Promising Biomarkers of Environmental Enteric Dysfunction: A Prospective Cohort study in Pakistani Children

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.

A novel histological index for evaluation of environmental enteric dysfunction identifies geographic-specific features of enteropathy among children with suboptimal growth

“…After a flurry of biopsy studies four decades ago [24][25][26][27][28], there has been a paucity of histologic studies of the small bowel until recently. However, markers in blood, stool, and urine (e.g., urine dual sugar permeability testing) have lent credence to the concept that poor growth and EED are tightly linked in children in LMICs [14,[29][30][31][32]. Nonetheless, the origin and pathophysiology of EED remains elusive.…”

EnteropathogenicEscherichia coli(EPEC) Infection Induces Diarrhea, Intestinal Damage, Metabolic Alterations and Increased Intestinal Permeability in a Murine Model

“…Myeloperoxidase (MPO), a marker of neutrophil activity in intestinal mucosa, and lipocalin-2 (LCN-2), a glycoprotein upregulated in tissue damage under infection conditions, have been considered as biomarkers of environmental enteric dysfunction, including EPEC, in children [35][36][37][38]. To ensure that our EPEC infection model mimics the alterations of these biomarkers as observed in children, we measured MPO and LCN-2 in the ileal and colonic tissues, as well as in cecal contents and stools.…”

Machine Learning Model Demonstrates Stunting at Birth and Systemic Inflammatory Biomarkers as Predictors of Subsequent Infant Growth – A Four-year Prospective Study.

“…As part of a 4-year prospective study, researchers at Aga Khan University in Pakistan collected data for 380 children from the rural village of Matiari, Sindh, Pakistan (12). The data comprised a combination of demographic, biometric, and laboratory measures.…”