To establish a biorepository of clinical, metabolomic, and microbiome samples from adolescents with obesity as they undergo lifestyle modification.
We enrolled 223 adolescents aged 10-18 years with Body Mass Index ≥ 95 th percentile, along with 71 healthy weight participants. We collected clinical data, fasting serum, and fecal samples at repeated intervals over 6 months. Here we present our study design, data collection methods, and an interim analysis, including targeted serum metabolite measurements and fecal 16S rRNA gene amplicon sequencing among adolescents with obesity (n=27) and healthy weight controls (n=27).
Adolescents with obesity have higher serum alanine aminotransferase, C-reactive protein, and glycated hemoglobin, and lower high-density lipoprotein cholesterol when compared with healthy weight controls. Metabolomics revealed differences in branched chain amino acid related metabolites. We also observed differential abundance of specific microbial taxa and lower species diversity among adolescents with obesity when compared with the healthy weight group.
The Duke Pediatric Metabolism and Microbiome Study biorepository is available as a shared resource. Early findings suggest evidence of a metabolic signature of obesity unique to adolescents, along with confirmation of previously reported findings describing metabolic and microbiome markers of obesity.
Clinical Trial Registration
Biorepository: NCT02959034 Observational Trial: NCT03139877
What is already known about this subject?
The intestinal microbiome plays an important role in adult obesity and regulation of metabolism. Although it is well-established that obesity has its roots in childhood, very little is known about the role of the microbiome in pediatric obesity and how it changes during adolescence.
What are the new findings in your manuscript?
This manuscript provides details of a new shared biorepository including clinical data, stool samples and plasma samples from a diverse cohort of 223 adolescents with obesity followed longitudinally over 6 months during a weight management intervention, as well as 71 adolescents with healthy weight as a comparison group. Interim analyses suggest that adolescents with obesity have microbiome signatures and metabolite profiles similar to adults, however key differences in microbial communities and metabolic by-products are identified.
How might your results change the direction of research or focus of clinical practice?
The POMMS biorepository will be available for investigators to use in future research, to elucidate the underlying mechanisms of obesity and related chronic health conditions. Preliminary data reveal metabolite profiles that suggest adolescence may be a window of metabolic plasticity and disease reversibility Microbiome and metabolomic signatures suggest potential biomarkers that may serve as prognostic or predictive factors in disease remission, or targets for future therapeutics.