title: An essential role of Ffar2 (Gpr43) in dietary fibre-mediated promotion of healthy composition of gut microbiota and suppression of intestinal carcinogenesis.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Regents University, Augusta, GA, USA.|Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences, Lubbock, TX, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sivaprakasam
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Regents University, Augusta, GA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Gurav
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Regents University, Augusta, GA, USA.
authors.forename: A V
authors.initials: AV
authors.lastname: Paschall
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Regents University, Augusta, GA, USA.
authors.forename: G L
authors.initials: GL
authors.lastname: Coe
authors.affiliation: Cancer Research Center, Georgia Regents University, Augusta, GA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Chaudhary
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Regents University, Augusta, GA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Pathology, Georgia Regents University, Augusta, GA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kolhe
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Regents University, Augusta, GA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Martin
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Regents University, Augusta, GA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Browning
authors.affiliation: Cancer Research Center, Georgia Regents University, Augusta, GA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Regents University, Augusta, GA, USA.|Cancer Research Center, Georgia Regents University, Augusta, GA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Medicine, Georgia Regents University, Augusta, GA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Sifuentes
authors.affiliation: Departments of Nutritional Sciences & Medicine, Pennsylvania State University, Medical Center, Hershey, PA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Vijay-Kumar
authors.affiliation: Department of Medicine, Georgia Regents University, Augusta, GA, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Thompson
authors.affiliation: Cancer Research Center, Georgia Regents University, Augusta, GA, USA.|Department of Pediatrics, Georgia Regents University, Augusta, GA, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Munn
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK.
authors.forename: A
authors.initials: A
authors.lastname: Mellor
authors.affiliation: Department of Immunology, University of Toronto, Toronto, ON, Canada.
authors.forename: T L
authors.initials: TL
authors.lastname: McGaha
authors.affiliation: College of Nursing, Georgia Regents University, Augusta, GA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Shiao
authors.affiliation: Department of Periodontics, Georgia Regents University, Augusta, GA, USA.
authors.forename: C W
authors.initials: CW
authors.lastname: Cutler
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Regents University, Augusta, GA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences, Lubbock, TX, USA.
authors.forename: V
authors.initials: V
authors.lastname: Ganapathy
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Regents University, Augusta, GA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Regents University, Augusta, GA, USA.|Cancer Research Center, Georgia Regents University, Augusta, GA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Singh