Wang He, Kang Tianyang, Li Weiwei
Department of Obstetrics, First Hospital of China Medical University, Shenyang, Shenyang, China.
Commun Biol. 2025 Jul 17;8(1):1063. doi: 10.1038/s42003-025-08469-y.
Gestational diabetes during pregnancy is associated with an increased risk of developmental abnormalities in offspring, but the underlying mechanisms remain unclear. It is not known how maternal metabolism and gut microbes influence kidney development in the fetus. Here we show that gestational diabetes alters maternal gut microbiota and reduces the production of key fatty acids that normally support kidney development in offspring. We find that these changes impair a molecular pathway involving the receptor GPR43, which promotes the growth and migration of kidney cells. In a mouse model, restoring short-chain fatty acids or transferring gut bacteria from healthy donors improves kidney development in offspring, while blocking GPR43 reverses this effect. This study reveals a previously unknown link between maternal gut metabolism and fetal kidney formation and may guide future strategies to prevent congenital kidney disorders in children born to mothers with gestational diabetes.
孕期的妊娠期糖尿病与后代发育异常风险增加有关，但其潜在机制仍不清楚。目前尚不清楚母体代谢和肠道微生物如何影响胎儿的肾脏发育。在此我们表明，妊娠期糖尿病会改变母体肠道微生物群，并减少通常支持后代肾脏发育的关键脂肪酸的产生。我们发现这些变化会损害一条涉及受体GPR43的分子途径，该途径促进肾细胞的生长和迁移。在小鼠模型中，恢复短链脂肪酸或移植健康供体的肠道细菌可改善后代的肾脏发育，而阻断GPR43则会逆转这种效应。这项研究揭示了母体肠道代谢与胎儿肾脏形成之间以前未知的联系，并可能为预防妊娠期糖尿病母亲所生儿童先天性肾脏疾病的未来策略提供指导。
