Environmental Enteric Dysfunction is Associated with Carnitine Deficiency and Altered Fatty Acid Oxidation

Richard David Semba, Indi Trehan, Ximin Li, Ruin Moaddel, M. Isabel Ordiz, Kenneth M. Maleta, Klaus Kraemer, Michelle Shardell, Luigi Ferrucci, Mark Manary

Research output: Contribution to journalArticle

Abstract

Background: Environmental enteric dysfunction (EED), a condition characterized by small intestine inflammation and abnormal gut permeability, is widespread in children in developing countries and a major cause of growth failure. The pathophysiology of EED remains poorly understood. Methods: We measured serum metabolites using liquid chromatography-tandem mass spectrometry in 400 children, aged 12-59. months, from rural Malawi. Gut permeability was assessed by the dual-sugar absorption test. Findings: 80.7% of children had EED. Of 677 serum metabolites measured, 21 were negatively associated and 56 were positively associated with gut permeability, using a false discovery rate approach (q. <. 0.05, p. <. 0.0095). Increased gut permeability was associated with elevated acylcarnitines, deoxycarnitine, fatty acid β-oxidation intermediates, fatty acid ω-oxidation products, odd-chain fatty acids, trimethylamine-N-oxide, cystathionine, and homocitrulline, and with lower citrulline, ornithine, polyphenol metabolites, hippurate, tryptophan, and indolelactate. Interpretation: EED is a syndrome characterized by secondary carnitine deficiency, abnormal fatty acid oxidation, alterations in polyphenol and amino acid metabolites, and metabolic dysregulation of sulfur amino acids, tryptophan, and the urea cycle. Future studies are needed to corroborate the presence of secondary carnitine deficiency among children with EED and to understand how these metabolic derangements may negatively affect the growth and development of young children.

Original languageEnglish (US)
JournalEBioMedicine
DOIs
StateAccepted/In press - Dec 7 2016

Fingerprint

Carnitine
Metabolites
Fatty Acids
Permeability
Oxidation
Polyphenols
Tryptophan
Cystathionine
Sulfur Amino Acids
Citrulline
Ornithine
Liquid chromatography
Malawi
Developing countries
Sugars
Mass spectrometry
Urea
Tandem Mass Spectrometry
Serum
Growth and Development

Keywords

  • Acylcarnitines
  • Carnitine
  • Environmental enteric dysfunction
  • Fatty acid oxidation
  • Hippurate
  • Polyphenols
  • Tryptophan
  • Urea cycle

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Environmental Enteric Dysfunction is Associated with Carnitine Deficiency and Altered Fatty Acid Oxidation. / Semba, Richard David; Trehan, Indi; Li, Ximin; Moaddel, Ruin; Ordiz, M. Isabel; Maleta, Kenneth M.; Kraemer, Klaus; Shardell, Michelle; Ferrucci, Luigi; Manary, Mark.

In: EBioMedicine, 07.12.2016.

Research output: Contribution to journalArticle

Semba, Richard David ; Trehan, Indi ; Li, Ximin ; Moaddel, Ruin ; Ordiz, M. Isabel ; Maleta, Kenneth M. ; Kraemer, Klaus ; Shardell, Michelle ; Ferrucci, Luigi ; Manary, Mark. / Environmental Enteric Dysfunction is Associated with Carnitine Deficiency and Altered Fatty Acid Oxidation. In: EBioMedicine. 2016.
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AU - Semba, Richard David

AU - Trehan, Indi

AU - Li, Ximin

AU - Moaddel, Ruin

AU - Ordiz, M. Isabel

AU - Maleta, Kenneth M.

AU - Kraemer, Klaus

AU - Shardell, Michelle

AU - Ferrucci, Luigi

AU - Manary, Mark

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AB - Background: Environmental enteric dysfunction (EED), a condition characterized by small intestine inflammation and abnormal gut permeability, is widespread in children in developing countries and a major cause of growth failure. The pathophysiology of EED remains poorly understood. Methods: We measured serum metabolites using liquid chromatography-tandem mass spectrometry in 400 children, aged 12-59. months, from rural Malawi. Gut permeability was assessed by the dual-sugar absorption test. Findings: 80.7% of children had EED. Of 677 serum metabolites measured, 21 were negatively associated and 56 were positively associated with gut permeability, using a false discovery rate approach (q. <. 0.05, p. <. 0.0095). Increased gut permeability was associated with elevated acylcarnitines, deoxycarnitine, fatty acid β-oxidation intermediates, fatty acid ω-oxidation products, odd-chain fatty acids, trimethylamine-N-oxide, cystathionine, and homocitrulline, and with lower citrulline, ornithine, polyphenol metabolites, hippurate, tryptophan, and indolelactate. Interpretation: EED is a syndrome characterized by secondary carnitine deficiency, abnormal fatty acid oxidation, alterations in polyphenol and amino acid metabolites, and metabolic dysregulation of sulfur amino acids, tryptophan, and the urea cycle. Future studies are needed to corroborate the presence of secondary carnitine deficiency among children with EED and to understand how these metabolic derangements may negatively affect the growth and development of young children.

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KW - Polyphenols

KW - Tryptophan

KW - Urea cycle

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