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

By Nagendra Singh, Ashish Gurav, Sathish Sivaprakasam, E. Brady, Ravi N. Padia, Huidong Shi, M. Thangaraju, P. Prasad, S. Manicassamy, D. Munn and 3 more. Immunity, 2014

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SUMMARY 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.

Subfields: Food Science, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/470e740adf464c5b84a4b96d2274ce4682fee2ab

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Citations in the corpus

Gut Microbiota and Immune System Interactions (2020, background): “Moreover, SCFA-mediated GPR43 signaling attenuates NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation and subsequent secretion of IL-18, [20,21], a pro-inflammatory cytokine with essential roles in colonic inflammation and inflammation-associated cancers [11,22].”
Defining dysbiosis and its influence on host immunity and disease (2014, background): “SCFAs are sensed by the host through a variety of receptors, including G-protein coupled receptors GPCR43 and GPR109a (Smith et al., 2013; Singh et al., 2014).”
Immunometabolism governs dendritic cell and macrophage function (2016, background): “DCs can also respond via specific GPCRs to the short chain fatty acid butyrate (Singh et al., 2014), which is a product of commensal bacteria, to adenosine/ATP (Li et al., 2012), and to lactic acid (Nasi et al., 2013).”
Short-chain fatty acids: linking diet, the microbiome and immunity (2024, neutral): “Indeed, the functions of butyrate cannot simply be labelled as anti-inflammatory or immunosuppressive as mice deficient in the butyrate receptor GPR109A, which is expressed on DCs and macrophages in the intestine, were more susceptible to developing colon cancer 77 , again highlighting a context-spe”
The role of short-chain fatty acids in immunity, inflammation and metabolism (2020, background): “However, there are also reports showing that in colitis, butyrate participates in the regulation of inflammation by activating GPR109A (Chai, Digby, and Choudhury 2013; Singh et al. 2014).”
Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine. (2015, positive): “Here, GPR109 might be a critical player, as has been recently shown for butyric acid (Singh et al., 2014), whereas receptors previously notedof importance,GPR41 andGPR43 (Kimet al., 2013), are not as relevant in our system.”
The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis? (2016, background): “, 2013), while GPR109a (now renamed to hydroxycarboxylic acid receptor 2, HCAR2 or HCA2) is activated by butyrate, monomethyl fumarate and the B3 vitamin niacin, which gave the encoding gene niacin receptor 1 (Niacr1) its initial name (Singh et al., 2014; Tang et al., 2008).”
Homeostatic immunity and the microbiota (2017, positive): “For instance, in the gut, SCFA can alter the gene expression profile of local macrophages via HDAC inhibition (Chang et al., 2014; Singh et al., 2014).”