Basic Study
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World J Gastroenterol. Mar 28, 2022; 28(12): 1257-1271
Published online Mar 28, 2022. doi: 10.3748/wjg.v28.i12.1257
Microbiologic risk factors of recurrent choledocholithiasis post-endoscopic sphincterotomy
Ying Li, Wen-Hui Tan, Jia-Chuan Wu, Zhi-Xin Huang, Yan-Yan Shang, Biao Liang, Jian-Hui Chen, Rui Pang, Xin-Qiang Xie, Ju-Mei Zhang, Yu Ding, Liang Xue, Mou-Tong Chen, Juan Wang, Qing-Ping Wu
Ying Li, Yan-Yan Shang, Rui Pang, Xin-Qiang Xie, Ju-Mei Zhang, Yu Ding, Liang Xue, Mou-Tong Chen, Juan Wang, Qing-Ping Wu, Guangdong Provincial Key Laboratory of Microbial Safety and Health, Key Laboratory of Agricultural Microbiomics and Precision Application, Ministry of Agriculture and Rural Affairs, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, Guangdong Province, China
Wen-Hui Tan, Jia-Chuan Wu, Biao Liang, Digestive Endoscopy Center, Guangdong Second Provincial General Hospital, Guangzhou 510000, Guangdong Province, China
Zhi-Xin Huang, Jian-Hui Chen, Division of Gastrointestinal Surgery Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
Author contributions: Li Y, Tan WH, Wu JC and Wu QP designed the research; Wu JC, Tan WH and Liang B recruited the clinical cohort, collected samples, and performed the follow-up surveys; Li Y, Huang ZX and Shang YY contributed to the amplicon sequencing; Li Y, Chen JH, Pang R and Xie XQ analyzed the data; Li Y, Wu JC, Huang ZX and Xue L wrote the paper; Zhang JM, Ding Y, Chen MT, Wang J, Tan WH and Wu QP performed critical revisions of the manuscript; Li Y, Tan WH and Wu JC contribute equally to the manuscript; all authors approved the final version of the article.
Supported by the research grants from Guangdong Provincial Key Laboratory, No. 2020B121201009; the Science Foundation of Guangdong Second Provincial General Hospital, No. YQ2019-014; and GDAS’ Project of Science and Technology Development, No. 2020GDASYL-20200301002.
Institutional review board statement: The study was reviewed and approved by the ethics committee of Guangdong Second Provincial General Hospital [Approval No. 2019-QNJJ-14-02].
Informed consent statement: Written consent was obtained from all patients in the study.
Conflict-of-interest statement: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
Data sharing statement: The 16S rRNA amplicon sequences data in this research have been deposited in GenBank under the BioProject ID PRJNA742858.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
CONSORT 2010 statement: The authors have read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 statement.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Qing-Ping Wu, PhD, Academic Fellow, Chairman, Professor, Senior Researcher, Senior Scientist, Guangdong Provincial Key Laboratory of Microbial Safety and Health, Key Laboratory of Agricultural Microbiomics and Precision Application, Ministry of Agriculture and Rural Affairs, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, No. 66 Yard 100 Xieliezhong Road, Guangzhou 510070, Guangdong Province, China. wuqp203@163.com
Received: September 29, 2021
Peer-review started: September 29, 2021
First decision: December 4, 2021
Revised: December 10, 2021
Accepted: February 15, 2022
Article in press: February 15, 2022
Published online: March 28, 2022
Processing time: 176 Days and 16.3 Hours
ARTICLE HIGHLIGHTS
Research background

Choledocholithiasis is a common and socially significant health problem worldwide, and endoscopic sphincterotomy (EST) has become widespread in treating choledocholithiasis; however, recurrence post-EST is relatively common. The bile microbiome has a profound influence on the recurrence of choledocholithiasis; however, the key pathogens and their functions are not fully elucidated.

Research motivation

To determine the microbiologic risk factors of recurrent choledocholithiasis post EST.

Research objectives

To investigate the biliary microbial characteristics of the recurrent choledocholithiasis post-EST, using next-generation sequencing.

Research methods

This cohort study included 43 choledocholithiasis patients who had undergone EST were followed up for over a year. They were divided into either the stable or recurrent groups and comparison of their bile microbiome was carried out through next-generation sequencing. Resulting sequences were analyzed for core microbiome and statistical differences between the microbiologic compositions and functions. Correlation between the key genera and metabolic pathways in bile, were analyzed using Pearson’s correlation test.

Research results

The results revealed distinct clustering of biliary microbiota in recurrent choledocholithiasis, in which higher relative abundances (RAs) of Fusobacterium and Neisseria and the absence of Lactobacillus were observed in the bile of the recurrent patients. Microbiological co-occurrence network revealed a mutual relationship among Fusobacterium, Neisseria, and Leptotrichia, and an antagonistic relationship among Lactobacillales, Fusobacteriales, and Clostridiales. Functional analysis revealed that the loss of microbiologic transcription and metabolic abilities may lead to the choledocholithiasis recurrence. Furthermore, the prediction model based on the RA of Lactobacillales in the bile was effective in identifying the risk of recurrent choledocholithiasis.

Research conclusions

We concluded the microbiologic differences in the bile of recurrent choledocholithiasis patients post EST, thereby adding to the current knowledge on its microbiologic etiology.

Research perspectives

The findings of our study will help develop new prevention strategies for post-surgery recurrence of choledocholithiasis.