Scholarlink

<p>Chronic heart failure (CHF) is the end-stage of cardiovascular disease and is linked to intestinal dysbiosis, yet the precise microbial culprits and therapeutic targets remain unclear. Here, we show that the Gram-negative genus <i>Segatella</i> is selectively expanded in the gut of 152 CHF patients versus 105 matched controls, correlating with impaired cardiac function and disrupted lipid and amino-acid metabolism. Mechanistically, <i>Segatella</i> dose-dependently intensified doxorubicin-induced apoptosis and oxidative stress in H9c2 cardiomyocytes via TLR4/NF-κB signalling; these effects were reversed by co-culture in low-carbohydrate medium. In a doxorubicin-driven CHF rat model, <i>Segatella</i> gavage further reduced left-ventricular ejection fraction, aggravated fibrosis and heightened myocardial TNF-α and IL-6, whereas an 8-week low-carbohydrate diet (LCD) lowered <i>Segatella</i> abundance, improved cardiac function, reduced fibrosis, and alleviated pulmonary oedema. Collectively, <i>Segatella</i> exacerbates CHF by orchestrating TLR4/NF-κB-mediated inflammation and metabolic toxicity, while LCD confers protection by reshaping the gut microbiota, supporting microbiota-targeted, non-pharmacological therapy for CHF.</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

Segatella exacerbates chronic heart failure via TLR4/NF-κB pathway and therapeutic potential of low-carbohydrate diet

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月21日

查看全文
  • Aihaidan Abudouwayiti,
  • Yan Xiao Li,
  • Salamaiti Aimaier,
  • Ying-Ying Zheng,
  • Ailiman Mahemuti

摘要

Chronic heart failure (CHF) is the end-stage of cardiovascular disease and is linked to intestinal dysbiosis, yet the precise microbial culprits and therapeutic targets remain unclear. Here, we show that the Gram-negative genus Segatella is selectively expanded in the gut of 152 CHF patients versus 105 matched controls, correlating with impaired cardiac function and disrupted lipid and amino-acid metabolism. Mechanistically, Segatella dose-dependently intensified doxorubicin-induced apoptosis and oxidative stress in H9c2 cardiomyocytes via TLR4/NF-κB signalling; these effects were reversed by co-culture in low-carbohydrate medium. In a doxorubicin-driven CHF rat model, Segatella gavage further reduced left-ventricular ejection fraction, aggravated fibrosis and heightened myocardial TNF-α and IL-6, whereas an 8-week low-carbohydrate diet (LCD) lowered Segatella abundance, improved cardiac function, reduced fibrosis, and alleviated pulmonary oedema. Collectively, Segatella exacerbates CHF by orchestrating TLR4/NF-κB-mediated inflammation and metabolic toxicity, while LCD confers protection by reshaping the gut microbiota, supporting microbiota-targeted, non-pharmacological therapy for CHF.