Regulation of CD4+ and CD8+ T Cell Biology by Short-Chain Fatty Acids and Its Relevance for Autoimmune Pathology

The gut microbiota encodes a broad range of enzymes capable of synthetizing various metabolites, some of which are still uncharacterized. One well-known class of microbiota-derived metabolites are the short-chain fatty acids (SCFAs) such as acetate, propionate, butyrate and valerate. SCFAs have long been considered a mere waste product of bacterial metabolism. Novel results have challenged this long-held dogma, revealing a central role for microbe-derived SCFAs in gut microbiota-host interaction. SCFAs are bacterial signaling molecules that act directly on host T lymphocytes by reprogramming their metabolic activity and epigenetic status. They have an essential biological role in promoting differentiation of (intestinal) regulatory T cells and in production of the anti-inflammatory cytokine interleukin-10 (IL-10). These small molecules can also reach the circulation and modulate immune cell function in remote tissues. In experimental models of autoimmune and inflammatory diseases, such as inflammatory bowel disease, multiple sclerosis or diabetes, a strong therapeutic potential of SCFAs through the modulation of effector T cell function was observed. In this review, we discuss current research activities toward understanding a relevance of microbial SCFA for treating autoimmune and inflammatory pathologies from in vitro to human studies.

Automated summary

The gut microbiota produces a variety of enzymes that can synthesize different metabolites, including short-chain fatty acids (SCFAs). Recent research has revealed a central role for microbe-derived SCFAs in the interaction between gut microbiota and the host, directly affecting the metabolic activity and epigenetic status of host T lymphocytes. SCFAs play a crucial biological role in promoting the development of regulatory T cells and the production of the anti-inflammatory cytokine interleukin-10 (IL-10). These small molecules can also circulate and modulate immune cell function in distant tissues, showing therapeutic potential in autoimmune and inflammatory diseases.