ProLung · The role of maternal microbiota in offspring lung development and function
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-01-01 → 2020-12-31
- EU contribution
- €212,195
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
The role of maternal microbiota in offspring lung development and function
Summary of the context: The traditional belief, that healthy human lungs are sterile, is now considered debunked and scientific reports show that lung microbiota is altered in lung diseases such as asthma, chronic obstructive pulmonary disease and bronchopulmonary dysplasia (BPD). The control of early lung development is highly regulated and orchestrated and, although some pathways and signals mediating these events have been described, much remains unknown. Whilst it now is well known, that microbiota drives the development of the intestinal mucosa and physiology in both mice and humans, it is completely unapproached, which influence the different microbiota could have on the development of the lung in early life. The scientific literature and my early proof-of-principle preliminary results appeared to support a role for microbiota manipulation in lung development, which could possibly intercept or ameliorate lung diseases. With the “ProLung” project, I wanted to show causation by transferring the changed lung phenotype with the microbiota between mice. I wanted to reveal underlying changes to lung gene expression, circulation growth factors and show how it could affect breathing patterns using whole body plethysmography, that records different breathing parameters over time. The overall objectives of the project: Objective 1) To identify the timing of the effect of microbiota on lung development Objective 2) To identify the mechanism behind the effect of microbiota on lung development Objective 3) To quantify enhanced lung function in a relevant lung disease model of BPD
Data: CORDIS, © European Union
Project objective
In early life, interactions between our microbiota and our bodies are key elements to health and disease prevention. While it is known that microbiota drives development of the gut mucosa, it is unknown which influence microbiota has on the development of the lung in early life. I have recently discovered large biologically and statistically significant effects between maternal probiotic treatment during pregnancy, maternal gut microbiota changes and alveolar development in mouse offspring. This type of effect has never been shown before and modulation of microbiota with probiotic bacteria thus appears to support lung development and could possibly intercept lung diseases. With “ProLung”, I want to reveal the mechanisms behind this effect on lung development. I will do that by determining; the timing of the effect, which microbiota is more important and what genes are differently regulated in dams and their pups. I will show causation by transferring microbiota and phenotype to germ-free mice. Finally, as a “proof of concept”, I will develop and employ an oxygen driven disease model of infant lung dysplasia and show if modulation of microbiota can enhance breathing and could be used to intercept this early life lung disease. The proposed “ProLung” action will be conducted under world-class supervision at University of Copenhagen, Denmark with strong partners, in a highly cross disciplinary international collaboration with University of Oxford (UK), University of Michigan (US) and co-funded by the world second largest chemical company Dupont. I have a unique background and track record suited to perform the proposed research. Furthermore the action will allow me to pursue several training objectives that will be instrumental for my future career in the cross-section between academia and industry.
Original text from CORDIS.
Participants
- KOBENHAVNS UNIVERSITET · KOBENHAVNCoordinatorDenmark
Links
Data: CORDIS, © European Union