The Pediatric Obesity Microbiome and Metabolism Study (POMMS): Methods, Baseline Data, and Early Insights
Authors: McCann Jessica R. , Bihlmeyer Nathan A. , Roche Kimberly , Catherine Cameron , Jawahar Jayanth , Kwee Lydia Coulter , Younge Noelle E. , Silverman Justin , Ilkayeva Olga , Sarria Charles , Zizzi Alexandra , Wootton Janet , Poppe Lisa , Anderson Paul , Arlotto Michelle , Wei Zhengzheng , Granek Joshua A. , Valdivia Raphael H. , David Lawrence A. , Dressman Holly K. , Newgard Christopher B. , Shah Svati H. , Seed Patrick C. , Rawls John F. , Armstrong Sarah C. 
Published: June 2020

Objective

To establish a biorepository of clinical, metabolomic, and microbiome samples from adolescents with obesity as they undergo lifestyle modification.

Methods

We enrolled 223 adolescents aged 10-18 years with Body Mass Index ≥ 95th 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).

Results

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.

Conclusions

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.