Analysis of gut microbiota profiles in patients with prostate cancer: The PROMISE-JAPAN study.

212 Background: Prostate cancer (PCa) is clinically associated with dietary habits such as high-fat diets. The gut microbiota is strongly influenced by dietary habits and is involved in the host immune response and metabolic pathways. Recently, the gut microbiota has been shown to influence a variety of diseases, including PCa. We have found that the gut microbiome and its metabolite, short-chain fatty acids (SCFA), promote cancer growth in PCa mouse models. To clarify the association between gut microbiota and PCa in humans, we conducted a study of PCa, gut microbiome, and lifestyle in Japan (PROMISE-JAPAN). In this study, we evaluated the gut microbiota profiles in PCa patients with a particular focus on differences between non-metastatic PCa (nmPCa) and metastatic PCa (mPCa). Methods: This multicenter, prospective, observational study enrolled 869 Japanese patients between 2020 and 2022. Eligibility criteria were men with suspected PCa who underwent prostate biopsy, and rectal swab samples were collected before prostate biopsy. Men who had taken antibiotics within 6 months before sample collection or whose previous antibiotic use was unknown were excluded. The gut microbiota composition was analyzed using 16S rRNA gene sequencing. The raw sequencing data was processed by the QIIME2 pipeline. The Mann-Whitney U tests were used to compare characteristics between groups. Results: A total of 723 participants were eligible for analysis, including 262 men without cancer and 461 men with PCa, including 56 men with mPCa. The composition of the gut microbiota differed significantly between the non-cancer and the PCa group, with PCa having more Lachnospiraceae, which produce SCFA. The mPCa group had a higher abundance of Ruminococcaceae (UCG-005 and NK4A214), which belong to the Firmicutes pylum, compared to the nmPCa group. The mPCa group had a lower abundance of Prevotella, which belongs to the Bacteroidota pylum, compared to the nmPCa group. In mPCa compared to nmPCa, 19 gut microbiota pathways were significantly altered. In particular, the androstenedione degradation pathway was significantly increased in the mPCa group (p=0.0287). Conclusions: The composition of the gut microbiota differed between the non-cancer, the nmPCa and the PCa group. The gut microbiome associated with androgen metabolism was more common in mPCa patients. Clinical trial information: UMIN000043489 .