Abstract
ABSTRACT.Examining the role of environmental enteric dysfunction (EED) in child growth requires noninvasive, field-appropriate biomarkers. Alternatives to the traditionally used lactulose:mannitol (L:M) test have been explored, but few studies have compared the L:M test to host fecal mRNA transcripts. The objectives of this study were to examine whether 1) host fecal mRNA transcripts could predict presence and severity of EED, measured using the L:M test, and 2) EED modifies the effect of specialized nutritious foods (SNFs) on recovery from moderate acute malnutrition (MAM). This substudy was nested within a cluster randomized trial comparing four SNFs in the treatment of MAM among children 6 to 59 months in Sierra Leone. EED was assessed at enrollment using the L:M test and 15 host fecal mRNA transcripts on 522 children. Recovery from MAM was defined as achieving mid-upper arm circumference ≥ 12.5 cm within 12 weeks of supplementation. Random forest classification models were used to examine prediction of presence and severity of EED by host fecal mRNA transcripts. Logistic regression was used to test for effect modification by L:M test variables including % lactulose excreted (%L). Eight host fecal mRNA transcripts (AQP9, REG3A, IFI30, DECR1, BIRC3, SELL, PIK3AP1, DEFA6) identified EED (%L ≥ 0.2) and severe EED (%L ≥ 0.45) with high sensitivity and specificity. The L:M test variables did not modify the effect of SNFs on recovery from MAM. In this study, we found host fecal mRNA transcripts that could be biomarkers of EED but did not find EED to modify the effect of SNFs on MAM treatment.
Highlights
Environmental enteric dysfunction (EED), an impairment of the structure and function of the small intestine, may be involved in processes contributing to undernutrition, including moderate acute malnutrition (MAM).[1]
CI 5 confidence interval; CSB1 w/ oil 5 corn soy blend plus with fortified vegetable oil; CSWB w/ oil 5 corn soy whey blend with fortified vegetable oil; EED 5 environmental enteric dysfunction; L:M 5 lactulose:mannitol; L:M excretion ratio (LMER) 5 lactulose:mannitol excretion ratio; %L 5 percent lactulose; %M 5 percent mannitol; MAM 5 moderate acute malnutrition; RUSF 5 ready-to-use supplementary food; SC1A 5 super cereal plus with amylase; Specialized nutritious foods (SNFs) 5 specialized nutritious foods
We found eight host fecal mRNA transcripts that identified presence of EED (%L $ 0.2) and severe EED (%L $ 0.45) with high sensitivity and specificity
Summary
Environmental enteric dysfunction (EED), an impairment of the structure and function of the small intestine, may be involved in processes contributing to undernutrition, including moderate acute malnutrition (MAM).[1] EED is characterized by morphologic changes including blunted villi, inflammation of the permeable intestinal walls, and poor absorption of nutrients.[2,3] Measuring EED is challenging. Biopsy of the small intestine is the only direct way to assess intestinal health, this invasive method is neither feasible nor ethical in most settings or in otherwise healthy subjects. The recovery of lactulose (%L) measures intestinal permeability, whereas the recovery of mannitol (%M) measures absorptive surface area. The ratio of the two sugars (L:M ratio) or the ratio of the recovery of the two sugars [L:M excretion ratio (LMER)] measures overall intestinal health. The L:M test has a number of drawbacks, such as inconvenience to participants (fasting requirements and long wait times) and inability to measure intestinal inflammation.[4]
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