Immunometabolism and microbial metabolites at the gut barrier: Lessons for therapeutic intervention in inflammatory bowel disease

The concept of immunometabolism has emerged recently whereby the repolarizing of inflammatory immune cells toward anti-inflammatory profiles by manipulating cellular metabolism represents a new potential therapeutic approach to controlling inflammation. Metabolic pathways in immune cells are tightly regulated to maintain immune homeostasis and appropriate functional specificity. Because effector and regulatory immune cell populations have different metabolic requirements, this allows for cellular selectivity when regulating immune responses based on metabolic pathways. Gut microbes have a major role in modulating immune cell metabolic profiles and functional responses through extensive interactions involving metabolic products and crosstalk between gut microbes, intestinal epithelial cells, and mucosal immune cells. Developing strategies to target metabolic pathways in mucosal immune cells through the modulation of gut microbial metabolism has the potential for new therapeutic approaches for human autoimmune and inflammatory diseases, such as inflammatory bowel disease. This review will give an overview of the relationship between metabolic reprogramming and immune responses, how microbial metabolites influence these interactions, and how these pathways could be harnessed in the treatment of inflammatory bowel disease.