J Korean Med Sci.  2021 Apr;36(15):e94. 10.3346/jkms.2021.36.e94.

Bile Microbiota in Patients with Pigment Common Bile Duct Stones

• Kim B
• Park JS
• Bae J
• Hwang N

• KMID: 2515035
• DOI: http://doi.org/10.3346/jkms.2021.36.e94

Abstract

Background
Common bile duct (CBD) stone is one of the most prevalent gastroenterological diseases, but the role played by biliary microbiota in the pathogenesis of CBD stones remains obscure. The aim of this study was to investigate the characteristics of the biliary tract core microbiome and its potential association with the formation of pigment stones.
Methods
Twenty-eight patients with biliary obstruction of various causes were enrolled. Thirteen had new-onset pigment CBD stone. Of the remaining 15, four had benign biliary stricture, four had gallbladder cancer, three had pancreatic cancer, 3 had distal CBD cancer, and one had hepatocellular carcinoma. Endoscopic retrograde cholangiopancreatography was used to collect bile samples for DNA extraction, 16S ribosomal RNA gene sequencing, and bile microbiota composition analysis.
Results
Proteobacteria (61.7%), Firmicutes (25.1%), Bacteroidetes (5%), Fusobacteria (4.6%), and Actinobacteria (2.6%) were the most dominant phyla in the bile of the 28 study subjects. A comparison between new-onset choledocholithiasis and other causes of biliary obstruction (controls) showed Enterococcus was found to be significantly abundant in the CBD stone group at the genus level (linear discriminant analysis score = 4.38; P = 0.03). However, no other significant compositional difference was observed.
Conclusion
This study demonstrates an abundance of microbiota in bile juice and presents a biliary microbiome composition similar to that of duodenum. The study also shows Enterococcus was significantly abundant in the bile juice of patients with a brown pigment stone than in controls, which suggests Enterococcus may play an important role in the development of pigment stones.

Keyword

Choledocholithiasis; Microbiota; Enterococcus

Figure

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  Fig. 1 Interindividual variation of microbiota compositions at the major phylum and genus levels in the bile of the study subjects. (A) Phylum level, (B) genus level.

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  Fig. 2 Alpha diversity values of patients with a pigment stone (S) and controls (N). Alpha diversity including Chao1 and Shannon index.N = none, S = stone.

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  Fig. 3 Differences between microbiota compositions in the control (N) and common bile duct stone (S) groups at the phylum and genus levels. (A) Phylum level, (B) genus level.N = none, S = stone, AVG = average.

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  Fig. 4 Non-metric multidimensional scaling plot showing the microbiota community differences between the common bile duct stone (S) and control groups (N). Pairwise community distances were determined using Bary-Curtis distances.N = none, S = stone.

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  Fig. 5 Characterization of microbiomes in the control group (N) and CBD pigment stone group (S) by LDA effect size analysis and LDA. Taxonomic representation of statistically and biologically consistent differences between the control (N) and CBD stone (S) groups.N = none, S = stone, LDA = linear discriminant analysis, CBD = common bile duct.

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