Pathogenesis, Clinical and Biological Predictors of Growth in Environmental enteric dysfunction (EED): An Infant Birth Inception Cohort
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA663330 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Environmental enteric dysfunction (EED) is a major impediment to the Sustainable Development Goals of improved childhood survival and healthy growth worldwide. Few studies have directly examined the affected intestine, limiting the development of effective interventions. The Study of Environmental Enteropathy and Malnutrition (SEEM, Pakistan) followed 416 at-risk children prospectively from birth to 24 months of age in a rural district of Pakistan with a high prevalence of undernutrition. The duodenal genome-wide methylome and transcriptome was determined in 52 undernourished SEEM participants refractory to nutritional interventions and 42 North American healthy controls and celiac disease patients. Biomarkers were measured at 9 months and tested for association with growth at 24 months in training (n=166) and validation (n=84) groups within SEEM.
2021-05-19 | GSE157914 | GEO
Project description:Background: Environmental enteric dysfunction (EED) is a major impediment to the Sustainable Development Goals of improved childhood survival and healthy growth worldwide. Few studies have longitudinally and endoscopically examined EED in children, limiting the development of effective interventions. Methods: The Study of Environmental Enteropathy and Malnutrition (SEEM, Pakistan) followed 416 at-risk children prospectively from birth to 24 months of age in a rural district of Pakistan with a high prevalence of undernutrition. The duodenal genome-wide methylome and transcriptome was determined in 52 undernourished SEEM participants refractory to nutritional interventions and 42 North American pediatric controls and coeliac disease patients. Biomarkers were measured at 9 months and tested for association with growth at 24 months. Findings: The EED core transcriptome exhibited suppression of genes regulating antioxidant and detoxification functions and lipid metabolism, and induction of genes encoding anti-microbial responses, interferon signaling, and lymphocyte activation. Relative to coeliac disease, suppression of genes encoding antioxidant and detoxification functions and induction of anti-microbial responses were EED-specific. At the epigenetic level, EED was notable for hyper-methylation of genes involved in epithelial metabolism and barrier function, and hypo-methylation of genes involved in immune responses and cell proliferation. Duodenal co-expression modules revealed associations between genes regulating lymphocyte proliferation and epithelial metabolism with histologic severity, faecal energy loss, and wasting (weight-for-height Z<-2.0), with data supporting epigenetic regulation. Immune response genes were attenuated by Giardia colonization. After accounting for growth at study entry, IGF-1 and ferritin predicted linear growth, whereas leptin correlated with expression of epithelial carbohydrate metabolism and stem cell renewal genes, and weight gain. Interpretation: Data suggest immune and metabolic pathways which may inform more effective interventions to improve outcomes in EED. A validated model may be used to identify infants at greatest risk for future poor growth.
2020-10-15 | GSE159495 | GEO
Project description:Environmental enteric dysfunction (EED), a chronic diffuse inflammation of the small intestine, is associated with stunting in children in the developing world. The pathobiology of EED is poorly understood because of the lack of a method to elucidate the host response. This study utilized a novel microarray method to interrogate the host transcriptome in feces in Malawian children with EED. Our data showed that the children studied had a range of %L values, consistent a spectrum of EED from normal to severe. We identified 12 transcripts associated with the severity of EED, including chemokines that stimulate T-cell proliferation, Fc fragments of multiple immunoglobulin families, interferon-induced proteins, activators of neutrophils and B-cells, and mediators that dampen cellular responses to hormones. EED associated transcripts mapped to pathways related to cell adhesion, and responses to a broad spectrum of viral, bacterial and parasitic microbes and enhanced phagocytosis. Several mucins, regulatory factors and protein kinases associated with the maintenance of the mucous layer were expressed less in children with EED than normal children. In conclusion, EED represents the focused activation of elements of the immune system and is associated with widespread intestinal barrier disruption. The differentially expressed transcripts may be explored as potential biomarkers. In 259 children, EED was measured by lactulose permeability (%L) in the small intestine. After isolating low copy numbers of mRNA, the transcriptome was reliably and reproducibly profiled. mRNA copy number was correlated with %L using analyses of covariance. The transcripts identified were mapped to biological pathways and processes.
2016-03-01 | E-GEOD-74681 | biostudies-arrayexpress
Project description:16S rRNA gene sequencing of the extremelly birth weight infant gut
| PRJEB17882 | ENA
Project description:Environmental enteric dysfunction (EED), a chronic diffuse inflammation of the small intestine, is associated with stunting in children in the developing world. The pathobiology of EED is poorly understood because of the lack of a method to elucidate the host response. This study utilized a novel microarray method to interrogate the host transcriptome in feces in Malawian children with EED. Our data showed that the children studied had a range of %L values, consistent a spectrum of EED from normal to severe. We identified 12 transcripts associated with the severity of EED, including chemokines that stimulate T-cell proliferation, Fc fragments of multiple immunoglobulin families, interferon-induced proteins, activators of neutrophils and B-cells, and mediators that dampen cellular responses to hormones. EED associated transcripts mapped to pathways related to cell adhesion, and responses to a broad spectrum of viral, bacterial and parasitic microbes and enhanced phagocytosis. Several mucins, regulatory factors and protein kinases associated with the maintenance of the mucous layer were expressed less in children with EED than normal children. In conclusion, EED represents the focused activation of elements of the immune system and is associated with widespread intestinal barrier disruption. The differentially expressed transcripts may be explored as potential biomarkers.
2016-03-01 | GSE74681 | GEO
Project description:Environmental enteric dysfunction (EED), a chronic diffuse inflammation of the small intestine, is associated with stunting in children in the developing world. The pathobiology of EED is poorly understood because of the lack of a method to elucidate the host response. This study utilized a novel microarray method to interrogate the host transcriptome in feces in Malawian children with EED. Our data showed that the children studied had a range of %L values, consistent a spectrum of EED from normal to severe. We identified 12 transcripts associated with the severity of EED, including chemokines that stimulate T-cell proliferation, Fc fragments of multiple immunoglobulin families, interferon-induced proteins, activators of neutrophils and B-cells, and mediators that dampen cellular responses to hormones. EED associated transcripts mapped to pathways related to cell adhesion, and responses to a broad spectrum of viral, bacterial and parasitic microbes and enhanced phagocytosis. Several mucins, regulatory factors and protein kinases associated with the maintenance of the mucous layer were expressed less in children with EED than normal children. In conclusion, EED represents the focused activation of elements of the immune system and is associated with widespread intestinal barrier disruption. The differentially expressed transcripts may be explored as potential biomarkers.
2016-03-01 | GSE75653 | GEO
Project description:Environmental enteric dysfunction (EED), a chronic diffuse inflammation of the small intestine, is associated with stunting in children in the developing world. The pathobiology of EED is poorly understood because of the lack of a method to elucidate the host response. This study utilized a novel microarray method to interrogate the host transcriptome in feces in Malawian children with EED. Our data showed that the children studied had a range of %L values, consistent a spectrum of EED from normal to severe. We identified 12 transcripts associated with the severity of EED, including chemokines that stimulate T-cell proliferation, Fc fragments of multiple immunoglobulin families, interferon-induced proteins, activators of neutrophils and B-cells, and mediators that dampen cellular responses to hormones. EED associated transcripts mapped to pathways related to cell adhesion, and responses to a broad spectrum of viral, bacterial and parasitic microbes and enhanced phagocytosis. Several mucins, regulatory factors and protein kinases associated with the maintenance of the mucous layer were expressed less in children with EED than normal children. In conclusion, EED represents the focused activation of elements of the immune system and is associated with widespread intestinal barrier disruption. The differentially expressed transcripts may be explored as potential biomarkers. This study was carried out, firstly using Affymetrix Human Transcriptome Array 2.0 (HTA2.0, data have already been deposited in the GEO database: GSE74681) to profile the transcriptome of the host stool RNAs in 259 subjects, and then using droplet digital PCR (ddPCR) assays to validate the microarray data in terms of signal correlation. The ddPCR assay was done for a total of 60 genes in 25 - 236 (median 67) of the 258 RNA samples per RNA availability (1 of 259 samples [stool_080B] was not used for any of the 60 assays due to lack of availability). The data of the first 42 assays (genes) in the matrix sheets were used in Figure 4 for signal correlation analysis, and the data of the rest 18 assays (genes) were used in Table 4 for validation of 18 significant genes identified in biological pathway analysis.
2016-03-01 | E-GEOD-75653 | biostudies-arrayexpress
Project description:Epigenetic regulatory mechanisms are underappreciated but critical for enteric nervous system (ENS) development and maintenance. We discovered that fetal loss of the epigenetic regulator Bap1 in the ENS lineage causes severe postnatal bowel dysfunction and early death in Tyrosinase-Cre; Bap1fl/fl mice. Bap1-depleted ENS appears normal in neonates, however, by postnatal day 15 (P15), Bap1-deficient enteric neurons are largely absent from the small and large intestine of Tyrosinase-Cre; Bap1fl/fl mice. Bowel motility becomes markedly abnormal with disproportionate loss of cholinergic neurons. Single-cell RNA sequencing at P5 shows that fetal Bap1 loss inTyrosinase-Cre; Bap1fl/fl mice markedly alters the composition and relative proportions of enteric neuron subtypes. In contrast, postnatal deletion of Bap1 did not cause enteric neuron loss or impaired bowel motility. These findings suggest that BAP1 is critical for postnatal enteric neuron differentiation and for enteric neuron survival.
2024-04-01 | GSE242001 | GEO
Project description:16S rRNA gene sequencing of Extremelly low birth weight infant
| PRJEB17783 | ENA
Project description:16S rRNA gene sequencing in extremely low birth weight infant gut
| PRJEB17754 | ENA