Abstract 3044: Integrative gut microbiome analysis of human and mouse prostate cancer

Abstract

Abstract Gut microbes are intricately involved in maintaining normal physiology and homeostasis and have become a major area of study to determine their relevance in human disease. In cancer, alterations to gut microbiota has been associated to resistance to chemo- and immuno-therapy, whereas supplementation with specific taxa improves antitumor treatment responses. Mouse models have been essential to study disease biology and drug discovery. However, mice are fundamentally quite different from humans, thus, questions have arisen regarding their utility as pertinent tools to study microbial influences and their impact on human disease. To address these questions, we have performed a cross-species comparative analysis of the fecal microbiota from a human cohort of prostate cancer patients and a preclinical mouse model of prostate cancer. Microbiota composition was determined by 16s RNA gene sequencing on stool samples from tumor-bearing prostate-specific conditional Pten-knockout and disease-free wildtype mice and 16s RNA gene sequencing data from a human cohort of patients with suspected prostate cancer was used. Human cases were assigned to no cancer and cancer groups based on diagnosis from prostate biopsy and as low-risk (negative biopsy of Gleason grade <3) or high-risk (Gleason grade ≥3). Community composition differed significantly between stool samples of cancer and disease-free individuals in mice but not humans. Operational taxonomic units (OTUs) corresponding to taxa associated with cancer in both mice and humans included Odoribacter spp. and Desulfovibrio spp. Comparing the profiles predicted with Tax4Fun revealed KEGG metabolic pathways associated prostate cancer. Pathways enriched in cancer bearing-mice and that are also associated in patients with prostate cancer included folate biosynthesis, biotin metabolism and ubiquinone & other terpenoid-quinone biosynthesis. Carbon metabolism was a pathway discordant between high-risk prostate cancer patients and cancer bearing mice. Although the basal composition of gut microbes differed between humans and mice, the functional microbiome showed greater similarities. Our cross-species comparative analysis shows that gut microbial dysbiosis is connected to prostate cancer provides additional insights into the biological processes involved. This study provides additional data that may help to bridge the gap between humans and mice. Citation Format: Chisato Wakamori, Marco A. De Velasco, Yurie Kura, Naomi Ando, Noriko Sako, Kazutoshi Fujita, Kazuko Sakai, Makoto Matsushita, Eri Banno, Yasunori Mori, Masahiro Nozawa, Mitsuhisa Nishimoto, Kazuhiro Yoshimura, Norio Nonomura, Kazuto Nishio, Hirotsugu Uemura. Integrative gut microbiome analysis of human and mouse prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3044.