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

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.

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Acknowledgements

The authors appreciate the support of Dr. Folake Samuel of the Department of Human Nutrition, University of Ibadan, UNICEF for supply of RUTF to the patients and Dr. A. A. Oloko of the Federal Medical Centre, Gusau for assistance during data collection and management of the patients. We are grateful to Linda Thomas, Yakult Ltd UK, for providing financial support for the project.

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Correspondence to Stephen J. Allen.

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The authors declare that they have no conflict of interests in relation to the work described.

Ethical approval

This study was approved by the Joint Ethical Review Committees of the University of Ibadan/University College Hospital, Ibadan, Nigeria, and was conducted in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Human stool and peripheral blood samples were collected after informed consent from all parents of children enrolled in the study.

Additional information

Amy McMillan and Adebola E. Orimadegun are joint first authors.

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McMillan, A., Orimadegun, A.E., Sumarah, M.W. et al. Metabolic derangements identified through untargeted metabolomics in a cross-sectional study of Nigerian children with severe acute malnutrition. Metabolomics 13, 13 (2017). https://doi.org/10.1007/s11306-016-1150-2

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Keywords

  • Severe acute malnutrition
  • Metabolomics
  • Nigerian children
  • Gut microbiota
  • LC-MS