The Gut–Adipose–Tumor Axis in Obesity-Related Cancer

The global obesity epidemic has emerged as a major driver of cancer incidence and mortality, with accumulating evidence highlighting the gut-adipose-tumor axis as a critical mediator of obesity-related carcinogenesis. The gut-adipose-tumor axis is a tripartite communication network, wherein the intestinal microbiome, adipose tissue, and tumor microenvironment engage in dynamic bidirectional crosstalk that alters cancer susceptibility and progression. This review synthesizes current understanding of the epidemiology, pathophysiology, therapeutic implications, and future directions of this axis. Obesity-induced gut dysbiosis leads to systemic dissemination of pro-inflammatory microbial products and metabolites. These gut-derived signals profoundly influence adipose tissue homeostasis, exacerbating chronic low-grade inflammation, promoting macrophage infiltration and polarization, and disrupting adipokine secretion patterns. Dysfunctional adipose tissue generates cancer-promoting mediators and metabolic perturbations. The convergence of gut-derived and adipose-derived signals creates a systemic pro-carcinogenic environment that reshapes the tumor microenvironment through multiple mechanisms. Understanding the gut-adipose-tumor axis as an integrated biological system offers opportunities for cancer prevention and treatment. This is of significant importance for exploring the mechanisms of obesity-related carcinogenesis and developing new therapeutic approaches for obesity-related cancers.