Metabolic Dysfunction Associated With Alterations in Gut Microbiota in Adolescents With Obesity

Abstract

Obesity in childhood is associated with adulthood obesity, type 2 diabetes (T2D), and future metabolic complications. The gut microbiota is a modifier of host metabolic function with altered bacterial composition associated with disease risk. Few studies have investigated the relationships among metabolic disease, inflammation, and the gut mi-crobiota in youth, in whom these connections likely origi-nate. Here, we characterized the gut microbiome of a cohort of 56 adolescents with obesity and without diabetes using fecal DNA sequencing with absolute bacterial quantitation together with immune and metabolic profil-ing. We observed multi–log order variation in absolute bacterial biomass dependent on host environment and associated with bacterial taxonomic composition based on a nested case-control comparison. Participants with higher biomass displayed a healthier phenotype with higher gut microbiome diversity; lower abundance of taxa associated with inflammation and pathogenicity, such as Escherichia coli; and lower levels of neutrophil activities. Further association analysis revealed sex-dependent variation, with higher levels of insulin resistance, fasting triglycerides, and markers of neutrophil activities in male adolescents with lower bacterial biomass. To-gether, these results suggest that intestinal bacterial biomass and composition are associated with metabolic and inflammatory dysregulation evident before T2D diagnosis and identify sex differences in microbiome-associated metabolic dysfunction in adolescents with obesity.