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Research Project: Pediatric Clinical Nutrition

Location: Children's Nutrition Research Center

Title: Environmental enteric dysfunction is associated with carnitine deficiency and altered fatty acid oxidation

item SEMBA, RICHARD - Johns Hopkins University School Of Medicine
item TREHAN, INDI - Washington University
item LI, XIMIN - Johns Hopkins School Of Public Health
item MOADDEL, RUIN - National Institute On Aging (NIA, NIH)
item ORDIZ, M - Washington University
item MALETA, KENNETH - University Of Malawi
item KRAEMER, KLAUS - Sight & Life
item SHARDELL, MICHELLE - National Institute On Aging (NIA, NIH)
item FERRUCCI, LUIGI - National Institute On Aging (NIA, NIH)
item MANARY, MARK - Children'S Nutrition Research Center (CNRC)

Submitted to: EBioMedicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/17/2017
Publication Date: 3/1/2017
Citation: Semba, R.D., Trehan, I., Li, X., Moaddel, R., Ordiz, M.I., Maleta, K.M., Kraemer, K., Shardell, M., Ferrucci, L., Manary, M. 2017. Environmental enteric dysfunction is associated with carnitine deficiency and altered fatty acid oxidation. EBioMedicine. 17:57-66.

Interpretive Summary: Poor gut health, chronic inflammation and leakiness of the gut is a common condition among children in the developing world, but the processes within the body that result in the physical changes and symptoms of the condition are vaguely understood. This study examined the association of metabolites from blood samples and poor gut health in 400 children from six villages in Malawi and found that increased gut leakiness was associated with an inability to metabolize the amino acid carnitine, which is needed for converting fat into energy. This study gives more insight into the atypical biological pathways and functions that might result from poor gut health and will help push more investigation of gut health and its related risk factors, biological changes in cellular function, and symptoms among the millions of children at risk for the condition.

Technical Abstract: 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. 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. 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 beta-oxidation intermediates, fatty acid omega-oxidation products, odd-chain fatty acids, trimethylamine-N-oxide, cystathionine, and homocitrulline, and with lower citrulline, ornithine, polyphenol metabolites, hippurate, tryptophan, and indolelactate. 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.