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<p>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 <i>GPR43</i>, 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 <i>GPR43</i> 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.</p>

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Reduced maternal SCFAs in GDM diminish GPR43 signaling and induce offspring CAKUT

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月17日

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  • He Wang,
  • Tianyang Kang,
  • Weiwei Li

摘要

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.