Gut-innervating nociceptors regulate the intestinal microbiota to promote tissue protection.
Gut-innervating nociceptors regulate the intestinal microbiota to promote tissue protection.
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DOI：
10.1016/j.cell.2022.09.008
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发表时间：
2022-10-27
期刊：
影响因子：
64.5
通讯作者：
Artis, David
中科院分区：
文献类型：
--
作者：
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
伤害性疼痛是包括炎症性肠病（IBD）在内的许多慢性炎症性疾病的标志，然而疼痛感测神经元是否影响肠道炎症仍然不清楚。采用化学基因沉默，腺病毒介导的结肠特异性沉默和TRPV1+伤害感受器的药理学消融，我们观察到更严重的炎症和有缺陷的组织保护性修复过程中的肠道损伤和炎症的小鼠模型。破坏的伤害感受导致肠道微生物群的显著改变和可传播的生态失调，而用革兰氏+梭菌属的无菌小鼠的单定殖。通过伤害感受器依赖性途径促进肠组织保护。从机制上讲，伤害感受的破坏导致P物质水平降低，P物质的治疗性递送促进TRPV1+伤害感受器以微生物群依赖性方式发挥的组织保护作用。最后，在IBD患者的肠活检组织中观察到伤害感受器基因表达失调。总的来说，这些发现表明伤害感受、肠道微生物群和肠道稳态恢复之间存在进化上保守的功能联系。
Nociceptive pain is a hallmark of many chronic inflammatory conditions including inflammatory bowel diseases (IBD), 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.
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影响因子：
30.5
作者：
通讯作者：
--
影响因子：
64.8
作者：
Alenghat, Theresa;Osborne, Lisa C.;Saenz, Steven A.;Kobuley, Dmytro;Ziegler, Carly G. K.;Mullican, Shannon E.;Choi, Inchan;Grunberg, Stephanie;Sinha, Rohini;Wynosky-Dolfi, Meghan;Snyder, Annelise;Giacomin, Paul R.;Joyce, Karen L.;Hoang, Tram B.;Bewtra, Meenakshi;Brodsky, Igor E.;Sonnenberg, Gregory F.;Bushman, Frederic D.;Won, Kyoung-Jae;Lazar, Mitchell A.;Artis, David
通讯作者：
Artis, David
DOI：
10.1126/science.1198469
发表时间：
2011-01-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Atarashi K;Tanoue T;Shima T;Imaoka A;Kuwahara T;Momose Y;Cheng G;Yamasaki S;Saito T;Ohba Y;Taniguchi T;Takeda K;Hori S;Ivanov II;Umesaki Y;Itoh K;Honda K
通讯作者：
Honda K
DOI：
10.4049/jimmunol.0900039
发表时间：
2009-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cyphert JM;Kovarova M;Allen IC;Hartney JM;Murphy DL;Wess J;Koller BH
通讯作者：
Koller BH
影响因子：
32.4
作者：
Chavan SS;Pavlov VA;Tracey KJ
通讯作者：
Tracey KJ