The maternal microbiome modulates fetal neurodevelopment in mice

Helen E. Vuong (), Geoffrey N. Pronovost, Drake W. Williams, Elena J. L. Coley, Emily L. Siegler, Austin Qiu, Maria Kazantsev, Chantel J. Wilson, Tomiko Rendon and Elaine Y. Hsiao
Additional contact information
Helen E. Vuong: University of California Los Angeles
Geoffrey N. Pronovost: University of California Los Angeles
Drake W. Williams: Oral Immunity and Inflammation Section, NIDCR, NIH
Elena J. L. Coley: University of California Los Angeles
Emily L. Siegler: University of California Los Angeles
Austin Qiu: University of California Los Angeles
Maria Kazantsev: University of California Los Angeles
Chantel J. Wilson: University of California Los Angeles
Tomiko Rendon: University of California Los Angeles
Elaine Y. Hsiao: University of California Los Angeles

Nature, 2020, vol. 586, issue 7828, 281-286

Abstract: Abstract ‘Dysbiosis’ of the maternal gut microbiome, in response to challenges such as infection1, altered diet2 and stress3 during pregnancy, has been increasingly associated with abnormalities in brain function and behaviour of the offspring4. 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41586-020-2745-3 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:586:y:2020:i:7828:d:10.1038_s41586-020-2745-3

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-020-2745-3

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().