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Characterization of biliary and duodenal microbiota in patients with primary and recurrent choledocholithiasis

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Abstract

Purpose

To explore the biliary and duodenal microbiota features associated with the formation and recurrence of choledocholithiasis (CDL).

Methods

We prospectively recruited patients with primary (P-CDL, n = 29) and recurrent CDL (R-CDL, n = 27) for endoscopic retrograde cholangiopancreatography (ERCP). Duodenal mucosa (DM), bile and bile duct stones (BDS) samples were collected in P- and R-CDL patients. DM samples were also collected in 8 healthy controls (HC). The microbiota profile analysis was performed with 16S rRNA gene sequencing.

Results

Short-course antibiotic application before ERCP showed no significant effects in alpha and beta diversities of the biliary and duodenal microbiota in CDL. Alpha diversity showed no difference between DM and bile samples in CDL. The duodenal microbial richness and diversity was lower in both P- and R-CDL than HC. The biliary microbiota composition showed a high similarity between P- and R-CDL. Fusobacterium and Enterococcus were higher abundant in DM, bile, and BDS samples of R-CDL than P-CDL, as well as Escherichia and Klebsiella in bile samples of R-CDL. The enriched duodenal and biliary bacteria in CDL were closely associated with cholecystectomy, inflammation and liver dysfunction. The bile-associated microbiota of R-CDL expressed enhanced capacity of D-glucuronide and D-glucuronate degradation, implicating an elevated level of β-glucuronidase probably produced by enriched Escherichia and Klebsiella in bile.

Conclusions

The duodenal microbiota was in an imbalance in CDL. The duodenal microbiota was probably the main source of the biliary microbiota and was closely related to CDL formation and recurrence. Enterococcus, Fusobacterium, Escherichia and Klebsiella might contribute to CDL recurrence.

Clinical trials

The study was registered at the Chinese Clinical Trial Registry (https://www.chictr.org.cn/index.html, ChiCTR2000033940).

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Acknowledgements

Thanks to Chenhuan Wang, Lijuan Xu, Hong Du, and Ting Yang for helping with sample collection.

Funding

No funding was received to assist with the preparation of this manuscript.

Author information

Author notes

  1. Fang Liu, Zi-Kai Wang contributed equally to this work.

Authors and Affiliations

  1. Medical School of Chinese PLA, Beijing, China

    Fang Liu, Zi-Kai Wang, Ming-Yang Li, Xiu-li Zhang & Wen Li

  2. Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, The First Medical Center, No. 28 Fuxing Road, Beijing, 100853, China

    Fang Liu, Zi-Kai Wang, Ming-Yang Li, Xiu-li Zhang, Feng-Chun Cai, Xiang-Dong Wang & Wen Li

  3. Integrative Microecology Clinical Center, Shenzhen Key Laboratory of Gastrointestinal Microbiota and Disease, Shenzhen Clinical Research Center for Digestive Disease, Shenzhen Technology Research Center of Gut Microbiota Transplantation, The Clinical Innovation & Research Center, Shenzhen Hospital, Southern Medical University, Shenzhen, 518000, Guangdong, China

    Xue-Feng Gao

  4. Minimally Invasive Digestive Disease Center, Beijing and Shenzhen United Family Hospital, Beijing, China

    Wen Li

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Contributions

LF, WZ, XG, and LW designed the study; XG and LF analyzed the omics data and created figures; LF, LM, ZX, CF, and WZ collected and interpreted the clinical data; LF and WZ drafted the manuscript; GX and LW revised the manuscript; all authors read and approved the final manuscript. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Xue-Feng Gao or Wen Li.

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Competing interest

The authors have no competing interests to declare that are relevant to the content of this article.

Ethical approval

The study was approved by the Ethics Committee of the PLA General Hospital (S-2019-274-01).

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13755_2023_267_MOESM1_ESM.tiff

Assessment of the effect of antibiotic prophylaxis on the duodenal and biliary microbiota diversity and composition in patients with CDL. Comparisons of the (A-C) alpha diversity (Choa1 index and Shannon index) and (D-F) beta diversity between patients with (ABX) and without (None) antibiotic prophylaxis treatment. Significance of comparing the alpha diversity was determined by the Wilcoxon rank sum test. Significance of Bray–Curtis dissimilarity was tested by PERMANOVA. Supplementary file1 (TIFF 24519 kb)

Supplementary file2 (XLSX 10 kb)

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Liu, F., Wang, ZK., Li, MY. et al. Characterization of biliary and duodenal microbiota in patients with primary and recurrent choledocholithiasis. Health Inf Sci Syst 12, 29 (2024). https://doi.org/10.1007/s13755-023-00267-2

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