BackgroundProstate cancer (PC) is the most common cancer in men worldwide. The incidence of PC varies significantly geographically, which might result e.g. from genetic factors and local discrepancies in screening policies, but also from differences in lifestyle such as diet. Novel environmental factor, namely gut microbiota (GM) has been recently associated with many pathological processes including tumor progression within human body but its role in PC is disputable.MethodsWithin a clinical prospective single center trial, the GM profiles were assessed from 181 men with clinical suspicion of PC utilizing 16S rRNA gene sequencing (Illumina). Sequences were assigned to operational taxonomic units (OTUs) after which differential abundance analysis, α- and β-diversities, and predictive functional (PICRUST) analysis were performed. Further, plasma steroid hormone levels correlated to predicted microbiota functions.ResultsPC was diagnosed in 60% (108/181). Apart for less smoking among subjects with PC, there were no life-style differences between the groups. The GM profiles of men with PC differed significantly from those without cancer, e.g. Prevotella 9, members of family Erysipelotrichaceae and potentially pathogenic Escherichia-Shigella were increased, and e.g. Jonquetella, Moryella, Anaeroglobus, Corynebacterium and CAG-352 were reduced in PC cases. Predictive functional analyses revealed increased 5-α-reductase activity (5-AR), copper absorption and retinal metabolism as functional results of different microbiota. Plasma testosterone negatively correlated with predicted microbial 5-AR activity (Wilcoxon rank sum p=0.057) and in a subgroup of men taking 5-AR inhibitors (n=17), plasma estrone (p=0.027), and estradiol (p=0.054) levels were higher in men with predicted increased microbial 5-AR function.ConclusionsCertain bacterial and functional features within GM composition are associated with PC risk and altered androgen, copper and retinol metabolism are potential mechanisms. Findings could explain the previously reported association of life-style effects and geographical differences observed in PC.Trial registration numberNCT02241122
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.
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