Bronchopulmonary dysplasia (BPD) results from disrupted lung development after premature birth and results in life long pulmonary morbidity. Intrauterine and postnatal lung inflammation contribute to structural airway simplification and increased pulmonary vascular resistance, critical components of BPD. The Human Microbiome Project is designed to understand the interactions between microbial communities that inhabit a host and the host itself. Emerging data suggest that imbalances between components of commensal organisms in the gastrointestinal tract are associated with atopy, allergic rhinitis, or recurrent wheezing. These data prompt consideration of the role for gut microbiota-mediated lung inflammation as a trigger for BPD. In this single center project, limited polysomnography and echocardiography will be used to non- invasively and longitudinally assess airspace and pulmonary vascular development in premature newborns <30 weeks'gestation who are at risk for developing BPD to test the hypothesis that signatures of the neonatal enteric microbiome are associated with BPD-related adverse pulmonary outcomes, including death, technology dependence, and need for bronchodilators or corticosteroids at 36 weeks and 1 year of age. Ongoing, parallel initiatives at Washington University that are characterizing the enteric microbiome of premature newborns will be leveraged to explore associations between this biomass and the development of BPD-related adverse pulmonary outcomes.
The Specific Aims are: 1) utilize existing data to determine differences in the composition of the microbiota between groups of linked mothers and premature newborns with and without BPD, and 2) utilize existing data to determine differences in the metagenomic and/or transcriptional repertoire of the enteric microbiota between linked mothers and premature newborns with and without BPD. The metagenomic and transcriptional differences identified in Specific Aim II that are associated with adverse pulmonary outcomes will permit identification of factors that are amenable to early intervention and prevention of BPD, and furthermore, will inform selection of candidate gene networks that can be interrogated for the multicenter component of this proposal in which next generation sequencing will be used to identify the interactions between and among alleles of the infant and microbiota that are associated with BPD-related adverse pulmonary outcomes.

Public Health Relevance

The proposed studies will evaluate whether bacteria in the intestinal tract of premature newborns play a role in the development of bronchopulmonary dysplasia, the most significant chronic lung problem of prematurity. Identifying the role that these bacteria play will permit early treatment in an effort to prevent the development of these lung problems.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL101465-04
Application #
8464209
Study Section
Special Emphasis Panel (ZHL1-CSR-D (F1))
Program Officer
Blaisdell, Carol J
Project Start
2010-05-01
Project End
2015-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
4
Fiscal Year
2013
Total Cost
$469,426
Indirect Cost
$136,226
Name
Washington University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Warner, Barbara B; Deych, Elena; Zhou, Yanjiao et al. (2016) Gut bacteria dysbiosis and necrotising enterocolitis in very low birthweight infants: a prospective case-control study. Lancet 387:1928-36
Brennan, Colleen; Ulm, Lara; Julian, Samuel et al. (2016) Thoracoabdominal Asynchrony Is Not Associated with Oxyhemoglobin Saturation in Recovering Premature Infants. Neonatology 111:297-302
Levy, Philip T; Machefsky, Aliza; Sanchez, Aura A et al. (2016) Reference Ranges of Left Ventricular Strain Measures by Two-Dimensional Speckle-Tracking Echocardiography in Children: A Systematic Review and Meta-Analysis. J Am Soc Echocardiogr 29:209-225.e6
Poindexter, Brenda B; Feng, Rui; Schmidt, Barbara et al. (2015) Comparisons and Limitations of Current Definitions of Bronchopulmonary Dysplasia for the Prematurity and Respiratory Outcomes Program. Ann Am Thorac Soc 12:1822-30
Maitre, N L; Ballard, R A; Ellenberg, J H et al. (2015) Respiratory consequences of prematurity: evolution of a diagnosis and development of a comprehensive approach. J Perinatol 35:313-21
Sanchez, Aura A; Levy, Philip T; Sekarski, Timothy J et al. (2015) Effects of frame rate on two-dimensional speckle tracking-derived measurements of myocardial deformation in premature infants. Echocardiography 32:839-47
Warner, Barbara B; Hamvas, Aaron (2015) Lungs, microbes and the developing neonate. Neonatology 107:337-43
Levy, Philip T; Dioneda, Brittney; Holland, Mark R et al. (2015) Right ventricular function in preterm and term neonates: reference values for right ventricle areas and fractional area of change. J Am Soc Echocardiogr 28:559-69
Coste, Ferdinand; Ferkol, Thomas; Hamvas, Aaron et al. (2015) Ventilatory control and supplemental oxygen in premature infants with apparent chronic lung disease. Arch Dis Child Fetal Neonatal Ed 100:F233-7
Pryhuber, Gloria S; Maitre, Nathalie L; Ballard, Roberta A et al. (2015) Prematurity and respiratory outcomes program (PROP): study protocol of a prospective multicenter study of respiratory outcomes of preterm infants in the United States. BMC Pediatr 15:37

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