Prebiotics supplementation during pregnancy induces a tolerogenic environment in utero

The gut microbiota is influenced by environmental factors such as food. Maternal diet during pregnancy modifies the gut microbiota composition and function, leading to the production of specific compounds that are transferred to the fetus and enhance the ontogeny and maturation of the immune system. Prebiotics are fermented by gut bacteria, leading to the release of short-chain fatty acids that can specifically interact with the immune system, inducing a switch toward tolerogenic populations and therefore conferring health benefits. In this murine study, we hypothesized that GOS/inulin supplementation during gestation could modify the maternal microbiota, favoring healthy immune imprinting in the fetus. GOS/inulin supplementation during gestation increases the abundance of Bacteroidetes and decreases that of Firmicutes in the gut microbiota, leading to increased production of fecal acetate, which was found for the first time in amniotic fluid. Prebiotic supplementation increased the abundance of regulatory B and T cells in gestational tissues and in the fetus. Interestingly, these regulatory cells remained later in life. In conclusion, prebiotic supplementation during pregnancy leads to the transmission of specific microbial and immune factors from mother to child, allowing the establishment of tolerogenic immune imprinting in the fetus that may be beneficial for infant health outcomes.

肠道微生物群（gut microbiota）受饮食等环境因素影响。妊娠期母体饮食可改变肠道微生物群的组成与功能，进而产生特定代谢产物，这些物质可传递至胎儿，促进免疫系统的个体发育与成熟。益生元（prebiotics）可被肠道细菌发酵，释放短链脂肪酸（short-chain fatty acids），这类物质能特异性作用于免疫系统，诱导细胞向耐受原性（tolerogenic）群体转化，从而带来健康益处。本项小鼠实验提出假说：妊娠期补充半乳糖低聚糖/菊粉（GOS/inulin）可调节母体微生物群，助力胎儿建立健康的免疫印记（immune imprinting）。实验结果显示，妊娠期补充GOS/inulin可提升肠道微生物群中拟杆菌门（Bacteroidetes）的丰度，降低厚壁菌门（Firmicutes）的占比，进而增加粪便乙酸的生成——这一现象首次在羊水（amniotic fluid）中被观测到。益生元补充可提升妊娠组织及胎儿体内调节性B细胞与调节性T细胞的丰度。值得注意的是，这类调节性细胞在子代体内可长期留存。综上，妊娠期补充益生元可实现母体向子代的特异性微生物与免疫因子传递，帮助胎儿建立耐受原性免疫印记，或可改善子代婴儿期的健康结局。