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Papers of the Week

Papers: 15 Oct 2022 - 21 Oct 2022

Animal Studies

2022 Oct 13


Editor's Pick

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


Zhang W, Lyu M, Bessman NJ, Xie Z, Arifuzzaman M, Yano H, Parkhurst CN, Chu C, Zhou L, Putzel GG, Li T-T, Jin W-B, Zhou J, Hu H, Tsou AM, Guo C-J, Artis D
Cell. 2022 Oct 13.
PMID: 36240781.


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 GramClostridium 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.