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

Wijeyesekera, A. ORCID: https://orcid.org/0000-0001-6151-5065, Wagner, J., De Goffau, M., Thurston, S., Rodrigues Sabino, A., Zaher, S., White, D., Ridout, J., Peters, M. J., Ramnarayan, P., Branco, R. G., Torok, M. E., Valla, F., Meyer, R., Klein, N., Frost, G., Parkhill, J., Holmes, E. and Pathan, N. (2019) Multi-compartment profiling of cacterial and host metabolites identifies intestinal dysbiosis and its functional consequences in the critically ill child. Critical care medicine, 47 (9). e727-e734. ISSN 1530-0293 doi: 10.1097/CCM.0000000000003841

Abstract/Summary

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. Prospective multicenter cohort study. Three U.K.-based PICUs. Mechanically ventilated critically ill (n = 60) and age-matched healthy children (n = 55). Collection of urine and fecal samples in children admitted to the PICU. A single fecal and urine sample was collected in healthy controls. 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). 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.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/84427
Item Type	Article
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences > Food Microbial Sciences Research Group
Publisher	Wolters Kluwer Health, Inc
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