Assessing the causal relationship between gut microbiota and prostate cancer: a two-sample Mendelian randomization study

Abstract

Abstract Background Numerous studies indicate that the gut microbiome is closely associated with prostate cancer (PCa), however, owing to various confounding factors, the causal relationship between gut microbiota and PCa remains unclear. Methods A two-sample Mendelian randomization (MR) analysis utilized genome-wide association study (GWAS) data on the gut microbiota of 18,340 participants and GWAS summary statistics on PCa involving 46,3010 participants. Inverse variance weighted (IVW) served as the primary method, complemented by the MR-Egger method, weighted median method (WME), simple mode method (SM), and weighted mode method (WM). Finally, to confirm the robustness of the results, heterogeneity test, pleiotropy test, and leave-one-out sensitivity test were conducted. Results IVW analysis revealed that 12 gut microbial taxa were potentially causally associated with PCa; the genera Victivallis, Akkermansia, Odoribacter, Butyrivibrio, and the families Enterobacteriaceae, Verrucomicrobiaceae, as well as the orders Verrucomicrobiales, Enterobacteriales and the class Verrucomicrobiae, were found to be positively associated with PCa risk. Conversely, the genera Eubacterium ruminantium group, Candidatus Soleaferrea, and RuminococcaceaeUCG003 were negatively associated with PCa risk. Conclusions Our MR study's results support a genetically predicted causal relationship between the gut microbiota and PCa, and they identify 12 specific gut microbial taxa. These findings could offer new targets for PCa screening and treatment.