Uremic Clearance Granules Regulate Immune Equilibrium via Gut Microbiome to Alleviate Chronic Renal Failure

Chronic renal failure (CRF) is the common end point of various chronic kidney diseases, and there is currently no specific drug for CRF. Effectively halting its progression remains a clinical challenge. Gut microbiota disorders are a key factor influencing immune dysfunction in chronic kidney disease patients. Intervening in gut microbiota to improve immune regulatory function in patients could serve as a new strategy for treating CRF with Traditional Chinese Medicine. Uremic Clearance Granules (UCG), a Traditional Chinese Medicine formulation, effectively attenuate CRF progression, but their active components and mechanisms remain undefined. This study investigates how UCG mitigate CRF via coordinated regulation of gut microbiota, metabolites, and the T helper 17 cells / regulatory T cell axis. Using an adenine-induced CRF mouse model, we combined gut microbiota depletion, fecal microbiota transplantation, 16S rRNA sequencing, and metabolomics to delineate the gut-kidney interactions underlying UCG efficacy. Flow cytometry quantified immune cell profiles in blood, and microbial intervention experiments verified the therapeutic role of Bifidobacterium animalis (B. animalis). In this study, we found that UCG treatment alleviated renal injury, reduced intestinal permeability, and up-regulated intestinal barrier markers. Microbiota depletion and fecal microbiota transplantation demonstrated that UCG's renoprotective effects depend on gut microbial modulation. Specifically, UCG ameliorates CRF through gut-kidney axis remodeling by enhancing B. animalis abundance and sophocarpine, thereby rebalancing T helper 17/regulatory T immunity and preserving renal function. These findings identify a microbiota-dependent immunometabolic mechanism for UCG and highlight a potential therapeutic strategy for CRF via the drug-microbiota axis.