Gut microbiota and immunometabolism in obesity.

The gut microbiota plays a central role in modulating both immunity and metabolism. Obesity-associated microbiota configuration is a critical driver of persistent inflammatory activation and immune dysfunction, ultimately leading to chronic metabolic disorders. Immunometabolism examines how metabolic demands shape immune cell function and how immune responses influence cellular metabolism. Emerging research on how the gut microbiota contribute to immune cell metabolic processes and the resulting health outcomes is deepening our understanding of the mechanisms underlying obesity and metabolic diseases. In this review, we summarize how intracellular metabolic pathways and master regulators, such as mTOR and AMPK, orchestrate immune cell function and how their dysregulation contributes to obesity-associated immune and metabolic dysfunction. We also discuss how gut microbiota influences the immunometabolism of different myeloid and lymphoid cell subsets and intestinal epithelial cells. Finally, we review the role of microbially produced metabolites, including short-chain fatty acids, lactate, succinate, bile acids, and amino acids, in reprogramming immune cell metabolism. We also discuss whether modulating gut microbiota function to regulate immunometabolic pathways could help restore immune homeostasis and reduce obesity-related complications.