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. 2017 Feb 8;96(2):465-472.
doi: 10.4269/ajtmh.16-0496. Epub 2016 Dec 19.

Dynamics and Trends in Fecal Biomarkers of Gut Function in Children from 1-24 Months in the MAL-ED Study

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Dynamics and Trends in Fecal Biomarkers of Gut Function in Children from 1-24 Months in the MAL-ED Study

Benjamin J J McCormick et al. Am J Trop Med Hyg. .

Abstract

Growth and development shortfalls that are disproportionately prevalent in children living in poor environmental conditions are postulated to result, at least in part, from abnormal gut function. Using data from The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) longitudinal cohort study, we examine biomarkers of gut inflammation and permeability in relation to environmental exposures and feeding practices. Trends in the concentrations of three biomarkers, myeloperoxidase (MPO), neopterin (NEO), and α-1-antitrypsin (AAT), are described from fecal samples collected during the first 2 years of each child's life. A total of 22,846 stool samples were processed during the longitudinal sampling of 2,076 children 0-24 months of age. Linear mixed models were constructed to examine the relationship between biomarker concentrations and recent food intake, symptoms of illness, concurrent enteropathogen infection, and socioeconomic status. Average concentrations of MPO, NEO, and AAT were considerably higher than published references for healthy adults. The concentration of each biomarker tended to decrease over the first 2 years of life and was highly variable between samples from each individual child. Both MPO and AAT were significantly elevated by recent breast milk intake. All three biomarkers were associated with pathogen presence, although the strength and direction varied by pathogen. The interpretation of biomarker concentrations is subject to the context of their collection. Herein, we identify that common factors (age, breast milk, and enteric infection) influence the concentration of these biomarkers. Within the context of low- and middle-income communities, we observe concentrations that indicate gut abnormalities, but more appropriate reference standards are needed.

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Figures

Figure 1.
Figure 1.
Distributions of the pooled log myeloperoxidase (MPO), neopterin (NEO), and α-1-antitrypsin (AAT) concentrations by month of age. Solid horizontal lines indicate the mean observed value. Dashed lines indicate values reported from in the literature,: MPO < 2,000 ng/mL; NEO < 70 nmol/L; and AAT < 270 μg/g.
Figure 2.
Figure 2.
Predicted concentrations of each fecal biomarker in the presence or absence of a single factor while keeping all other predictors equal. (left column) Effects of breast milk in the 7 days preceding the stool collection, with higher biomarker concentrations association with the presence of breast milk (3–12 months for myeloperoxidase [MPO] and α-1-antitrypsin [AAT]); (middle column) low (5th percentile) or high (95th percentile) cumulative pathogen detections, indicating slightly higher biomarker concentrations during the first and last 6 months for MPO associated with higher pathogen detections and in the second year of life for AAT. neopterin [NEO] is lower with higher cumulative pathogens detected; (right column) and the effect of low (5th percentile) or high (95th percentile) socioeconomic index (water and sanitation, assets, maternal education, and income [WAMI]) on biomarker concentrations and how these effects relate to the age of a child with higher socioeconomic status associated with lower MPO and AAT biomarker concentrations. Grey areas show the 95% confidence interval for the mean prediction of fixed effects (conditional on the site and child random effects).
Figure 3.
Figure 3.
The concentration of fecal biomarkers in children 7–24 months (pooled across sites) for children receiving breast or other (animal or formula) milks in the 7 days preceding the stool collection. Comparison between those children who received breast milk and those who received alternative sources of milk was made using Wilcox signed rank tests.

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