In a study recently published, the authors aimed to investigate gut bacterial diversity in prostate cancer. They also aimed to identify specific metabolic pathways related to microbiota and use of the intestinal microbiome as a biomarker.2 In this study 16S r RNA was used to sequence the DNA of patients. The consort diagram of the trial is seen in figure 1:
Figure 1 – Trial consort diagram:
In this study the authors attempted to investigate gut bacterial diversity and identify specific metabolic pathways which are associated with disease. They also aimed to develop a microbiome risk profile for prostate cancer. After prospective collection of 133 rectal swab samples 2 weeks before the transrectal prostate biopsy. The authors also performed 16S rRNA amplicon sequencing on 105 samples (64 with cancer, 41 without cancer). Regression analysis was used to determine pathway significance. The primary endpoint was the detection of prostate cancer on transrectal prostate needle biopsy.
The results clearly showed that there are significant associations between total community composition and cancer/non-cancer status (p < 0.01). Importantly, significant differences in enrichments of Bacteroides and Streptococcus species in cancer was found (all p < 0.04). Folate (LDA 3.8) and arginine (LDA 4.1) were the most significantly altered pathways. After forming a novel microbiome–derived risk factor for prostate cancer based on 10 aberrant metabolic pathways, the area under curve was = 0.64, p = 0.02.
The authors identified several factors in which the intestinal microbiome could be involved in men diagnosed with prostate cancer. These include
1. Microbiome analysis on men undergoing prostate biopsy with mostly overlapping bacterial communities between those with and without prostate cancer.
2. It was clear that Bacteria associated with carbohydrate metabolism pathway were in abundance, and natural B-vitamin production was lacking in patients with prostate cancer.
3. Lastly, identification of a new 10-microbiome metabolic pathway score may provide an additional risk factor for prostate cancer, which is potentially modifiable.
In summary, bacteroides can increase the risk of prostate cancer, while vitamin B microbiome can decrease the risk of cancer. We are left with the question whether targeting the microbiome metabolic pathways is the required next step (Figure 2). The fecal microbiome of men undergoing prostate biopsy is similar between cancer and non-cancer groups. However, the microbiome metabolic pathways provide interesting biological insights, but it is unlikely to produce a “cancer” microbiome predictive risk profile. The most interesting bacterial metabolic pathways are the ones that create natural folate, and other B-vitamins that are more common among those without prostate cancer warrant further investigation
Figure 2: - Evaluation of prostate cancer risk
Presented by: Michael A. Liss, MD, Assistant Professor, Medical Director of Research at UHS, UT Health San Antonio, San Antonio, TX
References:
1. Siva A et al. Science 2018
2. Liss MA et al. European Urology 2018
Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, @GoldbergHanan, at the 19th Annual Meeting of the Society of Urologic Oncology (SUO), November 28-30, 2018 –Phoenix, Arizona