Kidney Transplantation and the Gut-Kidney Axis: Microbial, Metabolic, and Nutritional Implications for Graft and Patient Outcomes.

BACKGROUND

Kidney transplantation is the preferred treatment for end-stage kidney disease (ESKD), but long-term outcomes remain limited by chronic allograft injury, infections, metabolic complications, and cardiovascular risk. Gut microbiota alterations and microbiota-derived metabolites may influence immune regulation, inflammation, drug metabolism, and graft outcomes through the gut-kidney axis. This review summarizes evidence on the gut microbiota in kidney transplantation, emphasizing immune tolerance, complications, cardiovascular risk, graft function, and perspectives.

METHODS

A structured search was conducted in PubMed, Scopus, and Web of Science to May 2026. Eligible publications included studies involving kidney transplant recipients (KTR), kidney disease or solid organ transplant populations, and mechanistic models. Evidence was synthesized narratively.

RESULTS

Gut microbiota alterations in KTR reflect pre-transplant dysbiosis and post-transplant exposures, including antibiotics, immunosuppression, infection, diet, hospitalization, and graft function. Dietary factors and nutrient-derived substrates may modulate microbial composition and production of relevant metabolites, including short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), tryptophan-derived compounds, bile acid derivatives, and uremic toxins. Microbiota-related pathways may involve barrier dysfunction, microbial translocation, innate immune activation, altered regulatory T cell/T helper 17 (Treg/Th17) balance, metabolite signaling, uremic toxin generation, and endothelial stress. Clinical studies associate dysbiosis and microbial metabolites with diarrhea, infections, delayed graft function (DGF), rejection-related shifts, tacrolimus variability, cardiovascular risk, graft dysfunction, graft failure, and mortality. Most findings need validation.

CONCLUSIONS

Gut microbiota signatures and microbial metabolites are promising markers of transplant-related risk, but not established causal determinants or therapeutic targets. Clinical translation requires standardized methods, multi-omics integration, and prospective patient- and graft-centered trials.