Characteristics and metabolic potential of biliary microbiota in patients with giant common bile duct stones

Abstract

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is an effective minimally invasive operation for the management of choledocholithiasis, while successful extraction is hampered by large diameter of stones. Emerging studies have revealed the close correlation between biliary microbiota and common bile duct stones (CBDS). In this study, we aimed to investigate the community characteristics and metabolic functions of biliary microbiota in patients with giant CBDS.

Methods: Eligible patients were prospectively enrolled in this study in First Affiliated Hospital of Soochow University from February 2022 to October 2022. 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 26 patients were successfully included into final analysis, 8 in giant stone (GS) group and 18 in control group. Distinct biliary microbial composition was identified in patients with giant CBDS, with a significantly higher abundance of Firmicutes at phylum level. The unique composition at genus level mainly consisted of Enterococcus, Citrobacter, Lactobacillus, Pyramidobacter, Bifidobacterium and Shewanella. Pyramidobacter was exclusively found in GS group, along with the absence of Robinsoniella and Coprococcus. The contents of free bile acids were significantly higher in GS group, including cholic acid (98.39μmol/mL vs. 26.15μmol/mL, p=0.035), chenodesoxycholic acid (54.69μmol/mL vs. 5.86μmol/mL, p=0.022) and ursodeoxycholic acid (2.70μmol/mL vs. 0.17μmol/mL, p=0.047). Decreasing tendency of conjugated bile acids were also observed. Metabolic pathways concerning cholelithiasis were abundant in GS group, including geranylgeranyl diphosphate biosynthesis, gluconeogenesis, glycolysis and L-methionine biosynthesis.

Conclusions: This study demonstrated the community structure and metabolic potential of biliary microbiota in patients with giant CBDS. The unique biliary microbial composition holds valuable predictive potential for clinical conditions. These findings provide new insights into the etiology of giant CBDS from the perspective of biliary microbiota.

Keywords: 16S rRNA sequencing; bile acid; biliary microbial community; choledocholithiasis; metabolic function.