Microbiota-Derived Metabolites in Developmental Programming: Bridging Early-Life Gut Microbiota to Childhood Metabolic Disorders.

The rising incidence of childhood metabolic disorders poses an increasingly serious public health challenge. The developmental programming of the gut microbiota during early life, shaped by perinatal and postnatal factors, establishes a functional trajectory that profoundly influences host metabolism, with microbiota-derived metabolites serving as critical bridging molecules that mechanistically link early-life exposures to metabolic outcomes in childhood. Key microbiota‒metabolite pathways underpin this process, including the fermentation of dietary fiber into short-chain fatty acids (SCFAs), the microbial metabolism of amino acids into both protective and detrimental products, the biotransformation of primary bile acids (BAs) into secondary BAs, and the generation of trimethylamine N-oxide (TMAO) from methylamine precursors. These metabolites exert their effects through diverse molecular mechanisms, spanning epigenetic regulation and receptor signaling (including farnesoid X receptor [FXR], G protein-coupled bile acid receptor 1 [TGR5], and other metabolite-sensing receptors). A deep understanding of these microbiota-derived metabolites in the context of developmental programming is therefore essential not only for advancing precise diagnosis and personalized treatment but also for informing early and targeted prevention strategies to reduce the burden of childhood metabolic diseases.