Mechanosensory Piezo2 regulated by gut microbiota participates in the development of visceral hypersensitivity and intestinal dysmotility

作者：Haonan Zheng, Yuzhu Chen, Siqi Lu, Zuojing Liu, Yinchao Ma, Cunzheng Zhang, Yiming Zhang, Jindong Zhang, Chang Liu, Ming Chu, Fei Pei, Shuang‐Jiang Liu, Liping Duan · 发表于：Gut Microbes · 年份：2025 · DOI：10.1080/19490976.2025.2497399 · 被引用次数：18 · 研究领域：Erythrocyte Function and Pathophysiology、Chemical and Physical Studies、Exercise and Physiological Responses

The gut microbiota plays a crucial role in the manifestation of intestinal dysfunction associated with irritable bowel syndrome (IBS). The mechanosensory Piezo2 has been implicated in the regulation of intestinal function. However, it remains unclear whether Piezo2 is modulated by the gut microbiota, thus contributing to the development of visceral hypersensitivity and gut dysmotility. The study enrolled patients with diarrhea-predominant IBS (IBS-D) alongside healthy controls (HC). Questionnaires, rectal barostat test, and colonoscopy with mucosal biopsy were conducted. Fecal microbiota transplantation (FMT) was performed using samples from HC or IBS-D patients, and interventions with Akkermansia muciniphila or Fusobacterium varium were carried out on colon- or dorsal root ganglion (DRG)- Piezo2 knockdown pseudo-germ-free mice. Visceral sensitivity and intestinal motility were assessed. Piezo2 levels were detected using western blot and immunofluorescence. Fecal 16S rRNA sequencing and cecum untargeted metabolomics analysis, followed by molecular docking predictions of Piezo2, were also performed. The ratio of Piezo2+/5-HT+ cells was lower in IBS-D patients, positively correlated with visceral sensation and intestinal dysbiosis. The mice that received FMT from IBS-D patients exhibited colonic dysmotility and visceral hypersensitivity, along with elevated Piezo2 protein levels in the colon and DRG. Knockdown of Piezo2 in the colon or DRG ameliorated the FMT-induced colonic dy...