The gut microbiota associated with high-Gleason prostate cancer.

We have found that intestinal bacteria and their metabolites, short-chain fatty acids (SCFAs), promote cancer growth in prostate cancer (PCa) mouse models. To clarify the association between gut microbiota and PCa in humans, we analysed the gut microbiota profiles of men with suspected PCa. 152 Japanese men undergoing prostate biopsies (96 with cancer and 56 without cancer) were included in the study and randomly divided into two cohorts: discovery cohort (114 samples) and test cohort (38 samples). The gut microbiota was compared between two groups, a high-risk group (men with Grade group 2 or higher PCa) and a negative + low-risk group (men with negative biopsy or Grade group 1 PCa) using 16S rRNA gene sequencing. The relative abundances of Rikenellaceae, Alistipes, and Lachnospira, all SCFAs-producing bacteria, were significantly increased in high-risk group. In receiver operating characteristic curve analysis, the index calculated from the abundance of 18 bacterial genera which were selected by least absolute shrinkage and selection operator regression, detected high-risk PCa in the discovery cohort with higher accuracy than the prostate specific antigen test (area under the curve (AUC) = 0.85 vs. 0.74). Validation of the index in the test cohort showed similar results (AUC = 0.81 vs. 0.67). The specific bacterial taxa were associated with high-risk PCa. The gut microbiota profile could be a novel useful marker for the detection of high-risk PCa and could contribute the carcinogenesis of PCa. Supporting Information Document S1: Mathematical structure of the FMPI.