Codevelopment of gut microbial metabolism and visual neural circuitry over human infancy

ABSTRACT Infancy is a time of elevated neuroplasticity supporting rapid brain and sensory development. The gut microbiome, also undergoing extensive developmental changes in early life, may influence brain development through the metabolism of neuroactive compounds. Here, we leverage longitudinal da...

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Main Authors: Kevin S. Bonham, Emma T. Margolis, Guilherme Fahur Bottino, Ana C. Sobrino, Fadheela Patel, Shelley McCann, Michal R. Zieff, Marlie Miles, Donna Herr, Lauren Davel, Cara Bosco, Curtis Huttenhower, Nicolò Pini, Daniel C. Alexander, Derek K. Jones, Steve C. R. Williams, Dima Amso, Melissa Gladstone, William P. Fifer, Kirsten A. Donald, Laurel J. Gabard-Durnam, Vanja Klepac-Ceraj
Format: Article
Language:English
Published: American Society for Microbiology 2025-08-01
Series:mBio
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Online Access:https://journals.asm.org/doi/10.1128/mbio.00835-25
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author Kevin S. Bonham
Emma T. Margolis
Guilherme Fahur Bottino
Ana C. Sobrino
Fadheela Patel
Shelley McCann
Michal R. Zieff
Marlie Miles
Donna Herr
Lauren Davel
Cara Bosco
Curtis Huttenhower
Nicolò Pini
Daniel C. Alexander
Derek K. Jones
Steve C. R. Williams
Dima Amso
Melissa Gladstone
William P. Fifer
Kirsten A. Donald
Laurel J. Gabard-Durnam
Vanja Klepac-Ceraj
author_facet Kevin S. Bonham
Emma T. Margolis
Guilherme Fahur Bottino
Ana C. Sobrino
Fadheela Patel
Shelley McCann
Michal R. Zieff
Marlie Miles
Donna Herr
Lauren Davel
Cara Bosco
Curtis Huttenhower
Nicolò Pini
Daniel C. Alexander
Derek K. Jones
Steve C. R. Williams
Dima Amso
Melissa Gladstone
William P. Fifer
Kirsten A. Donald
Laurel J. Gabard-Durnam
Vanja Klepac-Ceraj
author_sort Kevin S. Bonham
collection DOAJ
description ABSTRACT Infancy is a time of elevated neuroplasticity supporting rapid brain and sensory development. The gut microbiome, also undergoing extensive developmental changes in early life, may influence brain development through the metabolism of neuroactive compounds. Here, we leverage longitudinal data from 194 South African infants across the first 18 months of life to show that microbial genes encoding enzymes that metabolize molecules playing a key role in modulating early neuroplasticity are associated with visual cortical neurodevelopment, measured by the Visual-Evoked Potential (VEP). Neuroactive compounds included neurotransmitters GABA and glutamate, the amino acid tryptophan, and short-chain fatty acids involved in myelination, including acetate and butyrate. Microbial gene sets around 4 months of age were strongly associated with the VEP from around 9–14 months of age and showed more associations than concurrently measured gene sets, suggesting that microbial metabolism in early life may affect subsequent neural plasticity and development.IMPORTANCEOver the past decade, extensive research has revealed strong links between the gut microbiome and the brain, at least in adults or those with neuropsychiatric disorders. This study explores how these associations emerge in early development using a longitudinal sample of 194 infants with repeated microbiome metabolism and electroencephalography (EEG) measures during the critical early period of visual cortex neuroplasticity. We examined microbial genes encoding enzymes for neuroactive compounds (e.g., GABA, glutamate, tryptophan, and short-chain fatty acids) and their association with the visual-evoked potential (VEP). Genes from 4-month stool samples strongly correlated with VEP features between 9 and 14 months, suggesting that early microbial metabolism influences later visual neurodevelopment. These prospective associations were more numerous than the concurrent ones. Our findings suggest that early gut microbiome metabolic potential plays a crucial role in shaping neural plasticity and visual neurodevelopment.
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spelling doaj-art-d48017e3f23d4880b6ca7ea8af73fa982025-08-20T03:02:56ZengAmerican Society for MicrobiologymBio2150-75112025-08-0116810.1128/mbio.00835-25Codevelopment of gut microbial metabolism and visual neural circuitry over human infancyKevin S. Bonham0Emma T. Margolis1Guilherme Fahur Bottino2Ana C. Sobrino3Fadheela Patel4Shelley McCann5Michal R. Zieff6Marlie Miles7Donna Herr8Lauren Davel9Cara Bosco10Curtis Huttenhower11Nicolò Pini12Daniel C. Alexander13Derek K. Jones14Steve C. R. Williams15Dima Amso16Melissa Gladstone17William P. Fifer18Kirsten A. Donald19Laurel J. Gabard-Durnam20Vanja Klepac-Ceraj21Department of Biological Sciences, Wellesley College, Wellesley, Massachusetts, USADepartment of Psychology, Northeastern University, Boston, Massachusetts, USADepartment of Biological Sciences, Wellesley College, Wellesley, Massachusetts, USADepartment of Psychology, Northeastern University, Boston, Massachusetts, USADivision of Medical Microbiology, University of Cape Town, Cape Town, Western Cape, South AfricaDepartment of Biological Sciences, Wellesley College, Wellesley, Massachusetts, USADepartment of Paediatrics and Child Health, University of Cape Town, Cape Town, Western Cape, South AfricaDepartment of Paediatrics and Child Health, University of Cape Town, Cape Town, Western Cape, South AfricaDepartment of Paediatrics and Child Health, University of Cape Town, Cape Town, Western Cape, South AfricaDepartment of Paediatrics and Child Health, University of Cape Town, Cape Town, Western Cape, South AfricaDepartment of Psychology, Northeastern University, Boston, Massachusetts, USADepartment of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USADepartment of Psychiatry, Columbia University, Irving Medical Center, , New York, New York, USADepartment of Computer Science, Centre for Medical Image Computing, University College London, London, England, United KingdomCardiff University Brain Research Imaging Centre, Cardiff University, Cardiff, United KingdomDepartment of Neuroimaging, King's College London, London, England, United KingdomDepartment of Psychology, Columbia University, New York, New York, USADepartment of Women and Children’s Health, Institute of Life Course and Medical Science, Alder Hey Children’s NHS Foundation Trust University of Liverpool, Liverpool, England, United KingdomDepartment of Psychiatry, Columbia University, Irving Medical Center, , New York, New York, USADepartment of Paediatrics and Child Health, University of Cape Town, Cape Town, Western Cape, South AfricaDepartment of Psychology, Northeastern University, Boston, Massachusetts, USADepartment of Biological Sciences, Wellesley College, Wellesley, Massachusetts, USAABSTRACT Infancy is a time of elevated neuroplasticity supporting rapid brain and sensory development. The gut microbiome, also undergoing extensive developmental changes in early life, may influence brain development through the metabolism of neuroactive compounds. Here, we leverage longitudinal data from 194 South African infants across the first 18 months of life to show that microbial genes encoding enzymes that metabolize molecules playing a key role in modulating early neuroplasticity are associated with visual cortical neurodevelopment, measured by the Visual-Evoked Potential (VEP). Neuroactive compounds included neurotransmitters GABA and glutamate, the amino acid tryptophan, and short-chain fatty acids involved in myelination, including acetate and butyrate. Microbial gene sets around 4 months of age were strongly associated with the VEP from around 9–14 months of age and showed more associations than concurrently measured gene sets, suggesting that microbial metabolism in early life may affect subsequent neural plasticity and development.IMPORTANCEOver the past decade, extensive research has revealed strong links between the gut microbiome and the brain, at least in adults or those with neuropsychiatric disorders. This study explores how these associations emerge in early development using a longitudinal sample of 194 infants with repeated microbiome metabolism and electroencephalography (EEG) measures during the critical early period of visual cortex neuroplasticity. We examined microbial genes encoding enzymes for neuroactive compounds (e.g., GABA, glutamate, tryptophan, and short-chain fatty acids) and their association with the visual-evoked potential (VEP). Genes from 4-month stool samples strongly correlated with VEP features between 9 and 14 months, suggesting that early microbial metabolism influences later visual neurodevelopment. These prospective associations were more numerous than the concurrent ones. Our findings suggest that early gut microbiome metabolic potential plays a crucial role in shaping neural plasticity and visual neurodevelopment.https://journals.asm.org/doi/10.1128/mbio.00835-25visual cortex developmentmetagenomeinfant gut microbiomevisual-evoked potentialneuroplasticity
spellingShingle Kevin S. Bonham
Emma T. Margolis
Guilherme Fahur Bottino
Ana C. Sobrino
Fadheela Patel
Shelley McCann
Michal R. Zieff
Marlie Miles
Donna Herr
Lauren Davel
Cara Bosco
Curtis Huttenhower
Nicolò Pini
Daniel C. Alexander
Derek K. Jones
Steve C. R. Williams
Dima Amso
Melissa Gladstone
William P. Fifer
Kirsten A. Donald
Laurel J. Gabard-Durnam
Vanja Klepac-Ceraj
Codevelopment of gut microbial metabolism and visual neural circuitry over human infancy
mBio
visual cortex development
metagenome
infant gut microbiome
visual-evoked potential
neuroplasticity
title Codevelopment of gut microbial metabolism and visual neural circuitry over human infancy
title_full Codevelopment of gut microbial metabolism and visual neural circuitry over human infancy
title_fullStr Codevelopment of gut microbial metabolism and visual neural circuitry over human infancy
title_full_unstemmed Codevelopment of gut microbial metabolism and visual neural circuitry over human infancy
title_short Codevelopment of gut microbial metabolism and visual neural circuitry over human infancy
title_sort codevelopment of gut microbial metabolism and visual neural circuitry over human infancy
topic visual cortex development
metagenome
infant gut microbiome
visual-evoked potential
neuroplasticity
url https://journals.asm.org/doi/10.1128/mbio.00835-25
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