Pd38-08 Gut Microbiota-Mediated Bile Acid Metabolism Associated With the Response to Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer

You have accessJournal of UrologyBladder Cancer: Invasive IV (PD38) 1 May 2024PD38-08 GUT MICROBIOTA-MEDIATED BILE ACID METABOLISM ASSOCIATED WITH THE RESPONSE TO NEOADJUVANT CHEMOTHERAPY IN MUSCLE-INVASIVE BLADDER CANCER Tao Li, Tianyu Qi, and Kaijie Wu Tao LiTao Li, Tianyu QiTianyu Qi, and Kaijie WuKaijie Wu View All Author Informationhttps: //doi. org/10. 1097/01. JU. 0001009424. 64728. 0c. 08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Platinum-based neoadjuvant chemotherapy, such as gemcitabine/cisplatin (GC), followed by radical cystectomy (RC), represents the current standard of care for T2-T4aN0M0 muscle-invasive bladder cancer (MIBC). Regrettably, only 40% of patients who received neoadjuvant chemotherapy achieved a pathological complete response (pCR). Little is known about the mediators underlying the heterogeneous patient response. METHODS: This study was designed to explore the impact and mechanisms of gut microbiota on the efficacy of neoadjuvant chemotherapy through the metagenomic sequencing and metabolomic analysis of fecal samples obtained from MIBC patients who received GC chemotherapy. RESULTS: A total of 54 patients who received neoadjuvant GC chemotherapy were enrolled. 23 (42. 59%) exhibited a pathological response (responsive group), and 31 (57. 41%) showed no response (non-responsive group; no imaging changes or disease progression). Metagenomic sequencing on fecal samples from patients before and after therapy showed that the Shannon index in species level (1. 182 vs. 0. 954, p=0. 016) and abundance of Bacteroidesᵤniformis were significantly greater in the responsive group than non-responsive group. It suggested that responsive patients displayed higher species richness of gut microbiota. At the same time, KEGG database was used for functional analysis of the microbiota in two groups of patients, and there were a significant differences in Secondary bile acid biosynthesis and Primary bile acid biosynthesis, both of them were up-regulated in the responsive group. Further metabolomic analysis of stool showed that there were statistical differences in metabolites between the two groups. 922 different metabolites were up-regulated in the responsive group compared with non-responsive group, and 7-Ketodeoxycholic acid, a secondary bile acid metabolite, was also significantly up-regulated in the responsive group. The enrichment analysis of differential metabolites in KEGG database showed that the metabolites related to Primary bile acid biosynthesis accounted for 6. 82% of all the annotated differential metabolites, suggesting that the different bacteria may be related to this secondary bile acid. Their enrichment in the responsive group may affect the efficacy of later chemotherapy drugs. CONCLUSIONS: The efficacy of neoadjuvant GC chemotherapy in MIBC patients may be potentially influenced by the number of gut microbiota populations. Additionally, the potential application value of Bacteroidesᵤniformis and 7-Ketodeoxycholic acid in improving the efficacy of non-responsive patients is noteworthy. Source of Funding: Bethune Special Research Fund for Urological Oncology (mnzl202010) © 2024 by American Urological Association Education and Research, Inc. FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e810 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc. Metrics Author Information Tao Li More articles by this author Tianyu Qi More articles by this author Kaijie Wu More articles by this author Expand All Advertisement PDF downloadLoading. . .