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.
BackgroundSevere 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.ObjectiveTo 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.MethodsThis 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.Trial registrationClinicalTrials.gov # NCT05083637. Date of registration: October 19, 2021.
Campylobacter jejuni (C. jejuni) is considered to be one of the most frequent causes of bacterial gastroenteritis globally, especially in young children. The genome of C. jejuni contains many ...proteins with unknown functions termed as hypothetical proteins (HPs). These proteins might have essential biological role to show the full spectrum of this bacterium. Hence, our study aimed to determine the functions of HPs, pertaining to the genome of C. jejuni. An in-silico work flow integrating various tools were performed for functional assignment, three-dimensional structure determination, domain architecture predictors, subcellular localization, physicochemical characterization, and protein-protein interactions (PPIs). Sequences of 267 HPs of C. jejuni were analyzed and successfully attributed the function of 49 HPs with higher confidence. Here, we found proteins with enzymatic activity, transporters, binding and regulatory proteins as well as proteins with biotechnological interest. Assessment of the performance of various tools used in this analysis revealed an accuracy of 95% using receiver operating characteristic (ROC) curve analysis. Functional and structural predictions and the results from ROC analyses provided the validity of in-silico tools used in the present study. The approach used for this analysis leads us to assign the function of unknown proteins and relate them with the functions that have already been described in previous literature.
Because Helicobacter pylori (H. pylori) infection and Environmental Enteric Dysfunction (EED) follow a similar mode of transmission, there can be a complex interplay between H. pylori infection and ...EED, both of which can influence childhood growth. We sought to investigate the factors associated with H. pylori infection and identify its relationship with the fecal biomarkers of EED including Myeloperoxidase (MPO), Neopterin (NEO), Calprotectin, Reg1B and Alpha-1 antitrypsin (AAT), and nutritional status of the children.
Data from an on-going community-based nutrition intervention study was used for this analysis. Total 319 children aged between 12-18 months were evaluated at enrolment and at the end of a 90-day nutrition intervention. Multivariable linear regression with generalized estimating equations was done to examine the association of H. pylori infection with stool biomarker of EED and nutritional status of the children.
One-fifth of the participants had H. pylori infection at both the time points, with 13.8% overall persistence. Children living in crowded households had higher odds of being infected by H. pylori (AOR = 2.02; 95% CI = 1.02, 4.10; p-value = 0.045). At enrolment, 60%, 99%, 69% and 85% of the stool samples were elevated compared to the reference values set for MPO, NEO, AAT and Calprotectin in the non-tropical western countries. The proportions reduced to 52%, 99%, 67%, and 77% for the same biomarkers after the nutrition intervention. Infection with H. pylori had significant positive association with fecal AAT concentrations (Coefficient = 0.26; 95% CI = 0.02, 0.49; p-value = 0.03) and inverse relationship with Reg1B concentrations measured in the stool samples (Coefficient = -0.32; 95% CI = -0.59, -0.05; p-value = 0.02). However, H. pylori infection was not associated with the indicators of childhood growth.
The study findings affirmed that the acquisition and persistence of H. pylori infection in the early years of life may exert an adverse impact on intestinal health, induce gut inflammation and result in increased intestinal permeability.
We identified the determinants of positive (children who had a birth weight < 2.5 kg and/or maternal height < 145 cm but were nonstunted at 24 months of age) and negative (children who had a birth ...weight ≥ 2.5 kg and maternal height ≥ 145 cm but were stunted at 24 months of age) deviance in childhood linear growth. We found that socioeconomic status (β = 1.54, P < 0.01), serum retinol (β = 0.05, P < 0.01), hemoglobin (β = 0.36, P < 0.01), length-for-age Z-score (LAZ) at birth (β = 0.47, P < 0.01), and tetanus vaccine titer (β = 0.182, P < 0.05) were positively and maternal depressive symptom (β = -0.05, P < 0.01), serum ferritin (β = -0.03, P < 0.01), male sex (β = -1.08, P < 0.01), and α1-antitrypsin (β = -0.81, P < 0.01) were negatively associated with positive deviance. Further, diarrhea episodes (β = 0.02, P < 0.01), male sex (β = 0.72, P < 0.01), and α1-antitrypsin (β = 0.67, P < 0.01) were positively and hemoglobin (β= -0.28, P < 0.01), soluble transferrin receptor level (β = -0.15, P < 0.01), and LAZ score at birth (β = -0.90, P < 0.01) were negatively associated with negative deviance. To summarize, enteric protein loss, micronutrient deficiency, vaccine responses and maternal depressive symptoms were associated with linear growth deviance in early childhood. In such a background, public health approaches aimed at reducing the risk of intestinal inflammation and altered gut permeability could prove fruitful in ensuring desired linear growth in children. In addition, maternal mental health issue should also be considered, especially for promoting better nutritional status in children in the context of linear growth deviance.
Aflatoxin can cross the blood-brain barrier, damage brain tissues, and have the potential to harm the development of the human brain. Although dietary aflatoxin exposure is common in children, there ...is a paucity of data on aflatoxin exposure and child developmental outcomes. The child's cognitive, motor, and language functions were assessed using the Bayley Scales of Infant and Toddler Development-III or BSID-III at the same time points. Association between exposure to aflatoxin and subtests of BSID-III were examined using mixed-effect linear regression. Aflatoxin assays were performed on 194, 167, and 163 children at 15, 24, and 36 months of age, and chronic aflatoxin exposure was detected in 20.6%, 16.8%, and 60.7% of children, respectively. Multi-variable analyses showed that aflatoxin exposure was independently related to the children's cognitive score (β: -0.69; 95% CI: -1.36, -0.02), receptive language score (β: -0.90; 95% CI: -1.62, -0.17), and expressive language score (β: -1.01; 95% CI: -1.96, -0.05). We did not observe any association between exposure to aflatoxin and the motor function of children. Chronic exposure to aflatoxin exposure was linked to reduced cognitive, expressive, and receptive language scores of the study children. Further research is needed in a different setting to confirm this novel finding.
Infections and persistent immunological activation are linked to increased kynurenine (KYN) and the KYN-to-Tryptophan (TRP) or KT ratio and may be critical factors in undernutrition. We sought to ...determine the association between the KT ratio and adult malnutrition, as well as investigate if nutritional supplementation had any influence on the decrease of the KT ratio. A total of 525 undernourished adults aged 18-45 years were recruited and provided a nutrition intervention for 60 feeding days. TRP and KYN concentrations were determined from plasma samples using LC-MS/MS. At baseline, the median (interquartile range (IQR)) TRP, KYN and KT ratios were 24.1 (17.6, 34.3) µmol/L, 0.76 (0.53, 1.18) µmol/L and 30.9 (24.5, 41.7), respectively. Following intervention, the median (IQR) KYN and KT ratios were significantly reduced to 0.713 (0.46, 1.12) µmol/L and 27.5 (21.3, 35.8). The KT ratio was found to be inversely linked with adult BMI (coefficient: -0.09; 95% CI: -0.18, 0.004;
-value = 0.06) but not statistically significant. Additionally, Plasma CRP was correlated positively, while LRP1 was inversely correlated with the KT ratio. Our data suggest that in Bangladeshi adults, the KT ratio is not related to the pathophysiology of malnutrition but correlated with inflammatory and anti-inflammatory biomarkers, and the ratio can be reduced by a nutrition intervention.
Environmental enteric dysfunction (EED) causes gut inflammation and increased intestinal permeability leading to deficiencies in micronutrients such as zinc and iron. Fecal markers such as ...myeloperoxidase (MPO), neopterin (NEO), and alpha-1-anti-trypsin (AAT) can predict EED. The aim of this study was to examine the association between fecal markers of EED with zinc and iron status among children at first 2 years of life. Malnutrition and Enteric Disease Study Bangladeshi birth cohort data were used to conduct this analysis. Multivariable analyses using generalized estimating equations were performed to test the association between individual fecal markers with zinc or iron status of the children. A total of 265 children were enrolled in the study (male:female = 1:1). Of the 627 stool samples collected (
= 222 children), 535, 511, and 577 were accompanied by zinc, ferritin, and soluble transferrin receptor values, respectively. Median (interquartile range IQR) values of AAT, MPO, and NEO were 0.33 (0.18-0.62) mg/g, 3,895.42 (1,563.76-8,432.82) ng/mL, and 890.81 (331.57-2,089.04) nmol/L, respectively. Overall, 60%, 71%, and 97% of samples were above the values considered normal in nontropical settings for AAT, MPO, and NEO, respectively. High AAT levels were significantly associated with low ferritin values after adjusting for age and gender (coefficient = -5.85; 95% confidence interval = -11.23 to -0.47;
value = 0.03). No such association was found between AAT and plasma zinc status. Myeloperoxidase and NEO were not associated with plasma zinc or iron status. The study results imply the importance of enteric protein loss in contributing to reduced ferritin levels at first 2 years of life.
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.
We conducted an observational study to assess the prevalence and risk factors of vitamin D deficiency in 12-24 months old children living in urban and rural Bangladesh. Serum 25-hydroxyvitamin D ...(free 25(OH)D) level, socio-demographic status, anthropometric status, dietary intake, exposure to sunlight and single nucleotide polymorphisms in vitamin-D pathway genes were measured in 208 children. Vitamin D deficiency (free 25(OH)D < 50 nmol/l) was reported in 47% of the children. Multivariable logistic regression model identified duration to sunlight exposure (regression coefficient, β = - 0.01; 95% CI 0.00, - 0.02; p-value < 0.05), UV index (β = - 0.36; 95% CI 0.00, - 0.02; p-value < 0.05) and breast-feeding (β = - 1.15; 95% CI - 0.43, - 1.86; p-value < 0.05) to be negatively associated with vitamin D deficiency. We measured the role of single nucleotide polymorphisms in pathway genes (GC-rs7041 T > G, rs4588 C > A, CYP2R1-rs206793 A > G, CYP27B1-rs10877012 A > C and DHCR7-rs12785878 G > T) and found statistically significant differences in serum vitamin D levels between various genotypes. SNPs for CYP27B1 (CA & CC genotype) had statistically significant positive association (β = 1.61; 95% CI 2.79, 0.42; p-value < 0.05) and TT genotype of GC-rs7041 had negative association (β = - 1.33; 95% CI - 0.02, - 2.64; p-value < 0.05) with vitamin-D deficiency in the surveyed children.
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