Profiling of Bile Microbiome Identifies District Microbial Population between Choledocholithiasis and Cholangiocarcinoma Patients

OBJECTIVE: Choledocholithiasis (CDL), a potential risk for cholangiocarcinoma (CCA) development, is often a consequence of bacterial infection. Thus, the microbial population that contributes to CDL might also be involved in CCA development. We compared the microbiome in bile fluid of CDL patients and CCA patients. METHODS: Bile samples were collected from CDL (n = 30) and CCA (n =30) patients. Microbial profiling was performed individually by the sequencing of V3-V4 regions of the 16S rRNA gene. RESULTS: Enterobacter, Pseudomonas, and Stenotrophomonas species were much more abundant in bile samples from CCA compared to CDL (p<0.05). However, Cetobacterium, Pyramidobacter, and Streptococcus species were less abundant in bile samples of CCA compared to CDL (p<0.05). Although Escherichia was predominant in the CCA, Escherichia coli itself was more abundant in CDL than in CCA. One CDL case (3.3%) harbored genotoxin-producing E. coli as confirmed by PCR. Enterobacter and Pseudomonas also predominated in CCA according to linear discriminant-analysis effect size. CONCLUSION: we demonstrated vast differences between microbial communities in bile of CDL and CCA patients. These bacteria might be partly involved in CCA genesis and may provide novel biomarkers for CCA.