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

Richard D. 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 journalArticlepeer-review

17 Scopus citations

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
Pages (from-to)57-66
Number of pages10
JournalEBioMedicine
Volume17
DOIs
StatePublished - Mar 1 2017

Keywords

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

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