Scholarlink

<p>The intestinal microbiota maintains mucosal homeostasis through dynamic host–microbe interactions. When this balance is disrupted, gut dysbiosis drives inappropriate immune activation, leading to dysregulated inflammation that contributes to the pathogenesis of chronic inflammatory diseases, including inflammatory bowel diseases (IBD). Chronic inflammation in patients with IBD increases the risk of intestinal fibrosis and colorectal cancer. However, therapeutic options for patients with IBD with fibrosis or neoplasia remain limited and challenging. Adherent-invasive <i>Escherichia coli</i> (AIEC) have emerged as key metabolic drivers of disease in IBD. We previously demonstrated that the AIEC-derived genotoxin colibactin and the siderophore yersiniabactin (Ybt) promote tumorigenesis through DNA damage and fibrosis via pro-fibrotic macrophage–fibroblast interactions, respectively. Because fibrosis and tumorigenesis involve overlapping pathways such as extracellular matrix remodeling, transforming growth factor-beta signaling, angiogenesis, and epithelial-to-mesenchymal transition, AIEC-derived metabolites may be functionally interconnected and could drive distinct pathological outcomes depending on the context of the disease. This Review highlights how AIEC-derived metabolites amplify inflammation, fibrosis, and neoplasia, outlines potential crosstalk between colibactin and Ybt, and discusses therapeutic opportunities targeting AIEC metabolite production in parallel with host-directed antifibrotic and cancer-prevention strategies.</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

From inflammation to fibrosis and cancer: the emerging role of AIEC-derived metabolites in intestinal disease progression

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月19日

查看全文
  • Ju-Hyun Ahn,
  • Anthony Hazelton,
  • Juliane Nguyen,
  • Janelle C. Arthur

摘要

The intestinal microbiota maintains mucosal homeostasis through dynamic host–microbe interactions. When this balance is disrupted, gut dysbiosis drives inappropriate immune activation, leading to dysregulated inflammation that contributes to the pathogenesis of chronic inflammatory diseases, including inflammatory bowel diseases (IBD). Chronic inflammation in patients with IBD increases the risk of intestinal fibrosis and colorectal cancer. However, therapeutic options for patients with IBD with fibrosis or neoplasia remain limited and challenging. Adherent-invasive Escherichia coli (AIEC) have emerged as key metabolic drivers of disease in IBD. We previously demonstrated that the AIEC-derived genotoxin colibactin and the siderophore yersiniabactin (Ybt) promote tumorigenesis through DNA damage and fibrosis via pro-fibrotic macrophage–fibroblast interactions, respectively. Because fibrosis and tumorigenesis involve overlapping pathways such as extracellular matrix remodeling, transforming growth factor-beta signaling, angiogenesis, and epithelial-to-mesenchymal transition, AIEC-derived metabolites may be functionally interconnected and could drive distinct pathological outcomes depending on the context of the disease. This Review highlights how AIEC-derived metabolites amplify inflammation, fibrosis, and neoplasia, outlines potential crosstalk between colibactin and Ybt, and discusses therapeutic opportunities targeting AIEC metabolite production in parallel with host-directed antifibrotic and cancer-prevention strategies.