Immunometabolic network of childhood common obesity: multi-organ comorbidities mediated by gut microbiota-immune axis

Childhood obesity has become a major global public health concern. It is an early-onset systemic immunometabolic disorder closely associated with multi-organ complications, including insulin resistance and cardiovascular disease (CVD). By linking adipose tissue immune remodeling with gut microbiota dysbiosis, this review proposes the gut microbiota-immune axis as an integrative framework connecting obesity-associated immunometabolic disturbances to multi-organ complications. It further explains how local pathological changes in adipose tissue may progressively develop into systemic inflammation and multi-organ damage. Mechanistically, adipocyte hypertrophy, oxidative stress, and lipolysis initiate local adipose tissue remodeling, characterized predominantly by pro-inflammatory M1 macrophage polarization and activation of the Th1/Th17 pathways. Concurrently, diet-induced gut dysbiosis impairs the intestinal barrier, promotes metabolic endotoxemia, and reduces short-chain fatty acid (SCFA) production. Adipose tissue immune remodeling and gut microbiota dysbiosis may establish a bidirectional immunometabolic feedback loop that sustains systemic metaflammation. This review examines the regulatory role of the gut microbiota-immune axis in obesity, delineates differences and evidence gaps between pediatric and adult obesity, and compares the shared and organ-specific mechanisms underlying various complications. Pediatric-specific biomarkers and emerging intervention strategies are also summarized. Collectively, these findings provide a conceptual basis for early risk screening in childhood obesity and for the prevention and management of obesity-related complications.