# A comprehensive research resource to define mechanisms underlying microbial regulation of host metabolism in pediatric obesity and obesity-targeted therapeutics

> **NIH NIH R24** · DUKE UNIVERSITY · 2020 · $1,372,991

## Abstract

PROJECT SUMMARY
The current pandemic of obesity and insulin resistance across the lifespan presents an immense public health
challenge. Human observational studies and fecal transplantation studies in animal models (both largely
focused on adults) have found an interconnection among obesity, insulin resistance, and the microbiota.
Because epidemiology points to childhood origins for the genesis of obesity, there is a critical need to
understand the mechanisms of pediatric obesity and to develop tools for its prediction, prevention, and
treatment. Children with severe obesity mimic adult phenotypes in their development of metabolic and
cardiovascular risk, and yet are at the earliest stages of disease with fewer and less severe co-morbid
conditions. Thus children with obesity present a unique opportunity and an ideal population in which to garner
deeper insights into the obesity-associated microbiome. To enable such insights, the objective of this proposal
is to establish a comprehensive research resource to define mechanisms underlying microbial regulation of
host metabolism in adolescents with obesity (ages 12-18 yrs) before and after weight loss intervention. The
proposed research leverages Duke’s unique and well-established intervention program for pediatric obesity
and insulin resistance. Our prior studies have applied metabolomic technology to reveal that blood metabolites
such as branched chain amino acids (BCAA) are negatively associated with insulin sensitivity following adult
weight loss interventions, and we have used gnotobiotic mice to demonstrate their positive association with
microbiota-mediated weight gain. Our preliminary studies indicate that BCAA and related metabolites are also
associated with insulin resistance and weight gain in adolescents. Our central hypothesis is that human gut
bacteria control host weight gain and insulin resistance in adolescents by modifying host metabolism. This
hypothesis will be tested in two specific aims: Aim 1. Develop a resource to define associations between
intestinal microbiota and a severely obese population of adolescents enrolled in an outpatient weight
management intervention program. Aim 2. Define the molecular mechanisms by which human intestinal
bacteria regulate metabolic traits linked to pediatric obesity. Completion of this work will provide three key
resources for broad use by the scientific community: (1) a clinical sample, microbiota strain, and data
repository from a unique pediatric weight management intervention cohort, (2) a comprehensive suite of robust
genetic, molecular profiling, and phenotyping technologies that will yield unique insights into the microbial
communities that control body weight and responses to obesity intervention, and (3) insights into molecular
mechanisms by which BCAA and other identified microbial products influence metabolic health during
childhood and adolescence. These new resources, technologies, and mechanistic insights will have a positive
imp...

## Key facts

- **NIH application ID:** 10016253
- **Project number:** 5R24DK110492-05
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** John F Rawls
- **Activity code:** R24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,372,991
- **Award type:** 5
- **Project period:** 2016-09-25 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10016253

## Citation

> US National Institutes of Health, RePORTER application 10016253, A comprehensive research resource to define mechanisms underlying microbial regulation of host metabolism in pediatric obesity and obesity-targeted therapeutics (5R24DK110492-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10016253. Licensed CC0.

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