A Metagenomic Study of Biliary Microbiome Change Along the Cholecystitis-Carcinoma Sequence

Background: Gallbladder cancer (GBC) is the most common malignant tumour of the biliary tract, and chronic calculous cholecystitis (CCC) is associated with an increased risk of GBC mortality. Understanding the relationship between CCC and its carcinogenesis might enable us to prevent and cure GBC. In this study, we attempted to explore microbiome profile changes during the transition from chronic cholecystitis mucosae to malignant lesions. Methods: Seven paired human GBC and CCC samples were obtained from patients who underwent radical cholecystectomy or laparoscopic cholecystectomy. Mucosal DNA extraction and metagenomic sequencing were performed to evaluate the microbiota changes between the two groups. Findings: Seven paired human GBC and CCC samples were obtained from patients who underwent radical cholecystectomy or laparoscopic cholecystectomy. Mucosal DNA extraction and metagenomic sequencing were performed to evaluate the microbiota changes between the two groups. We found that GBC patients and CCC patients shared similar stable and permanent dominant species and apparent differences in their biliary microbial composition and gene function. Peptostreptococcus_stomatis and Enterococcus_faecium may have potentially role in GBC progression. In addition, metagenomic species profiles, co-abundance and co-exclusion correlations and CAZyme prevalence showed significant differences between the CCC and GBC groups. Interpretation: Our data suggest microbiota changes between CCC and GBC, which might help us deepen our understanding of the complex landscape of different microbiotas in the development of GBC. Funding Statement: This study was supported by the National Natural Science Foundation of China (31600075), Shanghai Key Laboratory of Biliary Tract Disease Research Foundation (17DZ2260200), the National Natural Science Foundation of China (No. 81572819, 81773043,91440203, 31601021), the Peak Plateau Discipline Construction Project of Shanghai Jiaotong University School of medicine (No. 20181808), the Program of Shanghai Academic Research Leader (No. 19XD1422700), the Shanghai Natural Science Foundation (No 17ZR1418500) and Shanghai Pujiang Program (No 17PJD025). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: This study was approved by the Ethics Committee of Xinhua Hospital affiliated with the Shanghai Jiao Tong University School of Medicine (No. XHEC-D-2019-049). All experiments were carried out in accordance with the approved guidelines. Informed consent was obtained from the patients.