Effects of children's microbiota on adipose and intestinal development in sex-matched mice persist into adulthood following a single fecal microbiota transplantation

Background: The global prevalence of obesity and type 2 diabetes, particularly among children, is rising, yet the long-term impacts of early-life fecal microbiota transplantation (FMT) on metabolic health remain poorly understood. Objectives: To investigate how early-life FMT from children to young,...

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Main Authors: Federica La Rosa, Maria Angela Guzzardi, Mercedes Pardo-Tendero, Monica Barone, Chiara Ruocco, Gabriele Conti, Daniele Panetta, Daria Riabitch, Silvia Bernardi, Assuero Giorgetti, Daniela Campani, Daniel Monleon, Enzo Nisoli, Patrizia Brigidi, Patricia Iozzo
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Language:English
Published: Elsevier 2025-07-01
Series:Molecular Metabolism
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Online Access:http://www.sciencedirect.com/science/article/pii/S221287782500064X
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author Federica La Rosa
Maria Angela Guzzardi
Mercedes Pardo-Tendero
Monica Barone
Chiara Ruocco
Gabriele Conti
Daniele Panetta
Daria Riabitch
Silvia Bernardi
Assuero Giorgetti
Daniela Campani
Daniel Monleon
Enzo Nisoli
Patrizia Brigidi
Patricia Iozzo
author_facet Federica La Rosa
Maria Angela Guzzardi
Mercedes Pardo-Tendero
Monica Barone
Chiara Ruocco
Gabriele Conti
Daniele Panetta
Daria Riabitch
Silvia Bernardi
Assuero Giorgetti
Daniela Campani
Daniel Monleon
Enzo Nisoli
Patrizia Brigidi
Patricia Iozzo
author_sort Federica La Rosa
collection DOAJ
description Background: The global prevalence of obesity and type 2 diabetes, particularly among children, is rising, yet the long-term impacts of early-life fecal microbiota transplantation (FMT) on metabolic health remain poorly understood. Objectives: To investigate how early-life FMT from children to young, sex-matched mice influences metabolic outcomes and adipose tissue function in later, adult life. Methods: Germ-free mice were colonized with fecal microbiota from either lean children or children with obesity. The impacts on brown adipose tissue (BAT), white adipose tissue (WAT), glucose metabolism, and gut health were analyzed in male and female mice. Microbial communities and metabolite profiles were characterized using sequencing and metabolomics. Results: Male mice receiving FMT from obese donors exhibited marked BAT whitening and impaired amino acid and glucose metabolism. In contrast, female recipients developed hyperglycemia, accompanied by gut barrier dysfunction and WAT impairment. Distinct microbial and metabolite profiles were associated with these phenotypes: Collinsella and trimethylamine in females; and Paraprevotella, Collinsella, Lachnospiraceae NK4A136, Bacteroides, Coprobacillus, and multiple metabolites in males. These phenotypic effects persisted despite changes in host environment and diet. Conclusions: Early-life FMT induced long-lasting effects on the metabolic landscape, profoundly affecting adipose tissue function and systemic glucose homeostasis in adulthood. Donor dietary habits correlated with the fecal microbial profiles observed in recipient mice. These findings highlight the critical need for identifying and leveraging beneficial exposures during early development to combat obesity and diabetes.
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spelling doaj-art-54fa7a4e77e94d72bf1524d0ca3c83ef2025-08-20T02:30:47ZengElsevierMolecular Metabolism2212-87782025-07-019710215710.1016/j.molmet.2025.102157Effects of children's microbiota on adipose and intestinal development in sex-matched mice persist into adulthood following a single fecal microbiota transplantationFederica La Rosa0Maria Angela Guzzardi1Mercedes Pardo-Tendero2Monica Barone3Chiara Ruocco4Gabriele Conti5Daniele Panetta6Daria Riabitch7Silvia Bernardi8Assuero Giorgetti9Daniela Campani10Daniel Monleon11Enzo Nisoli12Patrizia Brigidi13Patricia Iozzo14Institute of Clinical Physiology, National Research Council, via Moruzzi 1, 56124 Pisa, ItalyInstitute of Clinical Physiology, National Research Council, via Moruzzi 1, 56124 Pisa, Italy; Corresponding author.Department of Pathology, University of Valencia, Health Research Institute INCLIVA/CIBERFES for Frailty and Healthy Aging, Blasco Ibañez, 15, 46010, Valencia, SpainHuman Microbiomics Unit, Department of Medical and Surgical Sciences, University of Bologna, via Massarenti 9, 40138 Bologna ItalyCenter of Study and Research on Obesity, Department of Medical Biotechnology and Translational Medicine, University of Milan, via Vanvitelli 32, 20129 Milan, ItalyHuman Microbiomics Unit, Department of Medical and Surgical Sciences, University of Bologna, via Massarenti 9, 40138 Bologna ItalyInstitute of Clinical Physiology, National Research Council, via Moruzzi 1, 56124 Pisa, ItalyInstitute of Clinical Physiology, National Research Council, via Moruzzi 1, 56124 Pisa, ItalyInstitute of Clinical Physiology, National Research Council, via Moruzzi 1, 56124 Pisa, ItalyFondazione Toscana Gabriele Monasterio, via Moruzzi 1, 56124 Pisa, ItalyDepartment of Surgical, Medical, Molecular Pathology and Critical Care Medicine, Division of Pathology, Pisa University Hospital, 56124 Pisa, ItalyDepartment of Pathology, University of Valencia, Health Research Institute INCLIVA/CIBERFES for Frailty and Healthy Aging, Blasco Ibañez, 15, 46010, Valencia, SpainCenter of Study and Research on Obesity, Department of Medical Biotechnology and Translational Medicine, University of Milan, via Vanvitelli 32, 20129 Milan, ItalyHuman Microbiomics Unit, Department of Medical and Surgical Sciences, University of Bologna, via Massarenti 9, 40138 Bologna ItalyInstitute of Clinical Physiology, National Research Council, via Moruzzi 1, 56124 Pisa, Italy; Corresponding author.Background: The global prevalence of obesity and type 2 diabetes, particularly among children, is rising, yet the long-term impacts of early-life fecal microbiota transplantation (FMT) on metabolic health remain poorly understood. Objectives: To investigate how early-life FMT from children to young, sex-matched mice influences metabolic outcomes and adipose tissue function in later, adult life. Methods: Germ-free mice were colonized with fecal microbiota from either lean children or children with obesity. The impacts on brown adipose tissue (BAT), white adipose tissue (WAT), glucose metabolism, and gut health were analyzed in male and female mice. Microbial communities and metabolite profiles were characterized using sequencing and metabolomics. Results: Male mice receiving FMT from obese donors exhibited marked BAT whitening and impaired amino acid and glucose metabolism. In contrast, female recipients developed hyperglycemia, accompanied by gut barrier dysfunction and WAT impairment. Distinct microbial and metabolite profiles were associated with these phenotypes: Collinsella and trimethylamine in females; and Paraprevotella, Collinsella, Lachnospiraceae NK4A136, Bacteroides, Coprobacillus, and multiple metabolites in males. These phenotypic effects persisted despite changes in host environment and diet. Conclusions: Early-life FMT induced long-lasting effects on the metabolic landscape, profoundly affecting adipose tissue function and systemic glucose homeostasis in adulthood. Donor dietary habits correlated with the fecal microbial profiles observed in recipient mice. These findings highlight the critical need for identifying and leveraging beneficial exposures during early development to combat obesity and diabetes.http://www.sciencedirect.com/science/article/pii/S221287782500064XObesityType 2 diabetesPositron emission tomographyGut microbiotaMetabolomicsAdipose tissue
spellingShingle Federica La Rosa
Maria Angela Guzzardi
Mercedes Pardo-Tendero
Monica Barone
Chiara Ruocco
Gabriele Conti
Daniele Panetta
Daria Riabitch
Silvia Bernardi
Assuero Giorgetti
Daniela Campani
Daniel Monleon
Enzo Nisoli
Patrizia Brigidi
Patricia Iozzo
Effects of children's microbiota on adipose and intestinal development in sex-matched mice persist into adulthood following a single fecal microbiota transplantation
Molecular Metabolism
Obesity
Type 2 diabetes
Positron emission tomography
Gut microbiota
Metabolomics
Adipose tissue
title Effects of children's microbiota on adipose and intestinal development in sex-matched mice persist into adulthood following a single fecal microbiota transplantation
title_full Effects of children's microbiota on adipose and intestinal development in sex-matched mice persist into adulthood following a single fecal microbiota transplantation
title_fullStr Effects of children's microbiota on adipose and intestinal development in sex-matched mice persist into adulthood following a single fecal microbiota transplantation
title_full_unstemmed Effects of children's microbiota on adipose and intestinal development in sex-matched mice persist into adulthood following a single fecal microbiota transplantation
title_short Effects of children's microbiota on adipose and intestinal development in sex-matched mice persist into adulthood following a single fecal microbiota transplantation
title_sort effects of children s microbiota on adipose and intestinal development in sex matched mice persist into adulthood following a single fecal microbiota transplantation
topic Obesity
Type 2 diabetes
Positron emission tomography
Gut microbiota
Metabolomics
Adipose tissue
url http://www.sciencedirect.com/science/article/pii/S221287782500064X
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