Date Published: January 27, 2017
Publisher: Public Library of Science
Author(s): Brandie D. Wagner, Marci K. Sontag, J. Kirk Harris, Joshua I. Miller, Lindsey Morrow, Charles E. Robertson, Mark Stephens, Brenda B. Poindexter, Steven H. Abman, Peter M. Mourani, Heinz Fehrenbach.
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.
Infants born preterm are at high risk for developing bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurity. BPD is characterized by prolonged need for oxygen therapy, frequent pulmonary infections requiring hospitalizations, asthma, exercise intolerance, and pulmonary hypertension [1, 2]. BPD results from the adverse effects of early exposure of the lung to the extrauterine environment, as well as, the need for supportive interventions such as mechanical ventilation and high levels of oxygen delivery [3–5]. These stimuli can lead to inflammation of the immature lung that disrupt normal lung development . Thus, further understanding of risk factors and mechanisms that promote inflammation and impair lung development after preterm birth is critical to instituting better prevention and treatment strategies.
We evaluated the lower airway microbiome in preterm infants requiring mechanical ventilation in both cross-sectional and longitudinal analyses to determine if there is a relationship between the early respiratory tract microbiome and BPD severity. In a cross-sectional evaluation at 7 days of age there was no evidence that bacterial communities were associated with later BPD severity. Bacterial load and Shannon diversity of airway communities did not reveal a striking pattern that was strongly linked to BPD severity either on its own or in conjunction with clinical factors. Investigation of airway microbial communities over time by several measures indicated that there may be temporal trends that are associated with BPD severity. Although, a particular organism may not necessarily be associated with BPD severity, shifts in the community of airway organisms were observed more often in preterm infants who eventually developed severe BPD. Specifically, infants who developed more severe BPD exhibited greater bacterial community turnover with increasing time from birth, acquired less Staphylococcus in the first days after birth, and had higher initial RA of Ureaplasma.