Microbiome science may help doctors deliver more effective, personalized treatment to children with irritable bowel syndrome

A new, improved diagnostic classification technique enables stratification of pediatric patients with irritable bowel syndrome with greater precision so they can receive optimal treatment, reports The Journal of Molecular Diagnostics


Philadelphia, April 17, 2019

To improve the treatment of children with irritable bowel syndrome (IBS), investigators have developed a sophisticated way to analyze the microbial and metabolic contents of the gut. A report in The Journal of Molecular Diagnostics, published by Elsevier, describes how a new battery of tests enables researchers to distinguish patients with IBS from healthy children and identifies correlations between certain microbes and metabolites with abdominal pain. With this information, doctors envision tailoring nutritional and targeted therapies that address a child’s specific gastrointestinal problems.

“This research highlights the importance of the microbiome–gut–brain axis and our understanding of chronic abdominal pain. Development of new disease classifiers based on microbiome data enables precision diagnostics to be developed for IBS and similar disorders. Although other studies have found differences in the gut microbiomes of patients with IBS, this study is the first to combine deep microbiome analysis with development of new diagnostic strategies,” explained James Versalovic, MD, PhD, of the Department of Pathology & Immunology at Baylor College of Medicine and the Department of Pathology at Texas Children’s Hospital, Houston, TX, USA. The term microbiome refers to the genetic material of all the microbes—bacteria, fungi, protozoa, and viruses—that live on and inside the human body.

Samples for this study were obtained from 23 preadolescent children with IBS (age 7 to 12 years) and 22 healthy controls. Participants were asked to maintain daily pain and stool diaries for two weeks and to provide stool (fecal) samples.

Investigators found that there are differences in bacterial composition, bacterial genes, and fecal metabolites in children with IBS compared to healthy controls. In addition to identifying correlations of these factors with abdominal pain, they generated a highly accurate classifier using metagenomic and metabolic markers that distinguishes children with IBS from healthy controls with 80 percent or greater accuracy. This classifier assesses specific metabolites, types of bacteria, functional pathways, and other factors. “This disease classifier represents a significant advance in the diagnosis of IBS and could be clinically impactful,” commented Dr. Versalovic.

A multi-‘omic network of bacterial species (green triangles), metagenomic pathways (yellow diamonds), and metabolite abundances (blue spheres) separates pediatric irritable bowel syndrome (IBS) cases (red squares) from healthy controls (HC) (cyan squares)
A multi-‘omic network of bacterial species (green triangles), metagenomic pathways (yellow diamonds), and metabolite abundances (blue spheres) separates pediatric irritable bowel syndrome (IBS) cases (red squares) from healthy controls (HC) (cyan squares) (n=23 IBS, 22 HC).

This microbiome-based classifier can potentially help identify subpopulations of children with IBS that are more likely to benefit from microbiome-related therapies including diet modification, while guiding others to alternative appropriate treatment plans. The investigators also provide insights into how specific microbiome-related findings may be related to abdominal pain, thus opening up potential novel treatment approaches.

A chronic disease that is evaluated clinically can be stratified in the future based on differences in the composition and function of the intestinal microbiome. Dr. Versalovic envisions that these findings will begin to usher in an era of metagenomics-based, data-driven precision diagnostics for IBS and other functional gastrointestinal disorders. “Microbiome-based diagnosis and disease stratification of patients with IBS means that we create hope for tailored nutrition and targeted therapies in the future, leading to better outcomes for patients with chronic disease,” noted Dr. Versalovic.

IBS is a disruptive gastrointestinal condition characterized by bloating, changes in bowel habits, and pain that affects up to 20 percent of the world’s population (children and adults). Increasing evidence indicates that the onset and symptoms of IBS are related to the gut microbiome. Deficiencies or excesses of specific gut microbes or metabolites may contribute to the disease process of IBS.

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Notes for editors
The article is “Leveraging Human Microbiome Features to Diagnose and Stratify Children with Irritable Bowel Syndrome,” by Emily B. Hollister, Numan Oezguen, Bruno P. Chumpitazi, Ruth Ann Luna, Erica M. Weidler, Michelle Rubio-Gonzales, Mahmoud Dahdouli, Julia L. Cope, Toni-Ann Mistretta, Sabeen Raza, Ginger A. Metcalf, Donna M. Muzny, Richard A. Gibbs, Joseph F. Petrosino, Margaret Heitkemper, Tor C. Savidge, Robert J. Shulman, and James Versalovic (https://doi.org/10.1016/j.jmoldx.2019.01.006). It will appear in The Journal of Molecular Diagnostics, volume 21, issue 3 (May 2019) published by Elsevier.

Full text of this study is available to credentialed journalists upon request; contact Eileen Leahy at +1 732 238 3628 or jmdmedia@elsevier.com. Journalists wishing to interview the authors should contact Jenn Jacome at +1 832 824 2679 or jmjacome@texaschildrens.org.

This work was supported by awards from the National Institute of Diabetes, Digestive, and Kidney Diseases (UH2DK093990 and UH3DK083990); National Center for Complementary and Integrative Medicine (RO1AT004326.); National Cancer Institute (U01CA170930); National Human Genome Research Institute (U54HG004973); National Institute of Nursing Research (R01NR05337, R01NR013497, RC2NR011959); National Institute of Allergy and Infectious Diseases (U011AI24290-01 and R01AI10091401); Autism Speaks GI and Neurobehavioral Processes Grant (#9455); BCM Caroline Weiss Law Fund for Research in Molecular Medicine; and Daffy’s Foundation. The authors also acknowledge the tremendous support of the Human Microbiome Project funded by the National Institutes of Health in the past and the Texas Medical Center Digestive Diseases Center.

About The Journal of Molecular Diagnostics
The Journal of Molecular Diagnostics
, the official publication of the Association for Molecular Pathology, co-owned by the American Society for Investigative Pathology, and published by Elsevier, seeks to publish high quality original papers on scientific advances in the translation and validation of molecular discoveries in medicine into the clinical diagnostic setting, and the description and application of technological advances in the field of molecular diagnostic medicine. The editors welcome review articles that contain: novel discoveries or clinicopathologic correlations, including studies in oncology, infectious diseases, inherited diseases, predisposition to disease, or the description of polymorphisms linked to disease states or normal variations; the application of diagnostic methodologies in clinical trials; or the development of new or improved molecular methods for diagnosis or monitoring of disease or disease predisposition. jmd.amjpathol.org

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The Journal of Molecular Diagnostics
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