Immunopathology of metabolic syndrome: effects on gut microbiota and antibiotic resistance

The cluster of related metabolically derived disorders that confer increased risk of developing type 2 diabetes mellitus (T2D) and cardiovascular disease (CVD) is termed the Metabolic syndrome (MetS). Despite two decades of growing evidence on MetS pathogenesis, the immunopathological links between gut microbiota (GM) dysbiosis and metabolic derangements remain only partially elucidated. This review focuses on the complex nexus among MetS, GM composition and function, and the emerging antibiotic-resistance predicament. The gut commensal microbiome-defined as approximately 10 14 microorganisms that have been termed endocrine organs with key roles beyond gastrointestinal homeostasis, such as immune-mediated host inflammatory and metabolic regulation and barrier homeostasis- undergoes dysbiosis in MetS, characterized by marked losses of beneficial short-chain fatty acid (SCFA)-producing bacteria and overgrowth of pathobiont Proteobacteria , such as those bearing lipopolysaccharide. Increased gut permeability and Toll-like receptor 4 (TLR-4) activation, driven by increased luminal products, are termed metabolic endotoxemia and form the immunopathological bridge between gut dysbiosis and systemic low-grade inflammation and insulin resistance. Disturbances in microbial-mediated host metabolism of bile acids, tryptophan catabolism, and the regulatory T cell/T helper 17 axis further promote inflammation in adipose tissue, liver, and skeletal muscle. Antibiotic-driven dysbiosis, which reduces diversity and increases antibiotic-resistant gene elements within the host gut resistome, exacerbates metabolic abnormalities and is a key focus for developing personalized treatment approaches.