Metabolic Biosynthesis Pathways Identified from Fecal Microbiome Associated with Prostate Cancer

Michael A. Liss, James Robert White, Martin Goros, Jonathan Gelfond, Robin Leach, Teresa Johnson-Pais, Zhao Lai, Elizabeth Rourke, Joseph Basler, Donna Ankerst, Dimpy P. Shah

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Background: The fecal microbiome is associated with prostate cancer risk factors (obesity, inflammation) and can metabolize and produce various products that may influence cancer but have yet to be defined in prostate cancer. Objective: To investigate gut bacterial diversity, identify specific metabolic pathways associated with disease, and develop a microbiome risk profile for prostate cancer. Design, setting, and participants: After prospective collection of 133 rectal swab samples 2 wk before the transrectal prostate biopsy, we perform 16S rRNA amplicon sequencing on 105 samples (64 with cancer, 41 without cancer). Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was applied to infer functional categories associated with taxonomic composition. The p values were adjusted using the false discovery rate. The α- and β-diversity analyses were performed using QIIME. The Mann-Whitney U test was employed to evaluate the statistical significance of β-diversity distances within and between groups of interest, and least absolute shrinkage and selection operator (LASSO) regression analysis was used to determine pathway significance. Outcome measurements and statistical analysis: The detection of prostate cancer on transrectal prostate needle biopsy and 16s microbiome profile. Results and limitations: We identified significant associations between total community composition and cancer/non-cancer status (Bray-Curtis distance metric, p < 0.01). We identified significant differences in enrichments of Bacteroides and Streptococcus species in cancer (all p < 0.04). Folate (LDA 3.8) and arginine (LDA 4.1) were the most significantly altered pathways. We formed a novel microbiome–derived risk factor for prostate cancer based on 10 aberrant metabolic pathways (area under curve = 0.64, p = 0.02). Conclusions: Microbiome analyses on men undergoing prostate biopsy noted mostly similar bacterial species diversity among men diagnosed with and without prostate cancer. The microbiome may have subtle influences on prostate cancer but are likely patient-specific and would require paired analysis and precise manipulation, such as improvement of natural bacterial folate production. Patient summary: Microbiome evaluation may provide patients with personalized data regarding the presence or absence of particular bacteria that have metabolic functions and implications regarding prostate cancer risk. The study provides a basis to investigate the manipulation of aberrant microbiomes to reduce prostate cancer risk. We note minimal differences in the microbiome profiles between men diagnosed with and without prostate cancer. While a global microbiome profile is unlikely to predict prostate cancer, bacteria associated with a specific metabolic pathway, such as B vitamins, do seem to have an association with prostate cancer and warrant further investigation.

Original languageEnglish (US)
Pages (from-to)575-582
Number of pages8
JournalEuropean Urology
Volume74
Issue number5
DOIs
StatePublished - Nov 2018

Keywords

  • B vitamins
  • Biomarker
  • Biotin
  • Folate
  • Microbiome
  • Prostate cancer

ASJC Scopus subject areas

  • Urology

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