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Integrative Analysis of the Intestinal Metabolome of Childhood Asthma
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March 23 2019
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Source: J Allergy Clin Immunol. 144(2):442-454
[PDF-1.84 MB]
Details:
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Alternative Title:J Allergy Clin Immunol
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Personal Author:
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Description:Background:
The intestinal metabolome reflects biological consequences of diverse exposures and may provide insight into asthma pathophysiology.
Objective:
To perform an untargeted integrative analysis of the intestinal metabolome of childhood asthma in this ancillary study of the Vitamin D Antenatal Asthma Reduction Trial (VDAART).
Methods:
Metabolomic profiling was performed by mass spectrometry on fecal samples collected from 361 3-year-old subjects. Adjusted logistic regression analyses identified metabolites and modules of highly correlated metabolites associated with asthma diagnosis by age 3 years. Sparse canonical correlation analysis identified associations relevant to asthma between the intestinal metabolome and other “omics”: intestinal microbiome as measured by 16S rRNA sequencing, plasma metabolome as measured by mass spectrometry, and diet as measured by food frequency questionnaires.
Results:
Several intestinal metabolites were associated with asthma at age 3 years, including inverse associations between asthma and polyunsaturated fatty acids (adjusted logistic regression beta = −6.3, 95% CI −11.3, −1.4, p = 0.01) and other lipids. Asthma-associated intestinal metabolites were significant mediators of the inverse relationship between exclusive breastfeeding for the first 4 months of life and asthma (p for indirect association = 0.04), and the positive association between a diet rich in meats and asthma (p = 0.03). Specific intestinal bacterial taxa, including family Christensenellaceae, and plasma metabolites, including gamma-tocopherol/beta-tocopherol, were positively associated with asthma and with asthma-associated intestinal metabolites.
Conclusion:
Integrative analyses revealed significant interrelationships between the intestinal metabolome and the intestinal microbiome, plasma metabolome, and diet in association with childhood asthma. These findings require replication in future studies.
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Source:
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Pubmed ID:30914378
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Pubmed Central ID:PMC6688902
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Document Type:
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Funding:
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Volume:144
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Issue:2
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