BackgroundAlthough prostate cancer (PCa) 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 recently been associated with cancer progression, but its role in PCa is unclear.ObjectiveCharacterization of the gut microbiota and its functions associated with PCa.Design, setting, and participantsIn a prospective multicenter clinical trial (NCT02241122), the gut microbiota profiles of 181 men with a clinical suspicion of PCa were assessed utilizing 16S rRNA sequencing.Outcome measurements and statistical analysisSequences were assigned to operational taxonomic units, differential abundance analysis, and α- and β-diversities, and predictive functional analyses were performed. Plasma steroid hormone levels corresponding to the predicted microbiota steroid hormone biosynthesis profiles were investigated.Results and limitationsOf 364 patients, 181 were analyzed, 60% of whom were diagnosed with PCa. Microbiota composition and diversity were significantly different in PCa, partially affected by Prevotella 9, the most abundant genus of the cohort, and significantly higher in PCa patients. Predictive functional analyses revealed higher 5-α-reductase, copper absorption, and retinol metabolism in the PCa-associated microbiome. Plasma testosterone was associated negatively with the predicted microbial 5-α-reductase level.ConclusionsGut microbiota of the PCa patients differed significantly compared with benign individuals. Microbial 5-α-reductase, copper absorption, and retinol metabolism are potential mechanisms of action. These findings support the observed association of lifestyle, geography, and PCa incidence.Patient summaryIn this report, we found that several microbes and potential functions of the gut microbiota are altered in prostate cancer compared with benign cases. These findings suggest that gut microbiota could be the link between environmental factors and prostate cancer.

Fluoroquinolones are a commonly used prophylaxis in transrectal ultrasound-guided prostate biopsy (TRUS-Bx), even though fluoroquinolone-resistant Escherichia coli has been associated with infectious complications after TRUS-Bx. The present study describes fluoroquinolone resistance mechanisms and antimicrobial susceptibility among intestinal E. coli , isolated from TRUS-Bx patients in a prospective study showing very few infectious prostate biopsy adverse events. This Multi-IMPROD sub-study included a total of 336 patients who received either ciprofloxacin, levofloxacin, or fosfomycin as prophylaxis before TRUS-Bx. E. coli could be cultured from 278 fecal swab samples, and 27 (9.7%) of these showed resistance to ciprofloxacin, and 14 (5.0%) were susceptible with increased exposure (I). Chromosomal and transferable fluoroquinolone resistance mechanisms were found among ciprofloxacin non-susceptible isolates, but both qnr genes and single gyrA mutations were found also among the ciprofloxacin-susceptible E. coli population. Low-level fluoroquinolone resistance is commonly associated with ESBL production in Enterobacterales . However, ESBL and qnr genes were not associated in our material, 14 isolates were ESBL producers and only 14.3% of them had the qnr gene, although 85.7% of the ESBL producers were ciprofloxacin non-susceptible. In the Multi-IMPROD substudy, only two mild urinary tract infections were reported, indicating that the antimicrobial susceptibility or resistance pattern of E. coli does not correlate with the onset of post-biopsy adverse events. We conclude that in our clinical settings, ciprofloxacin and levofloxacin prophylaxis is effective, and no severe post-biopsy infections were detected despite the intestinal colonization of genotypically and phenotypically fluoroquinolone-resistant E. coli .

ABSTRACT Purpose Although 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. Methods In 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, α- and β-diversities, and predictive functional (PICRUSt) analyses were performed. Additionally, plasma steroid hormone levels were correlated with the predicted microbiota functions. Results Several 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-α-reductase, copper absorption, and retinal metabolism in the prostate cancer associated microbiome. Plasma testosterone associated negatively with the microbial 5-α-reductase activity (p=0.030). In a subgroup of men taking 5-α-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-α-reductase function. Conclusions Gut microbiota of the prostate cancer patients differed significantly compared to benign subjects. Microbial 5-α-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.