Diet-derived microbial metabolites as regulators of immune function

The intestinal microbiota transforms dietary components into bioactive metabolites that profoundly influence mucosal and systemic immunity. Short-chain fatty acids, secondary bile acids and tryptophan-derived indoles are among the most studied microbial metabolites shaping T, B and innate immune cell functions through a variety of mechanisms, including receptor signaling, epigenetic modification and metabolic reprogramming. Dietary habits strongly affect the composition of the intestinal microbiota and thus, the production and availability of these microbial metabolites, with consequences that range from protective immune regulation to detrimental inflammatory responses. Here, we review recent findings from mouse and human studies, highlighting how the microbiota-immunity axis can be modulated by diets and discuss implications for tissue homeostasis, infection and chronic inflammatory diseases. Understanding this complex interplay may guide the development of ad hoc dietary and microbial interventions to restore tolerance and improve therapeutic outcomes.