Gut Microbiota and Primary Liver Cancer: Mendelian Randomization and Network Pharmacology Used to Predict Potential Therapeutic Intervention With Traditional Chinese Medicine

Objective: The objective of this study is to employ Mendelian randomization (MR) to screen for gut microbiota (GM) exhibiting causal genetic effects on primary liver cancer (PLC) development and to predict promising traditional Chinese medicine (TCM) candidates capable of intervening in PLC by modulating the GM. Methods: Summary statistics from genome-wide association studies (GWASs) examining the relationship between GM and PLC were retrieved from the IEU OpenGWAS database. MR analysis was conducted using the two-sample MR package in R, employing the inverse variance weighted (IVW) method as the primary approach for assessing genetic causal effects. Functional enrichment analysis was performed on genes proximal to the instrumental variables (IVs) to investigate the signaling pathways through which the implicated microbiota may contribute to PLC pathogenesis. The CTD and Coremine Medical databases were combined to predict TCM compounds potentially regulating the genes proximal to the IVs. Result: Rose., among others. GO enrichment analysis revealed that these genes were significantly enriched in biological processes including positive regulation of the ERK1/ERK2 signaling pathway, posttranslational protein modification (such as deglutamylation), synaptic vesicle exocytosis, and urea transport. KEGG pathway enrichment analysis demonstrated predominant enrichment of these genes in the neurotrophin signaling pathway and the cAMP signaling pathway. Conclusion: This study provides novel insights for developing GM-based TCM strategies for PLC prevention and treatment.