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Gut microbiota in children hospitalized with oedematous and non-oedematous severe acute malnutrition in Uganda

ABSTRACT: Gut microbiota in children hospitalized with severe acute malnutrition in Uganda

PROVIDER: PRJEB10006 | ENA |

REPOSITORIES: ENA

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Biomarkers of post-stabilization mortality in severe acute malnutrition

Project description:A high rate of early post-discharge mortality has been observed in children admitted with Severe Acute Malnutrition (SAM) in sub-Saharan Africa but the underlying causes and mechanisms are not well understood. We investigated whether there are biomarkers measured before discharge following medical stabilization and nutritional rehabilitation of children treated for SAM predict early post-discharge mortality and provide insights into causal mechanisms.

2018-08-02 | MSV000082745 | MassIVE

Malnutrition-associated hepatic steatosis and ATP depletion is caused by peroxisomal and mitochondrial dysfunction and rescued by fenofibrate

Project description:Severe malnutrition in young children is associated with signs of hepatic dysfunction such as steatosis and hypoalbuminemia, but its etiology is unknown. To investigate the underlying mechanisms of hepatic dysfunction we used a rat model of malnutrition by placing weanling rats on a low protein or control diet (5% or 20% of calories from protein, respectively) for four weeks. Low protein diet-fed rats developed hypoalbuminemia and severe hepatic steatosis, consistent with the human phenotype. Hepatic peroxisome content was decreased and metabolomic analysis indicated impaired peroxisomal function. Loss of peroxisomes was followed by accumulation of dysfunctional mitochondria and decreased hepatic ATP levels. Fenofibrate supplementation restored hepatic peroxisome abundance and increased mitochondrial fatty acid β-oxidation capacity, resulting in reduced steatosis and normalization of ATP and plasma albumin levels. These findings provide important insight into the metabolic disturbances associated with malnutrition and have potentially profound clinical consequences with respect to the management of malnourished children worldwide.

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Gut Microbiota in Children Hospitalized with Oedematous and Non-Oedematous Severe Acute Malnutrition in Uganda.

Project description: Not available

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Edematous Severe Acute Malnutrition is Characterized by Hypomethylation of DNA

Project description:A slower transmethylation of one-carbon substrates in the edematous form of severe acute malnutrition (ESAM) suggests that downstream aberrations in DNA methylation could drive differences in acute pathogenesis between ESAM and non-edematous malnutrition (NESAM). Here, we integrate genome-wide assessments of DNA methylation with corresponding gene expression profiles and sequence variation to show that relative to NESAM, acute ESAM is characterized by significant hypomethylation at 99% of differentially methylated loci in two SAM cohorts, whereas recovered adults show no significant differences in methylation. Hypomethylated loci correlate with both up- and down-regulation of proximal genes, which are associated with the clinical sub-phenotypes of kwashiorkor and enriched for GWAS hits linked to over-nutrition, including fatty liver and diabetes. Methylation at these loci also appears to be influenced by nearby genetic variation in a manner that varies with nutritional status. Our findings implicate epigenetic and genetic variation in ESAM pathophysiology and support methyl-group supplementation in ESAM management.

2019-10-11 | GSE112893 | GEO

Molecular Distance to Health Transcriptional Score and Disease Severity in Children Hospitalized with Community-Acquired Pneumonia

Project description:Community-acquired pneumonia (CAP) is a leading cause of hospitalization and mortality in children. Diagnosis remains challenging and there are no reliable tools to objectively classify patients according to disease severity or predict clinical outcomes. Molecular distance to health (MDTH) is a genomic score that measures the global perturbation of the transcriptional profile that may help classify patients by disease severity. We assessed the value of MDTH to assess disease severity in children hospitalized with CAP.

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Edematous Severe Acute Malnutrition is Characterized by Hypomethylation of DNA

Project description:Edematous Severe Acute Malnutrition is Characterized by Hypomethylation of DNA

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Nasal DNA methylation differentiates severe from non-severe asthma in African-American (AA) children

Project description:Background: Asthma is highly heterogeneous and severity evaluation is key to asthma management. DNA methylation (DNAm) contributes to asthma pathogenesis. This study aimed to identify nasal epithelial DNAm differences between severe and non-severe asthmatic children and evaluate the impact of environmental exposures. Methods: Thirty-three non-severe and 22 severe asthmatic African-American children were included in an epigenome-wide association study. Genome-wide nasal epithelial DNAm and gene expression were measured. CpG sites associated with asthma severity and environmental exposures and predictive of severe asthma were identified. DNAm was correlated with gene expression. Enrichment for transcription factor (TF) binding sites or histone modifications surrounding DNAm differences were determined. Results: We identified 816 differentially methylated CpG positions (DMPs) and 10 differentially methylated regions (DMRs) associated with asthma severity. Three DMPs exhibited discriminatory ability for severe asthma. Intriguingly, six DMPs were simultaneously associated with asthma, allergic asthma, total IgE, environmental IgE, and FeNO in an independent cohort of children. 27 DMPs were associated with traffic-related air pollution or secondhand smoke. DNAm at 22 DMPs were altered by diesel particles or allergen in human bronchial epithelial cells. DNAm levels at 39 DMPs were correlated with mRNA expression. Proximal to 816 DMPs, three histone marks and several TFs involved in asthma pathogenesis were enriched. Conclusions: Significant differences in nasal epithelial DNAm were observed between non-severe and severe asthma in African-American children, a subset of which may be useful to predict disease severity. These CpG sites are subject to the influences of environmental exposures and may regulate gene expression.

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Host transcription profile in nasal epithelium and blood of hospitalized children under two years old with Respiratory Syncitial Virus infection [nasopharyngeal swaps]

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A monocyte/dendritic cell molecular signature of SARS-CoV2-related multisystem inflammatory syndrome in children (MIS-C) with severe myocarditis [Bulk RNAseq]

Project description:SARS-CoV-2 infection in children is generally milder than in adults, yet a proportion of cases result in hyperinflammatory conditions often including myocarditis. To better understand these cases, we applied a multi-parametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. The most severe forms of MIS-C (multisystem inflammatory syndrome in children related to SARS-CoV-2), that resulted in myocarditis, were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomic analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of myocarditis, characterized by sustained NF-kB activity, associated with decreased gene expression of NF-kB inhibitors and TNF-a signaling . We also found a weak response to type-I and type-II interferons, hyperinflammation and response to oxidative stress related to increased HIF-1a and VEGF signaling. These results provide potential for a better understanding of disease pathophysiology.

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