Pivotal gut microbiota and microbial metabolites involved in the regulation of simple obesity.

Introduction: Obesity increases the risk of multiple chronic diseases and has become a global health challenge. The gut microbiota influences the physiological and pathological processes associated with simple obesity. Elucidating the interactions between gut microbiota and simple obesity provides valuable insights for the development of effective weight-loss strategies. Methods: This study employed network pharmacology to investigate the molecular mechanisms between gut microbiota and simple obesity. Microbial metabolite targets were acquired from the Similarity Ensemble Approach (SEA) and Swiss Target Prediction (STP) databases, gut microbiota-related regulatory targets were retrieved from the gutMGene database, and disease-related targets were collected from GeneCards and the Online Mendelian Inheritance in Man (OMIM) database. Intersection analysis was performed to identify overlapping targets, and a gut microbiota-microbial metabolites-targets (MMTS) network was constructed. Molecular docking analysis was subsequently conducted to verify the binding affinity between key metabolites and targets. Results: Gut microbiota and microbial metabolites regulate simple obesity primarily through eight distinct targets, including IL6, PPARG, NFKB1, TLR4, TLR2, CXCL8, PTGS2, and HNF4A. A total of 23 microbial metabolites were identified, and numerous gut bacterial species associated with the core targets were characterized. Strains from the genera Discussion: These findings provide insights for understanding the role of gut microbiota and microbial metabolites in the regulation of simple obesity and provide scientific support for probiotics and metabolite-based interventions.