Wnt signaling arranges the fate of lipid metabolism: the role of gut microbes

Disrupted lipid metabolism contributes to metabolic diseases and cancer. Gut microbes and their metabolites influence lipid absorption, synthesis, storage, and oxidation, while the Wnt signaling pathway is not only associated with lipid metabolism as a downstream metabolic pathway, but also serves as a regulatory system linking adipocyte lineage determination, tissue remodeling, and specific metabolic functions in mature adipocytes. How these components interact to form a gut microbes–metabolites–Wnt signaling axis, however, remains incompletely understood. Thus, this review focuses on the structure and physiological functions of Wnt, the association between Wnt signaling and host lipid metabolism. This review then examines how bile acids, amino acid metabolites, and short-chain fatty acids intersect with Wnt-related pathways across intestinal, hepatic, adipose, and cancer models. It further discusses the targeting of the gut microbes–metabolites–Wnt signaling axis for treatment , and explored the application prospects and challenges of gut microbes and their metabolites in the prevention and treatment of metabolic diseases and cancer.