Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis.
Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis.
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DOI：
10.1016/j.immuni.2013.12.007
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发表时间：
2014-01-16
期刊：
影响因子：
32.4
通讯作者：
Ganapathy V
中科院分区：
文献类型：
--
作者：
Singh N;Gurav A;Sivaprakasam S;Brady E;Padia R;Shi H;Thangaraju M;Prasad PD;Manicassamy S;Munn DH;Lee JR;Offermanns S;Ganapathy V
肠道菌群和膳食纤维通过未知靶点预防结肠炎症和结肠癌。丁酸盐，一种来自结肠中膳食纤维发酵的细菌产物，与这一过程有关。GPR 109 A（由Niacr 1编码）是结肠中丁酸盐的受体。GPR 109 A也是烟酸的受体，烟酸也由肠道微生物群产生，并抑制肠道炎症。在这里，我们发现Gpr 109 a信号促进结肠巨噬细胞和树突状细胞的抗炎特性，并使它们能够诱导Treg细胞和产生IL-10的T细胞的分化。此外，Gpr 109 a是必不可少的丁酸介导的诱导IL-18在结肠上皮。因此，Niacr 1 −/−小鼠易患结肠炎症和结肠癌。烟酸是一种药理学Gpr 109 a激动剂，以Gpr 109 a依赖的方式抑制结肠炎和结肠癌。因此，Gpr 10a在介导肠道微生物群和膳食纤维在结肠中的有益作用方面具有重要作用。
Commensal gut microflora and dietary fiber protect against colonic inflammation and colon cancer through unknown targets. Butyrate, a bacterial product from fermentation of dietary fiber in the colon, has been implicated in this process. GPR109A (encoded by Niacr1) is a receptor for butyrate in the colon. GPR109A is also a receptor for niacin, which is also produced by gut microbiota and suppresses intestinal inflammation. Here we showed that Gpr109a signaling promoted anti-inflammatory properties in colonic macrophages and dendritic cells and enabled them to induce differentiation of Treg cells and IL-10-producing T cells. Moreover, Gpr109a was essential for butyrate-mediated induction of IL-18 in colonic epithelium. Consequently, Niacr1−/− mice were susceptible to development of colonic inflammation and colon cancer. Niacin, a pharmacological Gpr109a agonist, suppressed colitis and colon cancer in a Gpr109a-dependent manner. Thus, Gpr10a has an essential role in mediating the beneficial effects of gut microbiota and dietary fiber in colon.
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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
影响因子：
6.7
作者：
Jeon SG;Kayama H;Ueda Y;Takahashi T;Asahara T;Tsuji H;Tsuji NM;Kiyono H;Ma JS;Kusu T;Okumura R;Hara H;Yoshida H;Yamamoto M;Nomoto K;Takeda K
通讯作者：
Takeda K
影响因子：
64.8
作者：
Grivennikov, Sergei I.;Wang, Kepeng;Mucida, Daniel;Stewart, C. Andrew;Schnabl, Bernd;Jauch, Dominik;Taniguchi, Koji;Yu, Guann-Yi;Oesterreicher, Christoph H.;Hung, Kenneth E.;Datz, Christian;Feng, Ying;Fearon, Eric R.;Oukka, Mohamed;Tessarollo, Lino;Coppola, Vincenzo;Yarovinsky, Felix;Cheroutre, Hilde;Eckmann, Lars;Trinchieri, Giorgio;Karin, Michael
通讯作者：
Karin, Michael
影响因子：
32.4
作者：
Huber S;Gagliani N;Esplugues E;O'Connor W Jr;Huber FJ;Chaudhry A;Kamanaka M;Kobayashi Y;Booth CJ;Rudensky AY;Roncarolo MG;Battaglia M;Flavell RA
通讯作者：
Flavell RA
影响因子：
11.2
作者：
Erdman, SE;Sohn, JJ;Schauer, DB
通讯作者：
Schauer, DB