JACI                                                             
Integrative Analysis of the Intestinal Metabolome of Childhood Asthma
https://doi.org/10.1016/j.jaci.2019.02.032
 Abstract:
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.
All Author:
Kathleen A.Lee-SarwarMD, MS12Rachel S.KellyPhD2JessicaLasky-SuScD2Robert S.ZeigerMD, PhD3George T.O’ConnorMD, MS4Megan T.SandelMD5Leonard B.BacharierMD6AvrahamBeigelmanMD, MSCI6NancyLaranjo2Diane R.GoldMD, MPH27Scott T.WeissMD, MS2 Augusto A.LitonjuaMD, MPH8