The causal relationship between gut microbiota and end-stage liver disease: a bidirectional Mendelian randomization analysis

Patients with end-stage liver disease often have intestinal flora dysbiosis. Exploring the causal relationship between intestinal flora abundance and liver cirrhosis or liver cancer is significant. In this study, we first demonstrated liver cirrhosis was detrimental to liver cancer by two-sample Mendelian randomization (MR) analysis. Then, we used bidirectional MR to verify the two-way causal relationship between gut flora abundance (including 16 classes, 32 families, 119 genera, 20 orders, and 9 phyla) and end-stage liver diseases. Inverse variance weighted (IVW) was the primary method for examining causality. MR-Egger, weighted median (WM) approaches were adopted to provide sensitivity analyses for the results. We revealed the impact of intestinal flora on liver cirrhosis and liver cancer, and we identified 11 and 5 causal relationships, respectively. Subsequently, we demonstrated that cirrhosis and liver cancer will genetically affect 3 and 13 intestinal flora abundance, respectively. We found that the family Lactobacillaceae (id:1836) and genus Lactobacillus(id:1837) may be involved in the crosstalk between cirrhosis and liver cancer. A negative feedback loop may exist between such flora and end-stage liver disease.