Format

Send to

Choose Destination
J Allergy Clin Immunol. 2019 Aug;144(2):442-454. doi: 10.1016/j.jaci.2019.02.032. Epub 2019 Mar 23.

Integrative analysis of the intestinal metabolome of childhood asthma.

Author information

1
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass. Electronic address: klee-sarwar@partners.org.
2
Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.
3
Departments of Allergy and Research and Evaluation, Kaiser Permanente Southern California, San Diego and Pasadena, Calif.
4
Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, Mass.
5
Department of Pediatrics, Boston Medical Center, Boston, Mass.
6
Division of Pediatric Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Washington University School of Medicine, St Louis, and St Louis Children's Hospital, St Louis, Mo.
7
Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass; Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Mass.
8
Division of Pediatric Pulmonary Medicine, Golisano Children's Hospital at Strong, University of Rochester Medical Center, Rochester, NY. Electronic address: augusto_litonjua@urmc.rochester.edu.

Abstract

BACKGROUND:

The intestinal metabolome reflects the biological consequences of diverse exposures and might provide insight into asthma pathophysiology.

OBJECTIVE:

We sought 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.

METHODS:

Metabolomic profiling was performed by using mass spectrometry on fecal samples collected from 361 three-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": the intestinal microbiome as measured by using 16S rRNA sequencing, the plasma metabolome as measured by using mass spectrometry, and diet as measured by using 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 β = -6.3; 95% CI, -11.3 to -1.4; P = .01) and other lipids. Asthma-associated intestinal metabolites were significant mediators of the inverse relationship between exclusive breast-feeding for the first 4 months of life and asthma (P for indirect association = .04) and the positive association between a diet rich in meats and asthma (P = .03). Specific intestinal bacterial taxa, including the family Christensenellaceae, and plasma metabolites, including γ-tocopherol/β-tocopherol, were positively associated with asthma and 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.

KEYWORDS:

Asthma; Christensenellaceae; breast-feeding; diet; metabolome; microbiome; nutrition; vitamin E

PMID:
30914378
PMCID:
PMC6688902
[Available on 2020-08-01]
DOI:
10.1016/j.jaci.2019.02.032

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center