Short-chain fatty acids as molecular bridges between the gut microbiota and systemic inflammation: mechanisms, organ-specific axes, and therapeutic opportunities

The gut microbiota plays a fundamental role in maintaining host physiological homeostasis. Among the diverse metabolites produced by intestinal microbes, short-chain fatty acids (SCFAs) represent one of the most functionally significant groups. These metabolites arise primarily from the fermentation of non-digestible carbohydrates and serve as a major interface between microbial metabolism and host signaling.

SCFAs possess anti-inflammatory properties in the intestinal microenvironment, promoting regulatory T cell differentiation and immune tolerance, and strategies aimed at increasing SCFA availability have been explored clinically. Traditionally viewed as local energy sources for colonocytes, SCFAs are now recognized as systemic signaling molecules capable of influencing distant organs.

After absorption, they enter the portal circulation and reach peripheral tissues, where they modulate immune responses, metabolism, and tissue homeostasis. This review therefore mainly elaborates on the functions of SCFAs in various inter-organ axes as well as related therapeutic strategies.