Details

Autor(en) / Beteiligte

• Zhang, Wen
• Lyu, Mengze
• Bessman, Nicholas J.
• Xie, Zili
• Arifuzzaman, Mohammad
• Yano, Hiroshi
• Parkhurst, Christopher N.
• Chu, Coco
• Zhou, Lei
• Putzel, Gregory G.
• Li, Ting-Ting
• Jin, Wen-Bing
• Zhou, Jordan
• Hu, Hongzhen
• Tsou, Amy M.
• Guo, Chun-Jun
• Artis, David

Titel

Gut-innervating nociceptors regulate the intestinal microbiota to promote tissue protection

Ist Teil von

• Cell, 2022-10, Vol.185 (22), p.4170-4189.e20

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• Nociceptive pain is a hallmark of many chronic inflammatory conditions including inflammatory bowel diseases (IBDs); however, whether pain-sensing neurons influence intestinal inflammation remains poorly defined. Employing chemogenetic silencing, adenoviral-mediated colon-specific silencing, and pharmacological ablation of TRPV1+ nociceptors, we observed more severe inflammation and defective tissue-protective reparative processes in a murine model of intestinal damage and inflammation. Disrupted nociception led to significant alterations in the intestinal microbiota and a transmissible dysbiosis, while mono-colonization of germ-free mice with Gram+Clostridium spp. promoted intestinal tissue protection through a nociceptor-dependent pathway. Mechanistically, disruption of nociception resulted in decreased levels of substance P, and therapeutic delivery of substance P promoted tissue-protective effects exerted by TRPV1+ nociceptors in a microbiota-dependent manner. Finally, dysregulated nociceptor gene expression was observed in intestinal biopsies from IBD patients. Collectively, these findings indicate an evolutionarily conserved functional link between nociception, the intestinal microbiota, and the restoration of intestinal homeostasis. [Display omitted] •TRPV1+ nociceptors are protective in a murine model of intestinal inflammation•Ablation of TRPV1+ nociceptors leads to a transmissible microbial dysbiosis•Clostridium spp. colonization drives nociceptor-mediated tissue protection in mice•TRPV1+ nociceptor-derived substance P promotes intestinal tissue protection Gut-innervating TRPV1+ nociceptors influence the composition of the intestinal microbiota to limit inflammation and promote intestinal tissue protection.