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Review
. 2016 Aug;164:144-51.
doi: 10.1016/j.pharmthera.2016.04.007. Epub 2016 Apr 23.

Benefits of Short-Chain Fatty Acids and Their Receptors in Inflammation and Carcinogenesis

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Free PMC article
Review

Benefits of Short-Chain Fatty Acids and Their Receptors in Inflammation and Carcinogenesis

Sathish Sivaprakasam et al. Pharmacol Ther. .
Free PMC article

Abstract

Epidemiological studies have linked increased incidence of inflammatory diseases and intestinal cancers in the developed parts of the world to the consumption of diets poor in dietary fibers and rich in refined carbohydrates. Gut bacteria residing in the intestinal lumen exclusively metabolize dietary fibers. Butyrate, propionate and acetate, which are collectively called short-chain fatty acids (SCFAs), are generated by fermentation of dietary fibers by gut microbiota. Evidences indicate that SCFAs are key players in regulating beneficial effect of dietary fibers and gut microbiota on our health. SCFAs interact with metabolite-sensing G protein-coupled receptors GPR41, GPR43 and GPR109A expressed in gut epithelium and immune cells. These interactions induce mechanisms that play a key role in maintaining homeostasis in gut and other organs. This review summarizes the protective roles of GPR41, GPR43 and GPR109A in dietary fibers-, gut microbiota- and SCFAs-mediated suppression of inflammation and carcinogenesis in gut and other organs.

Keywords: Dietary fibers; Gut microbiota; Inflammation and cancer; Short-chain fatty acid receptors; Short-chain fatty acids.

Figures

Figure 1
Figure 1
SCFA receptors link dietary fibers and gut microbiota to intestinal homeostasis. A simplified model showing regulation of gut homeostasis by SCFA receptors. Beneficial gut bacteria (symbionts) ferment dietary fibers into SCFAs. Butyrate induces production of IL-10 and retinoic acid (RA) by dendritic cells. These DCs stimulate conversion of naïve T cells into Treg cells and suppress generation of Th17 cells. Activation of Gpr43 on Treg cells by SCFAs induces Treg cells proliferation. Treg cells are known to suppres colonic inflammation and carcinogenesis, where as Th17 cells promote inflammation and carcinogenesis in colon. Additionally, Gpr109a signaling induces transcription of IL-18, whereas Gpr43 signaling induces K+ flux, which activates Nlrp3 inflasmmasome resulting in maturation of IL-18 from its pro-peptide. Activation of Gpr43 downregulates expression chemotactic receptor CXCR2 in neutrophils and thus inhbits their chemotaxis. Gpr109a signaling inhbitis activation of NF-κB in colonic epithelium.

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