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Nasopharyngeal Lactobacillus is associated with a reduced risk of childhood wheezing illnesses following acute respiratory syncytial virus infection in infancy - 06/11/18

Doi : 10.1016/j.jaci.2017.10.049 
Christian Rosas-Salazar, MD, MPH a, b, , Meghan H. Shilts, MHS, MS c, e, g, , Andrey Tovchigrechko, PhD f, Seth Schobel, PhD f, James D. Chappell, MD, PhD a, Emma K. Larkin, PhD b, c, Tebeb Gebretsadik, MPH b, d, Rebecca A. Halpin, MS e, Karen E. Nelson, PhD h, Martin L. Moore, PhD b, i, Larry J. Anderson, MD b, i, R. Stokes Peebles, MD b, c, Suman R. Das, PhD c, e, g, , Tina V. Hartert, MD, MPH b, c,
a Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tenn 
b Center for Asthma Research, Vanderbilt University School of Medicine, Nashville, Tenn 
c Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tenn 
d Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tenn 
e Infectious Disease Group, J. Craig Venter Institute, Rockville, Md 
f Bioinformatics Group, J. Craig Venter Institute, Rockville, Md 
g Infectious Disease Group, J. Craig Venter Institute, La Jolla, Calif 
h Genomic Medicine Group, J. Craig Venter Institute, La Jolla, Calif 
i Department of Pediatrics, Emory University School of Medicine, Atlanta, Ga 

Corresponding author: Tina V. Hartert, MD, MPH, Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, 6107 Medical Center East, Nashville, TN 37232.Division of Allergy, Pulmonary, and Critical Care MedicineDepartment of MedicineVanderbilt University School of Medicine6107 Medical Center EastNashvilleTN37232∗∗Suman R. Das, PhD, Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, 1211 21st Ave South, Nashville, TN 37232.Division of Infectious DiseasesDepartment of MedicineVanderbilt University School of Medicine1211 21st Ave SouthNashvilleTN37232

Abstract

Background

Early life acute respiratory infection (ARI) with respiratory syncytial virus (RSV) has been strongly associated with the development of childhood wheezing illnesses, but the pathways underlying this association are poorly understood.

Objective

To examine the role of the nasopharyngeal microbiome in the development of childhood wheezing illnesses following RSV ARI in infancy.

Methods

We conducted a nested cohort study of 118 previously healthy, term infants with confirmed RSV ARI by RT-PCR. We used next-generation sequencing of the V4 region of the 16S ribosomal RNA gene to characterize the nasopharyngeal microbiome during RSV ARI. Our main outcome of interest was 2-year subsequent wheeze.

Results

Of the 118 infants, 113 (95.8%) had 2-year outcome data. Of these, 46 (40.7%) had parental report of subsequent wheeze. There was no association between the overall taxonomic composition, diversity, and richness of the nasopharyngeal microbiome during RSV ARI with the development of subsequent wheeze. However, the nasopharyngeal detection and abundance of Lactobacillus was consistently higher in infants who did not develop this outcome. Lactobacillus also ranked first among the different genera in a model distinguishing infants with and without subsequent wheeze.

Conclusions

The nasopharyngeal detection and increased abundance of Lactobacillus during RSV ARI in infancy are associated with a reduced risk of childhood wheezing illnesses at age 2 years.

Le texte complet de cet article est disponible en PDF.

Key words : Microbiome, Lactobacillus, Staphylococcus, nasopharynx, respiratory syncytial virus, asthma, wheezing, 16S ribosomal RNA sequencing, infants

Abbreviations used : ARI, INSPIRE, IQR, OTU, rRNA, RSS, RSV


Plan


 This work was supported in whole or in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under award numbers U19AI095227, K24AI77930, HHSN272200900007 C, and U19AI110819; the Vanderbilt Institute for Clinical and Translational Research grant support (National Center for Advancing Translational Sciences, National Institutes of Health, Department of Health and Human Services, under award numbers UL1 TR000445 and U54RR24975); the Vanderbilt Faculty Research Scholars Program; and the Parker B. Francis Fellowship Program.
 Disclosure of potential conflict of interest: C. Rosas-Salazar has received a grant from the Francis Family Foundation. M. Shilts has received a grant and travel support from the National Institutes of Health. A. Tovchigrechko has received grants from J. Craig Venter Institute and the National Institutes of Health and is employed by and receives stock/stock options from MedImmune LLC. S. Schobel has received a grant from the J. Craig Venter Institute and the National Institutes of Health and is employed by the Henry M. Jackson Foundation. J. Chappell has received a grant from the National Institutes of Health. M. Moore has received a grant from the National Institutes of Health and is the founder of Meissa Vaccines. R. Peebles has received a grant from the National Institutes of Health. S. Das has received grants from the National Institutes of Health, Emergent Biosolution, Cargill, Abviro, and the Centers for Disease Control and is employed by Vanderbilt University Medical Center. T. Hartert has received grants from the National Institutes of Health and the Agency for Healthcare Research and Quality and is Associate Editor for the American Journal of Respiratory and Critical Care Medicine. The rest of the authors declare that they have no relevant conflicts of interest.


© 2018  American Academy of Allergy, Asthma & Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
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