Causal associations between gut microbiota and primary biliary cholangitis: a bidirectional two-sample Mendelian randomization study

Jiahao Zhang; Gefeng Wu; Yuhong Tang; Huanxiang Liu; Xinyu Ge; Rui Peng; Jun Cao; Daoyuan Tu; Bingbing Su; Shengjie Jin; Guoqing Jiang; Chi Zhang; Dousheng Bai

doi:10.3389/fmicb.2023.1273024

Causal associations between gut microbiota and primary biliary cholangitis: a bidirectional two-sample Mendelian randomization study

Front Microbiol. 2023 Nov 15:14:1273024. doi: 10.3389/fmicb.2023.1273024. eCollection 2023.

Authors

Jiahao Zhang^#^{1

2}, Gefeng Wu^#^{1

2}, Yuhong Tang¹, Huanxiang Liu¹, Xinyu Ge^{1

2}, Rui Peng¹, Jun Cao¹, Daoyuan Tu¹, Bingbing Su¹, Shengjie Jin¹, Guoqing Jiang¹, Chi Zhang¹, Dousheng Bai¹

Affiliations

¹ Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China.
² The Yangzhou School of Clinical Medicine of Dalian Medical University, Dalian, Liaoning, China.

^# Contributed equally.

Abstract

Background: Previous studies have suggested an association between gut microbiota and primary biliary cholangitis (PBC). Nonetheless, the causal relationship between gut microbiota and PBC risk remains unclear.

Methods: A bidirectional two-sample Mendelian Randomization (MR) study was employed using summary statistical data for gut microbiota and PBC from the MiBioGen consortium and Genome-Wide Association Studies (GWAS) database to investigate causal relationships between 211 gut microbiota and PBC risk. Inverse variance weighted (IVW) method was the primary analytical approach to assess causality, and the pleiotropy and heterogeneity tests were employed to verify the robustness of the findings. Additionally, we performed reverse MR analyses to investigate the possibility of the reverse causal association.

Results: The IVW method identified five gut microbiota that demonstrated associations with the risk of PBC. Order Selenomonadales [odds ratio (OR) 2.13, 95% confidence interval (CI) 1.10-4.14, p = 0.03], Order Bifidobacteriales (OR 1.58, 95% CI 1.07-2.33, p = 0.02), and Genus Lachnospiraceae_UCG_004 (OR 1.64, 95%CI 1.06-2.55, p = 0.03) were correlated with a higher risk of PBC, while Family Peptostreptococcaceae (OR 0.65, 95%CI 0.43-0.98, p = 0.04) and Family Ruminococcaceae (OR 0.33, 95%CI 0.15-0.72, p = 0.01) had a protective effect on PBC. The reverse MR analysis demonstrated no statistically significant relationship between PBC and these five specific gut microbial taxa.

Conclusion: This study revealed that there was a causal relationship between specific gut microbiota taxa and PBC, which may provide novel perspectives and a theoretical basis for the clinical prevention, diagnosis, and treatment of PBC.

Keywords: Mendelian randomization study; causal effect; genome-wide association study; gut microbiota; primary biliary cholangitis.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was funded by the National Natural Science Foundation of China (Grant Nos. and 82373034, 82203716), the “13th Five-Year Plan” Science and Education Strong Health Project Innovation Team of Yangzhou (LJRC20181 and YZCXTD201801), Provincial-Level Discipline Leader of the NJPH (DTRA202214), Cross-Cooperation Special Projects of the NJPH (YJCHZ-2021-08), Beijing iGanDan Foundation (GDXZ-08-19), and the Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX22_3568, KYCX23_3617, and SJCX23_2028).