[Microbiome as a Novel Player in the Development and Treatment of Renal Cancer: A Systematic Review and...

Growing evidence highlights the significant role of the human microbiota and microbiome in the pathogenesis of malignant tumors, including renal cell carcinoma (RCC). This systematic review evaluates studies addressing the associations between the microbiota/microbiome and the development and progression of RCC, as well as the influence of the microbiota on therapeutic efficacy in this malignancy.

The review was conducted in accordance with PRISMA guidelines. A systematic search of bibliographic databases (PubMed, Scopus, etc.) using the keywords ("renal cell carcinoma"/"kidney cancer"/"renal cancer" and "microbiota"/"microbiome") identified 12,547 publications. After removal of duplicates and screening for eligibility, 33 studies directly examining the relationship between the microbiota and RCC were included in the analysis. Studies not relevant to the topic or focusing on tumor growth without specific reference to kidney cancer were excluded.

The review summarizes the composition and alterations of the microbiota in RCC: (1) the intratumoral microbiota of renal tumors differs from that of adjacent healthy kidney tissue, showing reduced diversity and distinct bacterial profiles; (2) the gut microbiota of RCC patients is dysbiotic compared with healthy controls, characterized by enrichment of potentially pro-carcinogenic taxa and depletion of protective bacteria; (3) the urinary microbiome also undergoes changes in RCC, though data remain limited. Potential mechanisms have been proposed: microbiota-derived metabolites (e.g., tryptophan-kynurenine pathway intermediates, short-chain fatty acids, trimethylamine N-oxide [TMAO]) may influence the tumor microenvironment, immune response, and metastatic potential. Importantly, gut microbiota composition has been shown to modulate response to immunotherapy in RCC: higher microbial diversity and the presence of specific taxa (e.g., Akkermansia muciniphila) are associated with improved response to immune checkpoint inhibitors, whereas dysbiosis and antibiotic exposure correlate with diminished efficacy. Several studies have demonstrated that modulation of the microbiome (via probiotics, prebiotics, or fecal microbiota transplantation) can enhance antitumor immunity and improve treatment outcomes in RCC, although clinical data specifically addressing RCC onset and progression remain limited.

The microbiota and microbiome are increasingly recognized as key factors in the development and progression of renal cell carcinoma, also influencing the effectiveness of contemporary therapeutic strategies. Further research is required to establish causal relationships and to develop microbiome-oriented approaches for the prevention and treatment of RCC.