Chen ZT, Ding CC, Chen KL, Gu YJ, Lu CC, Li QY. Causal roles of gut microbiota in cholangiocarcinoma etiology suggested by genetic study. World J Gastrointest Oncol 2024; 16(4): 1319-1333 [PMID: 38660662 DOI: 10.4251/wjgo.v16.i4.1319]
Corresponding Author of This Article
Qi-Yong Li, PhD, Deputy Director, Researcher, Surgeon, Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, No. 848 Dongxin Road, Hangzhou 310000, Zhejiang Province, China. liqiyong@zju.edu.cn
Research Domain of This Article
Oncology
Article-Type of This Article
Observational Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Zhi-Tao Chen, Yang-Jun Gu, Qi-Yong Li, Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou 310000, Zhejiang Province, China
Chen-Chen Ding, Pediatric Psychology, The Affiliated Mental Health Centre & Hangzhou Seventh People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
Kai-Lei Chen, School of Medicine, Zhejiang Shuren University, Hangzhou 310000, Zhejiang Province, China
Chi-Cheng Lu, School of Medicine, Zhejiang Chinese Medical University Zhejiang Shuren College, Hangzhou 310000, Zhejiang Province, China
Author contributions: Li QY interpreted the study design; Chen ZT and Ding CC downloaded data, performed statistical analysis, and drafted the manuscript; Chen KL, Gu YJ, and Lu CC performed data analysis and revised manuscript; Chen ZT, Ding CC, and Li QY helped revised our manuscript; all authors agreed to submit to the current journal, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.
Institutional review board statement: The research does not involve any animal experiments and clinical data or human subjects, which does not require any special ethical clearance as per the guidelines of our institution.
Informed consent statement: Informed consent statement is not required since our manuscript solely utilizes publicly available data for analysis.
Conflict-of-interest statement: The authors declare that they have no competing interests.
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.
Data sharing statement: The datasets used and analyzed in the present study are available from the corresponding authors on reasonable request. The datasets generated and/or analyzed during the current study are available in GWAS Catalog (https://www.ebi.ac.uk/gwas/) and MiBioGen (https://mibiogen.gcc.rug.nl) database.
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: Qi-Yong Li, PhD, Deputy Director, Researcher, Surgeon, Division of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, No. 848 Dongxin Road, Hangzhou 310000, Zhejiang Province, China. liqiyong@zju.edu.cn
Received: October 23, 2023 Peer-review started: October 23, 2023 First decision: December 12, 2023 Revised: December 20, 2023 Accepted: January 15, 2024 Article in press: January 15, 2024 Published online: April 15, 2024 Processing time: 170 Days and 12.2 Hours
ARTICLE HIGHLIGHTS
Research background
Cholangiocarcinoma (CCA) is a highly malignant biliary tract cancer with poor prognosis. Previous studies have implicated the gut microbiota in CCA, but evidence for causal mechanisms is lacking.
Research motivation
To investigate the causal relationship between gut microbiota and CCA risk.
Research objectives
To investigate the causal relationship between gut microbiota and CCA risk.
Research methods
We performed a two-sample mendelian randomization study to evaluate potential causal associations between gut microbiota and CCA risk using genome-wide association study summary statistics for 196 gut microbial taxa and CCA. Genetic variants were used as instrumental variables. Multiple sensitivity analyses assessed result robustness.
Research results
Fifteen gut microbial taxa showed significant causal associations with CCA risk. Higher genetically predicted abundance of genus Eubacteriumnodatum group, Genus Ruminococcustorques group, Coprococcus, Dorea, and Actinobacteria were associated with reduced risk of gallbladder cancer and extrahepatic CCA. Increased intrahepatic CCA risk was associated with higher abundance of Veillonellaceae, Alistipes, Enterobacteriales, and Firmicutes. Protective effects against CCA were suggested for Collinsella, Eisenbergiella, Anaerostipes, Paraprevotella, Parasutterella, and Verrucomicrobia. Sensitivity analyses indicated these findings were reliable without pleiotropy.
Research conclusions
This pioneering study provides novel evidence that specific gut microbiota may play causal roles in CCA risk. Further experimental validation of these candidate microbes is warranted to consolidate causality and mechanisms.
Research perspectives
Experimental validation of the candidate microbes identified to be causally associated with CCA risk. Further in vitro and in vivo studies could be conducted to consolidate the causal effects and explore the underlying molecular mechanisms. Analysis of species-level resolution of gut microbiota through metagenomic shotgun sequencing or other techniques. The current study was limited to genus-level associations due to 16S rRNA gene sequencing. A more detailed characterization at the species level could provide further insights.
