The maternal prenatal and offspring early-life gut microbiome of childhood asthma phenotypes

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  • Kathleen A. Lee-Sarwar
  • Yih Chieh Chen
  • Yuan Yao Chen
  • Anita L Kozyrskyj
  • Piush J. Mandhane
  • Stuart E. Turvey
  • Padmaja Subbarao
  • Hans Bisgaard
  • Jakob Stokholm
  • Søren J. Sørensen
  • Rachel S Kelly
  • Jessica Lasky-Su
  • Robert S. Zeiger
  • George T. O'Connor
  • Megan T. Sandel
  • Leonard B. Bacharier
  • Avraham Beigelman
  • Vincent J Carey
  • Benjamin J. Harshfield
  • Nancy Laranjo
  • Diane R. Gold
  • Scott T Weiss
  • Augusto A. Litonjua

Background: The infant fecal microbiome is known to impact subsequent asthma risk, but the environmental exposures impacting this association, the role of the maternal microbiome, and how the microbiome impacts different childhood asthma phenotypes are unknown. Methods: Our objective was to identify associations between features of the prenatal and early-life fecal microbiomes and child asthma phenotypes. We analyzed fecal 16 s rRNA microbiome profiling and fecal metabolomic profiling from stool samples collected from mothers during the third trimester of pregnancy (n = 120) and offspring at ages 3–6 months (n = 265), 1 (n = 436) and 3 years (n = 506) in a total of 657 mother–child pairs participating in the Vitamin D Antenatal Asthma Reduction Trial. We used clinical data from birth to age 6 years to characterize subjects with asthma as having early, transient or active asthma phenotypes. In addition to identifying specific genera that were robustly associated with asthma phenotypes in multiple covariate-adjusted models, we clustered subjects by their longitudinal microbiome composition and sought associations between fecal metabolites and relevant microbiome and clinical features. Results: Seven maternal and two infant fecal microbial taxa were robustly associated with at least one asthma phenotype, and a longitudinal gut microenvironment profile was associated with early asthma (Fisher exact test p =.03). Though mode of delivery was not directly associated with asthma, we found substantial evidence for a pathway whereby cesarean section reduces fecal Bacteroides and microbial sphingolipids, increasing susceptibility to early asthma. Conclusion: Overall, our results suggest that the early-life, including prenatal, fecal microbiome modifies risk of asthma, especially asthma with onset by age 3 years.

OriginalsprogEngelsk
TidsskriftAllergy: European Journal of Allergy and Clinical Immunology
Vol/bind78
Udgave nummer2
Sider (fra-til)418-428
ISSN0105-4538
DOI
StatusUdgivet - 2023

Bibliografisk note

Publisher Copyright:
© 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

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