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

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
Highlights • Environmental enteric dysfunction (EED) affects millions of children in developing countries. • We used metabolomics to gain insight into the pathogenesis of EED. • EED is characterized by secondary carnitine deficiency and abnormal fatty acid oxidation. • Alterations in sulfur amino acids, tryptophan, urea cycle, and polyphenols were also present. Environmental enteric dysfunction (EED), an asymptomatic condition of small intestine inflammation and increased gut permeability, is widespread in developing countries and a major cause of growth failure in children. Clinical trials to ameliorate EED have been disappointing. The pathogenesis of EED is poorly understood. We examined the relationship between circulating metabolites and EED in young children in Africa. Children with EED had a serum metabolite profile consistent with secondary carnitine deficiency and impaired β-oxidation of fatty acids. Carnitine is a conditionally essential nutrient primarily found in animal source foods or synthesized endogenously from lysine and methionine. This study suggests that secondary carnitine deficiency may contribute to the altered metabolic profile related to energy balance in young children with EED.