Abstract
Gastric cancer is a malignant tumor that seriously threatens human health. In this study, we explored the potential mechanism and immunomodulatory effects of gut microbiota (GM) metabolites on gastric cancer through network pharmacology and molecular docking. The GM metabolites, targets of GM metabolites and gastric cancer were obtained from the public databases. The cross-targets of GM metabolites and gastric cancer were analyzed and the common key targets were further got. GO function and KEGG analysis were conducted to identify potential functions and regulatory mechanisms. A GMMTGM network was built, and then the drug likeness and toxicity of obtained GM metabolites were screened. The molecular docking was employed to assess binding affinity between GM metabolites and corresponding targets. The expression of key targets was validated, and the relationship between key targets with immune cell infiltration levels and immune checkpoints was analyzed in gastric cancer. We identified eight overlapping key targets between GM metabolites and gastric cancer. HIF-1 and TNF signaling pathways were the main signaling pathways. Furthermore, nine GM metabolites were expected to be as drug‑likeness and low-toxicity compounds, and six GM metabolites had good binding affinity with corresponding protein, and their binding affinities under - 5 kcal/mol. The expressions of AKT1, CASP3, GAPDH, HIF1A and STAT3 in gastric cancer and normal sample were statistically significant (P < 0.01). Moreover, the results of immune-related analysis showed that key genes may mediate the occurrence and development of gastric cancer by influencing the immune cell infiltration levels and immune checkpoints. GM metabolites primarily exert their therapeutic effects on gastric cancer through multiple targets, pathways, immune cell infiltration levels and immune checkpoints. Further in vitro and in vivo studies are needed to validate these findings.