<b>Gut flora-derived metabolites mediate protective effect of high fermentable fiber against placental inflammation in gestational diabetes mellitus.</b>

Inflammation-associated insulin resistance is a key trigger of gestational diabetes mellitus (GDM), but the underlying mechanisms and effective interventions remain unclear. Here, we report the association of placental inflammation (tumor necrosis factor-α) and abnormal maternal glucose metabolism in GDM patients, and a high fermentable dietary fiber (HFDF, <i>Konjac</i>) could reduce GDM development through gut microbiota-short-chain fatty acids-placental inflammation axis in GDM mice model. Mechanistically, HFDF increases abundances of <i>Lachnospiraceae</i> and butyrate, reduces placental-derived inflammation by enhancing gut barrier and inhibiting the transfer of bacterial-derived lipopolysaccharide, and ultimately resists high fat diet-induced insulin resistance. Butyrate abundances in placentae of GDM patients and mice are negatively correlated with placental TNF-α. Moreover, <i>Lachnospiraceae</i> and butyrate have similar anti-GDM and anti-placental inflammation effects. These findings demonstrate the involvement of important placental inflammation-related mechanisms in the progression of GDM and the great potential of HFDFs to reduce susceptibility to GDM through gut-microbiota-placenta axis. In version 20240303, we corrected the incorrectly recorded source data.

炎症相关胰岛素抵抗是妊娠糖尿病（gestational diabetes mellitus, GDM）的关键诱因，但其潜在分子机制与有效干预策略仍未明确。本研究揭示了GDM患者胎盘炎症相关的肿瘤坏死因子-α（tumor necrosis factor-α, TNF-α）与母体糖代谢异常的关联，并证实高可发酵膳食纤维（high fermentable dietary fiber, HFDF，魔芋（Konjac））可通过GDM小鼠模型中的肠道菌群-短链脂肪酸-胎盘炎症轴，降低GDM的发病风险。从机制层面而言，HFDF可提升毛螺菌科（Lachnospiraceae）与丁酸的丰度，通过增强肠道屏障、抑制细菌源性脂多糖的转运以减轻胎盘源性炎症，最终抵抗高脂饮食诱导的胰岛素抵抗。GDM患者与小鼠的胎盘中，丁酸丰度与胎盘TNF-α呈负相关。此外，毛螺菌科与丁酸具有相似的抗GDM及抗胎盘炎症作用。本研究结果证实了胎盘炎症相关关键机制参与GDM的疾病进展，并表明HFDF可通过肠道菌群-胎盘轴降低GDM易感性，具备极大的应用潜力。在20240303版本中，我们修正了此前记录有误的源数据。