Gut microbiota-immune crosstalk in childhood and adolescent obesity: mechanistic insights and therapeutic potential focused on short-chain fatty acids and emerging metabolites.

Childhood and adolescent obesity should not be explained only as a problem of eating too much energy and using too little energy. Research now shows that obesity in young people is also linked to changes in gut bacteria, changes in the way the body uses energy, and long-term mild inflammation during key stages of growth. Acting as a central metabolic nexus, the gut microbiota converts dietary substrates into short-chain fatty acids (SCFAs) along with a broad spectrum of other functional metabolites that shape the microbiota-immune-obesity axis. This review focuses on how SCFAs affect intestinal immunity, how they may be involved in innate immune training, and how they may help promote heat production in fat tissue. These effects are mainly related to the activation of cell receptors called G protein-coupled receptors (GPCRs) and the inhibition of histone deacetylase (HDAC). We further clarify the contributions of several emerging classes of metabolites: aromatic amino acid (AAA) catabolites that affect intestinal barrier integrity and mucosal inflammation; secondary bile acids that modulate energy metabolism through farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5); and N-acyl amides that act on endocannabinoid-like pathways to adjust appetite. Based on these insights, we propose a three-level intervention strategy focused on microbial metabolites-upstream reshaping of beneficial communities using prebiotics and high-fiber dietary patterns, midstream development of pediatric-specific SCFA formulations and targeted metabolite supplements, and downstream exploration of receptor-targeted pharmacotherapy. Future advances rely on integrated multi-omics designs, rigorous causal evidence from human studies, and development-appropriate personalized regimens, which will ultimately create new precision pathways for the prevention and treatment of early-life obesity.