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

Nagendra Singh, Ashish Gurav, Sathish Sivaprakasam, Evan Brady, Ravi Padia, Huidong Shi, Muthusamy Thangaraju, Puttur D Prasad, Santhakumar Manicassamy, David H Munn, Jeffrey R Lee, Stefan Offermanns, Vadivel Ganapathy

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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 languageEnglish (US)
Pages (from-to)128-139
Number of pages12
JournalImmunity
Volume40
Issue number1
DOIs
StatePublished - Jan 16 2014

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Butyrates
Niacin
Colonic Neoplasms
Carcinogenesis
Inflammation
Dietary Fiber
Colon
Interleukin-18
Regulatory T-Lymphocytes
Colitis
Interleukin-10
Dendritic Cells
Fermentation
Anti-Inflammatory Agents
Macrophages
Pharmacology
Gastrointestinal Microbiome

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 journalArticle

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. / Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. In: Immunity. 2014 ; Vol. 40, No. 1. pp. 128-139.
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