Codevelopment of gut microbial metabolism and visual neural circuitry over human infancy.
| Title: | Codevelopment of gut microbial metabolism and visual neural circuitry over human infancy. |
|---|---|
| Authors: | Bonham KS; Department of Biological Sciences, Wellesley College, Wellesley, Massachusetts, USA.; Department of Medicine, Tufts Medical Center, Boston, Massachusetts, USA.; Margolis ET; Department of Psychology, Northeastern University, Boston, Massachusetts, USA.; Fahur Bottino G; Department of Biological Sciences, Wellesley College, Wellesley, Massachusetts, USA.; Sobrino AC; Department of Psychology, Northeastern University, Boston, Massachusetts, USA.; Patel F; Division of Medical Microbiology, University of Cape Town, Cape Town, Western Cape, South Africa.; McCann S; Department of Biological Sciences, Wellesley College, Wellesley, Massachusetts, USA.; Zieff MR; Department of Paediatrics and Child Health, University of Cape Town, Cape Town, Western Cape, South Africa.; Miles M; Department of Paediatrics and Child Health, University of Cape Town, Cape Town, Western Cape, South Africa.; Herr D; Department of Paediatrics and Child Health, University of Cape Town, Cape Town, Western Cape, South Africa.; Davel L; Department of Paediatrics and Child Health, University of Cape Town, Cape Town, Western Cape, South Africa.; Bosco C; Department of Psychology, Northeastern University, Boston, Massachusetts, USA.; Huttenhower C; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.; Pini N; Department of Psychiatry, Columbia University, Irving Medical Center, , New York, New York, USA.; Division of Developmental Neuroscience, New York State Psychiatric Institute, New York, New York, USA.; Alexander DC; Department of Computer Science, Centre for Medical Image Computing, University College London, London, England, United Kingdom.; Jones DK; Cardiff University Brain Research Imaging Centre, Cardiff University, Cardiff, United Kingdom.; Williams SCR; Department of Neuroimaging, King's College London, London, England, United Kingdom.; Amso D; Department of Psychology, Columbia University, New York, New York, USA.; Gladstone M; Department 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 Kingdom.; Fifer WP; Department of Psychiatry, Columbia University, Irving Medical Center, , New York, New York, USA.; Division of Developmental Neuroscience, New York State Psychiatric Institute, New York, New York, USA.; Donald KA; Department of Paediatrics and Child Health, University of Cape Town, Cape Town, Western Cape, South Africa.; Neuroscience Institute, University of Cape Town, Cape Town, Western Cape, South Africa.; Gabard-Durnam LJ; Department of Psychology, Northeastern University, Boston, Massachusetts, USA.; Klepac-Ceraj V; Department of Biological Sciences, Wellesley College, Wellesley, Massachusetts, USA. |
| Corporate Authors: | Khula South African Data Collection Team; Department of Paediatrics and Child Health, University of Cape Town, Cape Town, Western Cape, South Africa. |
| Source: | MBio [mBio] 2025 Aug 13; Vol. 16 (8), pp. e0083525. Date of Electronic Publication: 2025 Jun 30. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, D.C. : American Society for Microbiology |
| MeSH Terms: | Gastrointestinal Microbiome*/physiology ; Visual Cortex*/growth & development ; Visual Cortex*/physiology; Brain/growth & development ; Humans ; Infant ; Evoked Potentials, Visual ; Male ; Female ; Neuronal Plasticity ; Longitudinal Studies ; Electroencephalography |
| 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. |
| Competing Interests: | The authors declare no conflict of interest. |
| References: | Nat Neurosci. 2018 Feb;21(2):218-227. (PMID: 29358666); Cell. 2024 Apr 11;187(8):1853-1873.e15. (PMID: 38574728); Nat Rev Gastroenterol Hepatol. 2019 Aug;16(8):461-478. (PMID: 31123355); Neuropharmacology. 2016 Dec;111:14-33. (PMID: 27561972); Nat Rev Gastroenterol Hepatol. 2009 May;6(5):306-14. (PMID: 19404271); Arch Gerontol Geriatr. 2021 Sep-Oct;96:104464. (PMID: 34174489); JAMA Netw Open. 2022 Feb 1;5(2):e2143941. (PMID: 35133436); Proc Natl Acad Sci U S A. 2023 Jan 24;120(4):e2216941120. (PMID: 36669102); Doc Ophthalmol. 2024 Apr;148(2):75-85. (PMID: 38488946); Sci Adv. 2023 Dec 22;9(51):eadi0497. (PMID: 38134274); Genome Med. 2016 Feb 17;8(1):17. (PMID: 26884067); Cell Host Microbe. 2018 Jun 13;23(6):716-724. (PMID: 29902437); Nat Commun. 2022 Sep 23;13(1):5370. (PMID: 36151114); Front Hum Neurosci. 2009 Nov 16;3:48. (PMID: 19949455); Sci Rep. 2023 Feb 16;13(1):2819. (PMID: 36797287); Int J Dev Neurosci. 1988;6(1):59-75. (PMID: 3213570); Br J Nutr. 2017 Mar;117(6):775-783. (PMID: 28393748); Bioinformatics. 2007 May 15;23(10):1282-8. (PMID: 17379688); Neuroimage. 2014 Jan 1;84:742-52. (PMID: 24095814); Eur J Neurosci. 2011 Jan;33(1):49-57. (PMID: 21156002); Elife. 2021 May 04;10:. (PMID: 33944776); Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5221-6. (PMID: 15784740); Neuroimage. 2016 Jan 15;125:988-995. (PMID: 26577887); Science. 1998 Nov 20;282(5393):1504-8. (PMID: 9822384); Cereb Cortex. 2007 Jan;17(1):100-7. (PMID: 16467566); Biol Psychiatry. 2018 Jan 15;83(2):148-159. (PMID: 28793975); Nat Commun. 2023 Feb 2;14(1):571. (PMID: 36732517); Cell Host Microbe. 2015 May 13;17(5):690-703. (PMID: 25974306); J Neurosci. 2008 Feb 20;28(8):1943-8. (PMID: 18287510); Dev Psychobiol. 2019 Jul;61(5):772-782. (PMID: 30640409); Neuroimage. 2006 May 15;31(1):86-108. (PMID: 16480895); Doc Ophthalmol. 2003 Nov;107(3):225-33. (PMID: 14711154); Nat Rev Microbiol. 2012 Nov;10(11):735-42. (PMID: 23000955); Trends Neurosci. 2018 Jul;41(7):413-414. (PMID: 29933773); Nat Commun. 2017 Jan 10;8:13995. (PMID: 28072399); Dev Neurobiol. 2015 Oct;75(10):1080-90. (PMID: 25649764); Cell Metab. 2021 Nov 2;33(11):2260-2276.e7. (PMID: 34731656); Cell Rep. 2022 Jan 11;38(2):110212. (PMID: 35021093); Nat Commun. 2022 Jun 9;13(1):3202. (PMID: 35680879); Brain Res Bull. 2002 Jan 15;57(2):231-6. (PMID: 11849830); J Neurosci. 2003 Jul 2;23(13):5816-26. (PMID: 12843286); Gut Microbes. 2022 Jan-Dec;14(1):2102878. (PMID: 35903003); Neuroreport. 2000 Feb 7;11(2):249-53. (PMID: 10674464); mSystems. 2020 Jan 21;5(1):. (PMID: 31964767); Dev Cogn Neurosci. 2022 Oct;57:101140. (PMID: 35926469); Front Physiol. 2018 Oct 31;9:1534. (PMID: 30429801); Psychopharmacology (Berl). 2019 May;236(5):1641-1651. (PMID: 30604186); J Neuroinflammation. 2019 Aug 9;16(1):165. (PMID: 31399117); Eur J Neurosci. 1995 Jun 1;7(6):1146-53. (PMID: 7582087); ILAR J. 2015;56(2):169-78. (PMID: 26323627); Int J Mol Sci. 2019 Mar 25;20(6):. (PMID: 30934533); Prog Brain Res. 2013;207:3-34. (PMID: 24309249); Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50. (PMID: 16199517); Front Nutr. 2022 Feb 10;9:823893. (PMID: 35242798); Dev Cogn Neurosci. 2024 Jun;67:101396. (PMID: 38820695); Nat Commun. 2025 Jan 14;16(1):660. (PMID: 39809768); Neuron. 2021 Aug 18;109(16):2616-2626.e6. (PMID: 34228960); Sci Rep. 2018 Apr 3;8(1):5443. (PMID: 29615691); Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4578-85. (PMID: 20668239); Science. 1988 May 6;240(4853):740-9. (PMID: 3283936); Nat Microbiol. 2019 Apr;4(4):623-632. (PMID: 30718848); Invest Ophthalmol Vis Sci. 2011 Aug 29;52(9):6911-8. (PMID: 21791585); Vision Res. 1999 Nov;39(22):3673-80. (PMID: 10746137); Front Syst Neurosci. 2013 Apr 23;7:9. (PMID: 23630473); Sci Transl Med. 2016 Jun 15;8(343):343ra81. (PMID: 27306663); Cell. 2015 Apr 9;161(2):264-76. (PMID: 25860609); Nat Methods. 2018 Nov;15(11):962-968. (PMID: 30377376); Spat Vis. 2001;15(1):99-111. (PMID: 11893127); J Cereb Blood Flow Metab. 2001 Oct;21(10):1232-9. (PMID: 11598501); Brain Res Dev Brain Res. 2002 Dec 15;139(2):121-9. (PMID: 12480126); Neuropsychopharmacology. 2013 May;38(6):1105-12. (PMID: 23361120); Dev Med Child Neurol. 2007 Jan;49(1):28-33. (PMID: 17209973); Nat Microbiol. 2018 Apr;3(4):456-460. (PMID: 29531366); Nat Rev Gastroenterol Hepatol. 2024 Apr;21(4):222-247. (PMID: 38355758); Nucleic Acids Res. 2004 Jan 1;32(Database issue):D277-80. (PMID: 14681412); Dev Psychol. 2024 Sep;60(9):1673-1698. (PMID: 38512192); Nat Med. 2018 Apr 10;24(4):392-400. (PMID: 29634682); Nature. 2000 Mar 9;404(6774):183-6. (PMID: 10724170); Gut Microbes. 2020;11(2):135-157. (PMID: 31368397); Dev Psychopathol. 2020 Feb;32(1):309-328. (PMID: 30919798); Proc Natl Acad Sci U S A. 2019 Dec 26;116(52):27074-27083. (PMID: 31843913); Oxid Med Cell Longev. 2013;2013:104024. (PMID: 24089628) |
| Grant Information: | United Kingdom WT_ Wellcome Trust |
| Contributed Indexing: | Investigator: L Bradford; S Williams; L Davel; T Mhlakwaphalwa; B Methola; K Nkubungu; C Knipe; Z Madi; N Mlandu; Keywords: infant gut microbiome; metagenome; neuroplasticity; visual cortex development; visual-evoked potential |
| Molecular Sequence: | BioProject PRJNA1128723. |
| Entry Date(s): | Date Created: 20250630 Date Completed: 20250826 Latest Revision: 20260707 |
| Update Code: | 20260708 |
| PubMed Central ID: | PMC12345167 |
| DOI: | 10.1128/mbio.00835-25 |
| PMID: | 40586263 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't