The maternal microbiome modulates fetal neurodevelopment in mice
Vuong H, Pronovost G, Williams D, Coley E, Siegler E, Qiu A, Kazantsev M, Wilson C, Rendon T, Hsiao E (2020) Nature 2020 Sep 23. doi: 10.1038/s41586-020-2745-3
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.FAB RESEARCH COMMENT:
For the related news article please see:For further information on this topic please see:
- Enduring consequences of maternal obesity for brain inflammation and behavior of offspring
- MIA - “Transformational” Breakthroughs In Our Understandings of Nutrition and Brain Health
- Chronic Consumption of a High-Fat Diet during Pregnancy Causes Perturbations in the Serotonergic System and Increased Anxiety-Like Behavior in Nonhuman Primate Offspring
- Mouse maternal protein restriction during preimplantation alone permanently alters brain neuron proportion and adult short-term memory
- Neonatal Insulin Action Impairs Hypothalamic Neurocircuit Formation in Response to Maternal High-Fat Feeding
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