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

Rungtiwa Dangtakot,Yaovalux Chamgramol,Petcharakorn Hanpanich,Anucha Ahooja,Somchai Pinlaor,Porntip Pinlaor,Kitti Intuyod,Aroonlug Lulitanond,Jitraporn Wongwiwatchai

doi:10.31557/apjcp.2021.22.1.233

Rungtiwa Dangtakot, Yaovalux Chamgramol + Show 7 more

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https://doi.org/10.31557/apjcp.2021.22.1.233

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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.

Highlights

Gut microbiota are involved in host immunity and disease conditions as well as being implicated in the development of hepatobiliary tumors, including cholangiocarcinoma (CCA) (Mima et al, 2017)
The more similar the communities are among samples, the closer their corresponding data points are on the non-metric multi-dimensional scaling analysis (NMDS) graph
The NMDS analysis based on operational taxonomic units (OTUs) showed that the community of bacteria differed among groups (Figure 2C)

Summary

Introduction

Gut microbiota are involved in host immunity and disease conditions as well as being implicated in the development of hepatobiliary tumors, including cholangiocarcinoma (CCA) (Mima et al, 2017). Previous studies showed that genetic and epigenetic abnormalities of patients with liver fluke-associated CCA are obviously different from those of patients with non-liver fluke-associated CCA (Ong et al, 2012; Chan-On et al, 2013) These suggest that different tumorigenesis processes are occurred in CCA with different etiological factors. Besides PSC and liver fluke infections, other hepatobiliary diseases, choledocholithiasis (CDL), a gallstone in the bile duct which is usually associated with bacterial infection, have been recognized as risk factors for CCA development (Welzel et al, 2007; Cai et al, 2015).

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