data on early feeding practices, allergen introduction, atopic conditions, and family history. It documented suspected allergic reactions, symptoms, and diagnostic procedures. RESULTS Of the 3030 mothers surveyed, 2920 provided complete feeding data for the first 4 months. Among them, 39.0% exclusively breastfed, 12.1% used CMF, and 48.9% partially breastfed. There were 392 infants with FAs, totaling 480 cases involving cow's milk, sesame, egg, or peanut. Of these cases, 122 (25.4%) were in the breastfeeding group, and 358 (74.6%) were in the other groups. Exclusively breastfed infants had lower odds of egg (odds ratio [OR] = 0.53), sesame (OR = 0.58), and peanut (OR = 0.53) allergies than others. The interaction between feeding patterns and atopic dermatitis (AD) related to these FAs was not significant. Exposure to CMF in the nursery, exclusively breastfed, was associated with higher odds of developing a cow's milk allergy. Delayed exposure to sesame in infants with AD has been linked to increased odds of developing a sesame allergy. CONCLUSION Exclusive breastfeeding may reduce the risk of IgE-mediated FA development, regardless of AD status.
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Affiliation(s)
- Nadira Musallam
- Division of Allergy & Clinical Immunology, Bnai Zion Medical Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel
| | - Meital Almog
- Division of Allergy & Clinical Immunology, Bnai Zion Medical Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel
| | - Roni Wagner
- Division of Allergy & Clinical Immunology, Bnai Zion Medical Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel
| | - Larisa Epov
- Division of Allergy & Clinical Immunology, Bnai Zion Medical Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel
| | - Vika Dor
- Division of Allergy & Clinical Immunology, Bnai Zion Medical Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel
| | - Aharon Kessel
- Division of Allergy & Clinical Immunology, Bnai Zion Medical Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel.
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26
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Bélteky M, Wahlberg J, Ludvigsson J. Infections and antibiotic use in early childhood have limited importance in developing manifest type 1 diabetes - The ABIS cohort study. Front Endocrinol (Lausanne) 2025; 16:1529447. [PMID: 40060384 PMCID: PMC11885132 DOI: 10.3389/fendo.2025.1529447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Accepted: 01/30/2025] [Indexed: 05/13/2025] Open
Abstract
Aims To investigate the effect of early childhood infections and antibiotic use on the risk of type 1 diabetes in a general population cohort. Research Design and Methods The All Babies In Southeast Sweden (ABIS) cohort followed 16 428 children from birth. Questionnaires collected at 1 year (n=11 093), 3 years (n=8 890) and 5 years of age (n=7 445) included data on infections and antibiotic use and were validated against national registers. After a mean follow-up of 25 years, 168 individuals have been diagnosed with type 1 diabetes (1.0% of the original cohort, aged 1-24.5 years). Results There were few significant differences in type or frequency of early childhood infections or antibiotic use between cases with type 1 diabetes and the reference group (remaining individuals who did not develop type 1 diabetes) after adjusting for sex, heredity and socioeconomic status. A small number of type 1 diabetes children (4.8% compared to 0.8% of the reference group) reported six or more episodes of gastroenteritis in the 1-3-year age group, resulting in an adjusted odds ratio (aOR) of 8.21; 95% CI 2.70-25.01, p<0.001. Cases of type 1 diabetes with an increased genetic risk (n=91) reported fewer episodes of the common cold between 1 and 3 years of age compared to the reference group (aOR 0.27; 0.13-0.58, p<0.001). Individuals with type 1 diabetes without risk-associated HLA alleles (n=14) reported a higher frequency of pneumonia in the 1-3- and 3-5-year age group (aOR 26.08; 6.29-108.17, p<0.001 and aOR 35.63; 4.10-309.96, p=0.001 respectively), and had more viral and total infections registered in the National Patient Register from 0-5 years (aOR 5.72; 1.59-20.57, p=0.008 and aOR 18.71; 1.95-179.55, p=0.01). Conclusions Childhood infections could increase the risk of developing type 1 diabetes in a small group of individuals without risk-associated HLA alleles, but this was not seen in the majority with HLA-risk. More research is required for this overlooked population, including screening and prevention trials. The association to frequent gastrointestinal infections in the first years of life needs to be reproduced in other studies to be confirmed.
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Affiliation(s)
- Malin Bélteky
- Crown Princess Victoria’s Children´s Hospital, Region Östergötland and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Jeanette Wahlberg
- Department of Acute Internal Medicine and Geriatrics in Linköping, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
- Faculty of Medical Sciences, Örebro University, Örebro, Sweden
| | - Johnny Ludvigsson
- Crown Princess Victoria’s Children´s Hospital, Region Östergötland and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
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27
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Klomp K, Alkema M, Knol J, Malinowska AM, Belzer C. A randomized controlled study protocol of the TOBBI trial: the effect of a 6 weeks intervention with synbiotics on the recovery speed of the gut microbiota after antibiotic treatment in Dutch toddlers. BMC Pediatr 2025; 25:117. [PMID: 39955511 PMCID: PMC11829333 DOI: 10.1186/s12887-025-05405-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 01/07/2025] [Indexed: 02/17/2025] Open
Abstract
BACKGROUND Antibiotic-induced disruption of the gut microbiome in the first 1000 days of life is linked to an increased risk of the development of immunological, metabolic, and neurobehavioral childhood-onset conditions. Supporting the recovery of the gut microbial community after it has been perturbed by antibiotics might be a promising strategy to reduce these risks. In this clinical study, the effect of a 6 weeks supplementation with synbiotics (Bifidobacterium breve M-16 V, short chain galacto-oligosaccharides and long chain fructo-oligosaccharides) after antibiotic treatment on the recovery speed of the gut microbiota of toddlers will be studied. METHODS/DESIGN A cohort of 126 Dutch toddlers aged 12 to 36 months old, who receive an amoxicillin or amoxicillin/clavulanic acid treatment, will be followed for 12 weeks. Participants will be randomized into an intervention group, who will consume the study product over a 6 weeks period starting at the last day of the antibiotic treatment or into a control group that will continue their usual eating pattern. Stool samples and their characteristics will be collected weekly by both groups. Stool samples will be analyzed for total microbiota and Bifidobacterium spp.. The differences in the proportion of Bifidobacterium out of total gut microbiota, composition of species belonging to Bifidobacterium, and beta diversity overtime will be compared between the two groups to study the effect of the intervention on the gut microbiota after perturbation. Furthermore, the effect of the treatment will also be studied in terms of the gut microbiota metabolic activity and stool characteristics. Additionally, food intake will be recorded to investigate whether diet, especially dietary fibers, may influence the gut microbiota as well. The findings may highlight a potential intervention strategy to support the recovery of the gut community after it has been perturbed by antibiotics in early life. TRIAL REGISTRATION The TOBBI trial was approved by the board of Medical Ethics Review Committee NedMec in June 2022 and registered at https://www.onderzoekmetmensen.nl/en/trial/20358 under the code NL75975.081.20, and at the World Health Organization at https://trialsearch.who.int/Trial2.aspx?TrialID=NL-OMON20358 under NTR-new: NL8996.
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Affiliation(s)
- Kelly Klomp
- Laboratory of Microbiology, Wageningen University and Research, Stippeneng 4, Wageningen, 6708WE, The Netherlands
| | - Maaike Alkema
- Laboratory of Microbiology, Wageningen University and Research, Stippeneng 4, Wageningen, 6708WE, The Netherlands
| | - Jan Knol
- Laboratory of Microbiology, Wageningen University and Research, Stippeneng 4, Wageningen, 6708WE, The Netherlands
- Danone Research & Innovation, Uppsalalaan 12, Utrecht, 3584 CT, The Netherlands
| | - Anna M Malinowska
- Laboratory of Microbiology, Wageningen University and Research, Stippeneng 4, Wageningen, 6708WE, The Netherlands
| | - Clara Belzer
- Laboratory of Microbiology, Wageningen University and Research, Stippeneng 4, Wageningen, 6708WE, The Netherlands.
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28
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Zou W, Ma D, Sun F, Chen Z, Chen Y, Li X, Chen M, Lin M, Shi H, Wu B, Chen L, Liang Z, Liu J. Maternal OM-85 administration alleviates offspring allergic airway inflammation by downregulating IL-33/ILC2 axis. Pediatr Allergy Immunol 2025; 36:e70044. [PMID: 39927900 DOI: 10.1111/pai.70044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 01/23/2025] [Accepted: 01/30/2025] [Indexed: 02/11/2025]
Abstract
BACKGROUND Type 2 innate lymphoid cells (ILC2s) are essential for maintaining immune regulation and promoting tissue homeostasis in allergic asthma. How the development of gut microbiota on neonatal ILC2s influences allergic airway inflammation remains unclear. Here we focus on offspring ILC2 development in the context of alterations in maternal gut microbiota. METHODS C57BL/6 maternal mice were gavaged with OM-85 during pregnancy and/or lactation, ILC2-driven allergic airway inflammation in the OVA-sensitized adult offspring was observed. ILC2 development in offspring early life were investigated using recombinant (r)IL-33, rIL-25 and Bromodeoxyuridine in the vivo experiments. Further ILC2 promoting factors- IL-33 and IL-25 production in offspring early life were analysed. Finally, we examined the changes in gut microbiota and its metabolites in both dams and pups, and explored the effects of short-chain fatty acids (SCFAs) on IL-33 expression and secretion. RESULTS Maternal OM-85 administration restrained ILC2-driven allergic airway inflammation in the OVA-sensitized adult offspring. During ILC2 development in offspring early life, maternal OM-85 administration suppressed IL-33 and IL-25 production to inhibit ILC2 expansion and ILC2 responsiveness to alarmins, and infantile ILC2s could persist into adulthood. Maternal OM-85 administration increased SCFAs in breast milk and SCFA-producing gut probiotics (predominant Bacteroides and Blautia) in offspring, especially during pregnancy and lactation. SCFAs down-regulated IL-33 expression and reduced IL-33 secretion by inhibited gasdermin D (GSDMD) formation. CONCLUSION Maternal OM-85 administration restrains ILC2-driven allergic airway inflammation in adult offspring by increasing offspring intestinal SCFAs to modulate ILC2 development at an early stage, demonstrating that the transgenerational effects of maternal OM-85 exposure on offspring innate immunity.
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Affiliation(s)
- Wei Zou
- Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
- Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
- Department of Thoracic Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
| | - Donghai Ma
- Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
| | - Fengfei Sun
- Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
- Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
| | - Zehu Chen
- Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
- Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
| | - Ying Chen
- Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
- Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
| | - Xuegang Li
- Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
| | - Meizhu Chen
- Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
| | - Minmin Lin
- Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
| | - Honglei Shi
- Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
- Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
| | - Baihe Wu
- Department of Gastroenterology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
| | - Lei Chen
- Oncology Central Laboratory, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
- Department of Neurosurgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
| | - Zibin Liang
- Department of Thoracic Oncology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
| | - Jing Liu
- Department of Pulmonary and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
- Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
- Department of Allergy, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
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Kaneko K. Gut dysbiosis as a susceptibility factor in childhood idiopathic nephrotic syndrome. Pediatr Neonatol 2025; 66 Suppl 1:S2-S7. [PMID: 39521679 DOI: 10.1016/j.pedneo.2024.10.003] [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] [Indexed: 11/16/2024] Open
Abstract
Idiopathic nephrotic syndrome (INS) is a relatively common renal disorder of childhood characterized by severe proteinuria and associated hypoproteinemia and edema. Although the pathogenesis of INS remains unknown, the prevailing theory of its pathogenesis is as follows. Antigenic stimulation, such as viral infections or vaccines, in children with susceptibility factors for INS triggers abnormal immune responses, resulting in production of pathogenic substances that injure podocytes (renal glomerular epithelial cells). The injured podocytes then change their function and morphology, resulting in increased permeability of plasma proteins. Consequently, plasma proteins, especially albumin, are leaked into urine and massive proteinuria ensues. Research on susceptibility factors for INS has focused on polymorphisms in several genes including human leukocyte antigen class II genes. However, we propose that dysbiosis of the intestinal microbiota could be a susceptibility factor for relapse. This proposal is based on our research group finding that children with INS and frequent relapses have gut dysbiosis characterized by a decreased proportion of beneficial bacteria such as short-chain fatty acid-producing bacteria. Dysbiosis from the neonatal period to infancy may result from environmental factors, such as cesarean section delivery and antibiotic administration, which prevent the establishment of a normal intestinal microbiota. Dysbiosis leads to aberrant gut immunity and is characterized by a decreased ratio of T helper 1 cells/T helper 2 cells and an increased ratio of T helper 17 cells/regulatory T-cells. Therefore, relapse occurs when immunologically pathogenic factors that injure podocytes are produced in response to trigger events in children with INS and gut dysbiosis. Our recent clinical trial suggested that long-term oral administration of butyric acid-producing bacterium as a probiotic is promising for suppressing relapse. Therefore, studying the causal relationship between dysbiosis and relapses in patients with INS in a larger number of patients is necessary.
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Affiliation(s)
- Kazunari Kaneko
- Department of Pediatrics, Kansai Medical University, 2-5-1, Shin-machi, Hirakata, Osaka, 573 1010, Japan.
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30
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Miyoshi J, Hisamatsu T. Effect of maternal exposure to antibiotics during pregnancy on the neonatal intestinal microbiome and health. Clin J Gastroenterol 2025; 18:1-10. [PMID: 39709577 DOI: 10.1007/s12328-024-02088-6] [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: 08/16/2024] [Accepted: 12/12/2024] [Indexed: 12/23/2024]
Abstract
Antibiotics are widely used during pregnancy. Recent epidemiological studies suggest that maternal exposure to antibiotics during pregnancy is associated with increased risks of various diseases in offspring; host-microbiome interactions are considered to be involved in pathogenesis, as antibiotic-induced perturbations (dysbiosis) of the maternal microbiome can be transmitted to offspring. We reviewed the current status of antibiotic usage during pregnancy, transmission of maternal antibiotic-induced dysbiosis to offspring, and several diseases in offspring reported to be associated with maternal antibiotic exposure. Antibiotics must be properly used when necessary. While the adverse effect of maternal antibiotic exposure during pregnancy on the health of offspring has been demonstrated by several studies, more robust clinical evidence is necessary to define the best practice for antibiotic use during pregnancy. Epidemiologic studies have limitations in establishing causal links beyond associations; animal studies provide benefits in examining these links, however, microbiomes, gestation courses, and aging vary between host species. Understanding the underlying mechanisms of epidemiologic findings as well as the healthy microbiome during pregnancy and early life in humans would contribute to developing future microbial interventions for restoring antibiotic-induced dysbiosis during pregnancy.
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Affiliation(s)
- Jun Miyoshi
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan.
| | - Tadakazu Hisamatsu
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan
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31
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Johnson DE, Jones RB. Predicting child health with gut microbiome development trajectories. Nat Microbiol 2025; 10:265-266. [PMID: 39856389 DOI: 10.1038/s41564-024-01920-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2025]
Affiliation(s)
- Douglas E Johnson
- Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
| | - Roshonda B Jones
- Department of Biology, North Carolina Agricultural and Technical State University, Greensboro, NC, USA.
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32
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Frazier AN, Ferree L, Belk AD, Al-Lakhen K, Cramer MC, Metcalf JL. Stochasticity Highlights the Development of Both the Gastrointestinal and Upper-Respiratory-Tract Microbiomes of Neonatal Dairy Calves in Early Life. Animals (Basel) 2025; 15:361. [PMID: 39943131 PMCID: PMC11816138 DOI: 10.3390/ani15030361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Revised: 01/24/2025] [Accepted: 01/25/2025] [Indexed: 02/16/2025] Open
Abstract
The microbiome of dairy calves undergoes extensive change due to various forces during the first weeks of life. Importantly, diseases such as bovine respiratory disease (BRD) and calf diarrhea can have profound impacts on the early-life microbiome. Therefore, a longitudinal, repeated-measures pilot study was designed to characterize the establishment of nasal and fecal microbiomes of dairy calves, assess the governing forces of microbial assembly, and evaluate how disease states impact these microbial ecologies. Dairy calves (n = 19) were clinically evaluated for gastrointestinal and respiratory disease across three weeks beginning at age ≤ seven days old. Fecal (n = 57) and nasal (n = 57) microbial samples were taken for paired-end 16S rRNA gene amplicon sequencing. Taxonomy and diversity analyses were used to characterize early-life nasal and fecal microbiomes. Stochasticity and determinism were measured using normalized stochasticity testing (NST) and Dirichlet multinomial model (DMM). All analyses were tested for statistical significance. Clinical diarrhea was observed in 11 of the 19 calves. Clinical BRD was not independently observed among the cohort; however, two calves presented clinical signs of both BRD and diarrhea. Taxonomic analysis revealed that fecal samples were highlighted by Bacteroidaceae (40%; relative abundance), Ruminococcaceae (13%), and Lachnospiraceae (10%), with changes in diversity (Kruskal-Wallis; p < 0.05) and composition (PERMANOVA; p < 0.05). Clinical diarrhea reduced diversity in the fecal microbiome but did not impact composition. Nasal samples featured Moraxellaceae (49%), Mycoplasmataceae (16%), and Pasteurellaceae (3%). While no diversity changes were seen in nasal samples, compositional changes were observed (p < 0.05). NST metrics (Kruskal-Wallis; p > 0.01) and DMM (PERMANOVA; p < 0.01) revealed that stochastic, neutral theory-based assembly dynamics govern early-life microbial composition and that distinct microbial populations drive community composition in healthy and diarrheic calves.
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Affiliation(s)
- A. Nathan Frazier
- United States Department of Agriculture—Agricultural Research Service (USDA-ARS), Bushland, TX 79012, USA
| | - Logan Ferree
- Department of Animal Science, Colorado State University, Fort Collins, CO 80523, USA
| | - Aeriel D. Belk
- Department of Animal Science, Auburn University, Auburn, AL 36849, USA
| | - Khalid Al-Lakhen
- Department of Animal Science, Colorado State University, Fort Collins, CO 80523, USA
| | - M. Caitlin Cramer
- Department of Animal Science, Colorado State University, Fort Collins, CO 80523, USA
| | - Jessica L. Metcalf
- Department of Animal Science, Colorado State University, Fort Collins, CO 80523, USA
- Canadian Institute for Advanced Research (CIFAR) Azrieli Global Scholars Program, CIFAR, Toronto, ON M5G 1M1, Canada
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33
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Mak IEK, Yao Y, Ng MTT, Kim JE. Influence of dietary protein and fiber intake interactions on the human gut microbiota composition and function: a systematic review and network meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr 2025:1-19. [PMID: 39815995 DOI: 10.1080/10408398.2025.2452362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2025]
Abstract
Quantity and source of dietary protein intakes impact the gut microbiota differently. However, these effects have not been systematically studied. This review aimed to investigate these effects whilst controlling for fiber intake. Seven databases were searched, with 50 and 15 randomized controlled trials selected for the systematic review and network meta-analysis respectively. Most gut microbiota-related outcomes showed no significant differences between different protein and fiber intake combinations. Compared to Normal Protein, High Fiber intakes, High Protein, Low Fiber (HPLF) intakes showed greater fecal valerate (SMD = 0.79, 95% CrI: 0.35, 1.24) and plasma trimethylamine N-oxide (TMAO) (SMD = 2.90, 95% CrI: 0.16, 5.65) levels. HPLF intakes also showed greater fecal propionate (SMD = 0.49, 95% CrI: 0.02, 1.07) and valerate (SMD = 0.79, 95% CrI: 0.31, 1.28) levels compared to High Protein, High Fiber intakes. Greater plasma TMAO levels were observed with greater animal protein intakes. Overall, protein quantity and source do not generally alter the gut microbiota composition, although protein quantity can influence microbiota function via modulations in proteolytic fermentation. Both protein and fiber intake should be considered when assessing the impact of dietary protein on the gut microbiota. This trial was registered at PROSPERO (CRD42023391270).
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Affiliation(s)
- Ian En Kai Mak
- Department of Food Science and Technology, National University of Singapore, Singapore, Singapore
| | - Yueying Yao
- Department of Food Science and Technology, National University of Singapore, Singapore, Singapore
| | - Magdeline Tao Tao Ng
- National University of Singapore Libraries, National University of Singapore, Singapore, Singapore
| | - Jung Eun Kim
- National University of Singapore Libraries, National University of Singapore, Singapore, Singapore
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Xie K, Cai W, Li L, Yu B, Luo Y, Huang Z, Mao X, Yu J, Zheng P, Yan H, Li H, He J. Probiotic administration aggravates dextran sulfate sodium salt-induced inflammation and intestinal epithelium disruption in weaned pig. Anim Microbiome 2025; 7:8. [PMID: 39819657 PMCID: PMC11740613 DOI: 10.1186/s42523-024-00375-8] [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: 11/01/2024] [Accepted: 12/31/2024] [Indexed: 01/19/2025] Open
Abstract
BACKGROUND A. muciniphila (AKK) has attracted extensive research interest as a potential next-generation probiotics, but its role in intestinal pathology is remains unclear. Herein, this study was conducted to investigate the effects of A. muciniphila DSM 22,959 on growth performance, intestinal barrier function, microecology and inflammatory response of weaned piglets stimulated by dextran sulfate sodium salt (DSS). METHOD Twenty-four Duroc × Landrace × Yorkshire (DLY) weaned piglets used for a 2 × 2 factorial arrangement of treatments were divided into four groups with six piglets in each group. From 1 to 15 d, the CA and DA groups were orally fed with 1.0 × 1011 colony-forming units A. muciniphila per day, while the CON and DCON groups were received gastric infusion of anaerobic sterile saline per day. The pigs were orally challenged (DCON, DA) or not (CON, CA) with DSS from day 9 to the end of the experiment and slaughtered on day 16. RESULTS Presence of A. muciniphila in DSS-challenged weaned pigs resulted in numerically increased diarrhea rate, blood neutrophilic granulocyte, serum C-reactive protein and immunoglobulin M levels, and numerically reduced final weight, average daily feed intake and average daily gain. The decrease in intestinal villus height, villous height: crypt depth ratio and digestibility was accompanied by lower expression of ZO1, ZO2, Claudin1, DMT1, CAT1, SGLT1 and PBD114 genes, as well as decreased enzyme activities of intestinal alkaline phosphatase, lactase, sucrase and maltase of piglets in DA group compared to piglets in DCON group. The abundance of Bifdobacterium, Lactobacillus, A. muciniphila, Ruminococcus gnavus was numerically higher in digesta of pigs in DA group than those in DCON group. The inflammatory responses of piglets were dramatically changed by the simultaneous presence of A. muciniphila and DSS: expression level of IL17A, IL17F, IL23, RORγt, Stat3 was elevated in DA pigs compared to the other pig groups. CONCLUSIONS Our result showed that the oral A. muciniphila aggravates DSS-induced health damage of weaned piglet, which may attribute to the deteriorating intestinal morphology, dysbiosis of microbiota and inflammatory response disorders.
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Affiliation(s)
- Kunhong Xie
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, 611130, P.R. China
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, P.R. China
| | - Weidong Cai
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, 611130, P.R. China
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, P.R. China
| | - Lingjie Li
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, 611130, P.R. China
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, P.R. China
| | - Bing Yu
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, 611130, P.R. China
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, P.R. China
| | - Yuheng Luo
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, 611130, P.R. China.
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, P.R. China.
| | - Zhiqing Huang
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, 611130, P.R. China
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, P.R. China
| | - Xiangbing Mao
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, 611130, P.R. China
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, P.R. China
| | - Jie Yu
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, 611130, P.R. China
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, P.R. China
| | - Ping Zheng
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, 611130, P.R. China
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, P.R. China
| | - Hui Yan
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, 611130, P.R. China
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, P.R. China
| | - Hua Li
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, 611130, P.R. China
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, P.R. China
| | - Jun He
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, 611130, P.R. China.
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Chengdu, Sichuan, P.R. China.
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Profir M, Enache RM, Roşu OA, Pavelescu LA, Creţoiu SM, Gaspar BS. Malnutrition and Its Influence on Gut sIgA-Microbiota Dynamics. Biomedicines 2025; 13:179. [PMID: 39857762 PMCID: PMC11762760 DOI: 10.3390/biomedicines13010179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 01/02/2025] [Accepted: 01/09/2025] [Indexed: 01/27/2025] Open
Abstract
In the current era, malnutrition is seen as both undernutrition and overweight and obesity; both conditions are caused by nutrient deficiency or excess and improper use or imbalance in the intake of macro and micronutrients. Recent evidence suggests that malnutrition alters the intestinal microbiota, known as dysbiosis. Secretory immunoglobulin A (sIgA) plays an important role in maintaining and increasing beneficial intestinal microbiota populations and protecting against pathogenic species. Depletion of beneficial bacterial populations throughout life is also conditioned by malnutrition. This review aims to synthesize the evidence that establishes an interrelationship between diet, malnutrition, changes in the intestinal flora, and sIgA levels. Targeted nutritional therapies combined with prebiotic, probiotic, and postbiotic administration can restore the immune response in the intestine and the host's homeostasis.
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Affiliation(s)
- Monica Profir
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (M.P.); (O.A.R.); (L.A.P.)
- Department of Oncology, Elias University Emergency Hospital, 011461 Bucharest, Romania
| | - Robert Mihai Enache
- Department of Radiology and Medical Imaging, Fundeni Clinical Institute, 022328 Bucharest, Romania;
| | - Oana Alexandra Roşu
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (M.P.); (O.A.R.); (L.A.P.)
- Department of Oncology, Elias University Emergency Hospital, 011461 Bucharest, Romania
| | - Luciana Alexandra Pavelescu
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (M.P.); (O.A.R.); (L.A.P.)
| | - Sanda Maria Creţoiu
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (M.P.); (O.A.R.); (L.A.P.)
| | - Bogdan Severus Gaspar
- Department of Surgery, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
- Surgery Clinic, Bucharest Emergency Clinical Hospital, 014461 Bucharest, Romania
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Rakhshandehroo M, Harvey L, de Bruin A, Timmer E, Lohr J, Tims S, Schipper L. Maternal exposure to purified versus grain-based diet during early lactation in mice affects offspring growth and reduces responsivity to Western-style diet challenge in adulthood. J Dev Orig Health Dis 2025; 16:e3. [PMID: 39780545 DOI: 10.1017/s2040174424000436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
The nutritional environment during fetal and early postnatal life has a long-term impact on growth, development, and metabolic health of the offspring, a process termed "nutritional programming." Rodent models studying programming effects of nutritional interventions use either purified or grain-based rodent diets as background diets. However, the impact of these diets on phenotypic outcomes in these models has not been comprehensively investigated. We used a previously validated (C57BL/6J) mouse model to investigate the effects of infant milk formula (IMF) interventions on nutritional programming. Specifically, we investigated the effects of maternal diet type (i.e., grain-based vs purified) during early lactation and prior to the intervention on offspring growth, metabolic phenotype, and gut microbiota profile. Maternal exposure to purified diet led to an increased post-weaning growth velocity in the offspring and reduced adult diet-induced obesity. Further, maternal exposure to purified diet reduced the offspring gut microbiota diversity and modified its composition post-weaning. These data not only reinforce the notion that maternal nutrition significantly influences the programming of offspring vulnerability to an obesogenic diet in adulthood but emphasizes the importance of careful selection of standard background diet type when designing any preclinical study with (early life) nutritional interventions.
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Affiliation(s)
| | - L Harvey
- Danone Research & Innovation Center, Utrecht, The Netherlands
| | - A de Bruin
- Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
| | - E Timmer
- Danone Research & Innovation Center, Utrecht, The Netherlands
| | - J Lohr
- Danone Research & Innovation Center, Utrecht, The Netherlands
| | - S Tims
- Danone Research & Innovation Center, Utrecht, The Netherlands
| | - L Schipper
- Danone Research & Innovation Center, Utrecht, The Netherlands
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Yan S, Gan Y, Xu H, Piao H. Bacterial carrier-mediated drug delivery systems: a promising strategy in cancer therapy. Front Bioeng Biotechnol 2025; 12:1526612. [PMID: 39845371 PMCID: PMC11750792 DOI: 10.3389/fbioe.2024.1526612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Accepted: 12/17/2024] [Indexed: 01/24/2025] Open
Abstract
Cancer is a major killer threatening modern human health and a leading cause of death worldwide. Due to the heterogeneity and complexity of cancer, traditional treatments have limited effectiveness. To address this problem, an increasing number of researchers and medical professionals are working to develop new ways to treat cancer. Bacteria have chemotaxis that can target and colonize tumor tissue, as well as activate anti-tumor immune responses, which makes them ideal for biomedical applications. With the rapid development of nanomedicine and synthetic biology technologies, bacteria are extensively used as carriers for drug delivery to treat tumors, which holds the promise of overcoming the limitations of conventional cancer treatment regimens. This paper summarizes examples of anti-cancer drugs delivered by bacterial carriers, and their strengths and weaknesses. Further, we emphasize the promise of bacterial carrier delivery systems in clinical translation.
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Affiliation(s)
- Sizuo Yan
- Department of Neurosurgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Shenyang, China
| | - Yu Gan
- Department of Neurosurgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Shenyang, China
| | - Huizhe Xu
- Institute of Cancer Medicine, Dalian University of Technology, Dalian, China
- Central Laboratory, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Shenyang, China
| | - Haozhe Piao
- Department of Neurosurgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Shenyang, China
- Institute of Cancer Medicine, Dalian University of Technology, Dalian, China
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38
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Novelle MG, Naranjo-Martínez B, López-Cánovas JL, Díaz-Ruiz A. Fecal microbiota transplantation, a tool to transfer healthy longevity. Ageing Res Rev 2025; 103:102585. [PMID: 39586550 DOI: 10.1016/j.arr.2024.102585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 10/13/2024] [Accepted: 11/12/2024] [Indexed: 11/27/2024]
Abstract
The complex gut microbiome influences host aging and plays an important role in the manifestation of age-related diseases. Restoring a healthy gut microbiome via Fecal Microbiota Transplantation (FMT) is receiving extensive consideration to therapeutically transfer healthy longevity. Herein, we comprehensively review the benefits of gut microbial rejuvenation - via FMT - to promote healthy aging, with few studies documenting life length properties. This review explores how preconditioning donors via standard - lifestyle and pharmacological - antiaging interventions reshape gut microbiome, with the resulting benefits being also FMT-transferable. Finally, we expose the current clinical uses of FMT in the context of aging therapy and address FMT challenges - regulatory landscape, protocol standardization, and health risks - that require refinement to effectively utilize microbiome interventions in the elderly.
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Affiliation(s)
- Marta G Novelle
- Department of Genetics, Physiology and Microbiology (Unity of Animal Physiology), Faculty of Biology, Complutense University of Madrid (UCM), Madrid, Spain; CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Spain
| | - Beatriz Naranjo-Martínez
- Laboratory of Cellular and Molecular Gerontology, Precision Nutrition and Aging, Madrid Institute for Advanced Studies - IMDEA Food, CEI UAM+CSIC, Madrid, Spain
| | - Juan L López-Cánovas
- Laboratory of Cellular and Molecular Gerontology, Precision Nutrition and Aging, Madrid Institute for Advanced Studies - IMDEA Food, CEI UAM+CSIC, Madrid, Spain
| | - Alberto Díaz-Ruiz
- Laboratory of Cellular and Molecular Gerontology, Precision Nutrition and Aging, Madrid Institute for Advanced Studies - IMDEA Food, CEI UAM+CSIC, Madrid, Spain; CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Spain.
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Denys ME, Kozlova EV, Liu R, Bishay AE, Do EA, Piamthai V, Korde YV, Luna CN, Lam AA, Hsiao A, Currás-Collazo M. Maternal probiotic supplementation protects against PBDE-induced developmental, behavior and metabolic reprogramming in a sexually dimorphic manner: Role of gut microbiome. Arch Toxicol 2025; 99:423-446. [PMID: 39520540 PMCID: PMC11748483 DOI: 10.1007/s00204-024-03882-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 09/23/2024] [Indexed: 11/16/2024]
Abstract
Polybrominated diphenyl ethers (PBDEs) are endocrine-disrupting persistent organic pollutants (POPs) used as flame retardants in a wide range of commercial applications. We have previously reported neurobehavioral and metabolic reprogramming produced by developmental PBDEs. PBDEs perturb the microbiome, an influencer of life-long health, while probiotic supplementation with Limosilactobacillus reuteri (LR) can avert neurobehavioral and endocrine disruption. We, therefore, tested the hypothesis that perinatal maternal LR supplementation would protect gut microbiome richness and diversity, developmental milestones, adult neurobehavior and metabolic homeostasis in PBDE-exposed offspring. C57BL/6N dams were orally exposed to a commercial penta-mixture of PBDEs, DE-71, at 0.1 mg/kg/day, or corn oil vehicle (VEH/CON) during gestation and lactation. Mice offspring received DE-71 or VEH/CON with or without co-administration of LR (ATCC-PTA-6475) indirectly via their mother from gestational day (GD) 0 until postnatal day (P)21 (Cohort 1), or continued to receive LR directly from P22 through adulthood (Cohort 2). Results of fecal 16S rRNA sequencing indicated age- and sex-dependent effects of DE-71 on gut microbial communities. Maternal LR treatment protected against DE-71-induced reduction in α-diversity in P22 females and against β-diversity alterations in P30 males. In females, DE-71 changed the relative abundance of specific bacterial taxa, such as Tenericutes and Cyanobacteria (elevated) and Deferribacterota (reduced). In males, several Firmicutes taxa were elevated, while Proteobacteria, Chlamydiae, and several Bacteroidota taxa were reduced. The number of disrupted taxa normalized by maternal LR supplementation was as follows: 100% in P22 females and 33% in males at P22 and 25% at P30. Maternal LR treatment protected against DE-71-induced delay of postnatal body weight gain in males and ameliorated the abnormal timing of incisor eruption in both sexes. Further, DE-71 produced exaggerated digging in both sexes as well as locomotor hyperactivity in females, effects that were mitigated by maternal LR only in females. Other benefits of LR therapy included normalization of glucose tolerance, insulin-to-glucose ratio and plasma leptin in adult DE-71 females (Cohort 2). This study provides evidence that probiotic supplementation can mitigate POP-induced reprogramming of neurodevelopment, adult neurobehavior, and glucose metabolism in association with modified gut microbial community structure in a sex-dependent manner.
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Affiliation(s)
- Maximillian E Denys
- Department of Molecular Cell and Systems Biology, University of California, Riverside, CA, 92521, USA
| | - Elena V Kozlova
- Department of Molecular Cell and Systems Biology, University of California, Riverside, CA, 92521, USA
- Neuroscience Graduate Program, University of California, Riverside, CA, USA
| | - Rui Liu
- Department of Microbiology and Plant Pathology, University of California, Riverside, CA, USA
| | - Anthony E Bishay
- Department of Molecular Cell and Systems Biology, University of California, Riverside, CA, 92521, USA
| | - Elyza A Do
- Department of Microbiology and Plant Pathology, University of California, Riverside, CA, USA
- Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, CA, USA
| | - Varadh Piamthai
- Department of Microbiology and Plant Pathology, University of California, Riverside, CA, USA
| | - Yash V Korde
- Department of Molecular Cell and Systems Biology, University of California, Riverside, CA, 92521, USA
| | - Crystal N Luna
- Department of Molecular Cell and Systems Biology, University of California, Riverside, CA, 92521, USA
| | - Artha A Lam
- Department of Molecular Cell and Systems Biology, University of California, Riverside, CA, 92521, USA
| | - Ansel Hsiao
- Department of Microbiology and Plant Pathology, University of California, Riverside, CA, USA
| | - Margarita Currás-Collazo
- Department of Molecular Cell and Systems Biology, University of California, Riverside, CA, 92521, USA.
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Coppola S, Paparo L, Bedogni G, Nocerino R, Costabile D, Cuomo M, Chiariotti L, Carucci L, Agangi A, Napolitano M, Messina F, Passariello A, Berni Canani R. Effects of Mediterranean diet during pregnancy on the onset of overweight or obesity in the offspring: a randomized trial. Int J Obes (Lond) 2025; 49:101-108. [PMID: 39289583 PMCID: PMC11683001 DOI: 10.1038/s41366-024-01626-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 08/26/2024] [Accepted: 08/29/2024] [Indexed: 09/19/2024]
Abstract
BACKGROUND/OBJECTIVES The PREMEDI study was designed to assess the efficacy of nutritional counseling aimed at promoting Mediterranean Diet (MD) during pregnancy on the incidence of overweight or obesity at 24 months in the offspring. METHODS PREMEDI was a parallel-arm randomized-controlled trial. 104 women in their first trimester of pregnancy were randomly assigned in a 1:1 ratio to standard obstetrical and gynecological care alone (CT) or with nutritional counseling promoting MD. Women enrolled in the MD arm were provided with 3 sessions of nutritional counseling (one session per trimester). The main outcome was the proportion of overweight or obesity among the offspring at the age of 24 months. Maternal MD-adherence and weight gain during pregnancy were also evaluated. Lastly, the evaluation of epigenetic modulation of metabolic pathways in the offspring was analyzed in cord blood. RESULTS Five women in the MD arm and 2 in the CT arm were lost to follow-up, so a total of 97 completed the study. At 24 months, children of MD mothers were less likely to have overweight or obesity than those of the CT mothers (6% vs. 30%, absolute risk difference = -24%, 95% CI -38% to -9%, p = 0.003, number needed to treat 4, 95% CI 2 to 12, per-protocol analysis). A significantly higher increase of MD-adherence during the trial was observed in the MD arm compared to the CT arm. A similar body weight gain at the end of pregnancy was observed in the two arms. The mean (SD) methylation rate of the leptin gene in cord blood was 30.4 (1.02) % and 16.9 (2.99) % in the MD and CT mothers, respectively (p < 0.0001). CONCLUSIONS MD during pregnancy could be an effective strategy for preventing pediatric overweight or obesity at 24 months. This effect involves, at least in part, an epigenetic modification of leptin expression.
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Affiliation(s)
- Serena Coppola
- Department of Translational Medical Science, University of Naples Federico II, Via Sergio Pansini 5, 80131, Naples, Italy
- CEINGE Advanced Biotechnologies, University of Naples Federico II, Via Gaetano Salvatore 486, 80131, Naples, Italy
| | - Lorella Paparo
- Department of Translational Medical Science, University of Naples Federico II, Via Sergio Pansini 5, 80131, Naples, Italy
- CEINGE Advanced Biotechnologies, University of Naples Federico II, Via Gaetano Salvatore 486, 80131, Naples, Italy
| | - Giorgio Bedogni
- Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Via Massarenti 9, 40138, Bologna, Italy
- Department of Primary Health Care, Internal Medicine Unit Addressed to Frailty and Aging, S. Maria delle Croci Hospital, AUSL Romagna, Viale Randi 5, 48121, Ravenna, Italy
| | - Rita Nocerino
- Department of Translational Medical Science, University of Naples Federico II, Via Sergio Pansini 5, 80131, Naples, Italy
- CEINGE Advanced Biotechnologies, University of Naples Federico II, Via Gaetano Salvatore 486, 80131, Naples, Italy
| | - Davide Costabile
- CEINGE Advanced Biotechnologies, University of Naples Federico II, Via Gaetano Salvatore 486, 80131, Naples, Italy
| | - Mariella Cuomo
- CEINGE Advanced Biotechnologies, University of Naples Federico II, Via Gaetano Salvatore 486, 80131, Naples, Italy
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via Sergio Pansini 5, 80131, Naples, Italy
| | - Lorenzo Chiariotti
- CEINGE Advanced Biotechnologies, University of Naples Federico II, Via Gaetano Salvatore 486, 80131, Naples, Italy
- Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via Sergio Pansini 5, 80131, Naples, Italy
| | - Laura Carucci
- Department of Translational Medical Science, University of Naples Federico II, Via Sergio Pansini 5, 80131, Naples, Italy
- CEINGE Advanced Biotechnologies, University of Naples Federico II, Via Gaetano Salvatore 486, 80131, Naples, Italy
| | - Annalisa Agangi
- Neonatal Intensive Care Unit, Villa Betania Evangelical Hospital, Via Argine 604, 80147, Naples, Italy
| | - Marcello Napolitano
- Neonatal Intensive Care Unit, Villa Betania Evangelical Hospital, Via Argine 604, 80147, Naples, Italy
| | - Francesco Messina
- Neonatal Intensive Care Unit, Villa Betania Evangelical Hospital, Via Argine 604, 80147, Naples, Italy
| | - Annalisa Passariello
- Department of Pediatric Cardiology, Monaldi Hospital, Via Leonardo Bianchi, 80131, Naples, Italy
| | - Roberto Berni Canani
- Department of Translational Medical Science, University of Naples Federico II, Via Sergio Pansini 5, 80131, Naples, Italy.
- CEINGE Advanced Biotechnologies, University of Naples Federico II, Via Gaetano Salvatore 486, 80131, Naples, Italy.
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Ionescu MI, Zahiu CDM, Vlad A, Galos F, Gradisteanu Pircalabioru G, Zagrean AM, O'Mahony SM. Nurturing development: how a mother's nutrition shapes offspring's brain through the gut. Nutr Neurosci 2025; 28:50-72. [PMID: 38781488 DOI: 10.1080/1028415x.2024.2349336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/25/2024]
Abstract
Pregnancy is a transformative period marked by profound physical and emotional changes, with far-reaching consequences for both mother and child. Emerging research has illustrated the pivotal role of a mother's diet during pregnancy in influencing the prenatal gut microbiome and subsequently shaping the neurodevelopment of her offspring. The intricate interplay between maternal gut health, nutrition, and neurodevelopmental outcomes has emerged as a captivating field of investigation within developmental science. Acting as a dynamic bridge between mother and fetus, the maternal gut microbiome, directly and indirectly, impacts the offspring's neurodevelopment through diverse pathways. This comprehensive review delves into a spectrum of studies, clarifying putative mechanisms through which maternal nutrition, by modulating the gut microbiota, orchestrates the early stages of brain development. Drawing insights from animal models and human cohorts, this work underscores the profound implications of maternal gut health for neurodevelopmental trajectories and offers a glimpse into the formulation of targeted interventions able to optimize the health of both mother and offspring. The prospect of tailored dietary recommendations for expectant mothers emerges as a promising and accessible intervention to foster the growth of beneficial gut bacteria, potentially leading to enhanced cognitive outcomes and reduced risks of neurodevelopmental disorders.
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Affiliation(s)
- Mara Ioana Ionescu
- Department of Functional Sciences, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Pediatrics, Marie Curie Emergency Children's Hospital, Bucharest, Romania
| | - Carmen Denise Mihaela Zahiu
- Department of Functional Sciences, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Adelina Vlad
- Department of Functional Sciences, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Felicia Galos
- Department of Pediatrics, Marie Curie Emergency Children's Hospital, Bucharest, Romania
- Department of Pediatrics, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Gratiela Gradisteanu Pircalabioru
- Research Institute of the University of Bucharest, Section Earth, Environmental and Life Sciences, Section-ICUB, Bucharest, Romania
- Academy of Romanian Scientists, Bucharest, Romania
| | - Ana-Maria Zagrean
- Department of Functional Sciences, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Siobhain M O'Mahony
- Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
- APC Microbiome Ireland, University College Cork, Cork, Ireland
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Pala R, Kenny K. Nurturing futures through the maternal microbiome. SOCIOLOGY OF HEALTH & ILLNESS 2025; 47:e13828. [PMID: 39110548 PMCID: PMC11684494 DOI: 10.1111/1467-9566.13828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Accepted: 07/18/2024] [Indexed: 01/02/2025]
Abstract
Recently there has been growing recognition of the productive and protective features of our microbial kin and the crucial role of 'commensal' microbes in supporting and sustaining health. Current microbiological and pharmacological literature is increasingly highlighting the role of maternal gut microbiomes in the long-term health of both mothers and children. Drawing on the information and advice directed towards Australian parents from conception through the first years of a child's life, we consider its messaging about the need to secure for the foetus/future-child an enduring, optimal state of health by managing the maternal microbiome. We argue that this post-Pasteurian trend gives rise to relations of care that are, at once, newly collective and more-than-human-but also disciplinary in ways that position the maternal microbiome as a new site of scrutiny that disproportionately responsibilises and burdens mothers. We notice how microbiome research is used both to reframe motherhood as a form of micro(bial)-management and to maintain motherhood as a medicalised process. The feminist and more-than-human potential that this research can provide is missing in the way these resources are presented to parents.
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Affiliation(s)
- Roberta Pala
- Sydney Centre for Healthy SocietiesThe University of SydneySydneyNew South WalesAustralia
| | - Katherine Kenny
- Sydney Centre for Healthy SocietiesThe University of SydneySydneyNew South WalesAustralia
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Capelletti MM, Montini O, Ruini E, Tettamanti S, Savino AM, Sarno J. Unlocking the Heterogeneity in Acute Leukaemia: Dissection of Clonal Architecture and Metabolic Properties for Clinical Interventions. Int J Mol Sci 2024; 26:45. [PMID: 39795903 PMCID: PMC11719665 DOI: 10.3390/ijms26010045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 12/17/2024] [Accepted: 12/19/2024] [Indexed: 01/13/2025] Open
Abstract
Genetic studies of haematological cancers have pointed out the heterogeneity of leukaemia in its different subpopulations, with distinct mutations and characteristics, impacting the treatment response. Next-generation sequencing (NGS) and genome-wide analyses, as well as single-cell technologies, have offered unprecedented insights into the clonal heterogeneity within the same tumour. A key component of this heterogeneity that remains unexplored is the intracellular metabolome, a dynamic network that determines cell functions, signalling, epigenome regulation, immunity and inflammation. Understanding the metabolic diversities among cancer cells and their surrounding environments is therefore essential in unravelling the complexities of leukaemia and improving therapeutic strategies. Here, we describe the currently available methodologies and approaches to addressing the dynamic heterogeneity of leukaemia progression. In the second section, we focus on metabolic leukaemic vulnerabilities in acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL). Lastly, we provide a comprehensive overview of the most interesting clinical trials designed to target these metabolic dependencies, highlighting their potential to advance therapeutic strategies in leukaemia treatment. The integration of multi-omics data for cancer identification with the metabolic states of tumour cells will enable a comprehensive "micro-to-macro" approach for the refinement of clinical practices and delivery of personalised therapies.
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Affiliation(s)
- Martina Maria Capelletti
- School of Medicine and Surgery, University of Milan-Bicocca, 20126 Milan, Italy; (M.M.C.); (O.M.); (E.R.); (A.M.S.)
- Tettamanti Center, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
| | - Orsola Montini
- School of Medicine and Surgery, University of Milan-Bicocca, 20126 Milan, Italy; (M.M.C.); (O.M.); (E.R.); (A.M.S.)
- Tettamanti Center, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
| | - Emilio Ruini
- School of Medicine and Surgery, University of Milan-Bicocca, 20126 Milan, Italy; (M.M.C.); (O.M.); (E.R.); (A.M.S.)
| | - Sarah Tettamanti
- Tettamanti Center, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
| | - Angela Maria Savino
- School of Medicine and Surgery, University of Milan-Bicocca, 20126 Milan, Italy; (M.M.C.); (O.M.); (E.R.); (A.M.S.)
- Tettamanti Center, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
| | - Jolanda Sarno
- School of Medicine and Surgery, University of Milan-Bicocca, 20126 Milan, Italy; (M.M.C.); (O.M.); (E.R.); (A.M.S.)
- Tettamanti Center, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
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Jiang S, Cai M, Li D, Chen X, Chen X, Huang Q, Zhong C, Zheng X, Zhou D, Chen Z, Zhang L, Ching JYL, Chen A, Lu S, Zhang L, Hu L, Liao Y, Li Y, He Z, Wu J, Huo H, Liang Y, Li W, Zou Y, Luo W, Ng SC, Chan FKL, Chen X, Deng Y. Association of breast milk-derived arachidonic acid-induced infant gut dysbiosis with the onset of atopic dermatitis. Gut 2024; 74:45-57. [PMID: 39084687 PMCID: PMC11671956 DOI: 10.1136/gutjnl-2024-332407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 06/27/2024] [Indexed: 08/02/2024]
Abstract
OBJECTIVE The specific breast milk-derived metabolites that mediate host-microbiota interactions and contribute to the onset of atopic dermatitis (AD) remain unknown and require further investigation. DESIGN We enrolled 250 mother-infant pairs and collected 978 longitudinal faecal samples from infants from birth to 6 months of age, along with 243 maternal faecal samples for metagenomics. Concurrently, 239 corresponding breast milk samples were analysed for metabolomics. Animal and cellular experiments were conducted to validate the bioinformatics findings. RESULTS The clinical findings suggested that a decrease in daily breastfeeding duration was associated with a reduced incidence of AD. This observation inspired us to investigate the effects of breast milk-derived fatty acids. We found that high concentrations of arachidonic acid (AA), but not eicosapentaenoic acid (EPA) or docosahexaenoic acid, induced gut dysbiosis in infants. Further investigation revealed that four specific bacteria degraded mannan into mannose, consequently enhancing the mannan-dependent biosynthesis of O-antigen and lipopolysaccharide. Correlation analysis confirmed that in infants with AD, the abundance of Escherichia coli under high AA concentrations was positively correlated with some microbial pathways (eg, 'GDP-mannose-derived O-antigen and lipopolysaccharide biosynthesis'). These findings are consistent with those of the animal studies. Additionally, AA, but not EPA, disrupted the ratio of CD4/CD8 cells, increased skin lesion area and enhanced the proportion of peripheral Th2 cells. It also promoted IgE secretion and the biosynthesis of prostaglandins and leukotrienes in BALB/c mice fed AA following ovalbumin immunostimulation. Moreover, AA significantly increased IL-4 secretion in HaCaT cells costimulated with TNF-α and INF-γ. CONCLUSIONS This study demonstrates that AA is intimately linked to the onset of AD via gut dysbiosis.
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Affiliation(s)
- Suhua Jiang
- Department of paediatrics, The First People's Hospital of Foshan, Foshan, People's Republic of China
| | - Mengyun Cai
- Institute of translational medicine, The First People's Hospital of Foshan, Foshan, People's Republic of China
| | - Dingru Li
- Institute of translational medicine, The First People's Hospital of Foshan, Foshan, People's Republic of China
- South China University of Technology School of Biology and Biological Engineering, Guangzhou, Guangdong, People's Republic of China
| | - Xiangping Chen
- Institute of translational medicine, The First People's Hospital of Foshan, Foshan, People's Republic of China
| | - Xiaoqian Chen
- Department of paediatrics, The First People's Hospital of Foshan, Foshan, People's Republic of China
| | - Qitao Huang
- Department of obstetrics, The First People's Hospital of Foshan, Foshan, People's Republic of China
| | - Caimei Zhong
- Department of Dermatology, Shunde District Center for Prevention and Cure of Chronic Diseases, Foshan, China
| | - Xiufeng Zheng
- Department of Dermatology, Shunde Hospital, Southern Medical University, Lunjiao, Shunde, Foshan, People's Republic of China
| | - Dan Zhou
- Department of Breast Surgery, The First People's Hospital of Foshan, Foshan, People's Republic of China
| | - Zhiyan Chen
- Department of Breast Surgery, The First People's Hospital of Foshan, Foshan, People's Republic of China
| | - Lin Zhang
- Microbiota I-Center (MagIC), The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
- Centre for Gut Microbiota Research, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
- Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinse University of Hong Kong, Hong Kong SAR, People's Republic of China
| | - Jessica YL Ching
- Microbiota I-Center (MagIC), The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
| | - Ailing Chen
- Department of paediatrics, The First People's Hospital of Foshan, Foshan, People's Republic of China
| | - Shaoxia Lu
- Department of obstetrics, The First People's Hospital of Foshan, Foshan, People's Republic of China
| | - Lifang Zhang
- Institute of translational medicine, The First People's Hospital of Foshan, Foshan, People's Republic of China
| | - Ling Hu
- Institute of translational medicine, The First People's Hospital of Foshan, Foshan, People's Republic of China
| | - Yan Liao
- Department of obstetrics, The First People's Hospital of Foshan, Foshan, People's Republic of China
| | - Ying Li
- Department of paediatrics, The First People's Hospital of Foshan, Foshan, People's Republic of China
| | - Zhihua He
- Department of obstetrics, The First People's Hospital of Foshan, Foshan, People's Republic of China
| | - Jingjing Wu
- Department of obstetrics, The First People's Hospital of Foshan, Foshan, People's Republic of China
| | - Huiyi Huo
- Department of paediatrics, The First People's Hospital of Foshan, Foshan, People's Republic of China
| | - Yongqi Liang
- Department of paediatrics, The First People's Hospital of Foshan, Foshan, People's Republic of China
| | - Wanwen Li
- Department of paediatrics, The First People's Hospital of Foshan, Foshan, People's Republic of China
| | - Yanli Zou
- The Second People's Hospital of Foshan, Foshan, People's Republic of China
| | - Wei Luo
- Institute of translational medicine, The First People's Hospital of Foshan, Foshan, People's Republic of China
| | - Siew C Ng
- Microbiota I-Center (MagIC), The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
- Centre for Gut Microbiota Research, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
- Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinse University of Hong Kong, Hong Kong SAR, People's Republic of China
| | - Francis KL Chan
- Microbiota I-Center (MagIC), The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China
| | - Xia Chen
- Central Laboratory of the Medical Research Center, The First Affiliated Hospital of Ningbo University, Ningbo, People's Republic of China
| | - Yuhua Deng
- Institute of translational medicine, The First People's Hospital of Foshan, Foshan, People's Republic of China
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Heras-Molina A, Estellé J, Vázquez-Gómez M, López-García A, Pesantez-Pacheco JL, Astiz S, Garcia-Contreras C, Escudero R, Isabel B, Gonzalez-Bulnes A, Óvilo C. The impact of host genetics on porcine gut microbiota composition excluding maternal and postnatal environmental influences. PLoS One 2024; 19:e0315199. [PMID: 39652543 PMCID: PMC11627362 DOI: 10.1371/journal.pone.0315199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 11/21/2024] [Indexed: 12/12/2024] Open
Abstract
The gut microbiota of the pig is being increasingly studied due to its implications for host homeostasis and the importance of the pig as a meat source and biomedical model of human diseases. However, most studies comparing the microbiome between different breeds do not consider the influence of maternal environment during the colonization of the microbiota. The aim of the present study was to compare the gut microbiota during postnatal growth between two pig genotypes (purebred Iberian vs. crossbreds Iberian x Large White pigs), gestated in a single maternal environment (pure Iberian mothers) inseminated with heterospermic semen. Postnatally, piglets were maintained in the same environmental conditions, and their microbiota was studied at 60 and 210 days old. Results showed that age had the greatest influence on alpha and beta diversity, and genotype also affected beta diversity at both ages. There were differences in the microbiome profile between genotypes at the ASV and genus levels when jointly analyzing the total number of samples, which may help to explain phenotypical differences. When each time-point was analyzed individually, there were more differences at 210 days-old than 60 days-old. Fecal short-chain fatty acids (SCFA) were also affected by age, but not by genotype. These results may be a basis for further research on host genotype interactions with the gut microbiota.
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Affiliation(s)
- Ana Heras-Molina
- Faculty of Veterinary Medicine, UCM, Ciudad Universitaria s/n, Madrid, Spain
- CSIC-INIA, Madrid, Spain
| | - Jordi Estellé
- Université Paris-Saclay, INRAE, AgroParisTech, GABI, Jouy-en-Josas, France
| | - Marta Vázquez-Gómez
- Sorbonne université, INSERM, Nutrition et obésités: approaches systémiques, Nutriomics, Paris, France
| | | | - José-Luis Pesantez-Pacheco
- CSIC-INIA, Madrid, Spain
- School of Veterinary Medicine and Zootechnics, Faculty of Agricultural Sciences, University of Cuenca, Cuenca, Ecuador
| | | | | | - Rosa Escudero
- Faculty of Veterinary Medicine, UCM, Ciudad Universitaria s/n, Madrid, Spain
| | - Beatriz Isabel
- Faculty of Veterinary Medicine, UCM, Ciudad Universitaria s/n, Madrid, Spain
| | - Antonio Gonzalez-Bulnes
- Faculty of Veterinary Medicine, Universidad Cardenal Herrera-CEU, CEU Universities, Valencia, Spain
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Azcarate-Peril MA. Has the two decades of research on the gut microbiome resulted in making healthier choices? GUT MICROBIOME (CAMBRIDGE, ENGLAND) 2024; 5:e10. [PMID: 39703542 PMCID: PMC11658936 DOI: 10.1017/gmb.2024.13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 07/30/2024] [Accepted: 09/03/2024] [Indexed: 12/21/2024]
Abstract
The gut microbiome is widely recognized for its significant contribution to maintaining human health across all life stages, from infancy to adulthood and beyond. This perspective article focuses on the impacts of well-supported microbiome research on global caesarean delivery rates, breastfeeding practices, and antimicrobial use. The article also explores the impact of dietary choices, particularly those involving ultra-processed foods, on the gut microbiota and their potential contribution to conditions like obesity, metabolic syndrome, and inflammatory diseases. This perspective aims to emphasize the need for updated guidelines and policy interventions to address the increasing global trends of caesarean deliveries, reduced breastfeeding, overuse of antibiotics, and consumption of highly processed foods to counter their adverse effects on gut health.
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Affiliation(s)
- M. Andrea Azcarate-Peril
- Center for Gastrointestinal Biology and Disease (CGIBD), Department of Medicine, Division of Gastroenterology and Hepatology, School of Medicine, UNC Microbiome Core, University of North Carolina, Chapel Hill, NC, USA
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Aparicio A, Sun Z, Gold DR, Lasky‐Su JA, Litonjua AA, Weiss ST, Lee‐Sarwar K, Liu Y. Genotype-microbiome-metabolome associations in early childhood and their link to BMI. MLIFE 2024; 3:573-577. [PMID: 39744095 PMCID: PMC11685832 DOI: 10.1002/mlf2.12153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 09/03/2024] [Accepted: 09/28/2024] [Indexed: 01/19/2025]
Abstract
Through the analysis of data from children aged 6 months to 8 years enrolled in the Vitamin D Antenatal Asthma Reduction Trial (VDAART), significant simultaneous associations were identified between variants in the fragile histidine triad (FHIT) gene, children's body mass index, microbiome features related to obesity, and key lipids and amino acids. These patterns represent evidence of the genotype influence in shaping the host microbiome in developing stages and new potential biomarkers for childhood obesity, insulin resistance, and type 2 diabetes.
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Affiliation(s)
- Andrea Aparicio
- Department of Medicine, Brigham and Women's Hospital and Harvard Medical SchoolChanning Division of Network MedicineBostonMassachusettsUSA
| | - Zheng Sun
- Department of Medicine, Brigham and Women's Hospital and Harvard Medical SchoolChanning Division of Network MedicineBostonMassachusettsUSA
| | - Diane R. Gold
- Department of Medicine, Brigham and Women's Hospital and Harvard Medical SchoolChanning Division of Network MedicineBostonMassachusettsUSA
- Department of Environmental HealthHarvard T.H. Chan School of Public HealthBostonMassachusettsUSA
| | - Jessica A. Lasky‐Su
- Department of Medicine, Brigham and Women's Hospital and Harvard Medical SchoolChanning Division of Network MedicineBostonMassachusettsUSA
| | - Augusto A. Litonjua
- Division of Pediatric Pulmonary Medicine, Golisano Children's Hospital at StrongUniversity of Rochester Medical CenterRochesterNew YorkUSA
| | - Scott T. Weiss
- Department of Medicine, Brigham and Women's Hospital and Harvard Medical SchoolChanning Division of Network MedicineBostonMassachusettsUSA
| | - Kathleen Lee‐Sarwar
- Department of Medicine, Brigham and Women's Hospital and Harvard Medical SchoolChanning Division of Network MedicineBostonMassachusettsUSA
- Division of Allergy and Clinical ImmunologyBrigham and Women's Hospital and Harvard Medical SchoolBostonMassachusettsUSA
- Vertex PharmaceuticalsBostonMassachusettsUSA
| | - Yang‐Yu Liu
- Department of Medicine, Brigham and Women's Hospital and Harvard Medical SchoolChanning Division of Network MedicineBostonMassachusettsUSA
- Center for Artificial Intelligence and Modeling, The Carl R. Woese Institute for Genomic BiologyUniversity of Illinois at Urbana‐ChampaignChampaignIllinoisUSA
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48
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Chandra M. Developmental Origins of Non-Communicable Chronic Diseases: Role of Fetal Undernutrition and Gut Dysbiosis in Infancy. CHILDREN (BASEL, SWITZERLAND) 2024; 11:1387. [PMID: 39594962 PMCID: PMC11592819 DOI: 10.3390/children11111387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 10/31/2024] [Accepted: 11/06/2024] [Indexed: 11/28/2024]
Abstract
There is an increasing prevalence of non-communicable chronic diseases (NCCDs) like obesity, metabolic syndrome, type 2 diabetes mellitus (T2DM), hypertension, allergic asthma, and neuro-developmental/psychiatric problems in many parts of the world. A suboptimal lifestyle as an adult is often blamed for the occurrence of NCCDs. This review discusses the developmental origin of health and disease theory and how suboptimal nutrition in intrauterine life and the establishment of a suboptimal gut microbiome during infancy can influence the predisposition to NCCDs.
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Affiliation(s)
- Manju Chandra
- Division of Pediatric Nephrology, Department of Pediatrics, New York University Grossman Long Island School of Medicine, Mineola, NY 11501, USA
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49
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Colberg O, Hermes GDA, Licht TR, Wichmann A, Baker A, Laursen MF, Wellejus A. Development of an infant colon simulating in vitro model, I-TIM-2, to study the effects of modulation strategies on the infant gut microbiome composition and function. Microbiol Spectr 2024; 12:e0072424. [PMID: 39377603 PMCID: PMC11537066 DOI: 10.1128/spectrum.00724-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 09/15/2024] [Indexed: 10/09/2024] Open
Abstract
The early life stages are critical for the development of the gut microbiome. Variables such as antibiotics exposure, birth-mode via Cesarean section, and formula feeding are associated with disruptions in microbiome development and are related to adverse health effects later in life. Studying the effects of microbiome-modulating strategies in infants is challenged by appropriate ethical constraints. Therefore, we developed I-TIM-2, an infant in vitro colonic model based on the validated, computer-controlled, dynamic model of the colon, TIM-2. The system, consisting of four separate compartments, was inoculated with feces from four healthy, primarily breastfed infants, displaying distinctive microbiome profiles. For each infant's fecal sample, a 96-h experiment was performed, with two compartments receiving an infant diet adapted medium and two compartments additionally receiving five human milk oligosaccharides (HMOs) in physiological concentrations and proportions. Bacterial composition was determined by shotgun metagenomics and qPCR. Concentrations of short-chain fatty acids (SCFAs) and HMOs were determined by LC-MS. Microbial diversity and high amounts of inoculum-derived species were preserved in the model throughout each experiment. Microbiome composition and SCFA concentrations were consistent with published data from infants. HMOs strongly modulated the microbiome composition by stimulating relative proportions of Bifidobacterium. This affected the metabolic output and resulted in an increased production of acetic and formic acid, characteristic of bifidobacterial HMO metabolism. In conclusion, these data demonstrate the development of a valid model to study the dynamics and modulations of the infant gut microbiome and metabolome.IMPORTANCEThe infant gut microbiome is intricately linked to the health of its host. This is partly mediated through the bacterial production of metabolites that interact with the host cells. Human milk shapes the establishment of the infant gut microbiome as it contains human milk sugars that select for primarily bifidobacteria. The establishment can be disrupted by modern interventions such as formula feeding. This can alter the microbiome composition and metabolite production profile, which can affect the host. In this article, we set up an infant in vitro colonic model to study microbiome interactions and functions. In this model, we investigated the effects of human milk sugars and their promotion of bifidobacteria at the expense of other bacteria. The model is an ideal system to assess the effects of various modulating strategies on the infant gut microbiome and its interactions with its host.
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Affiliation(s)
- Olivia Colberg
- Novonesis, Human Health Research, Hørsholm, Denmark
- Technical University of Denmark, National Food Institute, Lyngby, Denmark
| | | | - Tine Rask Licht
- Technical University of Denmark, National Food Institute, Lyngby, Denmark
| | | | - Adam Baker
- Novonesis, Human Health Research, Hørsholm, Denmark
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50
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Wu F, Liu Y, Zhang M, Yuan X, Ji T, Jin Y, Li Y, Wang R, Hao Y, Fang B. Effects of 1-oleate-2-palmitate-3-linoleate glycerol supplementation on the small intestinal development and gut microbial composition of neonatal mice. Food Res Int 2024; 195:114993. [PMID: 39277254 DOI: 10.1016/j.foodres.2024.114993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 08/21/2024] [Accepted: 08/22/2024] [Indexed: 09/17/2024]
Abstract
Recent studies have shown that 1-oleo-2-palmito-3-linoleyl glycerol (OPL) is the most abundant triacylglycerol in human breast milk in China. Epidemiologic studies have shown that sn-2 palmitate improves the absorption of fatty acids and calcium in infants. However, there have been few studies of the specific mechanism by which OPL affects intestinal function. In the present study, we have characterized the effects of various levels of OPL supplementation on the development of the intestinal epithelium and the intestinal microbiota of neonatal mice. OPL supplementation increased the body masses and intestinal lengths of weaned mice and promoted defecation. These positive effects were related to the effect of OPL to promote the development of intestinal villi and crypts. OPL increased the expression of the intestinal stem cell markers Olfm4 and Sox9 in the jejunum and ileum, which promoted their differentiation into goblet cells and Paneth cells. It also promoted the integrity of the epithelial barrier by increasing the secretion of mucin 2 and lysozyme 1 and the expression of the tight junction proteins occludin, ZO1, claudin 2, and claudin 3. More importantly, we found that low dose-OPL promotes the transformation of the intestinal microbiota of neonatal mice to the mature state in 3-month-old mice, increases the proportion of Firmicutes, and reduces the proportion of Bacteroidota. The proportions of anaerobic genera of bacteria, such as Lachnospiraceae_NK4A136_group, Lachnoclostridium, Ligilactobacillus, and Bifidobacterium were higher, as were the key producers of short-chain fatty acids, such as Bacteroides and Blautia. OPL also increased the butyric acid content of the feces, which significantly correlated with the abundance of Lactobacillus. High-dose OPL tended to be more effective at promoting defecation and the development of the villi and crypts, but these effects did not significantly differ from those achieved using the lower dose. A low dose of OPL was more effective at increasing the butyric acid content and causing the maturation of microbes. In summary, the OPL supplementation of newborn mice promotes the establishment of the intestinal epithelial layer structure and barrier function, and also promotes the transformation of the intestinal microbiota to a mature state. This study lays a theoretical foundation for the inclusion of OPL in infant formula and provides a scientific basis for the development of intestinal health products.
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Affiliation(s)
- Fang Wu
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China
| | - Yaqiong Liu
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China
| | - Ming Zhang
- School of Food Science and Chemical Engineering, Beijing Technology and Business University, Beijing, China
| | - Xinlei Yuan
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China; College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin, China
| | - Tengteng Ji
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China
| | - Yutong Jin
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China
| | - Yixuan Li
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China
| | - Ran Wang
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China
| | - Yanling Hao
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China
| | - Bing Fang
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China.
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