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

Autor:	Hollister EB; Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Texas Children's Microbiome Center, Texas Children's Hospital, Houston, Texas; Diversigen, Inc., Houston, Texas; Department of Pathology, Texas Children's Hospital, Houston, Texas., Oezguen N; Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Texas Children's Microbiome Center, Texas Children's Hospital, Houston, Texas; Department of Pathology, Texas Children's Hospital, Houston, Texas., Chumpitazi BP; Department of Pediatrics, Baylor College of Medicine, Houston, Texas; Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Texas Children's Hospital, Houston, Texas., Luna RA; Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Texas Children's Microbiome Center, Texas Children's Hospital, Houston, Texas; Department of Pathology, Texas Children's Hospital, Houston, Texas., Weidler EM; Department of Pediatrics, Baylor College of Medicine, Houston, Texas; Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Texas Children's Hospital, Houston, Texas; Children's Nutrition Research Center, Houston, Texas., Rubio-Gonzales M; Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Texas Children's Microbiome Center, Texas Children's Hospital, Houston, Texas; Department of Pathology, Texas Children's Hospital, Houston, Texas., Dahdouli M; Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Texas Children's Microbiome Center, Texas Children's Hospital, Houston, Texas; Department of Pathology, Texas Children's Hospital, Houston, Texas., Cope JL; Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Texas Children's Microbiome Center, Texas Children's Hospital, Houston, Texas; Department of Pathology, Texas Children's Hospital, Houston, Texas., Mistretta TA; Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Texas Children's Microbiome Center, Texas Children's Hospital, Houston, Texas; Department of Pathology, Texas Children's Hospital, Houston, Texas., Raza S; Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Texas Children's Microbiome Center, Texas Children's Hospital, Houston, Texas; Department of Pathology, Texas Children's Hospital, Houston, Texas., Metcalf GA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas., Muzny DM; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas., Gibbs RA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas., Petrosino JF; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas; Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas., Heitkemper M; Department of Biobehavioral Nursing and Health Informatics, University of Washington, Seattle, Washington., Savidge TC; Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Texas Children's Microbiome Center, Texas Children's Hospital, Houston, Texas; Department of Pathology, Texas Children's Hospital, Houston, Texas., Shulman RJ; Department of Pediatrics, Baylor College of Medicine, Houston, Texas; Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Texas Children's Hospital, Houston, Texas; Children's Nutrition Research Center, Houston, Texas., Versalovic J; Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas; Texas Children's Microbiome Center, Texas Children's Hospital, Houston, Texas; Department of Pathology, Texas Children's Hospital, Houston, Texas; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas. Electronic address: jamesv@bcm.edu.
Jazyk:	angličtina
Zdroj:	The Journal of molecular diagnostics : JMD [J Mol Diagn] 2019 May; Vol. 21 (3), pp. 449-461. Date of Electronic Publication: 2019 Apr 17.
DOI:	10.1016/j.jmoldx.2019.01.006
Abstrakt:	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. (Copyright © 2019 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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