Role of Immune Cells in Mediating the Effect of Gut Microbiota on Renal Cell Carcinoma

Background The gut microbiota plays a crucial role in the development of various illnesses, including immune-related disorders. However, the potential association between renal cell carcinoma (RCC) and gut microbiota remains underexplored. Methods We utilized data from Genome-Wide Association Studies (GWAS) public databases to perform a bidirectional Mendelian randomization (MR) analysis with two samples, aiming to investigate the causal relationship between gut microbiota and RCC. The primary analysis employed the inverse variance weighted (IVW) method. Extensive sensitivity analyses were conducted to evaluate heterogeneity and horizontal pleiotropy. Additionally, a two-step MR was used to identify potential mediator. Results Our analysis identified significant associations between 22 microbiota taxa and RCC, along with several immune cell traits implicated in RCC modulation by gut microbiota. For instance, Demequinaceae affected RCC through CD14- CD16- AC and CD45 on HLA DR + NK cells. Mediation effect proportions were used to explore the intricate relationships among gut microbiota exposures, immune markers, and their impact on RCC. Conclusion This study reveals the complex interplay between the gut microbiome, immune cells, and RCC. The associations and mediated effects of gut microbiota management for RCC offer valuable insights for future therapeutic strategies.