Traditional Chinese medicine interventions targeting the gut–kidney axis in diabetic kidney disease: pharmacological evidence and translational challenges

Diabetic kidney disease (DKD) is a major cause of chronic kidney disease and kidney failure worldwide. The gut–kidney axis, encompassing gut microbial dysbiosis, altered microbial metabolites, intestinal barrier dysfunction, and systemic and intrarenal inflammation, has emerged as a potential contributor to DKD progression. Traditional Chinese medicine (TCM) formulas, single botanical drugs, botanical extracts and enriched fractions, and purified phytochemicals or their chemically modified derivatives have increasingly been investigated as modulators of this axis, although the underlying mechanisms remain incompletely understood. This narrative review summarizes current clinical and preclinical evidence concerning the effects of TCM interventions on the gut–kidney axis in DKD. Literature searches of PubMed and Web of Science from database inception to September 2026, supplemented by manual screening of relevant reference lists, informed this review. Available studies suggest that TCM interventions may improve renal phenotypes in association with restoration of intestinal barrier integrity, modulation of gut microbial composition, and regulation of metabolites such as short-chain fatty acids, indole derivatives, protein-bound uremic toxins, bile acids, and trimethylamine N-oxide. However, only a limited number of studies have used antibiotic-mediated microbiota depletion, fecal microbiota transplantation, or direct metabolite intervention to examine microbiota-related causality. Product characterization, dose justification, randomization, blinding, and analytical quality control also remain inconsistently reported, while clinical evidence is still limited. Overall, current findings suggest a potential contribution of the gut microbiota and its metabolites to the renoprotective effects of TCM. Future studies using chemically standardized preparations, pharmacologically relevant dosing, rigorous experimental controls, causal microbiome approaches, systematic safety assessment, and adequately powered clinical trials are needed.