Impact of Androgen Deprivation Therapy on the Gastrointestinal Microbiota of Prostate Cancer Patients

Abstract

Background: Prostate Cancer (PCa) is one of the leading causes of cancer in men. Androgen deprivation therapy (ADT), the standard of care for advanced PCa, has been associated with developing the metabolic syndrome. The gastrointestinal microbiota (GIM) plays a central role in governing host metabolic processes. We aimed to prospectively investigate the short and long-term impact of ADT on the GIM of PCa patients. We hypothesized that there will be a reduction in gastrointestinal bacteria associated with promoting human health (Clostridiaceae and Bifidobacteriaceae families) and an enrichment of bacteria associated with human pathologies (Bacteroidaceae and Enterobacteriaceae families) in men following ADT initiation. Methods: Men with PCa prior to ADT initiation or those on a watchful waiting protocol (WWP) were enrolled by the Centre of Applied Urological Research. Stool, blood, urine and saliva specimens were collected from men at baseline (prior to ADT initiation) and then prospectively 3, 6, 9 and 12 months following enrolment. Participants were asked to complete a questionnaire about food habits, basic demographics, medication use and history of gastrointestinal inflammatory disorders. DNA isolated from stool samples was sequenced on an Illumina MiSeq 2000 and analyzed on MicrobiomeAnalyst and Prism 8, using alpha and beta diversity metrics for community level analysis, and nonparametric Friedman tests with Dunn’s multiple comparisons, for bacterial level analysis. Results: Fifteen PCa ADT-naïve men were enrolled; 11/15 initiated ADT, while 4/15 were on a WWP. The median age of both cohorts was 76, while mean weight, body-mass index, and waist circumference was significantly different between the two groups at baseline (p = 0.001, p = 0.018, p = 0.050, respectively). Sequencing analysis revealed no significant differences in community diversity between the two cohorts at baseline. ADT initiation was associated with no significant changes after 3 months, however 6 months of ADT was associated with a complete loss in Bifidobacteriaceae family (p = 0.04). Conclusions: The reduction of the family Bifidobacteriaceae may be linked to the metabolic changes associated with ADT initiation. Our study is the first to provide a prospective analysis on the impact of ADT on the GIM of PCa patients.