Authors of a comprehensive review highlight the gut-kidney axis as a potential contributor to both acute kidney injury (AKI) and chronic kidney disease (CKD). Kidney disease–associated dysbiosis is characterized by loss of beneficial microbes and short-chain fatty acids (SCFAs), disruption of intestinal barrier integrity, and increased production of uremic toxins such as indoxyl sulfate, p-cresyl sulfate, and trimethylamine N-oxide. These changes may amplify systemic inflammation, oxidative stress, and renal fibrosis through pathways including NF-κB, TGF-β/Smad, Nrf2, NLRP3, and aryl hydrocarbon receptor signaling. Distinct microbial and metabolic alterations have been reported across CKD, diabetic kidney disease, IgA nephropathy, membranous nephropathy, lupus nephritis, dialysis, transplantation, and the transition from AKI to CKD. This supports a bidirectional relationship in which kidney dysfunction promotes dysbiosis and dysbiosis may further aggravate kidney injury.
Targeting the microbiome is therefore being investigated as a therapeutic strategy. Probiotics, prebiotics, and synbiotics may help restore microbial balance, increase protective SCFAs, reduce uremic toxins, and modulate inflammatory pathways. Fecal microbiota transplantation and several natural products have also shown potential effects on renal inflammation, fibrosis, proteinuria, and metabolic dysfunction. However, much of this evidence comes from animal models and mechanistic studies, with more limited human clinical data. The authors emphasize that large, rigorous clinical trials are still needed before microbiome-directed approaches can be incorporated broadly into kidney disease management. The emerging evidence underscores the potential clinical importance of the gut-kidney axis while reinforcing that microbiome-based therapies remain investigational rather than established components of CKD or AKI treatment.
Reference: Jin Y, Zhang SJ, Zhuang S, et al. Microbiota-gut-kidney axis in health and renal disease. Int J Biol Sci. 2026 Jan 1;22(2):750-770. doi: 10.7150/ijbs.125140.
