Restructuring the gut microbiota in obesity: molecular mechanisms linking dysbiosis to systemic inflammation and therapeutic opportunities

Obesity is characterized by a chronic low-grade inflammatory state that contributes to insulin resistance, type 2 diabetes, and metabolic syndrome. The gut microbiota has emerged as a critical mediator of this inflammatory process through multiple interconnected mechanisms including metabolic endotoxemia, short-chain fatty acid dysregulation, and intestinal barrier dysfunction. This review synthesizes current evidence on the structural and functional alterations of the gut microbiome in obesity, examines the mechanistic pathways linking dysbiosis to systemic inflammation, and critically evaluates therapeutic strategies aimed at restructuring the obese gut microbial community. We focus on three major intervention approaches: fecal microbiota transplantation, probiotic and prebiotic supplementation, and next-generation targeted microbial therapies. Analysis of clinical and preclinical studies reveals that successful microbial restructuring requires not only compositional shifts but also functional restoration of microbial metabolite production, particularly short-chain fatty acids. The evidence supports a model wherein obesity-associated dysbiosis perpetuates chronic inflammation through increased lipopolysaccharide translocation, reduced butyrate production, and compromised intestinal barrier integrity. Restoring microbial eubiosis through targeted interventions offers a promising avenue for resolving chronic low-grade inflammation and improving metabolic health outcomes in obese individuals.