Uncovering the microbiota-metabolite axis across levels of metabolic complication burden in Chinese adolescents with obesity

Abstract

Pediatric obesity presents with diverse metabolic phenotypes, yet the gut microbiota and metabolite signatures associated with obesity-related metabolic complications remain poorly defined. Here, we applied 16S rRNA gene sequencing and untargeted fecal metabolomics to investigate microbial and metabolic alterations in children with obesity, stratified according to metabolic complication burden. Stratification revealed graded differences in microbial composition and metabolite profiles across levels of metabolic complication burden. Children with more complications exhibited elevated levels of primary bile acids, accompanied by enrichment of taxa previously associated with bile acid metabolism. Conversely, the abundance of short-chain fatty acid (SCFA)-producing taxa was lower in groups with greater complication burden, suggesting potentially reduced fermentative capacity. These patterns differed from those previously reported in adult obesity and may reflect the distinct developmental context of the pediatric gut ecosystem. Our findings highlight the value of complication-based stratification in characterizing obesity-related metabolic heterogeneity and identify microbiota-metabolite associations that warrant further validation in longitudinal and mechanistic studies. Children with obesity were stratified according to metabolic complication burden. Primary bile acid levels were higher in groups with greater complication burden, accompanied by enrichment of taxa previously associated with bile acid metabolism. The abundance of putative SCFA-producing taxa was lower in groups with greater complication burden. Graded microbiota-metabolite differences were observed across levels of metabolic complication burden. Microbiota-metabolite signatures may help characterize the metabolic heterogeneity of pediatric obesity and warrant further validation.