Biomarkers of environmental enteric dysfunction are differently associated with recovery and growth among children with moderate acute malnutrition in Sierra Leone

Akriti Singh, Shibani Ghosh, Honorine Ward, Mark J. Manary, Beatrice L. Rogers, Irwin H. Rosenberg

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: 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. Objectives: 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. Methods: 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 [α-1-antitrypsin (AAT), myeloperoxidase (MPO), neopterin (NEO)]. Anthropometry data were also collected and z scores were computed for length-forage (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. Results: 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 (β: -0.08; 95% CI: -0.14, -0.02) and WLZ (β: -0.03; 95% CI: -0.06, -0.01) were negatively associated with GI score. A high GD score (β: 0.36; 95% CI: 0.08, 0.64) and low AAT (β: -1.35; 95% CI: -2.35, -0.36) were associated with recovery from MAM. Conclusions: 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.

Original languageEnglish
Pages (from-to)1556-1564
Number of pages9
JournalAmerican Journal of Clinical Nutrition
Volume113
Issue number6
DOIs
StatePublished - Jun 1 2021

Keywords

  • Sierra Leone
  • biomarkers
  • environmental enteric dysfunction
  • fecal host mRNA transcripts
  • fecal host proteins
  • growth outcomes
  • intestinal antimicrobial defense
  • intestinal inflammation
  • intestinal permeability
  • lactulose: mannitol test

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