Introduction
Benign bile duct obstruction is commonly caused by choledocholithiasis, while hepato-biliary-pancreatic tumors contributed to the most of malignant obstruction. With the development of next generation sequencing technology, the existence of microbiota was confirmed in biliary system, both in healthy and illness population. The characteristics of biliary microbiota in malignant bile duct obstruction remains poorly understood.
Aims & Methods
This study aims to investigate the composition and metabolic functions of biliary microbiota in patients with malignant bile duct obstruction. The present study was designed as a case-control study, which was approved by the ethics committee of First Affiliated Hospital of Soochow University (approval number: 2020-082). Consecutive patients were prospectively enrolled from December 2022 to October 2023, including distal cholangiocarcinoma, hilar cholangiocarcinoma, pancreatic ductal adenocarcinoma, periampullary carcinoma and gallbladder carcinoma. The patients with choledocholithiasis served as controls. Bile samples were collected via endoscopic retrograde cholangiopancreatography. The inclusion criteria were as follows: (1) patients who suffered from bile duct obstruction; (2) all the diagnosis confirmed by imaging examinations or histopathological tests; (3) no antibiotics usage within the preceding three months. The exclusion criteria were as follows: (1) patients who were attacked by acute obstructive suppurative cholangitis or acute hepatic failure at the same time; (2) without gallbladder; (3) surgical history concerning upper gastrointestinal tract or common bile duct; (4) history of gastrointestinal or hepato-biliary-pancreatic neoplastic diseases. Bile samples were collected through ERCP. The microbiota was analyzed using 16S rRNA sequencing. Metabolic functions were predicted by PICRUSTs 2.0 calculation based on MetaCyc database. Bile acids were tested and identified using ultra performance liquid chromatography-tandem mass spectrometry.
Results
A total of 56 patients were successfully enrolled in this study, 25 in the tumor group and 31 in the stone group. No significant difference concerning demographics was found between the two groups. A distinct biliary microbial community was identified in patients with malignant bile duct obstruction. Firmicutes accounted for 40.67% at the phylum level in the tumor group, followed by Proteobacteria (36.44%), Bacteroidetes (11.33%), Actinobacteria (6.81%) and Fusobacteria (3.71%). The unique composition at genus level mainly consisted of Prevotella, Uruburuella, Atopostipes, Clostridium IV, Halomonas, Tannerella, Porphyromonas, Achromobacter, Rouxiella, Campylobacter, Corynebacterium, Turicibacter, Muribaculum, Selenomonas and Alloprevotella. Notably, Clostridium IV, Halomonas, Rouxiella and Turicibacter were exclusively present in the tumor group. Bile acids levels were significantly lower in the tumor group (p<0.05), except for ursodeoxycholic acid and taurocholic acid. There are 22 metabolic pathways were enriched in the tumor group.
Conclusion
This study elucidates the community and metabolic potential of biliary microbiota in malignant bile duct obstruction. The findings offer valuable insights for disease assessment and provide a foundation for further research into the role of biliary microbiota in malignancy.
References
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