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

Abstract

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.

Escherichia coli‐Induced cGLIS3‐Mediated Stress Granules Activate the NF‐κB Pathway to Promote Intrahepatic Cholangiocarcinoma Progression

“…[34][35][36] Previous studies by Chai et al have explored the microbial characteristics within ICC, confirming the potential role of microbiota in cancer treatment. [6] In this study, we focused on the potential pro-cancerous effects of E. coli on the bile microenvironment. In line with previous studies, we confirmed that E. coli was the predominant bacterium in the bile of patients with ICC and hepatolithiasis.…”

“…[ 4 ] While hepatolithiasis was once considered the primary cause of ICC, recent studies suggest that bacteria play a significant role in the formation of hepatolithiasis and the progression of ICC. [ 5 ] Bacteria facilitate the occurrence of hepatolithiasis by interacting with host bile tissue, [ 6 ] which leads to hepatolithiasis‐induced cholestasis, bacterial proliferation, and inflammatory responses. These events promote ICC progression.…”

Recurrent bacteremia with a hypermucoviscous Escherichia coli isolated from a patient with perihilar cholangiocarcinoma: insights from a comprehensive genome-based analysis

“…A 71-year-old male German patient presented to the emergency department with acute cholangitis caused by a perihilar cholangiocarcinoma, also known as “Klatskin tumor” [ 26 , 27 ], with hepatic and lymphogenic metastases. Comorbidities included chronic kidney insufficiency (KDIGO G2), type 2 diabetes mellitus and paroxysmal atrial fibrillation.…”

The intestinal and biliary microbiome in autoimmune liver disease—current evidence and concepts

“…Until recently, bile was considered a sterile fluid, but more recent reports show that a unique microbial ecosystem exists in subjects with and without hepatobiliary disorders [ 120 ]. Not only are cholestatic liver diseases associated with bile microbial alterations, but the bile microbiome also seems to vary by the etiology of cholestasis [ 121 , 122 ]. A pilot study from Finland by Färkkilä and colleagues revealed minor to no microbiome alterations in PSC patients compared to healthy controls [ 123 ].…”