Integrative Analysis of the Intestinal Metabolome of Childhood Asthma
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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.
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Gut dysbiosis is common in patients with asthma, and dysregulation of specific bacterial taxa is a powerful predictor of high asthma risk.
“Some studies have indicated that gut dysbiosis is common in patients with asthma, and dysregulation of specific bacterial taxa seems to be one of the powerful predictors of high asthma risk (17,(35)(36)(37).”
From The Role of Gut Microbiota in Lung Cancer: From Carcinogenesis to Immunotherapy (2021) · cites this paper as [36]
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- Authors
- Lee-Sarwar, K. A., Kelly, R. S., Lasky-Su, J., Zeiger, R. S., O'Connor, G. T., Sandel, M. T., Bacharier, L. B., Beigelman, A., Laranjo, N., Gold, D. R., Weiss, S. T., & Litonjua, A. A.
- Affiliations
- Brigham and Women's Hospital (US)
- Kaiser Permanente (US)
- Boston Medical Center (US)
- St. Louis Children's Hospital (US)
- University of Rochester Medicine (US)
- Corresponding author
- Litonjua, Augusto A.
- ORCID
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2019-08
- Volume
- 144
- Issue
- 2
- Pages
- 442-454
- ISSN
- 0091-6749 (ISSN-L)
- PMC
- PMC6688902
- OpenAlex
- W2912030764
- Cited by
- 99
- References
- 56
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 12 · 2023: 17 · 2022: 21 · 2021: 20 · 2020: 7 · 2019: 5
- FWCI
- 9.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Allergy and Clinical Immunology (acceptedVersion, other-oa)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute
- National Institute of Allergy and Infectious Diseases
- Topics
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- childhood asthma, intestinal metabolome, fecal metabolites, polyunsaturated fatty acids, exclusive breastfeeding, Christensenellaceae, plasma metabolome, gut microbiota, vitamin D, asthma pathophysiology
- MeSH terms
- Gastrointestinal Microbiome, Asthma, Bacteria, Child, Preschool, Feces, Female, Humans, Infant, Infant, Newborn, Male, RNA, Bacterial, RNA, Ribosomal, 16S, Metabolome
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