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

N Singh, A Gurav, S Sivaprakasam, E Brady, R Padia… - Immunity, 2014 - cell.com
Immunity, 2014cell.com
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 …
Summary
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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