Causal association between gut microbiota and risk of chronic prostatic diseases: A bi-directional two-sample Mendelian randomization study

Growing evidence suggests an association between gut microbiota and prostate diseases. However, the causal evidence between the two remains limited. This study aims to investigate the causal relationship between gut microbiota and prostate diseases in humans. Genome-wide association data for 119 types of gut microbiota genera were obtained from the MiBioGen consortium ( n = 18,340), and data for chronic prostatitis ( n = 1,106), benign prostatic hyperplasia ( n = 14,126) and prostate cancer ( n = 7,691) were obtained from the UK Biobank. To explore causal relationships between gut microbiota and the 3 chronic prostatic diseases comprehensively, two-sample bi-directional Mendelian randomization (MR) was conducted using multiplicative random effect-inverse variance weighted (MRE-IVW) and other 5 methods, and the MR estimate was reported using odds ratio (OR) and 95% confidence interval (CI). Heterogeneity and pleiotropy of instrumental variables were assessed. According to the results of the MRE-IVW method, Clostridium sensu stricto 1 (OR = 1.28, 95% CI: 1.08, 1.51), Eisenbergiella (OR = 0.75, 95% CI: 0.62, 0.90), Enterorhabdus (OR = 0.66, 95% CI: 0.55, 0.80), and Veillonella (OR = 0.71, 95% CI: 0.57, 0.87) were causally associated with chronic prostatitis. Dorea (OR = 0.79, 95% CI: 0.67, 0.94), Eubacterium (ruminantium group) (OR = 1.14, 95% CI: 1.06, 1.23), Eubacterium (nodatum group) (OR = 1.07, 95% CI: 1.02, 1.13), Oscillospira (OR = 1.15, 95% CI: 1.04, 1.27), and Paraprevotella (OR = 1.07, 95% CI: 1.02, 1.13) were significantly associated with benign prostatic hyperplasia. Elevated abundance in Butyrivibrio increased the risk of prostate cancer (OR = 1.11, 95% CI: 1.06, 1.16). The causal associations were reinforced by consistent directions observed in the other 5 MR methods, and no significant horizontal pleiotropy or heterogeneity among instrumental variables were observed. Furthermore, reverse MR analysis did not reveal any significant causal effect. This study found that gut microbiota was causally associated with chronic prostatic diseases, which presented a promising new target for preventing and treating prostatic diseases. Further studies are necessary to clarify the mechanisms and guide clinical practices.