Prognostic Role of Gut Microbiota and Clinical Parameters in Predicting Survival in Advanced Cholangiocarcinoma Patients Receiving Chemotherapy

Introduction: Cholangiocarcinoma (CCA) is high prevalent in Asia.Emerging evidence indicates gut and tissue microbiota are involved in CCA carcinogenesis and progression.This study investigated the potential role of gut and tissue microbiota as prognostic biomarkers associated with treatment outcomes in advanced intrahepatic CCA (ICCA) patients.Methods: This prospective study comprised two cohorts: hepatocellular carcinoma (HCC) or ICCA patients undergoing surgery or biopsy, and unresectable ICCA patients treated with cisplatin and gemcitabine.Gut bacterial profiles were characterized from pre-treatment fecal samples using 16S rRNA and analyzed with clinical outcomes.Tissue bacterial profiles were determined by real-time qPCR.Results: In 30 ICCA patients receiving chemotherapy, gut microbiota differed based on chemotherapy response, PFS, overall survival, and Opisthorchis viverrini infection.An increase in Acidaminococcus and Sutterella, along with a decrease in NK4A214_group, Lachnospiraceae_FCS020_group, and UCG-010, were associated with poor clinical outcomes.Notably, Intestinimonas levels were significantly associated with less progression of disease within six months (aOR 0.92).Of total 70 patients, bacterial profiles of ICCA and HCC tissues did not significantly differ.Conclusion: Advanced ICCA patients with poor outcomes following chemotherapy exhibited the distinct pattern of gut microbiota, which might be used as potential prognostic biomarkers.