Association of Fecal Markers of Environmental Enteric Dysfunction with Zinc and Iron Status among Children at First Two Years of Life in Bangladesh

Abstract

Abstract.Environmental enteric dysfunction (EED) causes gut inflammation and increased intestinal permeability leading to deficiencies in micronutrients such as zinc and iron. Fecal markers such as myeloperoxidase (MPO), neopterin (NEO), and alpha-1-anti-trypsin (AAT) can predict EED. The aim of this study was to examine the association between fecal markers of EED with zinc and iron status among children at first 2 years of life. Malnutrition and Enteric Disease Study Bangladeshi birth cohort data were used to conduct this analysis. Multivariable analyses using generalized estimating equations were performed to test the association between individual fecal markers with zinc or iron status of the children. A total of 265 children were enrolled in the study (male:female = 1:1). Of the 627 stool samples collected (N = 222 children), 535, 511, and 577 were accompanied by zinc, ferritin, and soluble transferrin receptor values, respectively. Median (interquartile range [IQR]) values of AAT, MPO, and NEO were 0.33 (0.18–0.62) mg/g, 3,895.42 (1,563.76–8,432.82) ng/mL, and 890.81 (331.57–2,089.04) nmol/L, respectively. Overall, 60%, 71%, and 97% of samples were above the values considered normal in nontropical settings for AAT, MPO, and NEO, respectively. High AAT levels were significantly associated with low ferritin values after adjusting for age and gender (coefficient = −5.85; 95% confidence interval = −11.23 to −0.47; P value = 0.03). No such association was found between AAT and plasma zinc status. Myeloperoxidase and NEO were not associated with plasma zinc or iron status. The study results imply the importance of enteric protein loss in contributing to reduced ferritin levels at first 2 years of life.

Helicobacter pylori infection is associated with fecal biomarkers of environmental enteric dysfunction but not with the nutritional status of children living in Bangladesh

“…In this study, the fecal biomarker values were much elevated in this cohort of children compared to the reference values for those living in western countries. This finding is consistent with the previous documents published earlier using data from both urban and rural areas of Bangladesh [57,58]. However, such elevation indicates the widespread perturbation of gut health and integrity in children living in resource limited urban settlement in Bangladesh.…”

“…MPO has been tested as a biomarker of EED in several studies [14,22,27,28]. Previously, MPO was found to be associated with markers of intestinal permeability including AAT [32,57,59]. A positive association of calprotectin with small intestinal bacterial overgrowth has also been determined in another study [59].…”

“…Stool biomarkers including Myeloperoxidase (MPO), Neopterin (NEO), Calprotectin, Reg1B, and Alpha-1 antitrypsin (AAT) are the non-invasive alternatives proposed for the assessment of EED [27,31]. MPO, Calprotectin, and NEO indicate intestinal inflammation, whereas AAT is a useful marker of enteric protein loss as well as intestinal permeability [32]. Reg1B is a newly proposed marker which points to epithelial tissue injury and subsequent repair in the small intestine [33].…”

“…Since AAT is not produced in the intestine, its presence in the gut lumen can be considered as a measure of gut inflammation [59]. AAT also reflects protein loss due to disruption of mucosal barrier and has been established as a marker of increased intestinal permeability [58,59]. Because AAT can be used for assessing both intestinal inflammation and increased gut permeability, two important domains of EED, several studies measured fecal AAT as a biomarker of EED [14,22,27,61].…”

“…Similar to AAT, children with H. pylori infection had higher concentrations of MPO and calprotectin at the end of nutrition intervention. Both MPO and calprotectin are released from neutrophils and indicates intestinal inflammation [32,67,68]. MPO has been tested as a biomarker of EED in several studies [14,22,27,28].…”