TY - JOUR
T1 - Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis
AU - Singh, Nagendra
AU - Gurav, Ashish
AU - Sivaprakasam, Sathish
AU - Brady, Evan
AU - Padia, Ravi
AU - Shi, Huidong
AU - Thangaraju, Muthusamy
AU - Prasad, Puttur D.
AU - Manicassamy, Santhakumar
AU - Munn, David H.
AU - Lee, Jeffrey R.
AU - Offermanns, Stefan
AU - Ganapathy, Vadivel
N1 - Funding Information:
This research was supported by National Institutes of Health grants AI085440 (N.S.) and CA152396 (V.G.). We thank L. Ignatowicz for helpful discussions.
PY - 2014/1/16
Y1 - 2014/1/16
N2 - 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 Tcells. Moreover, Gpr109a was essential for butyrate-mediated induction of IL-18 incolonicepithelium. 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.
AB - 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 Tcells. Moreover, Gpr109a was essential for butyrate-mediated induction of IL-18 incolonicepithelium. 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.
UR - http://www.scopus.com/inward/record.url?scp=84892449521&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84892449521&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2013.12.007
DO - 10.1016/j.immuni.2013.12.007
M3 - Article
C2 - 24412617
AN - SCOPUS:84892449521
SN - 1074-7613
VL - 40
SP - 128
EP - 139
JO - Immunity
JF - Immunity
IS - 1
ER -