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Metabolic derangements identified through untargeted metabolomics in a crosssectional study of Nigerian children with severe acute malnutrition

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McMillan, Amy, Orimadegun, Adebola E, Sumarah, Mark W, Renaud, Justin, da Encarnacao, Magdalena Muc, Gloor, Gregory B, Akinyinka, Olusegun O, Reid, Gregor and Allen, Stephen ORCID: https://orcid.org/0000-0001-6675-249X (2017) 'Metabolic derangements identified through untargeted metabolomics in a crosssectional study of Nigerian children with severe acute malnutrition'. Metabolomics, Vol 13, Issue 13.

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Abstract

Introduction:
Severe acute malnutrition (SAM) is a major cause of child mortality worldwide, however the pathogenesis of SAM remains poorly understood. Recent studies have uncovered an altered gut microbiota composition in children with SAM, suggesting a role for microbes in the pathogenesis of malnutrition.

Objectives:
To elucidate the metabolic consequences of SAM and whether these changes are associated with changes in gut microbiota composition.

Methods:
We applied an untargeted multi-platform metabolomics approach (gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS)) to stool and plasma samples from 47 Nigerian children with SAM and 11 control children. The composition of the stool microbiota was assessed by 16S rRNA gene sequencing.

Results:
The plasma metabolome discriminated children with SAM from controls, while no significant differences were observed in the microbial or small molecule composition of stool. The abundance of 585 features in plasma were significantly altered in malnourished children (Wilcoxon test, FDR corrected P < 0.1), representing approximately 15% of the metabolome. Consistent with previous studies, children with SAM exhibited a marked reduction in amino acids/dipeptides and phospholipids, and an increase in acylcarnitines. We also identified numerous metabolic perturbations which have not been reported previously, including increased disaccharides, truncated fibrinopeptides, angiotensin I, dihydroxybutyrate, lactate, and heme, and decreased bioactive lipids belonging to the eicosanoid and docosanoid family.

Conclusion:
Our findings provide a deeper understanding of the metabolic consequences of malnutrition. Further research is required to determine if specific metabolites may guide improved management, and/or act as novel biomarkers for assessing response to treatment.

Item Type: Article
Subjects: QU Biochemistry > Biochemistry of the Human Body > QU 120 Metabolism
WA Public Health > Health Problems of Special Population Groups > WA 320 Child Welfare. Child Health Services.
WD Disorders of Systemic, Metabolic or Environmental Origin, etc > Nutrition Disorders > WD 100 General works
WS Pediatrics > Child Care. Nutrition. Physical Examination > WS 115 Nutritional requirements. Nutrition disorders
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1007/s11306-016-1150-2
Depositing User: Jessica Jones
Date Deposited: 07 Dec 2016 10:17
Last Modified: 21 Jun 2018 14:37
URI: http://archive.lstmed.ac.uk/id/eprint/6424

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