Airway microbial community turnover differs by BPD severity in ventilated preterm infants

• Type of Material: Article
• Authors: Brandie D. Wagner, Colorado School of Public Health; Marci K. Sontag, Colorado School of Public Health; J. Kirk Harris, University of Colorado Anschutz Medical Campus; Joshua I. Miller, Colorado School of Public Health; Lindsey Morrow, Colorado School of Public Health; Charles E. Robertson, University of Colorado Anschutz Medical Campus; Mark Stephens, University of Colorado Anschutz Medical Campus; Brenda Poindexter, Emory University; Steven H. Abman, University of Colorado Anschutz Medical Campus; Peter M. Mourani, The Children's Hospital, Aurora
• Language: English
• Date: 2017-01-01
• Publisher: PLOS
• Publication Version: Final Published Version
• Copyright Statement: © 2017 Wagner et al
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0170120
• Title of Journal or Parent Work: PLoS ONE
• Volume: 12
• Issue: 1
• Start Page: e0170120
• End Page: e0170120
• Grant/Funding Information: This work was supported by: Gerber Foundation, http://www.gerberfoundation.org; National Institute of Health/National Center Research Resources K23RR021921; National Institute of Health National Heart Lung Blood Institute R01 HL085703; National Institute of Health/National Center for Advancing Translational Sciences Grant Number UL1 TR000154. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Keywords: Infant, Newborn; Lung; Birth Weight; Pregnancy; Staphylococcus; Premature Birth; Intubation, Intratracheal; RNA, Ribosomal, 16S; Male; Gestational Age; Trachea; Bronchopulmonary Dysplasia; Infant, Premature; Humans; Female; Respiration, Artificial
• Research Categories: Biology, Biostatistics; Health Sciences, Obstetrics and Gynecology; Health Sciences, Public Health

Abstract

Preterm birth exposes the developing lung to an environment with direct exposure to bacteria, often facilitated by endotracheal intubation. Despite evidence linking bacterial infections to the pathogenesis of bronchopulmonary dysplasia (BPD), systematic studies of airway microbiota are limited. The objective was to identify specific patterns of the early respiratory tract microbiome from tracheal aspirates of mechanically ventilated preterm infants that are associated with the development and severity of BPD. Infants with gestational age 34 weeks, and birth weight 500±1250g were prospectively enrolled. Mechanically ventilated infants had tracheal aspirate samples collected at enrollment, 7, 14, and 21 days of age. BPD was determined by modified NIH criteria with oxygen reduction tests; infants without BPD were excluded due to low numbers. Aspirates were processed for bacterial identification by 16S rRNA sequencing, and bacterial load by qPCR. Cross-sectional analysis was performed using 7 day samples and longitudinal analysis was performed from subjects with at least 2 aspirates. Microbiome analysis was performed on tracheal aspirates from 152 infants (51, 49, and 52 with mild, moderate, and severe BPD, respectively). Seventy-nine of the infants were included in the cross-sectional analysis and 94 in the longitudinal. Shannon Diversity, bacterial load, and relative abundance of individual taxa were not strongly associated with BPD status. Longitudinal analysis revealed that preterm infants who eventually developed severe BPD exhibited greater bacterial community turnover with age, acquired less Staphylococcus in the first days after birth, and had higher initial relative abundance of Ureaplasma. In conclusion, longitudinal changes in the airway microbial communities of mechanically ventilated preterm infants may be associated with BPD severity, whereas cross-sectional analysis of airway ecology at 7 days of age did not reveal an association with BPD severity. Further evaluation is necessary to determine whether the observed longitudinal changes are causal or in response to clinical management or other factors that lead to BPD.