Published August 12, 2022
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Putative Biomarkers of Environmental Enteric Disease Fail to Correlate in a Cross-Sectional Study in Two Study Sites in Sub-Saharan Africa.

Creators

  • 1. Unité de Pathogénie Microbienne, Institut Pasteur, 25-28 Rue du Dr Roux, 75015 Paris, France.
  • 2. Department of Fundamental Microbiology, University of Lausanne, Campus UNIL-Sorge, 1015 Lausanne, Switzerland.
  • 3. University of Lausanne
  • 4. Human and Animal Health Unit, Swiss Tropical and Public Health Institute & University of Basel, Kreuzstrasse 2, 4123 Allschwil, Switzerland.
  • 5. University of Basel
  • 6. Service de Coprologie Fonctionnelle, Hôpital Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris, 47-83 boulevard de l'Hôpital, 75013 Paris, France.
  • 7. Laboratoire de biochimie métabolique, Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, 149 Rue de Sèvres, 75015 Paris, France.
  • 8. Unité d'Epidémiologie et de Recherche Clinique, Institut Pasteur de Madagascar, BP 1274, Antananarivo 101, Madagascar.
  • 9. Unité d'Epidémiologie, Institut Pasteur de Bangui, Bangui BP 923, Central African Republic.
  • 10. Unité d'Immunologie des Maladies Infectieuses, Institut Pasteur de Madagascar, BP 1274, Antananarivo 101, Madagascar.
  • 11. Unité de Bactériologie Expérimentale, Institut Pasteur de Madagascar, BP 1274, Antananarivo 101, Madagascar.
  • 12. Cytometry and Biomarkers Unit of Technology and Service, Institut Pasteur and Université Paris Cité, 25-28 Rue du Dr Roux, 75015 Paris, France.
  • 13. University of Paris
  • 14. Complexe Hospitalo-Universitaire de Bangui, Bangui BP 923, Central African Republic.

Description

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.
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