The Pediatric Obesity Microbiome and Metabolism Study (POMMS): Methods, Baseline Data, and Early Insights.

Abstract

Objective

The purpose of this study was to establish a biorepository of clinical, metabolomic, and microbiome samples from adolescents with obesity as they undergo lifestyle modification.

Methods

A total of 223 adolescents aged 10 to 18 years with BMI ≥95th percentile were enrolled, along with 71 healthy weight participants. Clinical data, fasting serum, and fecal samples were collected at repeated intervals over 6 months. Herein, the study design, data collection methods, and interim analysis-including targeted serum metabolite measurements and fecal 16S ribosomal RNA gene amplicon sequencing among adolescents with obesity (n = 27) and healthy weight controls (n = 27)-are presented.

Results

Adolescents with obesity have higher serum alanine aminotransferase, C-reactive protein, and glycated hemoglobin, and they have lower high-density lipoprotein cholesterol when compared with healthy weight controls. Metabolomics revealed differences in branched-chain amino acid-related metabolites. Also observed was a differential abundance of specific microbial taxa and lower species diversity among adolescents with obesity when compared with the healthy weight group.

Conclusions

The Pediatric Metabolism and Microbiome Study (POMMS) 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 that describe metabolic and microbiome markers of obesity.

Department

Description

Provenance

Subjects

Citation

Published Version (Please cite this version)

10.1002/oby.23081

Publication Info

McCann, Jessica R, Nathan A Bihlmeyer, Kimberly Roche, Cameron Catherine, Jayanth Jawahar, Lydia Coulter Kwee, Noelle E Younge, Justin Silverman, et al. (2021). The Pediatric Obesity Microbiome and Metabolism Study (POMMS): Methods, Baseline Data, and Early Insights. Obesity (Silver Spring, Md.), 29(3). pp. 569–578. 10.1002/oby.23081 Retrieved from https://hdl.handle.net/10161/22397.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Younge

Noelle Elizabeth Younge

Jean and George W. Brumley, Jr., M.D. Assistant Professor of Pediatrics
Ilkayeva

Olga Ilkayeva

Assistant Professor in Medicine

Olga Ilkayeva, Ph.D., is the Director of the Metabolomics Core Laboratory at Duke Molecular Physiology Institute. She received her Ph.D. training in Cell Regulation from UT Southwestern Medical Center at Dallas, TX. Her postdoctoral research in the laboratory of Dr. Chris Newgard at Duke University Medical Center focused on lipid metabolism and regulation of insulin secretion. As a research scientist at the Stedman Nutrition and Metabolism Center, Dr. Ilkayeva expanded her studies to include the development of targeted mass spectrometry analyses. Currently, she works on developing and validating quantitative mass spectrometry methods used for metabolic profiling of various biological models with emphasis on diabetes, obesity, cardiovascular disease, and the role of gut microbiome in both health and disease.

Granek

Joshua Aaron Granek

Assistant Professor in Biostatistics & Bioinformatics

We have broad interests in using microbial genomics to understand how microbes interact with each other and their hosts. This interest includes the roles played by both beneficial and harmful bacteria, fungi, and viruses and how they interact with the immune system. We study single microbes and microbial communities, primarily using high-throughput sequencing methods. We have a particular interest in developing new experimental and analytical methods that leverage the power of high-throughput sequencing. We are also interested in using deep learning in microbiology research.

Valdivia

Raphael H. Valdivia

Nanaline H. Duke Distinguished Professor of Molecular Genetics and Microbiology

My laboratory is interested in microbes that influence human health, both in the context of host-pathogen and host-commensal interactions. For many pathogens, and certainly for most commensal microbes, we have an incomplete molecular understanding of how host and microbial factors contribute to health and disease. My research group focuses on two experimental systems:

Chlamydia trachomatis infections are responsible for the bulk of sexually transmitted bacterial diseases and are the leading cause of infectious blindness (trachoma) in the world. Chlamydia  resides within a membrane bound compartment (“inclusion”). From this location, the pathogen manipulates the cytoskeleton, inhibits lysosomal recognition of the inclusion, activates signaling pathways, re-routes lipid transport, and prevents the onset of programmed cell death. Our laboratory focuses on identifying and characterizing the bacterial factors that are secreted into the host cell cytoplasm to manipulate eukaryotic cellular functions. We use a combination of cell biology, biochemistry, genetics, genomics, proteomics and molecular biology to determining the function of virulence factors that reveal novel facets of the host-pathogen interaction. Our goal is to understand how these obligate intracellular bacterial pathogens manipulate host cellular functions to replicate, disseminate and cause disease, and in the process develop strategies to ameliorate the damage caused by these infections to the female reproductive organs.

Akkermansia muciniphila is prevalent member of the gut microbiota that proliferates in the mucus layers of our lower gastrointestinal tract and contribute to nutrient homeostasis and human immunological health. My research group developed genetic tools to characterize these microbes to define the mechanisms used to colonize the human gut and identify the molecular and cellular pathways that underscore Akkermansia's impact on immune homeostasis.  In the process, we seek to engineer strains of Akkermansia that enhance their probiotic potential.

David

Lawrence Anthony David

Associate Professor of Molecular Genetics and Microbiology
Newgard

Christopher Bang Newgard

W. David and Sarah W. Stedman Distinguished Professor of Nutrition in the School of Medicine

Over its 16 year history, our laboratory has investigated mechanisms of metabolic regulation and fuel homeostasis in mammalian systems. Major projects include: 1) Mechanisms involved in regulation of insulin secretion from pancreatic islet β-cells by glucose and other metabolic fuels; 2) Development of methods for protection of β-cells against immune-mediated damage; 3) Studies on spatial organization and regulation of systems controlling hepatic glucose balance; 4) Studies on the mechanisms involved in lipid-induced impairment of insulin secretion and action in diabetes.

Shah

Svati Hasmukh Shah

Ursula Geller Distinguished Professor of Research in Cardiovascular Diseases
Rawls

John F. Rawls

James B. Duke Distinguished Professor

We seek to understand how the intestinal microbiome contributes to vertebrate physiology and disease. To that end, we leverage complementary zebrafish and mouse models to study the integrative physiology of host-microbiome interactions. This work has identified novel and conserved mechanisms by which intestinal bacteria regulate dietary fat metabolism and systemic innate immunity. We also apply genomic approaches in these animal models to understand the transcriptional regulatory pathways utilized by the intestinal epithelium to mediate host responses to the microbiome. Using this approach, we have identified mechanisms of transcriptional and chromatin regulation that have been conserved during vertebrate evolution and also contribute to modern human diseases such as the inflammatory bowel diseases, obesity, and diabetes. To further advance our understanding of obesity pathophysiology, we developed the zebrafish as a model system for studying adipose tissues and identifying new environmental and genetic regulators of adiposity. We are also engaged in translational research in humans and animal models to define microbial and metabolic determinants of obesity and efficacy of weight loss intervention. Grounded in comparative and integrative physiology, our research program has been effective in discovering ancient mechanisms of host-microbiome interaction that are conserved across animal taxa and contribute to the etiology of modern human diseases. These insights are advancing our understanding of host-microbiome relationships in vertebrate physiology and identifying novel therapeutic targets for human diseases ranging from inflammatory bowel disease to obesity to neurological disorders.

Armstrong

Sarah Commisso Armstrong

Professor of Pediatrics

Dr. Armstrong's clinical and research interests include pediatric nutrition and the treatment of childhood and adolescent obesity, along with related health problems. As director of the Duke Children's Healthy Lifestyles Program, Dr. Armstrong oversees a cohort of over 3000 overweight children and teenagers. She is a member of the Executive Committee for the American Academy of Pediatrics Section on Obesity.  Dr. Armstrong's research focuses on leveraging innovative strategies to improve children's nutrition and activity, including mobile health interventions, community partnerships, and medication or surgical approaches.


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