Host Fecal mRNAs Predicted Environmental Enteric Dysfunction among Children with Moderate Acute Malnutrition in Sierra Leone

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  • 1 Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts;
  • | 2 School of Medicine, Tufts University, Boston, Massachusetts;
  • | 3 Department of Pediatrics, Washington University, St. Louis, Missouri

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 ≥ 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 ≥ 0.2) and severe EED (%L ≥ 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.

Author Notes

Address correspondence to Akriti Singh, Friedman School of Nutrition Science and Policy, Tufts University, 150 Harrison Avenue, Boston, MA 02111. E-mail: akriti.singh@tufts.edu

Financial support: This work was made possible by the generous support of the American people through the U.S. Agency for International Development’s Bureau for Humanitarian Assistance (USAID/BHA) and the Legacy Office of Food for Peace (FFP) under the terms of Contract No. AID-OAA-C-16-00020, managed by Tufts University.

Authors’ addresses: Akriti Singh, USAID Advancing Nutrition/Helen Keller Internaitonal, Washington, DC, E-mail: asingh@hki.org. Isabel Potani, The Hospital for Sick Children, Toronto, Canada, E-mail: isabel.potani@sickkids.ca. Stacy P. Griswold, Breanne Langlois, Ye Shen, Patrick Webb, Beatrice L. Rogers, and Irwin H. Rosenberg, Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, E-mails: stacy.griswold@tufts.edu, breanne.langlois@tufts.edu, ye.shen@tufts.edu and ye_shen@fas.harvard.edu, patrick.webb@tufts.edu, beatrice.rogers@tufts.edu, and irwin.rosenberg@tufts.edu. Devika Suri, University of Wisconsin–Madison, Madison, WI, E-mail: dsuri@wisc.edu. Shelley M. Walton, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, E-mail: swalton9@jhu.edu. Kenneth Kwan Ho Chui, School of Medicine, Tufts University, Boston, MA, E-mail: kenneth.chui@tufts.edu. Mark J. Manary, Department of Pediatrics, Washington University, St. Louis, MO, E-mail: manarymj@wustl.edu.

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