Short-Chain Fatty Acids as Modulators of the Gut–Immune Axis in Inflammatory Bowel Disease: Linking Metabolism, Immune Regulation, and Epithelial Barrier Function

Inflammatory bowel diseases (IBDs), which include Crohn’s disease (CD) and ulcerative colitis (UC), are chronic conditions associated with abnormalities in the immune response, gut microbiota dysbiosis, and disruption of the intestinal barrier homeostasis. A growing body of evidence suggests that the gut–immune axis plays a key role in the pathogenesis of IBD, and that metabolites of microbial origin influence the regulation of the immune response and the maintenance of intestinal barrier integrity. Particular importance is attributed to short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate. The aim of this review is to present the current knowledge regarding the role of SCFAs as modulators of the gut–immune axis in IBD, with particular emphasis on their mechanisms of action and therapeutic potential. Physiologically, SCFAs are produced through the fermentation of dietary fiber by the gut microbiota. However, in IBD, the composition of the gut microbiota is often disrupted. SCFAs influence the expression of inflammatory genes and regulate the function of immune cells. Furthermore, butyrate in particular strengthens the integrity of the intestinal barrier by improving the function of tight junctions (TJs), increasing mucus production, and supporting epithelial regeneration. SCFAs represent an important link between diet, the gut microbiota, and immunity. Strategies to increase their availability may represent a promising approach to supporting IBD treatment, but they require further evaluation in well-designed clinical trials involving humans.