Compositional differences in gastrointestinal microbiota in prostate cancer patients treated with androgen axis-targeted therapies

Abstract

BackgroundIt is well known that the gastrointestinal (GI) microbiota can influence the metabolism, pharmacokinetics, and toxicity of cancer therapies. Conversely, the effect of cancer treatments on the composition of the GI microbiota is poorly understood. We hypothesized that oral androgen receptor axis-targeted therapies (ATT), including bicalutamide, enzalutamide, and abiraterone acetate, may be associated with compositional differences in the GI microbiota.MethodsWe profiled the fecal microbiota in a cross-sectional study of 30 patients that included healthy male volunteers and men with different clinical states of prostate cancer (i.e., localized, biochemically recurrent, and metastatic disease) using 16S rDNA amplicon sequencing. Functional inference of identified taxa was performed using PICRUSt.ResultsWe report a significant difference in alpha diversity in GI microbiota among men with versus without a prostate cancer diagnosis. Further analysis identified significant compositional differences in the GI microbiota of men taking ATT, including a greater abundance of species previously linked to response to anti-PD-1 immunotherapy such as Akkermansia muciniphila and Ruminococcaceae spp. In functional analyses, we found an enriched representation of bacterial gene pathways involved in steroid biosynthesis and steroid hormone biosynthesis in the fecal microbiota of men taking oral ATT.ConclusionsThere are measurable differences in the GI microbiota of men receiving oral ATT. We speculate that oral hormonal therapies for prostate cancer may alter the GI microbiota, influence clinical responses to ATT, and/or potentially modulate the antitumor effects of future therapies including immunotherapy. Given our findings, larger, longitudinal studies are warranted.

Microbiota- and Radiotherapy-Induced Gastrointestinal Side-Effects (MARS) Study: A Large Pilot Study of the Microbiome in Acute and Late-Radiation Enteropathy

“…Moreover, no significant differences in genus-level taxa were found between patients with and without IBS in the late cohort, including Roseburia (p à ¼ 0.60; p > 0.1) and Clostridium IV (p à ¼ 0.59, p > 0.1). Because ADT has been associated with a modified microbiota in a previous report, we also examined in the microbiota of the late cohort stratified by active ADT or testosterone recovery status (26). No significant differences were found in a-diversity or in taxa (see Supplementary Data).…”

Alterations of gut microbiota composition in post-finasteride patients: a pilot study

“…Indeed, gonadectomy and hormone replacement have a clear effect on gut bacteria in rodents [58][59][60][61][62][63], for instance, the changes observed in Ruminococcaceae after orchidectomy in mice [58]. Alteration in Ruminococcaceae also occurred in prostate cancer patients treated with oral androgen receptor axis-targeted therapies [64]. On this basis, it is possible to hypothesize that gut microbiota changes observed in PFS patients may be ascribed to the alteration of steroid environment.…”

Demystifying the manipulation of host immunity, metabolism, and extraintestinal tumors by the gut microbiome

“…For example, a consortium of 11 bacterial strains, including B. rodentium, establishes anti-tumor immunity and confines melanoma growth when inoculated into GF mice. 35 There are discrepancies in the intestinal microbial composition and metabolic functions between patients with and without prostate cancer; [437][438][439][440] for instance, the aberrant metabolome of individuals with prostate cancer is characterized by the presence of high levels of bacteria associated with carbohydrate metabolism pathways while lacking bacteria associated with folate production. 437 Compared with male patients with prostate cancer, men without prostate cancer are characterized by higher αdiversity in the gut microbiome.…”

“…437 Compared with male patients with prostate cancer, men without prostate cancer are characterized by higher αdiversity in the gut microbiome. 438 There are measurable differences in the gut microbiome composition between prostate cancer patients undergoing oral androgen receptor axis-targeted therapies and those who are not. 438 The knowledge and understanding of the effects of the gut microbiome on the occurrence and development of lung carcinoma is extremely limited.…”

“…438 There are measurable differences in the gut microbiome composition between prostate cancer patients undergoing oral androgen receptor axis-targeted therapies and those who are not. 438 The knowledge and understanding of the effects of the gut microbiome on the occurrence and development of lung carcinoma is extremely limited. A clinical trial has shown an immediate association between gut microbiome and lung cancer.…”