Gut microbiota signatures associate with prostate cancer risk

PurposeAlthough prostate cancer is the most common cancer in men in Western countries, there is significant variability in geographical incidence. This might result from genetic factors, discrepancies in screening policies or differences in lifestyle. Gut microbiota has been recently associated with cancer progression, but its role in prostate cancer is unclear. MethodsIn a prospective multicenter clinical trial (NCT02241122), the gut microbiota profiles of 181 men with a clinical suspicion of prostate cancer were assessed utilizing 16S rRNA gene sequencing. Sequences were assigned to operational taxonomic units, and differential abundance analysis, - and {beta}-diversities, and predictive functional (PICRUSt) analyses were performed. Additionally, plasma steroid hormone levels were correlated with the predicted microbiota functions. ResultsSeveral differences in the gut microbiota between the subjects with and without prostate cancer were noted. Prevotella 9, members of the Erysipelotrichaceae family and Escherichia-Shigella were higher, and Jonquetella, Moryella, Anaeroglobus, Corynebacterium and CAG-352 were lower in the cancer group. Predictive functional analyses revealed higher 5--reductase, copper absorption, and retinal metabolism in the prostate cancer associated microbiome. Plasma testosterone associated negatively with the microbial 5--reductase activity (p=0.030). In a subgroup of men taking 5--reductase inhibitors (n=17), plasma estrone (p=0.027) and estradiol (p=0.059) levels were lower in men with predicted elevation of the microbial 5--reductase function. ConclusionsGut microbiota of the prostate cancer patients differed significantly compared to benign subjects. Microbial 5--reductase, copper absorption and retinol metabolism are potential mechanisms of action. These findings could explain the observed association of lifestyle, geography, and prostate cancer incidence.