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"id": "MGYS00005233",
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"accession": "MGYS00005233",
"bioproject": "PRJEB8463",
"samples-count": 537,
"is-private": false,
"last-update": "2020-02-10T16:25:51",
"secondary-accession": "ERP009546",
"centre-name": "Microbiology and Immunology",
"public-release-date": null,
"study-abstract": "Asthma is a multifactorial disease with an alarming increase in prevalence. Like several other immune-mediated diseases, asthma pathogenesis is being studied in the context of the hygiene hypothesis. Antibiotic-driven gut microbial shifts exclusively in the neonatal period increase airway inflammation in mice. We hypothesized that similar microbial changes in infant humans have a causal role in disease. To test this, 319 children enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) study were grouped into four phenotypes: atopic + wheeze (AW), atopic only, wheeze only, and controls, based on clinical data at 1 year. The fecal microbiome of 3-month and 1-year samples was evaluated by 16S rRNA gene sequencing (Illumina). A subset of samples in the AW and control groups was selected for qPCR, short chain fatty acid (SCFA) and urine metabolomic analyses. Finally, germ-free mice were inoculated with feces from one AW patient or with the same inoculum plus 4 bacterial strains found more commonly in controls. These mice were bred and the F1 generation was evaluated for OVA-induced airway inflammation. Results: At 3 months of age, 4 OTUs were identified by sequencing and qPCR as decreased in AW children, who also had a significantly increased risk of asthma diagnosis, based on their asthma predictive index at 3 years of age. These children exhibited decreased fecal acetate and propionate, and alterations in bacterial and host-derived metabolites mostly at 3 months of age. Finally, oral inoculation of mice with these 4 bacterial strains ameliorated airway inflammation. These results reveal taxonomic and functional gut microbial changes in infants associated with an increased risk of asthma. Decreased production of SCFA at this young age may lead to changes in energy harvest, bile acid and urobilinogen metabolism. This study suggests an associative and possibly causal role of early infancy shifts in gut microbiota with risk of asthma in human infants.",
"study-name": "CHILD gut microbiome and asthma",
"data-origination": "SUBMITTED"
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