Abstract 5637: Transformation of the gut microbiome in response to androgen deprivation and the transition to castration-resistant prostate cancer

Abstract

Abstract Androgen deprivation therapy (ADT) remains the standard care for men with advanced prostate cancer. Although initially effective, many patients fail to maintain durable responses and progress to lethal castration-resistant prostate cancer. Commensal bacteria play important role in maintaining homeostasis and proper immune function. However, ADT alters gut bacterial compositions and the ramifications being investigated. In this study, we used a mouse model of Pten-deficient prostate cancer to characterize differences in bacterial composition of gut bacteria in mice with castration naïve-prostate cancer (CNPC) and gut microbiota from mice three and six weeks after treatment ADT via surgical castration representing castration-sensitive prostate cancer (CSPC) and CRPC, respectively. Fecal samples were collected and processed for 16s rRNA amplicon sequencing. ADT resulted in significant changes to biological diversity and local diversity was highest in CSPC (Shannon index, P=0.04). Community composition also differed significantly different between the groups (Adonis OTU Bray-Curtis, P=0.001, NMDS stress=0.07). Despite dissimilarities between bacterial communities among the groups, CNPC and CRPC shared a greater similarity. Taxa associated with CNPC included Unclassified S247, Prevotella L. reuteri, unclassified Rikenellaceae and unclassified Bacteroidales; taxa associated with CSPC included R. gnavus, Dorea, unclassified Desulfovibrionaceae, Dehalobacterium, A. muciniphilia, Bifidobacterium, and B. producta; and taxa associated with CRPC included Turicibacter, R. flavefaciens, L. garvieae, unclassified Peptostreptococcaceae and unclassified Bacilli. Mice with CSPC and CRPC had an increased abundance genes associated with of catabolic metabolic pathways associated with aromatic compound, steroid Benzoate, and toluene degradation as well as genes associated to pathways corresponding to methane metabolism, phosphonate and phosphinate metabolism, and nitrogen metabolism. Genes enriched in fecal taxa from CNPC and CRPC mice were associated with folate biosynthesis, galactose metabolism, amino sugar and nucleotide sugar metabolism, and carbon fixation pathways in prokaryotes. This study provides preclinical evidence to support the association between the gut microbiome and prostate cancer phenotypes associated with sensitivity to ADT. Citation Format: Chisato Wakamori, Marco A. De Velasco, Kazuko Sakai, Yurie Kura, Naomi Ando, Kazutoshi Fujita, Eri Banno, Kazuhiro Yoshimura, Masahiro Nozawa, Kazuto Nishio, Hirotsugu Uemura. Transformation of the gut microbiome in response to androgen deprivation and the transition to castration-resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5637.