Gut microbiota affects prostate cancer risk through steroid hormone biosynthesis

Abstract

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

Gut microbiota in patients with prostate cancer: a systematic review and meta-analysis

“…After fulltext assessments of the remaining 34 articles, 27 were excluded due to non-conforming inclusion populations, lack of GM-related data, non-fecal sample origin, or absence of a control group. Consequently, 7 articles were included in this study [24][25][26][27][28][29][30], as illustrated in Fig. 1.…”

“…All studies employed 16sRNA sequencing, though the amplified regions of the 16S rRNA gene varied. Three studies targeted the V4 region [26,29,30], one the V3-V5 region [24], one the V3-V4 region [25], one the V6 region [27],…”

“…Five studies reported data on the relative abundance of bacteria at the family level [24][25][26][27]29]. Forest plots showed that the GM of the control group had higher proportions of Corynebacteriaceae, Veillonellaceae, Bacteroidaceae, and Actinomycetaceae compared to the PCa group.…”

Gut microbiota differs significantly between men with and without prostate cancer

“…Results from a prospective, multicenter study presented at the European Association of Urology annual congress (EAU22) and published as a preprint show significantly different gut microbiota in men with prostate cancer and men who do not have prostate cancer, and they suggest that variations in diet and lifestyle may play a role in prostate cancer risk 1 …”