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Association of the gut microbiome and metabolome with wheeze frequency in childhood asthma - 04/08/22

Doi : 10.1016/j.jaci.2022.02.005 
Kathleen Lee-Sarwar, MD, MS a, b, Sandra Dedrick, PhD a, c, Babak Momeni, PhD c, Rachel S. Kelly, PhD a, Robert S. Zeiger, MD, PhD d, George T. O’Connor, MD, MS e, Megan T. Sandel, MD f, Leonard B. Bacharier, MD g, Avraham Beigelman, MD, MSCI h, i, Nancy Laranjo a, Diane R. Gold, MD, MPH a, j, Jessica Lasky-Su, ScD a, Augusto A. Litonjua, MD, MPH k, Yang-Yu Liu, PhD a, , Scott T. Weiss, MD, MS a,
a Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass 
b Division of Rheumatology, Immunology, and Allergy, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass 
c Department of Biology, Boston College, Chestnut Hill, Mass 
d Departments of Clinical Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, Calif 
e Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, Mass 
f Department of Pediatrics, Boston Medical Center, Boston, Mass 
g Department of Pediatric Allergy, Immunology, and Pulmonary, Vanderbilt Children’s Hospital, Vanderbilt University Medical Center, Nashville, Tenn 
h Division of Pediatric Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Washington University School of Medicine, and St Louis Children’s Hospital, St Louis, Mo 
i Kipper Institute of Allergy and Immunology, Schneider Children’s Medical Center of Israel, Tel Aviv University, Tel Aviv, Israel 
j Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Mass 
k Division of Pediatric Pulmonary Medicine, Golisano Children’s Hospital at Strong, University of Rochester Medical Center, Rochester, NY 

Corresponding author: Yang-Yu Liu, PhD, or Scott T. Weiss, MD, MS, Channing Division of Network Medicine, 181 Longwood Ave, Boston, MA 02115.Channing Division of Network Medicine181 Longwood AveBostonMA02115

Abstract

Background

While the microbiome has an established role in asthma development, less is known about its contribution to morbidity in children with asthma.

Objective

In this ancillary study of the Vitamin D Antenatal Asthma Reduction Trial (VDAART), we analyzed the gut microbiome and metabolome of wheeze frequency in children with asthma.

Methods

Bacterial 16S ribosomal RNA microbiome and untargeted metabolomic profiling were performed on fecal samples collected from 3-year-old children with parent-reported physician-diagnosed asthma. We analyzed wheeze frequency by calculating the proportion of quarterly questionnaires administered between ages 3 and 5 years in which parents reported the child had wheezed (wheeze proportion). Taxa and metabolites associated with wheeze were analyzed by identifying log fold changes with respect to wheeze frequency and correlation/linear regression analyses, respectively. Microbe–metabolite and microbe–microbe correlation networks were compared between subjects with high and low wheeze proportion.

Results

Specific taxa, including the genus Veillonella and histidine pathway metabolites, were enriched in subjects with high wheeze proportion. Among wheeze-associated taxa, Veillonella and Oscillospiraceae UCG-005, which was inversely associated with wheeze, were correlated with the greatest number of fecal metabolites. Microbial networks were similar between subjects with low versus high wheeze frequency.

Conclusion

Gut microbiome features are associated with wheeze frequency in children with asthma, suggesting an impact of the gut microbiome on morbidity in childhood asthma.

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Graphical abstract




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Key words : Microbiome, metabolomics, asthma, wheeze

Abbreviations used : AA, CI, FDR, HMDB, ICS, PERMANOVA, RA, rRNA, SparCC, UCG, VDAART


Mappa


 The first 2 authors contributed equally to this article, and both should be considered first author. S.D. is currently affiliated with Excerpta Medica, Amsterdam, The Netherlands.
 The Vitamin D Antenatal Asthma Reduction Trial (VDAART) was funded by U01HL091528 from the National Heart, Lung, and Blood Institute. Additional funding came from National Institutes of Health grants R01HL108818, R01HL123915, R01HL141826, and K08 HL148178, and ECHO grant OD023268.
 Disclosure of potential conflict of interest: A. A. Litonjua has received author royalties from UpToDate Inc. S. T. Weiss has received royalties from UpToDate Inc. L. B. Bacharier participates on the Data Safety Monitoring Board of DBV Technologies. A. Beigelman holds stock from DBV Technologies, is a consultant for AstraZeneca and Raffa, and has received speaking honoraria from AstraZeneca, Novartis, and Sanofi. R. S. Zeiger is a consultant for AstraZeneca, DBV Technologies, Genentech Inc, GlaxoSmithKline, Merck & Co, Novartis, Quest Diagnostics, Regeneron/Sanofi, and Teva Pharmaceuticals, and has received research support from ALK Pharmaceuticals, AstraZeneca, Genentech Inc, GlaxoSmithKline, the National Heart, Lung, and Blood Institute, MedImmune, Merck, and Teva Pharmaceuticals. J. Lasky-Su is a consultant to Metabolon Inc. G. T. O’Connor is a coinvestigator on a grant from Janssen Pharmaceuticals to Boston University that funds a study of the pathogenesis of chronic obstructive pulmonary disease. The rest of the authors declare that they have no relevant conflicts of interest.


© 2022  American Academy of Allergy, Asthma & Immunology. Pubblicato da Elsevier Masson SAS. Tutti i diritti riservati.
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