Increased Akkermansia abundance is associated with increased colonic mucosal ω-3 fatty acids and decreased colonic mucosal PGE2 concentrations following healthy dietary pattern interventions

Abstract

ABSTRACTBoth increased dietary intake of ω-3 polyunsaturated fatty acids (PUFA) and subsequent increases in colonic mucosal ω-3 PUFA concentrations have been linked to improved gut barrier function and decreased risks of metabolic diseases and cancer. In addition, increased dietary ω-3 PUFA has been linked to eubiosis in mouse studies. Increased ω-3 PUFA function in part to reduce cyclooxygenase-(COX) mediated prostaglandin E2 (PGE2) production, a biomarker of cancer risk linked to compromised gut barrier function. We analyzed data from a dietary intervention study in individuals at increased risk of colon cancer to determine whether changes in the mucosal microbiome composition were associated with changes in colonic mucosal ω-3/ ω-6 PUFA ratio. Microbiome analyses of colonic biopsies before and after the dietary intervention from 86 participants were done by sequencing the V4 region of the 16S rRNA gene. Multivariable linear regression models were used to evaluate further whether changes in Akkermansia was associated with changes in each colonic tissue variable: ω-3/ω-6 PUFA ratios, PGE2 concentrations, and expression of COX-1 and COX-2. The median dietary intake and mucosal ω-3/ω-6 PUFA ratio increased after intervention. Greater increases in mucosal ω-3/ω-6 PUFA ratios after intervention were significantly associated with several changes in taxon abundance, including increased Akkermansia muciniphilia relative abundance. An increased abundance of Akkermansia muciniphilia also was associated significantly with decreased PGE2 concentrations but not with changes in COX expression. Further studies are warranted to elucidate mechanisms by which Akkermansia may affect or is affected by these pathways and the relative importance of individual dietary components.