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Research Project: Microbiota and Nutritional Health

Location: Children's Nutrition Research Center

Title: Host fecal mRNAs predicted environmental enteric dysfunction among children with moderate acute malnutrition in Sierra Leone

Author
item SINGH, AKRITI - Tufts University
item POTANI, ISABEL - Tufts University
item GRISWOLD, STACY - Tufts University
item SURI, DEVIKA - Tufts University
item LANGLOIS, BREANNE - Tufts University
item SHEN, YE - Tufts University
item WALTON, SHELLEY - Tufts University
item KWAN HO CHUI, KENNETH - Tufts University
item MANARY, MARK - Children'S Nutrition Research Center (CNRC)
item WEBB, PATRICK - Tufts University
item ROGERS, BEATRICE - Tufts University
item ROSENBERG, IRWIN - Tufts University

Submitted to: American Journal of Tropical Medicine and Hygiene
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/28/2021
Publication Date: 8/30/2021
Citation: Singh, A., Potani, I., Griswold, S.P., Suri, D., Langlois, B., Shen, Y., Walton, S.M., Kwan Ho Chui, K., Manary, M.J., Webb, P., Rogers, B.L., Rosenberg, I.H. 2021. Host fecal mRNAs predicted environmental enteric dysfunction among children with moderate acute malnutrition in Sierra Leone. American Journal of Tropical Medicine and Hygiene. 105(5):1376-1382. https://doi.org/10.4269/ajtmh.21-0348.
DOI: https://doi.org/10.4269/ajtmh.21-0348

Interpretive Summary: Environmental enteric dysfunction (EED) is the irritation of the upper gut lining where absorption of food occurs and can be measured by a gut leakiness test with sugar consumption. This sugar test was conducted and fecal samples were collected to measure the effect of four specialized nutritious foods on recovery from moderate acute malnutrition. Eight human genetic transcripts were identified in the feces that indicate the presence of EED and the presence of EED did not modify the effect of foods on malnutrition treatment.

Technical Abstract: Examining the role of environmental enteric dysfunction (EED) in child growth requires noninvasive, field-appropriate biomarkers. Alternatives to the traditionally used lactulose:mannitol (L:M) test have been explored, but few studies have compared the L:M test to host fecal mRNA transcripts. The objectives of this study were to examine whether 1) host fecal mRNA transcripts could predict presence and severity of EED, measured using the L:M test, and 2) EED modifies the effect of specialized nutritious foods (SNFs) on recovery from moderate acute malnutrition (MAM). This substudy was nested within a cluster randomized trial comparing four SNFs in the treatment of MAM among children 6 to 59 months in Sierra Leone. EED was assessed at enrollment using the L:M test and 15 host fecal mRNA transcripts on 522 children. Recovery from MAM was defined as achieving mid-upper arm circumference > or = 12.5 cm within 12 weeks of supplementation. Random forest classification models were used to examine prediction of presence and severity of EED by host fecal mRNA transcripts. Logistic regression was used to test for effect modification by L:M test variables including % lactulose excreted (%L). Eight host fecal mRNA transcripts (AQP9, REG3A, IFI30, DECR1, BIRC3, SELL, PIK3AP1, DEFA6) identified EED (%L > or = 0.2) and severe EED (%L > or = 0.45) with high sensitivity and specificity. The L:M test variables did not modify the effect of SNFs on recovery from MAM. In this study, we found host fecal mRNA transcripts that could be biomarkers of EED but did not find EED to modify the effect of SNFs on MAM treatment.