Scholarlink

<p>Alterations in gut microbiota have been linked to chronic kidney disease (CKD), but large-scale studies and mechanistic insights are limited. Here we analysed gut metagenome data from 1,550 older individuals (aged 65–93 years) with comprehensive kidney function measurements. <i>Segatella copri</i> was positively associated with kidney function through microbial ammonia metabolism-related pathways and the <i>asnA</i> gene, which encodes an ammonia-assimilating enzyme. These associations were replicated in two external studies. In mice, ammonia supplementation increased serum levels of creatinine and blood urea nitrogen, accelerating CKD progression. In vitro cultures of <i>S. copri</i> or <i>asnA</i>-overexpressing <i>Escherichia coli</i> reduced ammonia concentrations, which was markedly attenuated in <i>asnA</i>-knockout <i>S. copri</i>. Gavage of either <i>S. copri</i> or <i>asnA</i>-overexpressing <i>E. coli</i>, but not <i>asnA</i>-knockout <i>S. copri</i>, mitigated ammonia-induced CKD progression in mice. These findings highlight the role of gut microbial ammonia metabolism in CKD pathogenesis and underscore the therapeutic potential of microbial-based interventions.</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 copri and gut microbial ammonia metabolism contribute to chronic kidney disease pathogenesis

  • 期刊论文

  • 发表日期：

    2025年6月24日

查看全文
  • Shuchun Lin,
  • Zhonghan Sun,
  • Xinna Zhu,
  • Mengjing Wang,
  • Qian Zhang,
  • Jing Qian,
  • Hui Zhang,
  • Zhendong Mei,
  • Yanni Pu,
  • Mengmeng Kong,
  • Peifeng Guo,
  • Xiaofeng Zhou,
  • Jin Li,
  • Xuehui Sun,
  • Liang Ma,
  • Xueli Zhang,
  • Fangqing Zhao,
  • Jing Nie,
  • Shangyu Hong,
  • Jing Chen,
  • Xiaofeng Wang,
  • Xiao Li,
  • Yan Zheng

摘要

Alterations in gut microbiota have been linked to chronic kidney disease (CKD), but large-scale studies and mechanistic insights are limited. Here we analysed gut metagenome data from 1,550 older individuals (aged 65–93 years) with comprehensive kidney function measurements. Segatella copri was positively associated with kidney function through microbial ammonia metabolism-related pathways and the asnA gene, which encodes an ammonia-assimilating enzyme. These associations were replicated in two external studies. In mice, ammonia supplementation increased serum levels of creatinine and blood urea nitrogen, accelerating CKD progression. In vitro cultures of S. copri or asnA-overexpressing Escherichia coli reduced ammonia concentrations, which was markedly attenuated in asnA-knockout S. copri. Gavage of either S. copri or asnA-overexpressing E. coli, but not asnA-knockout S. copri, mitigated ammonia-induced CKD progression in mice. These findings highlight the role of gut microbial ammonia metabolism in CKD pathogenesis and underscore the therapeutic potential of microbial-based interventions.