TY - JOUR
T1 - Biomarkers of environmental enteric dysfunction are differently associated with recovery and growth among children with moderate acute malnutrition in Sierra Leone
AU - Singh, Akriti
AU - Ghosh, Shibani
AU - Ward, Honorine
AU - Manary, Mark J.
AU - Rogers, Beatrice L.
AU - Rosenberg, Irwin H.
N1 - Funding Information:
Supported by 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. The Feed the Future Innovation Lab for Nutrition, also funded by USAID under the terms of Contract No. AID- 0AA-L-10-00006, supported certain laboratory analysis. The funder of this study did not have a role in study design, data collection, data analysis, interpretation, writing of the manuscript, or in the decision to submit for publication.
Publisher Copyright:
© 2021 The Author(s).
PY - 2021/6/1
Y1 - 2021/6/1
N2 - 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.
AB - 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.
KW - Sierra Leone
KW - biomarkers
KW - environmental enteric dysfunction
KW - fecal host mRNA transcripts
KW - fecal host proteins
KW - growth outcomes
KW - intestinal antimicrobial defense
KW - intestinal inflammation
KW - intestinal permeability
KW - lactulose: mannitol test
UR - http://www.scopus.com/inward/record.url?scp=85107390793&partnerID=8YFLogxK
U2 - 10.1093/ajcn/nqaa434
DO - 10.1093/ajcn/nqaa434
M3 - Article
C2 - 33668048
AN - SCOPUS:85107390793
SN - 0002-9165
VL - 113
SP - 1556
EP - 1564
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
IS - 6
ER -