Location: Children's Nutrition Research CenterTitle: Biomarkers of environmental enteric dysfunction are differently associated with recovery and growth among children with moderate acute malnutrition in Sierra Leone
|SINGH, AKRITI - Friedman School Of Nutrition|
|GHOSH, SHIBANI - Friedman School Of Nutrition|
|WARD, HONORINE - Tufts Medical Center|
|MANARY, MARK - Washington University|
|ROGERS, BEATRICE - Friedman School Of Nutrition|
|ROSENBERG, IRWIN - Friedman School Of Nutrition|
Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/16/2020
Publication Date: 3/1/2021
Citation: Singh, A., Ghosh, S., Ward, H., Manary, M.J., Rogers, B.L., Rosenberg, I.H. 2021. Biomarkers of environmental enteric dysfunction are differently associated with recovery and growth among children with moderate acute malnutrition in Sierra Leone. American Journal of Clinical Nutrition. 113:1556-1564. https://doi.org/10.1093/ajcn/nqaa434.
Interpretive Summary: The surface of the bowel is where nutrients are taken into the body, and damage to this unseen surface is common in malnutrition. A variety of genetic messages that are shed into the stool were measured to determine the health of the bowel surface, also called gut health. This method to measure gut health can be used by others to determine how gut health is affected in other disease and nutrition states.
Technical Abstract: Environmental enteric dysfunction (EED) may influence growth during and recovery from moderate acute malnutrition (MAM), however, biomarkers to assess these relations have yet to be identified. The objectives of this study were to: 1) develop a score for EED based on host fecal mRNA transcripts, 2) compare biomarkers of EED with each other, and 3) examine associations between the EED biomarkers and recovery from MAM and growth outcomes. In a cohort of 520 Sierra Leonean MAM children, biomarkers of EED included the lactulose: mannitol (L: M) test, 15 host fecal mRNA transcripts, and host fecal proteins [a-1-antitrypsin (AAT), myeloperoxidase (MPO), neopterin (NEO)]. Anthropometry data were also collected and z scores were computed for length-for-age (LAZ) and weight-for-length (WLZ). Recovery from MAM was defined as midupper arm circumference >=12.5 cm. Factor analysis was used to identify EED scores using the mRNA transcripts, and mixed effects regression was conducted to test for associations. The 15 host fecal mRNA transcripts were clustered into 3 scores: gut inflammation (GI) score, gut structure (GS) score, and gut defense (GD) score. We found agreement between certain inflammation markers (GI score and MPO), and permeability markers (GS score and AAT; AAT and the L:M excretion ratio). Antimicrobial gut defense (GD score) was inversely associated with percent lactulose excreted, a measure of intestinal permeability. LAZ (B: –0.08; 95% CI: –0.14, –0.02) and WLZ (B: –0.03; 95% CI: –0.06, –0.01) were negatively associated with GI score. A high GD score (B: 0.36; 95% CI: 0.08, 0.64) and low AAT (B: –1.35; 95% CI: –2.35, –0.36) were associated with recovery from MAM. Scores derived from host fecal mRNA transcript variably correlated with the L: M test and host fecal proteins. Markers of intestinal inflammation, permeability, and defense were associated with growth outcomes and recovery from MAM.