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Research Project: Pediatric Clinical Nutrition

Location: Children's Nutrition Research Center

Title: Environmental enteric dysfunction is associated with altered bile acid metabolism

Author
item Semba, Richard - Johns Hopkins University School Of Medicine
item Gonzalez-freire, Marta - National Institute On Aging (NIA, NIH)
item Moaddel, Ruin - National Institute On Aging (NIA, NIH)
item Trehan, Indi - Washington University
item Maleta, Kenneth - University Of Malawi
item Khadeer, Mohammed - National Institute On Aging (NIA, NIH)
item Ordiz, Maria - Washington University
item Ferrucci, Luigi - National Institute On Aging (NIA, NIH)
item Manary, Mark - Children'S Nutrition Research Center (CNRC)

Submitted to: Journal of Pediatric Gastroenterology and Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/15/2016
Publication Date: 4/1/2017
Citation: Semba, R.D., Gonzalez-Freire, M., Moaddel, R., Trehan, I., Maleta, K.M., Khadeer, M., Ordiz, M.I., Ferrucci, L., Manary, M.J. 2017. Environmental enteric dysfunction is associated with altered bile acid metabolism. Journal of Pediatric Gastroenterology and Nutrition. 64(4):536-540.

Interpretive Summary: Poor gut health is a condition that affects millions of children in developing countries, it is characterized by gut inflammation and "leakiness", and is thought to me a major factor contributing to childhood stunting. This research aimed to examine children' gut health with amounts of bile acid, which are known to help with the digestion and absorption of lipids in the small intestine in addition to regulating other metabolic processes; the research showed that there may be alterations in bile acid metabolism among these children. The significance of this research is that further studies can examine this observed abnormality of bile acid metabolism in children with poor gut health and hopefully the evidence will contribute to potential therapeutic and prevention interventions to improve gut health.

Technical Abstract: Environmental enteric dysfunction (EED), a clinically asymptomatic condition characterized by inflammation of the small bowel mucosa, villous atrophy, and increased gut permeability, is common among children in developing countries. Because of abnormal gut mucosa and altered gut microbiome, EED could potentially affect the metabolism and enterohepatic circulation of bile acids. In 313 children, aged 12 to 59 months, EED was assessed by the dual sugar absorption test. Serum bile acids were measured using stable-isotope liquid chromatography-tandem mass spectrometry. In the overall study population, serum cholic acid and chenodeoxycholic acid were lower, whereas glycocholic acid, taurodeoxycholic acid, glycodeoxycholic acid, glycolithocholic acid, and glycoursodeoxycholic acid were significantly higher at older ages. Independent of age, serum taurochenodeoxycholic acid, tauromuricholic acid, and glycoursodeoxycholic acid were significantly different between 244 children with EED and 69 children without EED. Total serum bile acids (median, interquartile range) were 4.51 (2.45, 7.51) and 5.10 (3.32, 9.01) micro-mol/L in children with and without EED, respectively (age-adjusted, P'='0.0009). The proportion of bile acids conjugated with taurine instead of glycine was higher in children with EED (P'<'0.0001). EED is associated with altered bile acid metabolism in young children in rural Malawi. Further work is needed to determine the generalizability of these findings in other study populations.