Causal impact of gut microbiota on five liver diseases: insights from mendelian randomization and single-cell RNA sequencing

Na Li; Xuanyi Chen; Shuai Xiong; Yuxin Cheng; Jiali Deng; Junli Zhang; Fei Yu; Liyuan Hao; Shenghao Li; Xiaoyu Hu

doi:10.3389/fgene.2024.1362139

Causal impact of gut microbiota on five liver diseases: insights from mendelian randomization and single-cell RNA sequencing

Front Genet. 2024 Nov 11:15:1362139. doi: 10.3389/fgene.2024.1362139. eCollection 2024.

Authors

Na Li^#^{1

2}, Xuanyi Chen^#³, Shuai Xiong^{1

2}, Yuxin Cheng⁴, Jiali Deng^{1

2}, Junli Zhang⁵, Fei Yu^{1

2}, Liyuan Hao^{1

2}, Shenghao Li^{1

2}, Xiaoyu Hu²

Affiliations

¹ Department of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
² Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
³ Acupunctureand Tuina College, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
⁴ Department of Ophthalmology, Key Laboratory of Sichuan Province Ophthalmopathy Prevention and Cure and Visual Function Protection with TCM, Chengdu, Sichuan, China.
⁵ Department of Infectious Diseases, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.

^# Contributed equally.

Abstract

Background: Liver disease is among the top ten causes of death globally. With studies suggesting a link between gut microbiota (GM) and liver disease.

Method: We selected summary statistics data from the largest available whole-genome association study (n = 13,266) of GM by the MiBioGen consortium as the exposure, and obtained liver disease-related data from IEU Open GWAS and The NHGRI-EBI GWAS Catalog. A two-sample Mendelian Randomization (MR) analysis employing various methods, to establish the causal relationship between GM and five liver diseases. Meanwhile, single-cell RNA sequencing data were used to examine Prevotella-related genes expression under healthy and disease liver.

Results: The IVW analysis indicate a causal relationship between GM and liver diseases, with Prevotella exhibiting a protective effect in all five liver diseases: Alcoholic liver disease (OR:0.81,95% confidence interval:0.66-1.00,P _IVW = 0.0494); Cirrhosis (OR: 0.85,95% confidence interval: 0.73-0.99,P _IVW = 0.0397); Hepatic failure, not elsewhere classified (OR:0.60,95% confidence interval:0.37-0.95,P _IVW = 0.0305); Benign neoplasm:Liver (OR:0.39,95% confidence interval:0.2-0.75,P _IVW = 0.0046); Malignant neoplasm of liver, primary (OR:0.41, 95% confidence interval:0.18-0.93,P _IVW = 0.0334). The single-cell results suggest differential expression of Prevotella-related genes between liver disease patients and healthy individuals.

Conclusion: Our MR results show a causal relationship between the GM and liver disease. Prevotella displays a notable protective effect. This finding may enhance the precision of GM-based therapies and offer new insights for clinical research.

Keywords: Mendelian randomization; Prevotella; SNPs; five liver diseases; gut microbiota.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The present study was financially supported by the National Natural Science Foundation of China (No. 81973840); Sichuan Provincial Administration of Traditional Chinese Medicine Major Science and Technology projects (2021XYCZ004).