Scholarlink

<p>Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women. Accumulating evidence indicates that gut dysbiosis and metabolic disturbances are associated with the pathogenesis of PCOS. However, the mechanisms by which metabolic alterations influence gut homeostasis and contribute to PCOS progression remain poorly understood. Here, we show that N-acetylneuraminic acid (Neu5Ac) exacerbates dehydroepiandrosterone (DHEA)-induced PCOS phenotypes in female mice in a gut microbiota-dependent manner. Specifically, Neu5Ac promotes the expansion of the gut <i>Ligilactobacillus salivarius</i> (<i>L. sa</i>) with bile salt hydrolase (BSH) activity. Administration of <i>L. sa</i> to DHEA-treated mice worsens PCOS symptoms by reducing levels of the conjugated bile acid tauroursodeoxycholic acid (TUDCA) via BSH activity. Reduced TUDCA enhances intestinal farnesoid X receptor (FXR) activation, leading to suppression of IL-22 production. Mechanistically, IL-22 attenuates DHEA-induced ovarian ferroptosis by activating the STAT3 signaling pathway. These findings reveal that sialic acid-mediated bile acid–FXR–IL-22 signaling contributes to PCOS pathogenesis, highlighting a potential therapeutic strategy for PCOS intervention.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Sialic acid exacerbates polycystic ovary syndrome in mice by modulating gut microbiota-mediated bile acid metabolism and FXR activation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月31日

查看全文
  • Caijun Zhao,
  • Yue Zhang,
  • Ke Chen,
  • Zhuohan Li,
  • Lin Chen,
  • Xinyue Xing,
  • Huafeng Geng,
  • Yang Zheng,
  • Yun Zhang,
  • Shentong Wang,
  • Cong Ye,
  • Yunhe Fu

摘要

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women. Accumulating evidence indicates that gut dysbiosis and metabolic disturbances are associated with the pathogenesis of PCOS. However, the mechanisms by which metabolic alterations influence gut homeostasis and contribute to PCOS progression remain poorly understood. Here, we show that N-acetylneuraminic acid (Neu5Ac) exacerbates dehydroepiandrosterone (DHEA)-induced PCOS phenotypes in female mice in a gut microbiota-dependent manner. Specifically, Neu5Ac promotes the expansion of the gut Ligilactobacillus salivarius (L. sa) with bile salt hydrolase (BSH) activity. Administration of L. sa to DHEA-treated mice worsens PCOS symptoms by reducing levels of the conjugated bile acid tauroursodeoxycholic acid (TUDCA) via BSH activity. Reduced TUDCA enhances intestinal farnesoid X receptor (FXR) activation, leading to suppression of IL-22 production. Mechanistically, IL-22 attenuates DHEA-induced ovarian ferroptosis by activating the STAT3 signaling pathway. These findings reveal that sialic acid-mediated bile acid–FXR–IL-22 signaling contributes to PCOS pathogenesis, highlighting a potential therapeutic strategy for PCOS intervention.