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Immunity. 2014 Jan 16;40(1):128-39. doi: 10.1016/j.immuni.2013.12.007. Epub 2014 Jan 9.

Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis.

Author information

1
Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA; Cancer Research Center, Georgia Regents University, Augusta, GA 30912, USA. Electronic address: nasingh@gru.edu.
2
Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA.
3
Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA; Cancer Research Center, Georgia Regents University, Augusta, GA 30912, USA.
4
Cancer Research Center, Georgia Regents University, Augusta, GA 30912, USA.
5
Cancer Research Center, Georgia Regents University, Augusta, GA 30912, USA; Department of Pediatrics, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA.
6
Department of Pathology, Charlie Norwood Veterans Administration Medical Center, Augusta, GA 30904, USA.
7
Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.
8
Department of Biochemistry and Molecular Biology, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA; Cancer Research Center, Georgia Regents University, Augusta, GA 30912, USA. Electronic address: vganapat@gru.edu.

Abstract

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.

PMID:
24412617
PMCID:
PMC4305274
DOI:
10.1016/j.immuni.2013.12.007
[Indexed for MEDLINE]
Free PMC Article

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