Mendelian randomization analysis of causal relationship between gut microbiota and primary liver cancer in East Asian population from the genetic perspective

doi:10.3877/cma.j.issn.2095-3232.2026.01.013

Abstract

Abstract:

Objective

To investigate the potential causal relationship between gut microbiota (GM) and primary liver cancer (PLC) in East Asian population by Mendelian randomization (MR) analysis.

Methods

This study was conducted following the STROBE-MR guidelines. MR analysis was performed based on the assumptions of relevance, independence and exclusion restriction. The exposure data were collected from genome-wide association study (GWAS) summary statistics in 3 432 Chinese, covering 500 GM features. The data of PLC were obtained from Japanese Database (n=161 323) and IEU Open GWAS platform (n=197 611). The inverse variance weighted (IVW), weighted median, MR-Egger and Bayesian weighted MR methods were used to evaluate the causal relationship between GM and PLC.

Results

Specific GM such as Selenomonas, Porphyromonas endodontalis, Gemella sanguinis and Clostridium butyricum were associated the increased risk of PLC. However, Alistipes shahii and Bifidobacterium catenulatum-Bifidobacterium pseudotenatum complex might exert protective effects. The application of multiple MR analysis methods enhanced the reliability and robustness of the research results.

Conclusions

This study provides novel understanding of the role of GM in the incidence and progression of PLC from the genetic perspective and highlights the key role of GM in the pathogenesis of PLC.

Key words: Gut microbiome, Primary liver cancer, Mendelian randomization, Causality, East asia

Weiwei Xue, Kaihao Du, Zhanjin Wang, Xiaoge Dong, Jiejie He, Minghui Rolan, Wei Jiang, Zhan Wang. Mendelian randomization analysis of causal relationship between gut microbiota and primary liver cancer in East Asian population from the genetic perspective[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2026, 15(01): 79-88.

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References 46

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变量	第一作者	年份	样本量(例)	SNP数	种族	性别
GM	Liu X^[13]	2022	3 432	3 432	亚洲人	男女混合
肝癌	Ishigaki K^[14]	2020	197 611	197 611	亚洲人	男女混合
肝癌	Sakaue S^[15]	2021	161 323	161 323	亚洲人	男女混合

变量	第一作者	年份	样本量(例)	SNP数	种族	性别
GM	Liu X^[13]	2022	3 432	3 432	亚洲人	男女混合
肝癌	Ishigaki K^[14]	2020	197 611	197 611	亚洲人	男女混合
肝癌	Sakaue S^[15]	2021	161 323	161 323	亚洲人	男女混合

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