Integrative Analysis of the Intestinal Metabolome of Childhood Asthma

Details

• Alternative Title:
  J Allergy Clin Immunol
• Personal Author:
  Lee-Sarwar, Kathleen A. ; Kelly, Rachel S. ; Lasky-Su, Jessica ; Zeiger, Robert S. ; O’Connor, George T. ; Sandel, Megan T. ; Bacharier, Leonard B. ; Beigelman, Avraham ; Laranjo, Nancy ; Gold, Diane R. ; Weiss, Scott T. ; Litonjua, Augusto A.
• 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.
  
  
• Subjects:
  Article Asthma Bacteria Breastfeeding Child, Preschool Christensenellaceae Diet Feces Female Gastrointestinal Microbiome Humans Infant Infant, Newborn Male Metabolome Microbiome Nutrition RNA, Bacterial RNA, Ribosomal, 16S Vitamin E

  More +
• Source:
  J Allergy Clin Immunol. 144(2):442-454
• Pubmed ID:
  30914378
• Pubmed Central ID:
  PMC6688902
• Document Type:
  Journal Article
• Funding:
  U01 HL091528/HL/NHLBI NIH HHS/United States ; R01 HL141826/HL/NHLBI NIH HHS/United States ; R01 HL108818/HL/NHLBI NIH HHS/United States ; T32 AI007306/AI/NIAID NIH HHS/United States ; UG3 OD023268/CD/ODCDC CDC HHS/United States ; UG3 OD023268/OD/NIH HHS/United States ; R01 HL091528/HL/NHLBI NIH HHS/United States ; R01 HL123915/HL/NHLBI NIH HHS/United States ; UH3 OD023268/OD/NIH HHS/United States ; K01 HL146980/HL/NHLBI NIH HHS/United States
• Volume:
  144
• Issue:
  2
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:ca0eeabf0a494e4749ae08b32fb53c645445745ede13bc62b38014b0e5e51a27
• Download URL:
  https://stacks.cdc.gov/view/cdc/80609/cdc_80609_DS1.pdf
• File Type:
  [PDF - 1.84 MB ]