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.
Highlights
Researchers have proposed that a significant cause of growth faltering and malnutrition, which disproportionately occurs early in life in children residing in low- and middle-income countries (LMICs), is due to changes in gut function resulting from environmental exposures to enteropathogens and toxins, from inadequate nutrient intake, and from disease history, notably diarrhea.[1,2]
Various alterations in gut function have been associated with environmental enteropathy (EE), a condition histopathologically defined from examination of biopsy material characterized by changed morphology and altered inflammatory and immune responses.[1,3]
There is a need for noninvasive biomarkers to assess intestinal inflammation and permeability in young children
Summary
Researchers have proposed that a significant cause of growth faltering and malnutrition, which disproportionately occurs early in life in children residing in low- and middle-income countries (LMICs), is due to changes in gut function resulting from environmental exposures to enteropathogens and toxins, from inadequate nutrient intake, and from disease history, notably diarrhea.[1,2] Various alterations in gut function have been associated with environmental enteropathy (EE), a condition histopathologically defined from examination of biopsy material characterized by changed morphology (crypt depth and villus height) and altered inflammatory and immune responses.[1,3] In an effort to move to noninvasive diagnostics for EE, various biomarkers of gut and systemic inflammation and gut permeability have been proposed and studied The goal of such studies is to better characterize specific changes that are predictive of, and causally related to, the aforementioned physical growth and related developmental shortfalls.[3,4]. A better understanding of the role that such factors play in affecting the fecal concentrations of MPO, AAT, and NEO may be important to evaluate their utility as predictive or causal biomarkers and/or for establishing parameters for sampling or interpretation
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