Leveraging Human Microbiome Features to Diagnose and Stratify Children with Irritable Bowel Syndrome

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, James Versalovic

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)449-461
Number of pages13
JournalJournal of Molecular Diagnostics
Volume21
Issue number3
DOIs
StatePublished - May 2019

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Medicine

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