Abstract
Metabolic syndrome (MetS), with obesity as its primary pathogenic driver, is a major public health concern and a leading risk factor for type 2 diabetes (T2D) and cardiovascular disease. Increasing evidence highlights the critical role of the microbiota-gut-brain axis (MGBA) in the pathogenesis of these disorders through its regulation of energy homeostasis, metabolic function, and immune responses. This review summarizes current evidence on the mechanisms by which disturbances in MGBA signaling contribute to the development and progression of MetS. Gut microbiome dysbiosis may increase intestinal permeability, facilitating the translocation of bacterial lipopolysaccharide into the systemic circulation. This process may contribute to metabolic endotoxemia and chronic low-grade inflammation, potentially promoting insulin resistance, adipose tissue dysfunction, and metabolic impairment. In addition, alterations in microbiome composition and function influence the secretion of gut-derived hormones, vagal signaling, hypothalamic–pituitary–adrenal axis activity and bile acid metabolism, ultimately disrupting appetite regulation, glucose homeostasis, lipid metabolism and blood pressure control. Preclinical studies and limited clinical evidence suggest that gut microbiota-targeted interventions, including prebiotics and probiotics, may improve selected metabolic parameters. However, evidence demonstrating sustained clinical benefits or reductions in cardiometabolic events in patients with MetS remains insufficient. Although the MGBA represents a potential therapeutic target, further well-designed randomized controlled trials with predefined metabolic outcomes, direct assessment of microbial function, and adequate follow-up are needed to establish the clinical efficacy and long-term safety of microbiota-targeted interventions, including fecal microbiota transplantation (FMT).