Microbial Metabolites in Kidney Disease: From Molecular Signaling to Metabolite-Targeted Therapeutics

The gut microbiome functions as a dynamic endocrine organ, producing a wide range of bioactive metabolites that regulate host physiology. In Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD), research is rapidly moving beyond descriptive taxonomic surveys of “dysbiosis” toward a mechanistic understanding of how specific microbial metabolites act as signaling molecules to drive renal injury or support tissue repair.This Research Topic aims to move beyond traditional descriptive microbiome studies by focusing on the biological functions of gut-derived metabolites, including short-chain fatty acids, bile acids, tryptophan derivatives, polyamines, and uremic toxins in modulating renal inflammation, mitochondrial bioenergetics, fibrosis, and epigenetic programming. It will also highlight the emergence of metabolite-targeted therapeutic strategies, shifting from non-specific probiotic approaches toward more precise interventions such as postbiotics, small-molecule inhibitors of bacterial enzymes, metabolite-adsorption technologies, and engineered microbes designed to reshape the metabolic landscape.To advance understanding of kidney injury and disease, we welcome submissions addressing, but not limited to, the following themes:• Metabolites as Signaling Molecules: Mechanistic studies examining how microbial metabolites interact with host receptors, such as AhR, GPR43, GPR109A, and TGR5, to regulate immune responses, renal tubular cell function, and tissue repair.• The “Good” and the “Bad”: Studies differentiating the roles of protective metabolites, such as butyrate and propionate, from harmful uremic toxins, including indoxyl sulfate (IS), p-cresyl sulfate (PCS), and trimethylamine N-oxide (TMAO), in AKI-to-CKD transition, renal fibrosis, and disease progression.• Novel Therapeutic Strategies: Research on postbiotics, paraprobiotics, engineered bacteria, and other targeted approaches to reduce toxin production, enhance protective metabolite delivery, or modulate host–microbe metabolic interactions.• Epigenetic and Mitochondrial Regulation: Investigations into how gut microbial metabolites influence the renal epigenome, mitochondrial dynamics, oxidative stress, and cellular metabolism during kidney injury and repair.• Nutritional Modulation of the Metabolome: Studies exploring how dietary interventions, such as resistant starch, fiber enrichment, or amino acid restriction, reshape the gut-derived metabolome and contribute to renal protection.• Translational Metabolomics: Research identifying serum, urinary, or fecal microbial metabolite signatures as diagnostic, prognostic, or predictive biomarkers that may outperform traditional clinical indices.We particularly encourage submissions spanning basic, translational, and clinical research that clarify causal mechanisms and therapeutic potential at the interface of the gut microbiome and kidney disease. Topic editors: Liang Wu, Orestes Foresto-Neto, Kun Gao Source: https://www.frontiersin.org/research-topics/80571/microbial-metabolites-in-kidney-disease-from-molecular-signaling-to-metabolite-targeted-therapeutics