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The maternal microbiome modulates fetal neurodevelopment in mice

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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 & Elaine Y. Hsiao, 2020. "The maternal microbiome modulates fetal neurodevelopment in mice," Nature, Nature, vol. 586(7828), pages 281-286, October.
  • Handle: RePEc:nat:nature:v:586:y:2020:i:7828:d:10.1038_s41586-020-2745-3
    DOI: 10.1038/s41586-020-2745-3
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    Cited by:

    1. Eldin Jašarević & Elizabeth M. Hill & Patrick J. Kane & Lindsay Rutt & Trevonn Gyles & Lillian Folts & Kylie D. Rock & Christopher D. Howard & Kathleen E. Morrison & Jacques Ravel & Tracy L. Bale, 2021. "The composition of human vaginal microbiota transferred at birth affects offspring health in a mouse model," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    2. Wen-Xiang Liu & Hai-Ning Liu & Zhan-Ping Weng & Qi Geng & Yue Zhang & Ya-Feng Li & Wei Shen & Yang Zhou & Teng Zhang, 2023. "Maternal vitamin B1 is a determinant for the fate of primordial follicle formation in offspring," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Steven Schepanski & Mattia Chini & Veronika Sternemann & Christopher Urbschat & Kristin Thiele & Ting Sun & Yu Zhao & Mareike Poburski & Anna Woestemeier & Marie-Theres Thieme & Dimitra E. Zazara & Ma, 2022. "Pregnancy-induced maternal microchimerism shapes neurodevelopment and behavior in mice," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Fanette Fontaine & Sondra Turjeman & Karel Callens & Omry Koren, 2023. "The intersection of undernutrition, microbiome, and child development in the first years of life," Nature Communications, Nature, vol. 14(1), pages 1-9, December.

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