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 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 128-139 |
| Number of pages | 12 |
| Journal | Immunity |
| Volume | 40 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 16 2014 |
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ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases
Cite this
Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. / Singh, Nagendra; Gurav, Ashish; Sivaprakasam, Sathish; Brady, Evan; Padia, Ravi; Shi, Huidong; Thangaraju, Muthusamy; Prasad, Puttur D; Manicassamy, Santhakumar; Munn, David H; Lee, Jeffrey R; Offermanns, Stefan; Ganapathy, Vadivel.
In: Immunity, Vol. 40, No. 1, 16.01.2014, p. 128-139.Research output: Contribution to journal › Article
}
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
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
VL - 40
SP - 128
EP - 139
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 1
ER -