Multi-compartment profiling of bacterial and host metabolites identifies intestinal dysbiosis and its functional consequences in the critically ill child

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Title: Multi-compartment profiling of bacterial and host metabolites identifies intestinal dysbiosis and its functional consequences in the critically ill child
Authors: Wijeyesekera, A
Wagner, J
De Goffau, M
Thurston, S
Rodrigues Sabino, A
Zaher, S
White, D
Ridout, J
Peters, MJ
Ramnarayan, P
Branco, RG
Torok, ME
Valla, F
Meyer, R
Klein, N
Frost, G
Parkhill, J
Holmes, E
Pathan, N
Item Type: Journal Article
Abstract: OBJECTIVES: Adverse physiology and antibiotic exposure devastate the intestinal microbiome in critical illness. Time and cost implications limit the immediate clinical potential of microbial sequencing to identify or treat intestinal dysbiosis. Here, we examined whether metabolic profiling is a feasible method of monitoring intestinal dysbiosis in critically ill children. DESIGN: Prospective multicenter cohort study. SETTING: Three U.K.-based PICUs. PATIENTS: Mechanically ventilated critically ill (n = 60) and age-matched healthy children (n = 55). INTERVENTIONS: Collection of urine and fecal samples in children admitted to the PICU. A single fecal and urine sample was collected in healthy controls. MEASUREMENTS AND MAIN RESULTS: Untargeted and targeted metabolic profiling using 1H-nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry or urine and fecal samples. This was integrated with analysis of fecal bacterial 16S ribosomal RNA profiles and clinical disease severity indicators. We observed separation of global urinary and fecal metabolic profiles in critically ill compared with healthy children. Urinary excretion of mammalian-microbial co-metabolites hippurate, 4-cresol sulphate, and formate were reduced in critical illness compared with healthy children. Reduced fecal excretion of short-chain fatty acids (including butyrate, propionate, and acetate) were observed in the patient cohort, demonstrating that these metabolites also distinguished between critical illness and health. Dysregulation of intestinal bile metabolism was evidenced by increased primary and reduced secondary fecal bile acid excretion. Fecal butyrate correlated with days free of intensive care at 30 days (r = 0.38; p = 0.03), while urinary formate correlated inversely with vasopressor requirement (r = -0.2; p = 0.037). CONCLUSIONS: Disruption to the functional activity of the intestinal microbiome may result in worsening organ failure in the critically ill child. Profiling of bacterial metabolites in fecal and urine samples may support identification and treatment of intestinal dysbiosis in critical illness.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Issue Date: 4-Jun-2019
Date of Acceptance: 1-Jun-2019
URI: http://hdl.handle.net/10044/1/70857
DOI: https://doi.org/10.1097/CCM.0000000000003841
ISSN: 0090-3493
Publisher: Lippincott, Williams & Wilkins
Journal / Book Title: Critical Care Medicine
Copyright Statement: © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY) (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Emergency & Critical Care Medicine
1103 Clinical Sciences
1110 Nursing
1117 Public Health and Health Services
Publication Status: Published online
Conference Place: United States
Online Publication Date: 2019-06-01
Appears in Collections:Division of Surgery
Faculty of Medicine



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