Fig. 5: Functional interactions between long-chain polyunsaturated fatty acid, gut microbiota and prostate cancer development.

a TRAMP-C2 tumour growth in mice pre-treated with different purified versions of long-chain polyunsaturated fatty acids (PUFA); monoglyceride arachidonic acid (MAG-AA), MAG-docosahexaenoic acid (DHA) or MAG-eicosapentaenoic acid (EPA) and control high oleic sunflower oil (HOSO) (n = 12/group). p ≤ 0.05, Welch’s t-test. b Relative abundance, in % of total 16S rRNA sequences, of Ruminococcaceae 16srRNA from fecal DNA samples of mice with TRAMP-C2 pre-treated with different PUFA molecules (n = 8/group). p ≤ 0.05, Welch’s t-test. c qPCR validation of Ruminococcaceae 16S rRNA levels from fecal DNA samples of mice with TRAMP-C2 pre-treated with PUFA molecules. Data is presented as relative levels (fold change) normalized to total 16S rRNA sequences (n = 12/group). p ≤ 0.05, Welch’s t-test. d Relative abundance of Ruminococcaceae from fecal DNA samples of patients in relation to their prostate tumour grade change (Gleason score from histopathological analysis of prostate tumour at surgery compared to histological score of the biopsy of study enrolment), p ≤ 0.05, Welch’s t test. e A randomized clinical trial (NCT02333435) was performed at our clinical facility testing the effect of MAG-EPA PUFA on prostate cancer patients before radical prostatectomy. A subset of 41 patients donated fecal samples for research at study baseline and the morning before surgery, 7.2 ± 0.37 weeks later. Change in prostate tumour grade was compared between patients receiving MAG-EPA or placebo 7 weeks prior to surgery. The percentage of patients without any change in their cancer grade, with apparent downgrade or upgrade in their prostate cancer grade group score is shown as a fraction of the total cases per group. Statistical test was Chi square comparing % for the 3 categories between MAG-EPA (n = 21) and placebo control (n = 20). p ≤ 0.05, chi square test. f Using DNA extracted from fecal samples corresponding to (e), we used 16S rRNA metataxonomic to compare the profiles corresponding to men before and after 7.2 ± 0.37 weeks of MAG-EPA (n = 21) supplementation or placebo (n = 20). The relative abundance of sequences corresponding to Ruminococcaceae is shown, p ≤ 0.05, Paired–Wilcoxon test. Line colors represent Ruminococcaceae enrichment (red), depletion (green) or no change (grey). Graphs are mean ± SEM.