Microbiome–host gene interactions: Role of Bifidobacterium metabolites in obesity

Background: The gut microbiome (GM) plays a critical role in regulating host metabolism, and its dysbiosis has been closely associated with obesity. This study investigated how Bifidobacterium-derived metabolites influence obesity-related molecular pathways through host–gene interactions. Twenty-eight bioactive metabolites of Bifidobacterium were retrieved from the gutMGene database and analyzed using SwissTargetPrediction. Cross-comparison with 10,019 obesity-associated genes from GeneCards revealed 226 overlapping targets. Network and hub-gene analyses using STRING and Cytoscape (CytoHubba plugin) identified six key regulatory nodes: EGFR, PPARG, ESR1, STAT3, PTGS2, and TLR4. Functional enrichment indicated significant involvement of these genes in lipid metabolism, inflammatory signaling, and insulin resistance (adjusted p < 0.05). The results provide quantitative evidence supporting the role of Bifidobacterium-derived metabolites in modulating host metabolic networks implicated in obesity. These findings suggest that specific bacterial metabolites may serve as candidate molecules for obesity-targeted drug repurposing. Further experimental and clinical validation are warranted to clarify their mechanistic effects and translational potential.