Clinical and Translational Research
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jun 26, 2024; 12(18): 3497-3504
Published online Jun 26, 2024. doi: 10.12998/wjcc.v12.i18.3497
Association between gut microbiota and hepatocellular carcinoma and biliary tract cancer: A mendelian randomization study
Ye Zhang, Fa-Ji Yang, Qi-Rong Jiang, Heng-Jun Gao, Xie Song, Hua-Qiang Zhu, Xu Zhou, Jun Lu
Ye Zhang, Fa-Ji Yang, Qi-Rong Jiang, Heng-Jun Gao, Xie Song, Hua-Qiang Zhu, Xu Zhou, Jun Lu, Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong Province, China
Co-first authors: Ye Zhang and Fa-Ji Yang.
Author contributions: Lu J designed experiments; Jiang QR, Gao HJ, Song X, Zhu HQ and Zhou X collected and analyzed the data; Zhang Y wrote the manuscript; Yang FJ and Lu J made critical revisions to the article. All authors have read and approved the final manuscript.
Supported by Natural Science Foundation of China, No. 82200706.
Conflict-of-interest statement: The authors declare no potential conflicts of interests.
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: Jun Lu, MD, PhD, Chief Physician, Doctor, Professor, Surgeon, Surgical Oncologist, Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 9677 Jingshi Road, Jinan 250013, Shandong Province, China. lujunsd@126.com
Received: February 25, 2024
Revised: April 9, 2024
Accepted: April 23, 2024
Published online: June 26, 2024
Processing time: 114 Days and 7.2 Hours
Abstract
BACKGROUND

An increasing number of studies have begun to discuss the relationship between gut microbiota and diseases, yet there is currently a lack of corresponding articles describing the association between gut microbiota and hepatocellular carcinoma (HCC) and biliary tract cancer (BTC). This study aims to explore the relationship between them using Mendelian randomization (MR) analysis method.

AIM

To assess the relationship between gut microbiota and HCC and BTC.

METHODS

We obtained Genome-wide association study (GWAS) data for the gut microbiome from the intestinal microbiota genomic library (MiBioGen, https://mibiogen.gcc.rug.nl/). Additionally, we accessed data pertaining to HCC and BTC from the IEU open GWAS platform (https://gwas.mrcieu.ac.uk/). Our analysis employed fundamental instrumental variable analysis methods, including inverse-variance weighted, MR and Egger. To ensure the dependability of the results, we subjected the results to tests for multiple biases and heterogeneity.

RESULTS

During our investigation, we discovered 11 gut microbiota linked to an increased risk to BTC and HCC. The former included the genus Eubacterium hallii group (P = 0.017), Candidatus Soleaferrea (P = 0.034), Flavonifractor (P = 0.021), Lachnospiraceae FCS020 (P = 0.034), the order Victivallales (P = 0.018), and the class Lentisphaeria (P = 0.0.18). The latter included the genus Desulfovibrio (P = 0.042), Oscillibacter (P = 0.023), the family Coriobacteriaceae (P = 0.048), the order Coriobacteriales (P = 0.048), and the class Coriobacteriia (P = 0.048). Furthermore, in BTC, we observed 2 protective gut microbiota namely the genus Dorea (P = 0.041) and Lachnospiraceae ND3007 group (P = 0.045). All results showed no evidence of multiplicity or heterogeneity.

CONCLUSION

This study explores a causal link between gut microbiota and HCC and BTC. These insights may enhance the mechanistic knowledge of microbiota-related HCC and BTC pathways, potentially informing therapeutic strategies.

Keywords: Hepatocellular carcinoma, Biliary tract cancer, Gut microbiota, Mendelian randomization, Genetic variant

Core Tip: We apply the largest intestinal gut microbiota gene database to human disease genetic data, elucidating correlations between gut microbiota and diseases. This aids our understanding of how these bacteria influence or protect against diseases, thereby providing crucial insights into their role in such processes.