A Low Fiber Diet Minimize Colonic Short Chain Fatty Acids, Increase Severity and Prolongs Recovery in DSS Induced Colitis, Independent of Free Fatty Acid Receptor 2 and 3 Signaling

Short-chain fatty acids (SCFAs) are the major microbial metabolites produced in the gutthrough the fermentation of non-digestible fibers. SCFAs act through free fatty acid receptor 2 and3 (FFAR2 and 3), which are known to be expressed on glucagon-like peptide-1 (GLP-1)-secreting L-cells. This pathway is suggested to protect the intestinal mucosa. We aimed to investigate how lackof fiber affects the production of SCFAs and the vulnerability of the colon. Additionally, theinvolvement of FFAR2 and 3 in GLP-1 secretion and intestinal protection. SCFA concentrations inluminal contents from chow- or fiber-free diet-fed mice were analysed by LC‒MS. SCFAs wereapplied to isolated perfused colons from FFAR2/3 double KO and WT mice, and the secretion ofGLP-1 was measured. Dextran sulfate sodium (DSS) colitis was induced in chow- or fiber-free diet-fed mice as well as in FFAR2/3 KO and WT mice. The removal of dietary fiber significantlydecreased total colonic SCFA concentrations, with specific decreases in acetate, propionate, andbutyrate. SCFAs significantly increased colonic GLP-1 secretion but not in FFAR2/3 KO mice. In theDSS model, the removal of dietary fiber increased the severity and delayed recovery. Colitis severitywas independent of FFAR2 and FFAR3 signaling