Tryptophan, glutamine, leucine, and micronutrient supplementation improves environmental enteropathy in Zambian adults: a randomized controlled trial

Louis-Auguste, John; Besa, Ellen; Zyambo, Kanekwa; Munkombwe, Derick; Banda, Rosemary; Banda, Themba; Watson, Alastair; Mayneris‐Perxachs, Jordi; Kelly, Paul

doi:10.1093/ajcn/nqz189

Cited by 20 publications

(22 citation statements)

References 39 publications

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“…Fluorescein leakage measured endoscopically would reflect loss of epithelial continuity from microerosions but would also be reduced by any reduction in the surface area of damaged enterocytes. We previously reported fluorescein leakage in adults with environmental enteropathy from the same community in Lusaka as the children we report in this study 43,44 . It is of interest that increased crypt depth was associated with reduced fluorescein leakage.…”

Section: Discussionsupporting

confidence: 71%

“…CLE allows direct imaging of the small intestinal mucosa and fluorescein efflux allows quantification of epithelial leakage in vivo 43 , 44 . The reduction in fluorescein leakage with age is consistent with the reduction in microbial translocation shown using three blood biomarkers.…”

Section: Discussionmentioning

confidence: 99%

“…Biopsies were embedded in paraffin wax and stained with haematoxylin and eosin, then imaged on an Olympus VS120 scanning microscope. Morphometry was performed as described previously 44 (Fig. 5).…”

Section: Articlesmentioning

confidence: 99%

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Adaptation of the small intestine to microbial enteropathogens in Zambian children with stunting

et al. 2021

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Environmental enteropathy is a major contributor to growth faltering in millions of children in Africa and South Asia. We carried out a longitudinal, observational and interventional study in Lusaka, Zambia, of 297 children with stunting (aged 2–17 months at recruitment) and 46 control children who had good growth (aged 1–5 months at recruitment). Control children contributed data only at baseline. Children were provided with nutritional supplementation of daily cornmeal-soy blend, an egg and a micronutrient sprinkle, and were followed up to 24 months of age. Children whose growth did not improve over 4–6 months of nutritional supplementation were classified as having non-responsive stunting. We monitored microbial translocation from the gut lumen to the bloodstream in the cohort with non-responsive stunting (n = 108) by measuring circulating lipopolysaccharide (LPS), LPS-binding protein and soluble CD14 at baseline and when non-response was declared. We found that microbial translocation decreased with increasing age, such that LPS declined in 81 (75%) of 108 children with non-responsive stunting, despite sustained pathogen pressure and ongoing intestinal epithelial damage. We used confocal laser endomicroscopy and found that mucosal leakiness also declined with age. However, expression of brush border enzyme, nutrient transporter and mucosal barrier genes in intestinal biopsies did not change with age or correlate with biomarkers of microbial translocation. We propose that environmental enteropathy arises through adaptation to pathogen-mediated epithelial damage. Although environmental enteropathy reduces microbial translocation, it does so at the cost of impaired growth. The reduced epithelial surface area imposed by villus blunting may explain these findings.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

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Adaptation of the small intestine to microbial enteropathogens in Zambian children with stunting

et al. 2021

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“… 22 , 53 A possible role of TRP signaling in regulating the villus structure and nutrient-sensing capability of immune cell has also been observed. 54 A negative correlation was found for Reg1B with KYN and KT ratio both at baseline and endline, and again, negative correlation was found for AAT and calprotectin with KYN and KT ratio only at the endline. These negative correlations may be explained by the transient nature of EED markers in young children and need further elucidation with the KYN pathway.…”

Section: Discussionmentioning

confidence: 81%

Plasma Kynurenine to Tryptophan Ratio Is Negatively Associated with Linear Growth of Children Living in a Slum of Bangladesh: Results from a Community-Based Intervention Study

Gazi

Das

Siddique

et al. 2021

The American Journal of Tropical Medicine and Hygiene

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Chronic exposure to infectious agents results in environmental enteric dysfunction-a significant contributor to childhood stunting. Low plasma tryptophan (TRP), increased kynurenine (KYN), and KYN-TRP (KT) ratio are associated with infections and chronic immune activation. We postulated that both these conditions are interlinked, and therefore aimed to identify the association between KT ratio and the linear growth of Bangladeshi children. A total of 480 stunted and at risk of being stunted children aged 12-18 months were enrolled and provided nutrition intervention for 90 days. Plasma samples were assessed using liquid chromatography tandem mass spectrometry to measure TRP and KYN concentrations. Multivariable linear regression with generalized estimating equations was applied to analyze association between the KT ratio and linear growth. Tryptophan, KYN, and KT ratio were significantly higher in stunted children than in children at risk of being stunted both at baseline and at the end of nutrition intervention. Following intervention, the median (interquartile range [IQR]) KYN concentration was significantly reduced from 4.6 (3.6, 5.4) μmol/L to 3.9 (0.3, 7.6) μmol/L, and median (IQR) KT ratio decreased from 104 (80.9, 131) to 92.8 (6.6, 247) in stunted children. We also found KT ratio to be negatively associated (coefficient = −0.7; 95% CI = −1.13, −0.26; P-value = 0.002) with linear growth. In addition, KYN and KT ratio were positively correlated with fecal neopterin and plasma C-reactive protein, whereas TRP was negatively correlated with both of these biomarkers and alpha-1-acid glycoprotein. Our findings imply that KT ratio is associated in the pathophysiology of stunting as well as with biomarkers of inflammation in Bangladeshi children.

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“…In these studies, EED has been measured either by the lactulose-to-mannitol (L:M) ratio, a dual sugar absorption test, 35 , 38 , 39 CAL, 40 , 41 or confocal laser endomicroscopy and mechanistic target of rapamycin complex 1 nutrient responsiveness. 42 …”

Section: Introductionmentioning

confidence: 99%

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

Hinnouho

Wessells

Barffour

et al. 2020

The American Journal of Tropical Medicine and Hygiene

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. 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.

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Tryptophan, glutamine, leucine, and micronutrient supplementation improves environmental enteropathy in Zambian adults: a randomized controlled trial

Cited by 20 publications

References 39 publications

Adaptation of the small intestine to microbial enteropathogens in Zambian children with stunting

Adaptation of the small intestine to microbial enteropathogens in Zambian children with stunting

Plasma Kynurenine to Tryptophan Ratio Is Negatively Associated with Linear Growth of Children Living in a Slum of Bangladesh: Results from a Community-Based Intervention Study

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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