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 microbiota in youth, in whom these connections likely originate. 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 profiling. 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. Together, 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.
Article Highlights
- Previous obesity studies of the gut microbiome have focused on adults. Childhood obesity rates have risen substantially and confer elevated T2D risk. We investigated relationships among gut microbiota, metabolic function, and inflammation in adolescents with obesity at risk for type 2 diabetes (T2D).
- The aim of this study was to examine whether adolescents with obesity display variations in the microbiota associated with systemic inflammation or metabolic dysfunction.
- Variation in intestinal bacterial biomass, along with taxonomic composition, were associated with plasma lipids and insulin response among adolescents with obesity, with a greater impact on males.
- Variation in the intestinal microbiota is associated with metabolic and inflammatory dysregulation before T2D. Future sex-stratified studies through puberty are needed to inform strategies to reduce T2D.
