J Korean Med Sci.  2021 Jul;36(28):e189. 10.3346/jkms.2021.36.e189.

Association of Microbial Dysbiosis with Gallbladder Diseases Identified by Bile Microbiome Profiling

Affiliations
  • 1Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
  • 2Department of Pathology, Hanyang University College of Medicine, Seoul, Korea
  • 3Department of Computer Science and Engineering, College of Engineering, Hanyang University, Seoul, Korea
  • 4Department of Radiology, Hanyang University College of Medicine, Seoul, Korea
  • 5Department of Surgery, Hanyang University College of Medicine, Seoul, Korea
  • 6Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
  • 7Department of Laboratory Medicine, Hanyang University College of Medicine, Seoul, Korea

Abstract

Background
Cholecystitis is an important risk factor for gallbladder cancer, but the bile microbiome and its association with gallbladder disease has not been investigated fully. We aimed to analyze the bile microbiome in normal conditions, chronic cholecystitis, and gallbladder cancer, and to identify candidate bacteria that play an important role in gallbladder carcinogenesis.
Methods
We performed metagenome sequencing on bile samples of 10 healthy individuals, 10 patients with chronic cholecystitis, and 5 patients with gallbladder cancer, and compared the clinical, radiological, and pathological characteristics of the participants.
Results
No significant bacterial signal was identified in the normal bile. The predominant dysbiotic bacteria in both chronic cholecystitis and gallbladder cancer were those belonging to the Enterobacteriaceae family. Klebsiella increased significantly in the order of normal, chronic cholecystitis, and gallbladder cancer. Patients with chronic cholecystitis and dysbiotic microbiome patterns had larger gallstones and showed marked epithelial atypia, which are considered as precancerous conditions.
Conclusion
We investigated the bile microbiome in normal, chronic cholecystitis, and gallbladder cancer. We suggest possible roles of Enterobacteriaceae, including Klebsiella, in gallbladder carcinogenesis. Our findings reveal a possible link between a dysbiotic bile microbiome and the development of chronic calculous cholecystitis and gallbladder cancer.

Keyword

Microbiota; Bile; Gallbladder Diseases; Gallbladder Neoplasms; Chronic Cholecystitis
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