Putative Biomarkers of Environmental Enteric Disease Fail to Correlate in a Cross-Sectional Study in Two Study Sites in Sub-Saharan Africa.

Publisher: MDPI Publishing Country of Publication: Switzerland NLM ID: 101521595 Publication Model: Electronic Cited Medium: Internet ISSN: 2072-6643 (Electronic) Linking ISSN: 20726643 NLM ISO Abbreviation: Nutrients Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI Publishing

Biomarkers*/analysis ; Biomarkers*/metabolism ; Environmental Illness*/diagnosis ; Environmental Illness*/metabolism ; Intestinal Diseases*/diagnosis ; Intestinal Diseases*/etiology ; Intestinal Diseases*/metabolism ; Intestine, Small*/metabolism ; Intestine, Small*/pathology; Africa South of the Sahara ; C-Reactive Protein/metabolism ; Child, Preschool ; Citrulline/analysis ; Cross-Sectional Studies ; Growth Disorders ; Humans ; Leukocyte L1 Antigen Complex

Environmental enteric dysfunction (EED) is an elusive, inflammatory syndrome of the small intestine thought to be associated with enterocyte loss and gut leakiness and lead to stunted child growth. To date, the gold standard for diagnosis is small intestine biopsy followed by histology. Several putative biomarkers for EED have been proposed and are widely used in the field. Here, we assessed in a cross-sectional study of children aged 2-5 years for a large set of biomarkers including markers of protein exudation (duodenal and fecal alpha-1-antitrypsin (AAT)), inflammation (duodenal and fecal calprotectin, duodenal, fecal and blood immunoglobulins, blood cytokines, C-reactive protein (CRP)), gut permeability (endocab, lactulose-mannitol ratio), enterocyte mass (citrulline) and general nutritional status (branched-chain amino acids (BCAA), insulin-like growth factor) in a group of 804 children in two Sub-Saharan countries. We correlated these markers with each other and with anemia in stunted and non-stunted children. AAT and calprotectin, CRP and citrulline and citrulline and BCAA correlated with each other. Furthermore, BCAA, citrulline, ferritin, fecal calprotectin and CRP levels were correlated with hemoglobin levels. Our results show that while several of the biomarkers are associated with anemia, there is little correlation between the different biomarkers. Better biomarkers and a better definition of EED are thus urgently needed.
Competing Interests: The authors declare no conflict of interest.

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2014 Total Foundation; OPP1204689 Bill and Melinda Gates Foundation; 2016 Fondation Petram; 2016 Odyssey Re-Insurance company; P2EZP3_152159 Switzerland SNSF_ Swiss National Science Foundation; P300PA_177876 Switzerland SNSF_ Swiss National Science Foundation; P3P3PA_17877 Switzerland SNSF_ Swiss National Science Foundation; 2016 Roux-Cantarini Fellowship; 22017 L'Oréal-UNESCO for Women in Science France Fellowship; 2019 Excellence Scholarship from the University of Basel (Forschungsfonds, 2019)

Keywords: Sub-Saharan Africa; alpha-1-antitrypsin; anemia; biomarker; calprotectin; citrulline; environmental enteric dysfunction; insulin-like growth factor; lactulose-mannitol test; stunted child growth

0 (Biomarkers)
0 (Leukocyte L1 Antigen Complex)
29VT07BGDA (Citrulline)
9007-41-4 (C-Reactive Protein)

Date Created: 20220826 Date Completed: 20220829 Latest Revision: 20220912

20240628

PMC9412633

10.3390/nu14163312

36014817