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Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis
- Source :
- Immunity. 40(1)
- Publication Year :
- 2012
-
Abstract
- SummaryCommensal 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.
- Subjects :
- Colorectal cancer
Carcinogenesis
Gut flora
Receptors, Nicotinic
medicine.disease_cause
Lymphocyte Activation
T-Lymphocytes, Regulatory
Receptors, G-Protein-Coupled
Mice
0302 clinical medicine
T-Lymphocyte Subsets
Immunology and Allergy
Cells, Cultured
Mice, Knockout
0303 health sciences
biology
Microbiota
Interleukin-18
Cell Differentiation
Colitis
3. Good health
Interleukin-10
Interleukin 10
Butyrates
Infectious Diseases
030220 oncology & carcinogenesis
Colonic Neoplasms
Disease Susceptibility
medicine.symptom
Niacin
Signal Transduction
Colon
Immunology
Inflammation
Butyrate
Article
03 medical and health sciences
medicine
Animals
030304 developmental biology
Macrophages
Epithelial Cells
Dendritic Cells
biology.organism_classification
medicine.disease
digestive system diseases
Mice, Inbred C57BL
Cancer research
Subjects
Details
- ISSN :
- 10974180
- Volume :
- 40
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Immunity
- Accession number :
- edsair.doi.dedup.....5fcbddb75956dd647a773cca65b0e048