Gut Microbiome Analysis as a Non-Invasive Tool for the Early Diagnosis of Cholangiocarcinoma

Abstract

Background: The liver-microbiome axis is implicated in the pathogenesis of hepatobiliary cancer, and the role of the gut microbiota in cholangiocarcinoma (CCA) remains unclear. Method: We conducted a case-control study on the intestinal flora of 33 CCA patients and 47 cholelithiasis individuals. We performed 16S rRNA gene sequencing to identify disease-related gut microbiota and assess the potential of the intestinal microbiome as a non-invasive biomarker for CCA. Result: We found that gut microbiome of CCA patients had a significantly higher alpha diversity (Shannon and Observed species indices, p=0.006 and p=0.02, respectively) and an overall different microbial community composition (p=0.032). The genus Muribaculaceae_unclassified was most strongly associated with CCA (p<0.001). We put forward a disease predictive model including twelve intestinal microbiome genera distinguished CCA patients from CF patients with an area under curve (AUC) of approximately 0.93 (95%CI, 0.85–0.987). The forecasting performance of this model was better than CA19-9. Moreover, genera Ezakiella and Garciella were only observed among intrahepatic cholangiocarcinoma patients. Further, we assessed predicted functional modules alternations CCA patients and uncovered a microbiota pattern specific to CCA. Conclusion: Our findings provide evidence of the intestinal microbiome as a non-invasive biomarker for CCA. Funding Statement: This study was supported by grants from the National Natural Science Foundation of China (81772628, 82072685, 81703310), Provinces and Ministries Co-Contribution of Zhejiang, China (No.wkj-zj-1706). Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: This study was approved by the Ethics Committee of the First Affiliate Hospital of Wenzhou Medical University (Ref No. 2020-074), and all subjects provided written informed consent.