Abstract
Environmental Enteric Dysfunction (EED), a syndrome characterized by chronic gut inflammation, contributes towards stunting and poor response to enteric vaccines in children in developing countries. In this study, we evaluated major putative biomarkers of EED using growth faltering as its clinical proxy. Newborns (n = 380) were enrolled and followed till 18 months with monthly anthropometry. Biomarkers associated with gut and systemic inflammation were assessed at 6 and 9 months. Linear mixed effects model was used to determine the associations of these biomarkers with growth faltering between birth and 18 months. Fecal myeloperoxidase (neutrophil activation marker) at 6 months [β = −0.207, p = 0.005], and serum GLP 2 (enterocyte proliferation marker) at 6 and 9 months [6M: β = −0.271, p = 0.035; 9M: β = −0.267, p = 0.045] were associated with decreasing LAZ score. Ferritin at 6 and 9 months was associated with decreasing LAZ score [6M: β = −0.882, p < 0.0001; 9M: β = −0.714, p < 0.0001] and so was CRP [β = −0.451, p = 0.039] and AGP [β = −0.443, p = 0.012] at 9 months. Both gut specific and systemic biomarkers correlated negatively with IGF-1, but only weakly correlated, if at all with each other. We therefore conclude that EED may be contributing directly towards growth faltering, and this pathway is not entirely through the pathway of systemic inflammation.
Highlights
Environmental Enteric Dysfunction (EED), a syndrome characterized by chronic gut inflammation, contributes towards stunting and poor response to enteric vaccines in children in developing countries
After establishing a cohort of children at high risk of EED in a rural district of Pakistan, we tested the association of common biomarkers of gut inflammation, regeneration and enterocyte proliferation with growth faltering during the first 18 month of life
Systemic inflammatory markers, including ferritin, c-reactive protein (CRP) and acid glycoprotein (AGP) were negatively associated with linear growth faltering
Summary
Environmental Enteric Dysfunction (EED), a syndrome characterized by chronic gut inflammation, contributes towards stunting and poor response to enteric vaccines in children in developing countries. Using poor linear growth rate during the first 18 months of life as a proxy of EED, we aimed to validate putative biomarkers of growth faltering, selected based on their role in gut inflammation [fecal myeloperoxidase (MPO) and neopterin (NEO)], enterocyte regeneration (Reg-1b) and proliferation [Glucagon Like Peptide-2 (GLP2)]. We measured the association of a few systemic inflammatory biomarkers [serum Ferritin, c-reactive protein (CRP), α1 acid glycoprotein (AGP)] as well as Insulin-Like Growth factor 1 (IGF-1) with linear growth. If validated, these biomarkers could be considered as a monitoring tool in future studies that focus on preventing and treating EED
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