Airway Microbial Community Turnover Differs by BPD Severity in Ventilated Preterm Infants

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.

Gut and Lung Microbiota in Preterm Infants: Immunological Modulation and Implication in Neonatal Outcomes

“…An interesting finding was the decrease in Firmicutes such as Lactobacillus in airway microbiome of infants with chorioamnionitis and in preterm infants who went on to develop lung disease (90). This could be an important finding for the association of BPD and chorioamnionitis.…”

“…Even if an association of "antibiotics induced dysbiosis" with BPD has been reported (90), apparently, there are no significant differences in the initial specimen between infants who received empiric antibiotic treatment and those who did not (89). The comparison of the airway microbiome of infants whose mothers received prenatal antibiotics and the infants of mothers who didn't show differences either (90).…”

“…Most studies described the presence of an airway microbiome early at birth dominated by Staphylococcus and Ureaplasma (87, 88) and a longitudinal change in the first weeks of life with increasing bacterial loads (34,35,89,90). Lal et al described the composition of the airway microbiota by analyzing the tracheal aspirates of newborns in the first day of life: a predominance of Firmicutes and Proteobacteria and the presence of Actinobacteria, Bacteroidetes, Tenericutes, Fusobacterium, Cyanobacteria, and Verrucomicrobia was observed, without differences between preterm and full term infants (89).…”

“…In a study on 94 preterm infants, Wagner et al found that those who developed severe BPD acquired less initial Staphylococcus and high Ureaplasma in the first days after birth (90). A possible explanation is that Ureaplasma intrauterine exposure downregulates the host response to acute LPS exposure in the preterm sheep model (91).…”

How to decrease bronchopulmonary dysplasia in your neonatal intensive care unit today and “tomorrow”

“…Interestingly, Lactobacillus was noted to be decreased at birth in infants with chorioamnionitis and those subsequently developing BPD 59 . Longitudinal alterations in ventilated preterm infants who eventually developed severe BPD revealed greater bacterial community turnover with age, with decreased acquisition of Staphylococcus in the first days after birth but increased presence of Ureaplasma 60 . The gut–lung axis could also impact on the immunology of the lung 61 .…”