Severe acute malnutrition (SAM) and environmental enteric dysfunction (EED) are highly prevalent among children residing in resource-limited countries like Bangladesh. L-carnitine may play a role in ...improving the growth and ameliorating the EED among nutritionally vulnerable children. To investigate the role of L-carnitine supplementation on the rate of weight gain, duration of hospital stays, and EED biomarkers among children with severe acute malnutrition. This study is a double-blinded, placebo-controlled, randomized clinical trial aiming to enroll diarrheal children with SAM between 9-24 months of both sexes attending the nutritional rehabilitation unit (NRU) of Dhaka Hospital of icddr,b. It is an ongoing trial including two arms where one arm receives L-carnitine supplementation, and the other arms receive a placebo for 15 days in addition to the existing standard treatment of SAM. The primary outcome is the rate of weight gain, and the secondary outcomes include duration of hospital stay and EED biomarkers. Outcomes are assessed at baseline and 15 days of post-intervention. We hypothesize that the L- carnitine supplementation for 15 days in children with SAM will improve the rate of weight gain and biomarkers of EED.
There is paucity of knowledge on the histological features of the intestinal mucosa in malnourished adults of Bangladesh. The purpose of the study was to explore the histological features of the ...intestinal mucosa in malnourished adults of Bangladesh and to compare the findings with their well-nourished counterparts. 64 adults (37 malnourished with body mass index, BMI < 18.5 kg/m
and 27 controls with BMI > 18.5 kg/m
) from the Bangladesh Environmental Enteric Dysfunction (BEED) study, who underwent upper-gastrointestinal endoscopy, were selected for this study. With a view to address the association of environmental enteric dysfunction (EED) with malnutrition, upper-gastrointestinal endoscopy was performed and mucosal biopsies from the distal duodenum were studied for histopathology. Villous height, crypt depth, and presence of inflammatory infiltrates in lamina propria were investigated. Bivariate analysis was performed to quantify the relation between malnutrition and the histological features. About 95% adults, irrespective of nutritional status, were diagnosed to have chronic non-specific duodenitis on histopathology. Malnourished adults suffered significantly more from chronic active duodenitis compared to their well-nourished counterparts (p = 0.003). Malnourished adults also had significantly higher frequency of subtotal villous atrophy, crypt hyperplasia and marked cellular infiltration in the lamina propria than the healthy controls (p < 0.05).
The relationship of retinol binding protein 4 (RBP4) with biomarkers of intestinal health and gut integrity in adults is unknown. We sought to determine the correlation between plasma RBP4 level and ...BMI and investigate the relationship of circulating RBP4 concentration with biomarkers of environmental enteric dysfunction among lean adults (body mass index BMI < 25.0 kg/m2) in Bangladesh. Overall, 270 adults (135 undernourished with a BMI < 18.5 kg/m2 and 135 healthy controls with a BMI between 18.5 and 24.9 kg/m2) aged 18 to 45 years were evaluated. Multivariable linear regression was performed to test the association between RBP4 and fecal biomarkers of impaired gut health. RBP4 concentration was positively correlated (rho = 0.27, P < 0.001) with BMI and was significantly higher in healthy controls than undernourished adults (P < 0.001), in male than female (P < 0.001), and also in employed (P < 0.001), smokers (P = 0.048) and participants with low Self-Reporting Questionnaire (SRQ)-20 scores (an instrument to screen mental health disorders) (P = 0.049). Statistically significant negative correlations were observed between RBP4 and fecal biomarkers of gut enteropathy including myeloperoxidase (rho = -0.23, P < 0.001), neopterin (rho = -0.30, P < 0.001), and alpha-1 anti-trypsin (rho = -0.21, P < 0.001). Multivariable linear regression analysis showed that increased RBP4 concentration was associated with a significant reduction in fecal neopterin (coefficient = -0.95; 95% confidence interval: -1.44 to -0.45; P < 0.001) after adjustment for age, sex, nutritional status at enrollment, education, dietary diversity score, SRQ-20 score, improved sanitation, household animal exposure, and alpha-1-acid glycoprotein. The study findings revealed an inverse relationship of plasma RBP4 concentration with fecal biomarkers of altered gut health among slum-dwelling lean adults in Bangladesh.
There is lack of information on the histological characteristics of the intestinal mucosa in Bangladeshi children. Collection of intestinal biopsy samples and assessment of the histomorphological ...features is considered to be the traditional gold standard for diagnosis of environmental enteric dysfunction (EED). The purpose of the study was to evaluate the intestinal histological characteristics of stunted children aged between 12-18 months with possible EED. 110 children with chronic malnutrition (52 stunted with length-for-age Z score, LAZ<-2 and 58 at risk of stunting with LAZ <-1 to -2) from the Bangladesh Environmental Enteric Dysfunction (BEED) study protocol who underwent upper gastrointestinal (GI) endoscopy were selected for this study. To explore the association of EED with childhood stunting, upper GI endoscopy was done and the biopsy specimens were studied for histopathology. Villous height and crypt depth were measured and the presence and intensity of inflammatory infiltrates in the lamina propria was investigated. Bivariate analysis was performed to examine the relationship between stunting and histologic morphology. More than 90% children irrespective of nutritional status were diagnosed to have chronic non-specific duodenitis on histopathology. Half of the children from both groups had villous atrophy as well as crypt hyperplasia and lymphocytic infiltration was present in more than 90% children, irrespective of groups. However, no statistically significant difference was observed when compared between the groups. The prevalence of chronic non-specific duodenitis in Bangladeshi children, irrespective of nutritional status, was high. A significant number of these children had abnormal findings in intestinal histomorphology. Trial registration number: ClinicalTrials.gov ID: NCT02812615 Date of first registration: 24/06/2016. https://clinicaltrials.gov/ct2/results?cond=NCT02812615&term=&cntry=&state=&city=&dist.
Abstract
In the current world, a major challenge to diagnose environmental enteric dysfunction (EED) is the lack of validated non-invasive biomarkers. Intestine derived molecules, including ...intestinal fatty acid binding protein (I-FABP), trefoil factor-3 (TFF3), lactoferrin, lipocalin-2 (LCN2), and mucin-2, have been reported as indicators of intestinal inflammation and gut health. Therefore, we aimed to investigate the levels of these bio-molecules as biomarkers of EED among under-2 children in Bangladesh. A total of 140 children were recruited in a case–control design. All the biomarkers were measured by ELISA. Spearman’s rank correlation was performed to see the correlation between the biomarkers and the EED score. Moreover, multivariable linear regression was performed to investigate the association of biomarkers with length-for-age z-score (LAZ). TFF3 correlates positively with myeloperoxidase (r = 0.26, p < 0.05) and EED score (r = 0.17, p < 0.05). Likewise, LCN2 correlates positively with myeloperoxidase (r = 0.37, p < 0.05), neopterin (r = 0.33, p < 0.05) and EED score (r = 0.31, p < 0.05). Moreover, multivariable linear regression revealed a negative association of I-FABP with LAZ of the study participants. Our results imply that TFF3 and LCN2 might be promising biomarkers to diagnose intestinal inflammation and EED, while I-FABP is negatively associated with linear growth of Bangladeshi children.
Asymptomatic infection by fecal enteropathogens is a major contributor to childhood malnutrition. Here, we investigated the incidence rate of asymptomatic infection by enterotoxigenic Escherichia ...coli (ETEC) and assessed its association with childhood stunting, wasting, and being underweight among children under 2 years of age. The Malnutrition and Enteric Disease birth cohort study included 1,715 children who were followed from birth to 24 months of age from eight distinct geographic locations including Bangladesh, Brazil, India, Peru, Tanzania, Pakistan, Nepal, and South Africa. The TaqMan array card assay was used to determine the presence of ETEC in the nondiarrheal stool samples collected from these children. Poisson regression was used to estimate the incidence rate, and multiple generalized estimating equations with binomial family, logit link function, and exchangeable correlation were used to analyze the association between asymptomatic ETEC infection and anthropometric indicators such as stunting, wasting, and being underweight. The site-specific incidence rates of asymptomatic ETEC infections per 100 child-months were also higher at the study locations in Tanzania (54.81 95% CI: 52.64, 57.07) and Bangladesh (46.75 95% CI: 44.75, 48.83). In the Bangladesh, India, and Tanzania sites, the composite indicator of anthropometric failure was significantly associated with asymptomatic ETEC infection. Furthermore, a significant association between asymptomatic heat-stable toxin ETEC infections and childhood stunting, wasting, and being underweight was found in only the Bangladesh and Tanzania sites.
Fucosyltransferase 2 (FUT2) and 3 (FUT3) may influence host biological functions. We aim to assess the relationship between maternal and child FUT2 (Secretor) and FUT3 (Lewis) status with growth, ...body composition, gut health and histologic features in Bangladeshi children. We conducted a case-control study where secretor and Lewis status were ascertained from saliva samples of 408 mother-child dyads. Upper-arm fat area estimate (UFE) and total upper arm area (TUA) were found higher among children of Lewis negative mothers (p = 0.01 and p = 0.07, respectively). Changes in UFE after nutrition intervention were significantly greater among Lewis positive children than those of negative for Lewis (p = 0.05). Significant differences were observed for child UFE based on secretor and Lewis status of the mothers (p = 0.04). Lewis positive children had greater changes in WAZ (p = 0.07) and WLZ (p = 0.02) than Lewis negative children at the end of nutrition intervention. Fecal Reg1B was elevated in secretor positive children compared to their counterparts (p = 0.03). Lewis negative children had higher concentrations of MPO compared to Lewis positive children (p = 0.08). We also observed a higher frequency of subtotal villous atrophy among secretor negative and Lewis positive children (p = 0.09 and p = 0.01, respectively) than those of their counterparts. The findings provide insights for further studies to elucidate causal influences.
Objective
Environmental Enteric Dysfunction (EED) can be assessed by faecal biomarkers such as Myeloperoxidase (MPO), Neopterin (NEO) and Alpha‐1 anti‐trypsin (AAT). We aimed to test the association ...of intestinal pathogens with faecal markers of EED among slum‐dwelling children in first 2 years of life.
Methods
The MAL‐ED birth cohort data of Bangladesh site were used to conduct this analysis. Multivariable analyses using Generalized Estimating Equations (GEE) were performed to test the association between intestinal pathogens and faecal markers of EED.
Results
Giardiasis, ascariasis and trichuriasis were the most frequent parasitic infections and Campylobacter spp., Enteroaggregative Escherichia coli (EAEC) and Enterotoxigenic Escherichia coli (ETEC) were the common bacterial pathogens observed in stool samples of the children. Overall, 71%, 97% and 58% of stool samples were above values considered normal in non‐tropical settings for MPO, NEO and AAT respectively. Giardiasis was found to be significantly associated with MPO (Coefficient = 0.55; 95% CI = 0.15, 0.95; P‐value = 0.008) and AAT concentrations (Coefficient = 0.34; 95% CI = 0.04, 0.63; P‐value = 0.03). A significant association was found between trichuriasis and NEO (Coefficient = 0.90; 95% CI = 0.19, 1.61; P‐value = 0.01). Trichuriasis (Coefficient = 1.71; 95% CI = 0.32, 3.11; P‐value = 0.02) and giardiasis (Coefficient = 1.51; 95% CI = 0.79, 2.23; P‐value <0.001) were significantly associated with EED score. Children with EAEC had significantly higher MPO concentrations (Coefficient = 0.33; 95% CI = 0.06, 0.61; P‐value = 0.02).
Conclusion
The study results imply the importance of intestinal pathogens in contributing to intestinal inflammation and increased intestinal permeability in young children.
Objectif
La dysfonction environnementale entérique (DEE) peut être évaluée à l'aide de biomarqueurs fécaux tels que la myéloperoxydase (MPO), la néoptérine (NEO) et l'alpha‐1 anti‐trypsine (AAT). Nous avons cherché à tester l'association entre les pathogènes intestinaux et les marqueurs fécaux de la DEE chez les enfants vivant dans les bidonvilles au cours des deux premières années de la vie.
Méthodes
Les données de la cohorte de naissance MAL‐ED du site du Bangladesh ont été utilisées pour effectuer cette analyse. Des analyses multivariées utilisant des équations d'estimation généralisées ont été effectuées pour tester l'association entre les pathogènes intestinaux et les marqueurs fécaux de la DEE.
Résultats
La giardiase, l'ascaridiose et la trichocéphalose étaient les plus fréquentes infections parasitaires et Campylobacter spp., Escherichia coli entéroagrégative (EAEC) et Escherichia coli entérotoxigène (ETEC) étaient les agents pathogènes bactériens courants observés dans les échantillons de selles des enfants. Dans l'ensemble, 71%, 97% et 58% des échantillons de selles étaient au‐delà des valeurs considérées comme normales dans les milieux non tropicaux pour la MPO, la NEO et l'AAT, respectivement. La giardiase était significativement associée à la MPO (coefficient = 0,55; IC95%: 0,15 ‐ 0,95; valeur p = 0,008) et aux concentrations d'AAT (coefficient = 0,34; IC95%: 0,04 ‐ 0,63; valeur p = 0,03). Une association significative a été trouvée entre le trichocéphalose et la NEO (coefficient = 0,90; IC95%: 0,19 ‐ 1,61; valeur p= 0,01). La trichocéphalose (coefficient = 1,71; IC95%: 0,32 ‐ 3,11; valeur p = 0,02) et la giardiase (coefficient = 1,51; IC95%: 0,79 ‐ 2,23; valeur p <0,001) étaient significativement associées au score de DEE. Les enfants avec EAEC avaient des concentrations de MPO significativement plus élevées (coefficient = 0,33; IC95%: 0,06 ‐ 0,61; valeur p = 0,02).
Conclusion
Les résultats de l’étude impliquent l'importance des agents pathogènes intestinaux dans l'inflammation intestinale et l'augmentation de la perméabilité intestinale chez les jeunes enfants.
Recent evidence suggests that measures of maternal gut enteropathy are associated with unfavorable fetal outcomes. It is, therefore, crucial to identify and treat the features of intestinal ...enteropathy among reproductive-age women living in areas where enteropathy is highly prevalent. However, there is a lack of non-invasive diagnostic tests to determine EED, making it difficult to identify the disease in field settings. In this study, we tested the potential of fecal pH as a biomarker of gut enteropathy and investigated its relationship with fecal biomarkers of intestinal enteropathy in reproductive-age women living in resource-limited environments.
Data on socio-demographic information, anthropometry, and biological samples were collected from 78 apparently healthy women aged between 20 and 27 years from November 2018 to December 2019. The association of stool pH with two fecal biomarkers of gut enteropathy (i.e., intestinal alkaline phosphatase IAP and fecal lipocalin-2 LCN-2 was investigated using multiple linear regression models after adjusting for relevant covariates.
In the adjusted models, alkaline stool pH (pH > 7.2) was found to be significantly associated with a decrease in the fecal IAP level by 1.05 unit (95% CI: -1.68, -0.42; p < 0.001) in the log scale, and acidic stool pH (pH < 6) was found to be significantly associated with an increase in the fecal LCN-2 level by 0.89 units (95% CI: 0.12, 1.67; p < 0.025) in the log scale.
The study findings demonstrated an association of fecal pH with biomarkers of gut enteropathy indicating its applicability as a simple tool for understanding intestinal enteropathy among reproductive-age women living in resource-limited settings.
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