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Environmental Enteric Dysfunction Is Associated With Altered Bile Acid Metabolism

Semba, Richard D.*; Gonzalez-Freire, Marta; Moaddel, Ruin; Trehan, Indi‡,§; Maleta, Kenneth M.§; Khadeer, Mohammed; Ordiz, Maria Isabel; Ferrucci, Luigi; Manary, Mark J.‡,§

Journal of Pediatric Gastroenterology and Nutrition: April 2017 - Volume 64 - Issue 4 - p 536–540
doi: 10.1097/MPG.0000000000001313
Original Articles: Gastroenterology

Objectives: 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.

Methods: 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.

Results: 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) μmol/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).

Conclusions: 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.

*Wilmer Eye Institute, Johns Hopkins University School of Medicine

National Institute on Aging, National Institutes of Health, Baltimore, MD

Department of Pediatrics, Washington University in St Louis, MO

§Department of Community Health and Department of Pediatrics and Child Health, University of Malawi College of Medicine, Blantyre, Malawi.

Address correspondence and reprint requests to Richard D. Semba, MD, MPH, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Smith Building M015, 400 N, Broadway, Baltimore, MD 21287 (e-mail:

Received 21 March, 2016

Accepted 15 June, 2016

The National Institutes of Health R01 AG027012, R01 EY024596, R01 HL11271, the Intramural Research Program of the National Institute on Aging, the Children's Discovery Institute of Washington University and St Louis Children's Hospital, and the Hickey Family Foundation. The study sponsors had no role in study design, data collection, data analysis, or interpretation of data.

The authors report no conflicts of interest.

© 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,