1.
Validation of the Micronutrient and Environmental Enteric Dysfunction Assessment Tool and evaluation of biomarker risk factors for growth faltering and vaccine failure in young Malian children.
Arndt, MB, Cantera, JL, Mercer, LD, Kalnoky, M, White, HN, Bizilj, G, Boyle, DS, de Hostos, EL, Choy, RKM
PLoS neglected tropical diseases. 2020;(9):e0008711
Abstract
Environmental enteric dysfunction (EED) is an intestinal disorder common among children in low-resource settings and is associated with increased risk of growth stunting, cognitive deficits, and reduced oral vaccine immunogenicity. The Micronutrient and EED Assessment Tool (MEEDAT) is a multiplexed immunoassay that measures biomarkers previously associated with child growth faltering and/or oral vaccine immunogenicity: intestinal fatty acid-binding protein (I-FABP), soluble CD14 (sCD14), insulin-like growth factor 1 (IGF-1), and fibroblast growth factor 21 (FGF21). MEEDAT also measures systemic inflammation (α1-acid glycoprotein, C-reactive protein), ferritin, soluble transferrin receptor, retinol binding protein 4, thyroglobulin, and Plasmodium falciparum antigenemia (histidine-rich protein 2). The performance of MEEDAT was compared with commercially available enzyme-linked immunosorbent assays (ELISAs) using 300 specimens from Malian infant clinical trial participants. Regression methods were used to test if MEEDAT biomarkers were associated with seroconversion to meningococcal A conjugate vaccine (MenAV), yellow fever vaccine (YFV), and pentavalent rotavirus vaccine (PRV) after 28 days, or with growth faltering over 12 weeks. The Pearson correlations between the MEEDAT and ELISA results were 0.97, 0.86, 0.80, and 0.97 for serum I-FABP, sCD14, IGF-1, and FGF21, respectively. There were significant associations between I-FABP concentration and the probability of PRV IgG seroconversion and between IGF-1 concentration and the probability of YFV seroconversion. In multivariable models neither association remained significant, however there was a significant negative association between AGP concentration and YFV seroconversion. GLP-2 and sCD14 concentrations were significantly negatively associated with 12-week change in weight-for-age z-score and weight-for-height z-score in multivariable models. MEEDAT performed well in comparison to commercially-available ELISAs for the measurement of four analytes for EED and growth hormone resistance. Adoption of MEEDAT in low-resource settings could help accelerate the identification of interventions that prevent or treat child stunting and interventions that boost the immunogenicity of child vaccinations.
2.
Tryptophan, glutamine, leucine, and micronutrient supplementation improves environmental enteropathy in Zambian adults: a randomized controlled trial.
Louis-Auguste, J, Besa, E, Zyambo, K, Munkombwe, D, Banda, R, Banda, T, Watson, A, Mayneris-Perxachs, J, Swann, J, Kelly, P
The American journal of clinical nutrition. 2019;(5):1240-1252
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Abstract
BACKGROUND Environmental enteropathy (EE) refers to villus blunting, reduced absorption, and microbial translocation in children and adults in tropical or deprived residential areas. In previous work we observed an effect of micronutrients on villus height (VH). OBJECTIVE We aimed to determine, in a randomized controlled trial, if amino acid (AA) or multiple micronutrient (MM) supplementation can improve intestinal structure or barrier dysfunction in Zambian adults with EE. METHODS AA (tryptophan, leucine, and glutamine) and/or MM supplements were given for 16 wk in a 2 × 2 factorial comparison against placebo. Primary outcomes were changes in VH, in vivo small intestinal barrier dysfunction assessed by confocal laser endomicroscopy (CLE), and mechanistic (or mammalian) target of rapamycin complex 1 (MTORC1) nutrient responsiveness in lamina propria CD4+ lymphocytes. RESULTS Over 16 wk AA, but not MM, supplementation increased VH by 16% (34.5 μm) compared with placebo (P = 0.04). Fluorescein leak, measured by CLE, improved only in those allocated to both AA and MM supplementation. No effect was seen on MTORC1 activation, but posttreatment MTORC1 and VH were correlated (ρ = 0.51; P = 0.001), and change in MTORC1 was correlated with change in VH in the placebo group (ρ = 0.63; P = 0.03). In secondary analyses no effect was observed on biomarkers of microbial translocation. Metabolomic analyses suggest alterations in a number of microbial- and host-derived metabolites including the leucine metabolite β-hydroxy-β-methylbutyrate, which was increased by AA supplementation and correlated with VH. CONCLUSIONS In this phase 2 trial, AA supplementation protected against a decline in VH over the supplementation period, and improved barrier function when combined with micronutrients. Leucine and MTORC1 metabolism may be involved in the mechanism of effect. This trial was registered at www.pactr.org as PACTR201505001104412.
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Simulated amniotic fluid-like solution given enterally to neonates after obstructive bowel surgeries: A randomized controlled trial.
El-Farrash, RA, Gad, GI, Abdelkader, HM, Salem, DAD, Fahmy, SA
Nutrition (Burbank, Los Angeles County, Calif.). 2019;:187-191
Abstract
OBJECTIVES Withholding postoperative feeding is common in neonates recovering from surgeries for congenital abnormalities of the gastrointestinal tract (GIT), which leads to prolonged exposure to total parenteral nutrition, intestinal atrophy, and feeding intolerance. Because amniotic fluid plays a significant role in fetal gut maturation and development, the aim of this study was to test a hypothesis suggesting that feeding tolerance could be improved in neonates recovering from surgeries for congenital obstructive bowel abnormalities by enteral administration of simulated amniotic fluid-like solution given enterally (SAFE) containing recombinant human granulocyte colony-stimulating factor and erythropoietin. METHODS This prospective, double-blind, randomized, placebo-controlled trial was conducted with 40 late preterm/term neonates recovering from GIT surgeries. Neonates were randomly divided postoperatively into two groups: 20 neonates received the test solution (SAFE group) and 20 neonates received distilled water (placebo group) with a gestational age range (34.3-40.4 versus 34-40 wk, respectively) and mean gestational age (37.10 ± 1.68 versus 36.90 ± 1.83 wk, respectively). Treatment was started postoperatively and the test solution (or distilled water) was discontinued when daily enteral intake reached 100 mL/kg. RESULTS The study group showed better feeding tolerance as demonstrated as reflected by an earlier achievement of 50, 100, 120, and 150 mL/kg enteral feeding per day with a higher enteral caloric intake on day 7 post SAFE administration and a higher rate of weight gain (P < 0.05 for all). CONCLUSION Enteral administration of SAFE may improve postoperative feeding tolerance, enteral caloric intake, and weight gain.