The causality between gut microbiome and liver cirrhosis: a bi-directional two-sample Mendelian randomization analysis

Qing-Ao Xiao; Yun-Fei Yang; Lin Chen; Ying-Chun Xie; Hai-Tao Li; Zhi-Gang Fu; Qiang Han; Jia Qin; Jie Tian; Wen-Jiang Zhao; Fei Cai; Yin-Tao Hu; Lin-Feng Ai; Chao Li; Xu-Ying Chen; Decheng Wang; Yu-Yan Tan; Xuan Xia; Xiao-Lin Zhang

doi:10.3389/fmicb.2023.1256874

The causality between gut microbiome and liver cirrhosis: a bi-directional two-sample Mendelian randomization analysis

Front Microbiol. 2023 Oct 18:14:1256874. doi: 10.3389/fmicb.2023.1256874. eCollection 2023.

Authors

Qing-Ao Xiao^#^{1

2}, Yun-Fei Yang^#^{2

3}, Lin Chen^{2

4}, Ying-Chun Xie^{1

2}, Hai-Tao Li^{1

2}, Zhi-Gang Fu^{1

2}, Qiang Han^{1

2}, Jia Qin^{1

2}, Jie Tian^{1

2}, Wen-Jiang Zhao^{1

2}, Fei Cai^{1

2}, Yin-Tao Hu^{1

2}, Lin-Feng Ai^{1

2}, Chao Li^{1

2}, Xu-Ying Chen^{1

2}, Decheng Wang^{5

6}, Yu-Yan Tan^{2

3}, Xuan Xia^{5

6

7}, Xiao-Lin Zhang^{1

2}

Affiliations

¹ Department of Interventional Radiology, The First College of Clinical Medical Science, China Three Gorges University, Yichang, China.
² Yichang Central People's Hospital, Yichang, China.
³ Department of Surgery of Thyroid and Breast, The First College of Clinical Medical Science, China Three Gorges University, Yichang, China.
⁴ Department of Radiology, The First College of Clinical Medical Science, China Three Gorges University, Yichang, China.
⁵ Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Sciences, China Three Gorges University, Yichang, China.
⁶ Institute of Infection and Inflammation, China Three Gorges University, Yichang, China.
⁷ Department of Physiology and Pathophysiology, College of Medical School, China Three Gorges University, Yichang, Hubei, China.

^# Contributed equally.

Abstract

Background and aim: Previous studies have reported an association between gut microbiota and cirrhosis. However, the causality between intestinal flora and liver cirrhosis still remains unclear. In this study, bi-directional Mendelian randomization (MR) analysis was used to ascertain the potential causal effect between gut microbes and cirrhosis.

Methods: Large-scale Genome Wide Association Study (GWAS) data of cirrhosis and gut microbes were obtained from FinnGen, Mibiogen consortium, and a GWAS meta-analysis of Alcoholic cirrhosis (ALC). Two-sample MR was performed to determine the causal relationship between gut microbiota and cirrhosis. Furthermore, a bi-directional MR analysis was employed to examine the direction of the causal relations.

Result: In MR analysis, we found that 21 gut microbiotas were potentially associated with cirrhosis. In reverse MR analysis, 11 gut microbiotas displayed potentially associations between genetic liability in the gut microbiome and cirrhosis. We found that the family Lachnospiraceae (OR: 1.59, 95% CI:1.10-2.29) might be harmful in cirrhotic conditions (ICD-10: K74). Furthermore, the genus Erysipelatoclostridium might be a protective factor for cirrhosis (OR:0.55, 95% CI:0.34-0.88) and PBC (OR:0.68, 95% CI:0.52-0.89). Combining the results from the MR analysis and reverse MR analysis, we firstly identified the Genus Butyricicoccus had a bi-directional causal effect on PBC (Forward: OR: 0.37, 95% CI:0.15-0.93; Reverse: OR: 1.03, 95% CI:1.00-1.05).

Conclusion: We found a new potential causal effect between cirrhosis and intestinal flora and provided new insights into the role of gut microbiota in the pathological progression of liver cirrhosis.

Keywords: Mendelian randomization; alcoholic cirrhosis; cirrhosis; gut microbiome; primary biliary cirrhosis.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by Grants from National Natural Science Foundation of China (No. 31772709) and Hubei Natural Science Foundation (2015CFB316) of China.