Abstract
Background Chronic lung disease of prematurity (CLD), also called bronchopulmonary dysplasia, is a major consequence of preterm birth, but the role of the microbiome in its development remains unclear. Therefore, we assessed the progression of the bacterial community in ventilated preterm infants over time in the upper and lower airways, and assessed the gut–lung axis by comparing bacterial communities in the upper and lower airways with stool findings. Finally, we assessed whether the bacterial communities were associated with lung inflammation to suggest dysbiosis.
Methods We serially sampled multiple anatomical sites including the upper airway (nasopharyngeal aspirates), lower airways (tracheal aspirate fluid and bronchoalveolar lavage fluid) and the gut (stool) of ventilated preterm-born infants. Bacterial DNA load was measured in all samples and sequenced using the V3–V4 region of the 16S rRNA gene.
Results From 1102 (539 nasopharyngeal aspirates, 276 tracheal aspirate fluid, 89 bronchoalveolar lavage, 198 stool) samples from 55 preterm infants, 352 (32%) amplified suitably for 16S RNA gene sequencing. Bacterial load was low at birth and quickly increased with time, but was associated with predominant operational taxonomic units (OTUs) in all sample types. There was dissimilarity in bacterial communities between the upper and lower airways and the gut, with a separate dysbiotic inflammatory process occurring in the lower airways of infants. Individual OTUs were associated with increased inflammatory markers.
Conclusions Taken together, these findings suggest that targeted treatment of the predominant organisms, including those not routinely treated, such as Ureaplasma spp., may decrease the development of CLD in preterm-born infants.
Abstract
Respiratory colonisation was acquired after birth and associated with a pro-inflammatory response, suggesting an infectious process was present in babies at risk of developing chronic lung disease of prematurity (CLD), thus providing a target to reduce CLD http://bit.ly/31C27iX
Footnotes
This article has an editorial commentary: https://doi.org/10.1183/13993003.00551-2020
This article has supplementary material available from erj.ersjournals.com
Data sharing: All sequences have been uploaded to EBI's ENA (https://www.ebi.ac.uk/ena).
Author contributions: S. Kotecha was responsible for initial design, together with J.R. Marchesi and N. Klein. D. Gallacher and R. Wach were responsible for sample collection, overseen by S. Kotecha. D. Alber, D. Gallacher and E. Mitchell were responsible for the sample analyses, overseen by N. Klein and J.R. Marchesi. All were responsible for data collection and data analyses. The manuscript was written by all.
Conflict of interest: D. Gallacher has nothing to disclose.
Conflict of interest: E. Mitchell has nothing to disclose.
Conflict of interest: D. Alber has nothing to disclose.
Conflict of interest: R. Wach has nothing to disclose.
Conflict of interest: N. Klein has nothing to disclose.
Conflict of interest: J.R. Marchesi has nothing to disclose.
Conflict of interest: S. Kotecha has nothing to disclose.
Support statement: S. Kotecha receives funds from the Medical Research Council (MRC) (MR/M022552/1) and National Institute for Health Research (NIHR)/Health Technology Assessment (HTA) (16/111/106). For J.R. Marchesi, the Division of Integrative Systems Medicine and Digestive Disease at Imperial College London receives financial support from the NIHR Imperial Biomedical Research Centre (BRC) based at Imperial College Healthcare NHS Trust and Imperial College London. This article is independent research funded by the NIHR BRC, and the views expressed in this publication are those of the authors and not necessarily those of the NHS, NIHR or the Department of Health. Cardiff University provided the PhD studentship for E. Mitchell. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received September 26, 2019.
- Accepted February 1, 2020.
- Copyright ©ERS 2020
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