Abstract 3340: Prostate cancer alters gut microbiota in mice

Abstract

Commensal gut bacteria are essential for maintaining intestinal homeostasis, however, aging, environmental factors and pathological conditions can cause changes in microbial composition resulting in dysbiosis. Specific microbial communities can alter host immune functions and are implicated in promoting carcinogenesis, tumor progression and therapeutic resistance. In this study we use a genetically engineered mouse model of prostate cancer to characterize changes in gut microbiota. 16S marker sequencing data was used to perform a comprehensive profile of the fecal microbiomes of conditional Pten-knockout mice harboring prostate tumors versus wildtype mice with normal prostate. Unsupervised clustering of microbiota was performed by hierarchical clustering. Community composition (beta diversity) was determine by principal components analysis, principal coordinates analysis (PCoA) and Adonis (permutational manova (PERMANOVA)) and the Shannon index was used to determine alpha diversity. The linear discriminant analysis effect size method was used to identify features associated with cancer and multiple linear regression was performed to determine relevant features of fecal bacteria collected from the proximal and distal colon. Predictive biomarkers associated with prostate cancer were identified with the Wilcoxon rank test. Weighted correlation network analysis (WGCNA) was performed to identify clusters of taxa associated with the presence of prostate cancer. Taxon set enrichment analysis (TSEA) was carried out to identify taxon sets associated with host genetic variations, and host intrinsic and extrinsic factors. Overall, the presence of prostate cancer did not affect diversity, however, significant compositional differences were observed between the cohorts (Bray-Curtis Adonis, P=0.003). At the family level S24_7, Odoribacteraceae, and Peptococcaceae were associated with cancer bearing mice while Bifidobacteriaceae, Peptostreptococcaceae, Coriobacteriaceae, Ruminococcaceae and Erysipelotrichaceae were associated with healthy mice (P<0.05). Prevotella, Lactobacillus reuteri and various unclassified Clostridiales, S24_7 and Rikenellaceae were identified as predictive biomarkers associated with cancer. Clusters of highly correlated taxa were identified in both cohorts and their functional influences are summarized. Overall, our study provides an in-depth overview of fecal microbiome in the context of mouse prostate cancer and provides the foundation to further investigate the interactions with disease progression and cancer therapy. Citation Format: Marco A. De Velasco, Kazuko Sakai, Yurie Kura, Eri Banno, Naomi Ando, Noriko Sako, Kazuhiro Yoshikawa, Kazuto Nishio, Hirotsugu Uemura. Prostate cancer alters gut microbiota in mice [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3340.