Genome-wide Mendelian randomization identifies putatively causal gut microbiota for multiple peptic ulcer diseases

Jingwei Zhao; Yucheng Hou; Tianyi Xie; Yizhang Zhu; Xinyi Feng; Yong Zhang; Ziyi Yang; Wei Gong

doi:10.3389/fimmu.2023.1260780

Genome-wide Mendelian randomization identifies putatively causal gut microbiota for multiple peptic ulcer diseases

Front Immunol. 2023 Oct 5:14:1260780. doi: 10.3389/fimmu.2023.1260780. eCollection 2023.

Authors

Jingwei Zhao^{1

2}, Yucheng Hou³, Tianyi Xie⁴, Yizhang Zhu⁵, Xinyi Feng⁶, Yong Zhang^{1

2}, Ziyi Yang^{1

2}, Wei Gong^{1

2}

Affiliations

¹ Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, China.
³ Department of Cardiovascular Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
⁴ Laboratory of Medical Science, School of Medicine, Nantong University, Nantong, Jiangsu, China.
⁵ Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
⁶ Department of Gastroenterology, Wuzhong People's Hospital of Suzhou, Suzhou, China.

Abstract

Objective: The pathogenesis of peptic ulcer diseases (PUDs) involves multiple factors, and the contribution of gut microbiota to this process remains unclear. While previous studies have associated gut microbiota with peptic ulcers, the precise nature of the relationship, whether causal or influenced by biases, requires further elucidation.

Design: The largest meta-analysis of genome-wide association studies was conducted by the MiBioGen consortium, which provided the summary statistics of gut microbiota for implementation in the Mendelian randomization (MR) analysis. Summary statistics for five types of PUDs were compiled using the FinnGen Consortium R8 release data. Various statistical techniques, including inverse variance weighting (IVW), MR-Egger, weighted median (WM), weighted mode, and simple mode, were employed to assess the causal relationships between gut microbiota and these five PUDs.

Result: In the intestinal microbiome of 119 known genera, we found a total of 14 causal associations with various locations of PUDs and reported the potential pathogenic bacteria of Bilophila et al. Among them, four had causal relationships with esophageal ulcer, one with gastric ulcer, three with gastroduodenal ulcer, four with duodenal ulcer, and two with gastrojejunal ulcer.

Conclusion: In this study, the pathogenic bacterial genera in the gut microbiota that promote the occurrence of PUDs were found to be causally related. There are multiple correlations between intestinal flora and PUDs, overlapping PUDs have overlapping associated genera. The variance in ulcer-related bacterial genera across different locations underscores the potential influence of anatomical locations and physiological functions.

Keywords: Mendelian randomization; causal relationship; genus; gut microbiota; peptic ulcer.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Gastrointestinal Microbiome* / genetics
Genome-Wide Association Study
Humans
Mendelian Randomization Analysis
Peptic Ulcer* / genetics
Stomach Ulcer*
Ulcer

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the National Natural Science Foundation of China (No. 82172628, 81974371); Xinhua Hospital Funded Clinical Research (21XHDB10) and Shanghai Key Laboratory of Biliary Tract Disease Research Foundation (No.17DZ2260200).