A Preliminary Study of Biliary Microbiota in Patients with Bile Duct Stones or Distal Cholangiocarcinoma

Abstract

Background and Objective The distal cholangiocarcinoma (dCCA) is associated with many factors: genes, environment, infection, etc. The current changes in biliary flora are thought to be involved in the formation of many gastrointestinal tract (GIT) diseases, like colon adenocarcinoma. Therefore we want to investigate whether the dCCA has a certain correlation with biliary microecology, and to detect specific strains. Methods A total of 68 adults were enrolled, of whom 8 with dCCA, 16 with recurrent choledocholithiasis, and 44 with the onset of common bile duct stones. Endoscopic Retrograde Cholangiopancretography (ERCP) was utilized to collect bile samples for DNA extraction and 16S rRNA gene sequencing, followed by analysis of bile microbiota composition. Results First, Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria are the most dominant phyla in the bile of patients with dCCA and the onset of common bile duct stoes. Secondly, compared with the onset of common bile duct stones patients, we got a significant increase in the phylum Gemmatimonadetes, Nitrospirae, Chloroflexi, Latescibacteria, and Planctomycetes in dCCA patients. Finally, at the genus level, we obtained sequencing results of 252 bacterial genera from patients with dCCA, recurrent choledocholithiasis, and the new onset of common bile duct stones, revealing heterogeneity among individuals. Conclusion To the best of our knowledge, this is the first study of the dysbiosis of bile flora in patients with dCCA. This micro-ecological disorder may be a decisive factor in the formation of dCCA. At the same time, for the first time, this study provides a test chart of biliary microbial populations that may be associated with recurrent choledocholithiasis. The compositional changes of the core microbial group of the biliary tract have potentially important biological and medical significance for the microbiological biliary disorders of dCCA.

Gallstone Disease, Obesity and the Firmicutes/Bacteroidetes Ratio as a Possible Biomarker of Gut Dysbiosis

“…At the same time, bile samples from gallstone patients had reduced microbial diversity compared to healthy faecal samples [ 108 ]. Among patients with the new onset of common bile duct stones, five dominant phyla were identified: Proteobacteria (60%), Firmicutes (27%), Bacteroidetes (4%), Actinobacteria (3%), and Unclassified_Bacteria (3%) in biliary microbiota [ 111 ]. At the genus level, the five genera with the highest relative abundances in patients with the new onset of common bile duct stones were Escherichia/Shigella , Halomonas , Klebsiella, Streptococcus, and Enterococcus [ 111 ].…”

“…So, when analyzing available studies of intestinal and bile microbiota in animals and patients with GSD [ 5 , 6 , 15 , 79 , 80 , 81 , 82 , 92 , 93 , 100 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 ] there were no unidirectional changes in the Firmicutes/Bacteroidetes ratio. This situation with opposite results is typical not only for GSD.…”

The Liver Microbiome Is Implicated in Cancer Prognosis and Modulated by Alcohol and Hepatitis B

“…Through a similar mechanism, bacteria can theoretically enter the liver from the gut through the bile duct. There are also multiple reports of a biliary microbiome [21,22].…”

Analysis of Biliary Microbiota in Hepatobiliopancreatic Diseases Compared to Healthy People [MICROBILIO]: Study Protocol

“…On the other hand, the bile microbiota is still little studied, being sequenced in healthy individuals only recently [23]. Little is known about its composition in malignant diseases [24], with biliary lithiasis being the most studied and best characterized disease [23,25].…”