title: Environmental Enteric Dysfunction is Associated with Carnitine Deficiency and Altered Fatty Acid Oxidation.
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 12-59months, from rural Malawi. Gut permeability was assessed by the dual-sugar absorption test.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: rdsemba@jhmi.edu.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Semba
authors.affiliation: Department of Pediatrics, Washington University at St. Louis, St. Louis, MO, USA.
authors.forename: Indi
authors.initials: I
authors.lastname: Trehan
authors.affiliation: Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Ximin
authors.initials: X
authors.lastname: Li
authors.affiliation: National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: Ruin
authors.initials: R
authors.lastname: Moaddel
authors.affiliation: Department of Pediatrics, Washington University at St. Louis, St. Louis, MO, USA.
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Ordiz
authors.affiliation: College of Medicine, University of Malawi, Blantyre, Malawi.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Maleta
authors.affiliation: Sight and Life, Basel, Switzerland; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Klaus
authors.initials: K
authors.lastname: Kraemer
authors.affiliation: National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Shardell
authors.affiliation: National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.affiliation: Department of Pediatrics, Washington University at St. Louis, St. Louis, MO, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Manary
mesh_terms: D002331:Carnitine / Q000097:blood / Q000172:deficiency* / Q000378:metabolism; D002675:Child, Preschool; D004751:Enteritis / Q000097:blood / Q000453:epidemiology / Q000378:metabolism*; D004777:Environment; D005227:Fatty Acids / Q000097:blood* / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology; D008286:Malabsorption Syndromes / Q000097:blood / Q000453:epidemiology / Q000378:metabolism*; D008295:Malawi; D008297:Male; D010084:Oxidation-Reduction; D059808:Polyphenols / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D059808:Polyphenols; D002331:Carnitine
keywords: Acylcarnitines; Carnitine; Environmental enteric dysfunction; Fatty acid oxidation; Hippurate; Polyphenols; Tryptophan; Urea cycle