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Impact of Different Strategies for Delivering Supplemental Zinc on Selected Fecal Markers of Environmental Enteric Dysfunction among Young Laotian Children: A Randomized Controlled Trial.

ABSTRACT: The objective of this study was to assess the impact of different strategies for delivering supplemental zinc on fecal myeloperoxidase (MPO), neopterin (NEO), and calprotectin (CAL) among young Laotian children. In a double-blind controlled trial, children aged 6-23 months were randomized to receive either daily preventive zinc (PZ) tablets (7 mg/day), daily micronutrient powder (MNP; containing 10 mg zinc and 14 other micronutrients), therapeutic zinc (TZ) supplements for diarrhea treatment (20 mg/day for 10 days), or daily placebo powder and followed for ?36 weeks. Stool samples were collected at baseline and endline. Fecal MPO, NEO, and CAL concentrations were determined in a randomly selected subsample of 720 children using commercially available ELISA kits. At baseline, the mean age was 14.1 ± 4.9 months and prevalence of stunting was 39%. The endline prevalence of stunting was 43%; there was no overall treatment effect on physical growth in the parent trial. At endline, the mean (95% CI) MPO in the PZ group was 1,590 [1,396; 1,811] ng/mL and did not differ from that in the MNP (1,633 [1,434; 1,859] ng/mL), TZ (1,749 [1,535; 1,992] ng/mL), and control (1,612 [1,415; 1,836] ng/mL) groups (P = 0.749). Similarly, there was no overall treatment effect on NEO and CAL concentrations (P = 0.226 and 0.229, respectively). In this population, the provision of PZ or TZ supplements or MNP had no impact on growth or environmental enteric dysfunction (EED) as assessed by fecal MPO, NEO, and CAL. Additional research is needed to better understand the etiology and proposed mechanisms of EED pathogenesis.

SUBMITTER: Hinnouho GM

PROVIDER: S-EPMC7543857 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundEnvironmental enteric dysfunction (EED), a chronic inflammatory disorder of the small bowel, is suspected to impair absorption of micronutrients, including zinc.ObjectiveThe objective of this study was to compare zinc absorption from micronutrient powder (MNP) over a range of zinc doses in young children screened for EED with use of the lactulose:mannitol ratio (L:M).MethodsBangladeshi children aged 18-24 mo, grouped according to high and low L:M (≥0.09 and <0.09, respectively), were randomly assigned to MNP with 0, 5, 10, or 15 mg Zn/sachet (10 subjects per dose per L:M group). Over a day, fractional absorption of zinc was measured from an MNP-fortified meal and from unfortified meals with stable isotope tracers; total daily absorbed zinc (TAZ, milligrams per day) was determined as the primary outcome. Secondary outcomes included investigation of relations of TAZ to intake, to physiologic requirement, and to other variables, including biomarkers of systemic and intestinal inflammation, using nonlinear models. TAZ was also compared with published data on child zinc absorption.ResultsIn 74 subjects who completed the study, zinc absorption did not differ by L:M grouping. Most biomarkers of intestinal inflammation were elevated in both L:M groups. For combined L:M groups, mean ± SD TAZ for each MNP dose (0, 5, 10, and 15 mg/sachet) was 0.57 ± 0.30, 0.68 ± 0.31, 0.90 ± 0.43, and 1.0 ± 0.39 mg/d, respectively (P = 0.002), and exceeded the estimated physiologic requirement only for the 10- and 15-mg MNP doses. Zinc absorption was notably lower at all intake levels compared with published data (P < 0.0001) and was inversely related to serum α-1 acid glycoprotein and to fecal Entamoeba histolytica (P = 0.02).ConclusionResults indicate impaired absorption of zinc, which may predispose to zinc deficiency in young children with evidence of enteropathy. These findings suggest that current doses of zinc in MNP may be insufficient to yield zinc-related preventative benefits in similar settings. This study is registered at clinicaltrials.gov as NCT02758444.

Project description:Environmental enteric dysfunction (EED) (also referred to as environmental enteropathy) is a subclinical chronic intestinal disorder that is an emerging contributor to early childhood malnutrition. EED is common in resource-limited settings, and is postulated to consist of small intestinal injury, dysfunctional nutrient absorption, and chronic inflammation that results in impaired early child growth attainment. Although there is emerging interest in the hypothetical potential for chemical toxins in the environmental exposome to contribute to EED, the propensity of published data, and hence the focus of this review, implicates a critical role of environmental microbes. Early childhood malnutrition and EED are most prevalent in resource-limited settings where food is limited, and inadequate access to clean water and sanitation results in frequent gastrointestinal pathogen exposures. Even as overt diarrhea rates in these settings decline, silent enteric infections and faltering growth persist. Furthermore, beyond restricted physical growth, EED and/or enteric pathogens also associate with impaired oral vaccine responses, impaired cognitive development, and may even accelerate metabolic syndrome and its cardiovascular consequences. As these potentially costly long-term consequences of early childhood enteric infections increasingly are appreciated, novel therapeutic strategies that reverse damage resulting from nutritional deficiencies and microbial insults in the developing small intestine are needed. Given the inherent limitations in investigating how specific intestinal pathogens directly injure the small intestine in children, animal models provide an affordable and controlled opportunity to elucidate causal sequelae of specific enteric infections, to differentiate consequences of defined nutrient deprivation alone from co-incident enteropathogen insults, and to correlate the resulting gut pathologies with their functional impact during vulnerable early life windows.

Dataset Information

Impact of Different Strategies for Delivering Supplemental Zinc on Selected Fecal Markers of Environmental Enteric Dysfunction among Young Laotian Children: A Randomized Controlled Trial.

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