The maternal microbiome modulates fetal neurodevelopment in mice
Open accessAbstract
'Dysbiosis' of the maternal gut microbiome, in response to challenges such as infection 1, altered diet 2 and stress 3 during pregnancy, has been increasingly associated with abnormalities in brain function and behaviour of the offspring 4. However, it is unclear whether the maternal gut microbiome influences neurodevelopment during critical prenatal periods and in the absence of environmental challenges. Here we investigate how depletion and selective reconstitution of the maternal gut microbiome influences fetal neurodevelopment in mice. Embryos from antibiotic-treated and germ-free dams exhibited reduced brain expression of genes related to axonogenesis, deficient thalamocortical axons and impaired outgrowth of thalamic axons in response to cell-extrinsic factors. Gnotobiotic colonization of microbiome-depleted dams with a limited consortium of bacteria prevented abnormalities in fetal brain gene expression and thalamocortical axonogenesis. Metabolomic profiling revealed that the maternal microbiome regulates numerous small molecules in the maternal serum and the brains of fetal offspring. Select microbiota-dependent metabolites promoted axon outgrowth from fetal thalamic explants. Moreover, maternal supplementation with these metabolites abrogated deficiencies in fetal thalamocortical axons. Manipulation of the maternal microbiome and microbial metabolites during pregnancy yielded adult offspring with altered tactile sensitivity in two aversive somatosensory behavioural tasks, but no overt differences in many other sensorimotor behaviours. Together, our findings show that the maternal gut microbiome promotes fetal thalamocortical axonogenesis, probably through signalling by microbially modulated metabolites to neurons in the developing brain.
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Neuronal development is supported and shaped by maternal microbiota.
“In this period, neuronal development takes place (73) and it is supported and shaped by maternal microbiota (74–79).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [79]
Very recent experimental data show that maternal microbial modulation of brain development may occur via the action of microbial metabolites.
“while very recent experimental data show that maternal microbial modulation of brain development may occur via the action of microbial metabolites (247).”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [247]
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- Authors
- Vuong, H. E., Pronovost, G. N., Williams, D. W., Coley, E. J. L., Siegler, E. L., Qiu, A., Kazantsev, M., Wilson, C. J., Rendon, T., & Hsiao, E. Y.
- Affiliations
- University of California, Los Angeles (US)
- National Institutes of Health (US)
- Corresponding author
- Vuong, Helen E.
- ORCID
- Venue
- Nature
- Published
- 2020-09-23
- Volume
- 586
- Issue
- 7828
- Pages
- 281-286
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC7554197
- OpenAlex
- W3088211674
- Cited by
- 564
- References
- 61
- Citations by year
- 2026: 88 · 2025: 118 · 2024: 92 · 2023: 90 · 2022: 97 · 2021: 67 · 2020: 10 · 2019: 1 · 2013: 1
- FWCI
- 21.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute of Mental Health (F31MH090749)
- National Institute of General Medical Sciences (K12GM106996)
- National Institute of Dental and Craniofacial Research (F30DE025172)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K99HD101680, F31HD101270)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Keywords
- maternal gut microbiota, fetal brain development, germ-free mice, microbial metabolites, axon growth, tactile sensitivity, brain gene expression
- MeSH terms
- Gastrointestinal Microbiome, Animals, Axons, Brain, Cerebral Cortex, Computer Simulation, Female, Fetus, Male, Mice, Inbred C57BL, Mothers, Pregnancy, Pregnancy Complications, Thalamus, Principal Component Analysis, Mice, Dysbiosis
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