Escherichia coli
(
E. coli
) pathotypes are the most common cause of diarrhea, especially in developing countries. Environmental Enteric Dysfunction (EED) is presumed to be the result of infection ...with one or more pathotypes and can affect intestinal health and childhood growth. We sought to investigate the association of
E. coli
pathotypes infection with biomarkers of EED and nutritional status among slum-dwelling malnourished children in Bangladesh. This study comprised a total of 1050 stunted and at risk of stunting children. TaqMan Array Card assays were used to determine the presence of
E. coli
pathotypes in feces. Prevalence of infection with EAEC was highest (68.8%) in this cohort of children, followed by EPEC (55.9%), ETEC (44%), Shigella/EIEC (19.4%) and STEC (3.2%). The levels of myeloperoxidase and calprotectin were significantly higher in EAEC (P=0.02 and P=0.04), EPEC (P=0.02 and P=0.03) and Shigella/EIEC (P=0.05 and P=0.02) positive participants while, only calprotectin was significantly higher in ETEC (P=0.01) positive participants. Reg1B was significantly higher in participants with EAEC (P=0.004) while, neopterin levels were significantly lower in ETEC (P=0.003) and Shigella/EIEC (P=0.003) positive cases. A significant positive relationship was observed between EAEC and fecal levels of Reg1B (β = 0.28; 95% CI = 0.12, 0.43; p-value<0.001). Besides, ETEC was found to be positively and significantly associated with the levels of calprotectin (β = 0.14; 95 percent CI = 0.01, 0.26; p-value=0.037) and negatively with neopterin (β = -0.16; 95% CI = -0.30, -0.02; p-value=0.021). On the other hand, infection with EPEC was found to be negatively associated with length-for-age (β = -0.12; 95% CI = -0.22, -0.03; p-value=0.011) and weight-for-age (β = -0.11; 95% CI = -0.22, -0.01; p-value=0.037). The study findings suggest that infection with certain
E. coli
pathotypes (EAEC and ETEC) influences gut health and EPEC is associated with linear growth and underweight in Bangladeshi children.
Studies revealed that silencing of low-density lipoprotein receptor-related protein-1 (LRP1) expression can cause inhibition of adipogenesis in animal model and contribute to reduced body size. But ...there is no study that has explored the association of LRP1 with body mass index (BMI) of human adults. Therefore, the aim of this study was to investigate the relationship of LRP1 with undernutrition.
A total of 270 Bangladeshi slum-dwelling adults were enrolled as case control design. Their socio-economic, demographic, anthropometric and biomedical data were collected. Plasma LRP1, C-reactive protein (CRP), alpha-1 acid glycoprotein (AGP) and ferritin levels were measured by ELISA, haemoglobin by HemoCue and zinc by atomic absorption spectrometry.
The median (IQR) values of plasma LRP1 were 1673.1 (1382.5-1886.2) ng/mL in healthy participants and 707.7 (588.6-839.9) ng/mL in undernourished participants, respectively. A strong positive correlation (r = 0.70, p < 0.05) between LRP1 and BMI was found. Multivariable logistic regression analysis revealed a positive association between low plasma LRP1 (Adj. OR = 0.98, CI = 0.98, 0.99 and p < 0.05) and undernutrition.
The study found that increased level of LRP1 is associated with increased BMI, whereas lower level is associated with low BMI.
Aflatoxins are fungal toxins produced by molds in contaminated foods and feeding derivatives. Analytical methods for detection and quantification of aflatoxins must be specific, sensitive, reliable, ...and simple to carry out. Various chromatographic, immunochemical, and spectroscopic methods are commonly used to quantify aflatoxins. Developing countries with high incidence of aflatoxin exposure have limited access to these types of analytical methods. This review systematically evaluated and underlined the advantages and limitations of all the existing analytical methods for detection of aflatoxins. In addition, more streamlined, user-friendly and in some instances, nondestructive methods are also discussed.
Growth in young children is controlled through the release of several hormonal signals, which are affected by diet, infection, and other exposures. Stunting is clearly a growth disorder, yet limited ...evidence exists documenting the association of different growth biomarkers with child stunting. This study explored the association between different growth biomarkers and stunting in Bangladeshi children. A quasi-experimental study was conducted among 50 stunted (length-for-age
-score (LAZ) < -2 SD) and 50 control (LAZ ≥ -2 SD) children, aged 12-18 months, residing in a Bangladeshi slum. The enrolled stunted children received an intervention package, which included food supplementation for three months, psychosocial stimulation for six months, and routine clinical care on community nutrition center at the study field site. The controls received routine clinical care only. All children were clinically screened over the study period. Length, weight, fasting blood and fecal biomarkers were measured. All biomarkers levels were similar in both groups except for oxyntomodulin at enrolment. Leptin (adjusted odds ratio, AOR: 4.0,
< 0.01), leptin-adiponectin ratio (AOR 5.07 × 10
,
< 0.01), insulin-like growth factor-1 (IGF-1) (AOR 1.02,
< 0.05), and gamma interferon (IFN-γ) (AOR 0.92,
< 0.05) levels were independently associated with stunting at enrolment. Serum leptin, leptin-adiponectin ratio, interleukin-6 (IL-6), IL-10, tumor necrosis factor-alpha (TNF-α), and fecal alpha-1-antitrypsin (AAT) levels increased significantly (
< 0.001), while IFN-γ levels significantly decreased among stunted children after six months of intervention. Leptin, leptin-adiponectin ratio, IGF-1, and IFN-γ are independently associated with stunting in Bangladeshi children. This trial was registered at clinicaltrials.gov as NCT02839148.
Children living in resource-limited settings often suffer from multiple micronutrient deficiencies (MMD). However, there lacks evidence on the correlates of MMD in young children. We investigated the ...role of diets, water, sanitation and hygiene practice, enteric infections, and impaired gut health on MMD in children at 24 months of age using data from the multi-country MAL-ED birth cohort study. Co-existence of more than one micronutrient deficiency (e.g., anemia, iron, zinc, or retinol deficiency) was considered as MMD. We characterized intestinal inflammation by fecal concentrations of myeloperoxidase (MPO) and neopterin (NEO) measured in the non-diarrheal stool samples. Bayesian network analysis was applied to investigate the factors associated with MMD. A total of 1093 children were included in this analysis. Overall, 47.6% of the children had MMD, with the highest prevalence in Pakistan (90.1%) and lowest in Brazil (6.3%). MMD was inversely associated with the female sex OR: 0.72, 95% CI: 0.54, 0.92. A greater risk of MMD was associated with lower vitamin C intake OR: 0.70, 95% CI: 0.48, 0.94 and increased fecal concentrations of MPO OR: 1.31, 95% CI: 1.08, 1.51. The study results imply the importance of effective strategies to ameliorate gut health and improve nutrient intake during the early years of life.
BackgroundEnvironmental enteric dysfunction (EED) is thought to occur from persistent intestinal inflammation. Studies also revealed the association of lipocalin-2 (LCN2) and low-density lipoprotein ...receptor-related protein-1 (LRP1) with intestinal inflammation. Therefore, we intended to explore the relationship of LCN2 and LRP1 with gut inflammation and biomarkers of EED in Bangladeshi malnourished children.MethodsA total of 222 children (length-for-age z-score (LAZ) <-1) aged 12–18 months were enrolled in this study in a cross-sectional manner. Among the participants, 115 were stunted (LAZ <-2) and 107 were at risk of being stunted (LAZ −1 to −2) children. Plasma and faecal biomarkers were measured using ELISA. Spearman’s rank correlation was done to see the correlation among LCN2, LRP1 and biological biomarkers.ResultsLCN2 correlates positively with myeloperoxidase (r=0.19, p=0.005), neopterin (r=0.20, p=0.004), calprotectin (r=0.3, p=0.0001), Reg1B (r=0.20, p=0.003) and EED score (r=0.20, p=0.003). Whereas, LRP1 correlates negatively with myeloperoxidase (r = −0.18, p=0.006), neopterin (r = −0.30, p=0.0001), alpha-1-antitrypsin (r = −0.18, p=0.006), Reg1B (r=−0.2, p=0.003) and EED score (r = −0.29, p=0.0001).ConclusionsOur findings imply that LCN2 might be a promising biomarker to predict gut inflammation and EED. Whereas, increased level of LRP1 may contribute to alleviating intestinal inflammation.
The global control of tuberculosis (TB) remains a great challenge from the standpoint of diagnosis, detection of drug resistance, and treatment. Major serodiagnostic limitations include low ...sensitivity and high cost in detecting TB. On the other hand, treatment measures are often hindered by low efficacies of commonly used drugs and resistance developed by the bacteria. Hence, there is a need to look into newer diagnostic and therapeutic targets. The proteome information available suggests that among the 3906 proteins in Mycobacterium tuberculosis H37Rv, about quarter remain classified as hypothetical uncharacterized set. This study involves a combination of a number of bioinformatics tools to analyze those hypothetical proteins (HPs). An entire set of 999 proteins was primarily screened for protein sequences having conserved domains with high confidence using a combination of the latest versions of protein family databases. Subsequently, 98 of such potential target proteins were extensively analyzed by means of physicochemical characteristics, protein-protein interaction, sub-cellular localization, structural similarity and functional classification. Next, we predicted antigenic proteins from the entire set and identified B and T cell epitopes of these proteins in M. tuberculosis H37Rv. We predicted the function of these HPs belong to various classes of proteins such as enzymes, transporters, receptors, structural proteins, transcription regulators and other proteins. However, the structural similarity prediction of the annotated proteins substantiated the functional classification of those proteins. Consequently, based on higher antigenicity score and sub-cellular localization, we choose two (NP_216420.1, NP_216903.1) of the antigenic proteins to exemplify B and T cell epitope prediction approach. Finally we found 15 epitopes those located partially or fully in the linear epitope region. We found 21 conformational epitopes by using Ellipro server as well. In silico methodology used in this study and the data thus generated for HPs of M. tuberculosis H37Rv may facilitate swift experimental identification of potential serodiagnostic and therapeutic targets for treatment and control.
•We analyzed hypothetical proteins of M. tuberculosis H37Rv strains.•An entire set of 999 hypothetical proteins was primarily screened from 3906 proteins.•98 of such potential target proteins were extensively analyzed for functional, structural and epitopic prediction.•We predicted the function of these hypothetical proteins belong to various classes.•Found 15 linear epitopes and 21 conformational epitopes from two of the antigenic proteins.
Dysregulations in the mammalian target of rapamycin (mTOR) pathway are associated with several human anomalies. We aimed to elucidate possible implications for potential aberrations in the mTOR ...pathway with childhood malnutrition. We analyzed the activity of phospho-mTORC1 and the expressions of several mTOR pathway genes, namely:
,
,
,
and
from peripheral blood mononuclear cells isolated from venous blood of children suffering from different forms of malnutrition and compared them with those from healthy children. Significant reduction in the phosphorylation of mTORC1 was noted, as well as a decrease in expression of
gene and increase in
gene expression were observed between malnourished children in comparison to the healthy children. The deregulation in the activity of the
and
gene was significantly associated with all forms of childhood malnutrition. Our findings provide key insights into possible down-modulation in the overall activity of the mTOR pathway in childhood malnutrition. Further studies focusing on the analysis of a multitude of components involved in the mTOR pathway both at the gene and protein expression levels are required for conclusive evidence for the aforementioned proposition.
Childhood undernutrition is a major public health concern that needs special attention to achieve 2025 global nutrition targets. Moderate acute malnutrition (MAM), manifest as wasting (low ...weight-for-height), affects 33 million children under 5, yet there are currently no global guidelines for its treatment. We recently performed a randomized-controlled clinical study of a microbiota-directed complementary food formulation (MDCF-2) in 12-18-month-old Bangladeshi children with MAM. The results revealed that MDCF-2, freshly prepared each day, produced a significantly greater improvement in ponderal growth than a standard ready-to-use supplementary food (RUSF), an effect that is associated with repair of the disrupted gut microbial community development that occurs in children with MAM. To test the generalizability of these results in acutely malnourished children at other sites, there is a pressing need for a packaged, shelf-stable, organoleptically-acceptable formulation that is bioequivalent to MDCF-2. This report describes the protocol for a clinical study to evaluate candidate formulations designed to meet these criteria.
A randomized single-blind study will be conducted in 8-12-month-old Bangladeshi children with MAM to compare the efficacy of alternative shelf-stable MDCF prototypes versus the current MDCF-2 formulation that is produced fresh each day. V4-16S rDNA amplicon and shotgun sequencing datasets will be generated from faecal DNA samples collected from each child enrolled in each group prior to, during, and after treatment to determine the abundances of MDCF-2-responsive bacterial taxa. Efficacy will be assessed by quantifying the change in representation of MDCF-2-responsive gut bacterial taxa after 4-weeks of treatment with freshly prepared MDCF-2 compared to their changes in abundance after treatment with the prototype MDCFs. Equivalence will be defined as the absence of a statistically significant difference, after 4-weeks of treatment, in the representation of faecal bacterial taxa associated with the response to MDCF-2 in participants receiving a test MDCF.
This trial aims to establish acceptability and equivalence with respect to microbiota repair, of scalable, shelf-stable formulations of MDCF-2 in 8-12-month-old Bangladeshi children with moderate acute malnutrition.
ClinicalTrials.gov (NCT05094024). The trial has been registered before starting enrolment on 23 October 2021.
Although parasitic infections lead to extracorporeal iron loss resulting in iron deficiency anaemia (IDA), data associating IDA with parasitic infections in the first two years of life are limited. ...We sought to evaluate the prevalence and severity of anaemia and IDA during this period and to investigate the association between intestinal parasitic infections and IDA.
Data was collected under MAL-ED study protocol in Bauniabadh slum of Dhaka, Bangladesh. The presence of parasites in stool was detected using wet preparation microscopy at 7, 15, and 24 months. Anaemia was defined as serum haemoglobin < 11 g/dL and IDA was defined by serum haemoglobin < 11 g/dL, serum ferritin < 12 g/L and soluble transferrin receptor > 8.3 mg/L. Logistic regression was done to quantify the relation between stool parasite and IDA separately on samples collected at 7, 15 and 24 months.
265 children were enrolled after birth and samples were collected at 7, 15 and 24 months. Anaemia was detected at 7, 15 and 24 months in 117 (48.8%), 106 (44.2%) and 67 (27.9%) cases whereas IDA was found in 15 (6.3%), 47 (19.6%) and 39 (16.3%) cases, respectively. Iron deficiency anaemia at 24 months was significantly associated with Ascaris lumbricoides infection (OR 3.76; 95 % CI, 1.08-13.11).
The prevalence of anaemia and IDA in slum dwelling children of Dhaka is high and Ascaris lumbricoides infection was found to have a strong association with IDA at 24 months of age.
PDF
