Gut-kidney axis regulates renal immune homeostasis via short-chain fatty acids

Short-chain fatty acids (SCFAs) are key gut-derived metabolites, mainly including acetate, propionate, and butyrate, which directly and indirectly interact with or influence immunity. SCFAs regulate renal and systemic immune responses via G protein-coupled receptor (GPR) signaling, inhibition of histone deacetylase (HDAC) activity, and energy metabolism. SCFAs affect not only infiltrated immune cells but also renal resident cells, leading to changes in the renal inflammatory microenvironment. In this review, we summarize the role of SCFAs in systemic and renal immune regulation, by which they may affect the pathogenesis and progression of kidney diseases. Furthermore, we discuss the feasibility of SCFA-targeted intervention as a promising therapeutic strategy for kidney diseases and the challenges faced in clinical application.