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Activation of Gpr109a, Receptor for Niacin and the Commensal Metabolite Butyrate, Suppresses Colonic Inflammation and Carcinogenesis
Open accessAbstract
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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“Singh et al. demonstrated that butyrate was an agonist for GPR109A [73].”
From Gut microbiota-mediated immunomodulation in tumor (2021) · cites this paper as [73]
In the citing paper
“Separately, butyrate has also been shown to enhance Treg generation by promoting an anti-inflammatory phenotype in macrophages and DCs through activation of HCAR2 (Singh et al., 2014).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Singh et al., 2014
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“However, SCFAs have also been shown to affect DC maturation and function through HCAR2 and FFAR3, depending on the context (Singh et al., 2014; Trompette et al., 2014).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Singh et al., 2014
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“whereas propionate and butyrate, but not acetate, increase the de novo differentiation of naive T cells into Tregs (Arpaia et al., 2013; Furusawa et al., 2013; Singh et al., 2014; Smith et al., 2013).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Singh et al., 2014
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“In the gut, they influence expression of anti-inflammatory markers, such as interleukin (IL-)10 in macrophages and intestinal dendritic cells [55].”
From Effect of fecal microbiota transplant on symptoms of psychiatric disorders: a systematic review (2020) · cites this paper as [55]
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Metadata
- Authors
- Singh, N., Gurav, A., Sivaprakasam, S., Brady, E., Padia, R., Shi, H., Thangaraju, M., Prasad, P. D., Manicassamy, S., Munn, D. H., Lee, J. R., Offermanns, S., & Ganapathy, V.
- Affiliations
- Augusta University (US)
- Charlie Norwood VA Medical Center (US)
- Max Planck Institute for Heart and Lung Research (DE)
- Corresponding author
- Singh, Nagendra
- Ganapathy, Vadivel
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 40
- Issue
- 1
- Pages
- 128-139
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC4305274
- OpenAlex
- W1981266729
- Cited by
- 2,368
- References
- 48
- Citations by year
- 2026: 230 · 2025: 242 · 2024: 252 · 2023: 266 · 2022: 237 · 2021: 268 · 2020: 193 · 2019: 172 · 2018: 136 · 2017: 122 · 2016: 97 · 2015: 97 · 2014: 54
- FWCI
- 50.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Funders
- National Cancer Institute (R21CA152396, R01CA096651, CA152396, R01CA103320)
- National Institute of Allergy and Infectious Diseases (AI085440, R21AI085440)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK103576, R01DK097271)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- GPR109A, butyrate, nicotinic acid, colonic inflammation, colon cancer, gut microbiota, dietary fiber, regulatory T cells, IL-10, IL-18, colonic epithelium, colitis, dendritic cells, macrophages
- MeSH terms
- Animals, Butyrates, Cell Differentiation, Cells, Cultured, Colitis, Colon, Colonic Neoplasms, Dendritic Cells, Disease Susceptibility, Epithelial Cells, Lymphocyte Activation, Macrophages, Mice, Inbred C57BL, Niacin, Receptors, Nicotinic, Signal Transduction, T-Lymphocyte Subsets, Interleukin-10, Mice, Knockout, Interleukin-18, Receptors, G-Protein-Coupled, T-Lymphocytes, Regulatory, Mice, Carcinogenesis, Microbiota
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