Leveraging human microbiome features to diagnose and stratify children with irritable bowel syndrome

Authors: HOLLISTER, EMILY - Baylor College Of Medicine; OEZGUEN, NUMAN - Baylor College Of Medicine; CHUMPITAZI, BRUNO - Texas Children'S Hospital; LUNA, RUTH - Baylor College Of Medicine; WEIDLER, ERICA - Children'S Nutrition Research Center (CNRC); RUBIO-GONZALES, MICHELLE - Baylor College Of Medicine; DAHDOULI, MAHMOUD - Baylor College Of Medicine; COPE, JULIA - Baylor College Of Medicine; MISTRETTA, TONI-ANN - Baylor College Of Medicine; RAZA, SABEEN - Baylor College Of Medicine; METCALF, GINGER - Baylor College Of Medicine; MUZNY, DONNA - Baylor College Of Medicine; GIBBS, RICHARD - Baylor College Of Medicine; PETROSINO, JOSEPH - Baylor College Of Medicine; HEITKEMPER, MARGARET - University Of Washington; SAVIDGE, TOR - Baylor College Of Medicine; SHULMAN, ROBERT - Children'S Nutrition Research Center (CNRC); VERSALOVIC, JAMES - Baylor College Of Medicine

Submitted to: Molecular Diagnosis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/6/2019
Publication Date: 5/1/2019
Citation: Hollister, E.B., Oezguen, N., Chumpitazi, B.P., Luna, R., Weidler, E.M., Rubio-Gonzales, M., Dahdouli, M., Cope, J.L., Mistretta, T., Raza, S., Metcalf, G.A., Muzny, D.M., Gibbs, R.A., Petrosino, J.F., Heitkemper, M., Savidge, T.C., Shulman, R.J., Versalovic, J. 2019. Leveraging human microbiome features to diagnose and stratify children with irritable bowel syndrome. Molecular Diagnosis. 21(3):449-461. https://doi.org/10.1016/j.jmoldx.2019.01.006.
DOI: https://doi.org/10.1016/j.jmoldx.2019.01.006

Interpretive Summary: Approximately 15% of children and adults worldwide suffer from pain associated with functional gastrointestinal disorders such as irritable bowel syndrome. The cause of these disorders is unclear. As a result, the diagnosis of these disorders cannot be made through laboratory tests. We and others have shown that some of these individuals have a gut bacterial population that is different from healthy people. The gut bacteria play an important role in helping to digest (breakdown) certain foods we eat. These breakdown products (metabolites) could affect gut function and cause pain. In this study we identify differences in the types of gut bacteria and breakdown products (metabolites) in children with irritable bowel syndrome compared to those in healthy children. The changes in bacteria and metabolites was associated with how much pain the children with irritable bowel syndrome experienced. These studies are helping us understand how the gut bacteria can be beneficial or harmful to our health and nutritional strategies to address this.

Technical Abstract: Accurate diagnosis and stratification of children with irritable bowel syndrome (IBS) remain challenging. Given the central role of recurrent abdominal pain in IBS, we evaluated the relationships of pediatric IBS and abdominal pain with intestinal microbes and fecal metabolites using a comprehensive clinical characterization and multiomics strategy. Using rigorous clinical phenotyping, we identified preadolescent children (aged 7 to 12 years) with Rome III IBS (n = 23) and healthy controls (n = 22) and characterized their fecal microbial communities using whole-genome shotgun metagenomics and global unbiased fecal metabolomic profiling. Correlation-based approaches and machine learning algorithms identified associations between microbes, metabolites, and abdominal pain. IBS cases differed from controls with respect to key bacterial taxa (eg, Flavonifractor plautii and Lachnospiraceae bacterium 7_1_58FAA), metagenomic functions (eg, carbohydrate metabolism and amino acid metabolism), and higher-order metabolites (eg, secondary bile acids, sterols, and steroid-like compounds). Significant associations between abdominal pain frequency and severity and intestinal microbial features were identified. A random forest classifier built on metagenomic and metabolic markers successfully distinguished IBS cases from controls (area under the curve, 0.93). Leveraging multiple lines of evidence, intestinal microbes, genes/pathways, and metabolites were associated with IBS, and these features were capable of distinguishing children with IBS from healthy children. These multi-omics features, and their links to childhood IBS coupled with nutritional interventions, may lead to new microbiome-guided diagnostic and therapeutic strategies.