Bidirectional Mendelian randomization of causal relationship between gut microbiota and risk of liver cirrhosis

WEN Tingting; XU Min; ZHANG Dongyou; ZHANG Lei; MENG Pengli; MENG Defeng

doi:10.13276/j.issn.2097-1656.2025.10.012

Abstract：Objective To employ bidirectional Mendelian randomization(MR)to assess the causal relationship between gut microbiota and liver cirrhosis,as well as to identify potential etiological differences between gut microbiota and liver cirrhosis by further analysis.Methods The data on gut microbiota and liver cirrhosis were derived from genome-wide association study in UK Biobank.Single nucleotide polymorphisms significantly associated with the relative abundance of 418 gut microbiota were selected as instrumental variables based on preset thresholds.Forward MR analysis was conducted with liver cirrhosis as the outcome,followed by reverse MR analysis with liver cirrhosis as the exposure factor and 20 gut microbiota as the outcome.The primary analysis utilized the inverse-variance weighted approach,and bidirectional MR analyses were additionally carried out using the MR-Egger approach,weighted median approach,simple mode approach,and weighted mode approach,while evaluating the influence of heterogeneity and pleiotropy on the study findings.All statistical analyses were performed in R software(version 4.3.3),using the two-sample MR and MR-PRESSO software packages for analysis.Results In the forward MR analysis,a total of 20 gut microbiota(including 1 phylum,1 class,4 families,10 genera,and 4 species)were found to be associated with liver cirrhosis.Among them,4 bacteria such as the genus.Anaerofilum(OR=1.63,95％CI=1.22-2.18,P=0.001)might be risk factors for liver cirrhosis,while 16 bacteria such as the genus.Parabacteroides(OR=0.43,95％CI=0.23-0.82,P=0.01)might be protective factors for liver cirrhosis.In the reverse MR analysis,no causal relationship was found between liver cirrhosis and the above 20 gut microbiota(P＞0.05).Conclusion This study confirms the potential causal relationship between gut microbiota and liver cirrhosis,providing a reference for the role of gut microbiota in the clinical treatment progress of liver cirrhosis.