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An essential role of Ffar2 (Gpr43) in dietary fibre-mediated promotion of healthy composition of gut microbiota and suppression of intestinal carcinogenesis

Lookup NU author(s): Dr Lei HuangORCiD, Emeritus Professor Andrew MellorORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

Composition of the gut microbiota has profound effects on intestinal carcinogenesis. Diet and host genetics play critical roles in shaping the composition of gut microbiota. Whether diet and host genes interact with each other to bring specific changes in gut microbiota that affect intestinal carcinogenesis is unknown. Ability of dietary fibre to specifically increase beneficial gut microbiota at the expense of pathogenic bacteria in vivo via unknown mechanism is an important process that suppresses intestinal inflammation and carcinogenesis. Free fatty acid receptor 2 (FFAR2 or GPR43) is a receptor for short-chain fatty acids (acetate, propionate and butyrate), metabolites of dietary fibre fermentation by gut microbiota. Here, we show FFAR2 is down modulated in human colon cancers than matched adjacent healthy tissue. Consistent with this, Ffar2(-/-) mice are hypersusceptible to development of intestinal carcinogenesis. Dietary fibre suppressed colon carcinogenesis in an Ffar2-dependent manner. Ffar2 played an essential role in dietary fibre-mediated promotion of beneficial gut microbiota, Bifidobacterium species (spp) and suppression of Helicobacter hepaticus and Prevotellaceae. Moreover, numbers of Bifidobacterium is reduced, whereas those of Prevotellaceae are increased in human colon cancers than matched adjacent normal tissue. Administration of Bifidobacterium mitigated intestinal inflammation and carcinogenesis in Ffar2(-/-) mice. Taken together, these findings suggest that interplay between dietary fibre and Ffar2 play a key role in promoting healthy composition of gut microbiota that stimulates intestinal health.

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Author(s): Sivaprakasam S, Gurav A, Paschall AV, Coe GL, Chaudhary K, Cai Y, Kolhe R, Martin P, Browning D, Huang L, Shi H, Sifuentes H, Vijay-Kumar M, Thompson SA, Munn DH, Mellor A, McGaha TL, Shiao P, Cutler CW, Liu K, Ganapathy V, Li H, Singh N

Publication type: Article

Publication status: Published

Journal: Oncogenesis

Year: 2016

Volume: 5

Print publication date: 01/06/2016

Online publication date: 27/06/2016

Acceptance date: 18/04/2016

Date deposited: 18/08/2016

ISSN (electronic): 2157-9024

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/oncsis.2016.38

DOI: 10.1038/oncsis.2016.38

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