Biomarkers of Environmental Enteric Dysfunction Among Children in Rural Bangladesh

Abstract

Objectives Environmental enteric dysfunction (EED) may inhibit growth and development in low- and middle-income countries, but available assessment methodologies limit its study. In rural Bangladesh, we measured EED using the widely-used lactulose mannitol ratio (L:M) test and a panel of intestinal and systemic health biomarkers to evaluate convergence among biomarkers and describe risk factors for EED. Methods In 539 18-month-old children finishing participation in a randomized food supplementation trial, serum, stool and urine collected after lactulose and mannitol dosing were analyzed for biomarkers of intestinal absorption, inflammation, permeability and repair, and systemic inflammation. EED scores for each participant were developed using principal component analysis (PCA) and partial least squares regression (PLS). Associations between scores and L:M and with child sociodemographic and health characteristics were evaluated using regression analysis. Results EED prevalence (L:M>0.07) was 39.0%; 60% had elevated acute phase proteins (CRP>5mg/L or AGP>100mg/dL). Correlations between intestinal biomarkers were low, with the highest between myeloperoxidase and α-1 antitrypsin (r=0.33, p<0.01), and biomarker values did not differ by supplementation history. A one-factor PLS model with L:M as the dependent variable explained only 8.6% of L:M variability. In adjusted models, L:M was associated with child sex and SES index, while systemic inflammation was predicted mainly by recent illness, not EED. Conclusions Impaired intestinal health is widespread in this setting of prevalent stunting, but a panel of serum and stool biomarkers demonstrated poor agreement with L:M. Etiologies of intestinal and systemic inflammation are likely numerous and complex in resource-poor settings, underscoring the need for a better case definition with corresponding diagnostic methods to further the study of EED.

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].…”

“…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]. Prior report showed that fecal AAT as well as "EED composite score" comprising AAT were associated with impaired linear growth in children [22,62].…”

Nutritional status and risk factors for stunting in preschool children in Bhutan

“…Additional factors related to stunting to investigate should include environmental enteric dysfunction (Campbell, Schulze, et al, ), potential roles of micronutrient deficiencies (e.g., zinc) and other possible exposures such as aflatoxin, as recently reported to be endemic in neighbouring countries of Nepal and Bangladesh (Groopman et al, ).…”

“…Identified determinants of stunting included child age, residency in the eastern or western region (relative to Central), low socioeconomic status and suboptimal complementary feeding practices among children under one year of age (Aguayo et al, 2015;Zangmo et al, 2012), and determinants of wasting were child age, residency in the western region and inappropriate complementary feeding practices (Aguayo et al, 2017). Additional factors related to stunting to investigate should include environmental enteric dysfunction (Campbell, Schulze, et al, 2017), potential roles of micronutrient deficiencies (e.g., zinc) and other possible exposures such as aflatoxin, as recently reported to be endemic in neighbouring countries of Nepal and Bangladesh (Groopman et al, 2014).…”