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Maternal Probiotic Supplementation Effects on the Placenta-Brain Axis

ABSTRACT: The rate of probiotic usage by pregnant women in the US and Canada ranges from 1.3 to 3.6 %. Probiotic supplements are available without a prescription and have gained currency in treating a variety of ailment ranging from reducing risk of constipation, diarrhea, other gastrointestinal conditions, eczema, pre-term birth, and prevent adverse pregnancy outcomes, including gestational diabetes mellitus (GDM) and depression/anxiety. Three possible mechanisms by which maternal probiotic supplementation might influence the placenta are through 1) directly impacting possible bacteria residing in the placenta (placenta microbiome), 2) altering bacterial metabolites produced by gut microbiota within the mother that induce placental changes, and 3) maternal probiotics might affect the composition of the bacteria within the maternal gut that affects her immune cells and their responses to the heterologous placenta. For the second potential mechanism, bacterial metabolites that might influence placenta include short chain fatty acids (SCFAs), polyamines (PAs), and Vitamins B9 (Folic Acid) and 12 (Cobalamin), among others. This project aims to determine the effects maternal probiotic supplementation in mice might have on the fetal placenta. With the number of women taking over probiotic supplements increasing, further research is needed to determine how these bioactive agents may affect the placenta and health of the offspring.

ORGANISM(S): Mus musculus

PROVIDER: GSE309308 | GEO | 2025/09/26

REPOSITORIES: GEO

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Project description:“Dysbiosis" of the maternal gut microbiome, in response to environmental challenges such as infection, altered diet and stress during pregnancy, has been increasingly associated with abnormalities in offspring brain function and behavior. However, whether the maternal gut microbiome regulates neurodevelopment in the absence of environmental challenge remains unclear. In addition, whether the maternal microbiome exerts such influences during critical periods of embryonic brain development is poorly understood. 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 exhibit widespread transcriptomic alterations in the fetal brain relative to conventionally-colonized controls, with reduced expression of several genes involved in axonogenesis. In addition, embryos from microbiome-depleted mothers exhibit deficient thalamocortical axons and impaired thalamic axon outgrowth in response to cell-extrinsic guidance cues and growth factors. Consistent with the importance of fetal thalamocortical axonogenesis for shaping neural circuits for sensory processing, restricted depletion of the maternal microbiome from pre-conception through mid-gestation yields offspring that exhibit tactile hyposensitivity in select sensorimotor behavioral tasks. Gnotobiotic colonization of antibiotic-treated dams with a limited consortium of spore-forming bacteria indigenous to the gut microbiome prevents abnormalities in fetal brain gene expression, fetal thalamocortical axonogenesis and adult tactile sensory behavior associated with maternal microbiome depletion. Metabolomic profiling reveals that the maternal microbiota regulates levels of numerous small molecules in the maternal serum as well as the brains of fetal offspring. Select microbiota-dependent metabolites – trimethylamine N-oxide, 5-aminovalerate, imidazole propionate, and hippurate – sufficiently promote axon outgrowth from fetal thalamic explants. Moreover, maternal supplementation with the metabolites during early gestation abrogates deficiencies in fetal thalamocortical axons and prevents abnormalities in tactile sensory behavior in offspring from microbiome-depleted dams. Altogether, these findings reveal that the maternal gut microbiome promotes fetal thalamocortical axonogenesis and select tactile sensory behaviors in mice, likely by signaling of microbially modulated metabolites to neurons in the developing brain.

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Maternal Probiotic Supplementation Effects on the Placenta-Brain Axis

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