Potential mechanism of glyphosate affecting Crohn’s disease by regulating metabolites of Bacteroides: a comprehensive analysis based on multi omics and machine learning

Background: Glyphosate (GLY), a widely used herbicide, has been linked to chronic diseases through disruption of the gut microbiota. Bacteroides , a key gut symbiont, contributes to immune homeostasis via its metabolites. This study explores how GLY may influence Crohn’s Disease (CD) by affecting Bacteroides and their metabolites. Methods: We identified 25 Bacteroides -related metabolites from the gutMGene database and predicted 690 target genes using SEA and STP databases. Differential expression analysis of the GSE16879 dataset identified 2619 CD-related DEGs, with 60 overlapping genes. Four machine learning algorithms (LASSO, RF, SVM-RFE, and neural network), SHAP analysis, and external validation were used to identify hub genes. Single-cell and cell communication analysis explored pathway involvement. Molecular docking evaluation of GLY binding to hub proteins. Results: SETD7 and MMP1 were identified as hub genes. Functional enrichment showed their involvement in FOXO, PPAR, IL-17, and TNF signaling pathways. Both genes correlated with pro-inflammatory immune cells. Single cell analysis revealed that the target genes of metabolites regulate immune responses through the MIF signaling pathway. Molecular docking results showed that GLY does not directly interact with the hub target genes, but may indirectly modulate disease-related pathways through core metabolites. Conclusion: GLY may influence CD development by modulating the Bacteroides -metabolite–immune axis, potentially activating pro-inflammatory pathways. SETD7 and MMP1 emerge as key targets for future research, offering potential avenues for CD intervention.