RestoreGut | Restoration of the gut microbiome after delivery by caesarean section to prevent asthma

Summary
Associations between caesarean section (CS) and childhood asthma may be mediated through microbial changes. In 700 children followed prospectively from birth, I recently showed that microbial perturbations after delivery by CS explain the delivery mode-associated risk of developing asthma in the first 6 years of life. CS was associated with more than a doubled risk of later asthma and allergic sensitization as well as immense compositional changes in the gut microbiota. An increased asthma risk was only found in children born by caesarean section, if their microbiome did not normalize by age 1 year, suggesting that a healthy microbial maturation can alleviate the child’s increased asthma risk.
Under the hypothesis that asthma risk from CS can be avoided by restoring the early gut microbiome, the proposed project will identify key environmental, dietary and host factors that help restoring a CS perturbed microbiome, map the compositional and functional potential of the CS microbial profiles, evaluate the role of the virome in the CS associations and perform co-cultures of key microbial consortia that may restore a healthy trajectory. Finally, I will perform murine experimental models to validate the findings and perform pilot studies on CS microbiota restoration by fecal microbiota transplantation (FMT) and fecal virome transplantation (FVT) in newborns.
This will be a truly translational research project, with the potential to go from clinical observations to mechanisms based on bioinformatics and microbiological laboratory work and experimental models and a pilot human trial to infer causal relationships with the perspective of developing a potential future intervention strategy.
If successful, this strategy will be groundbreaking for understanding the microbiome’s role in asthma development after CS and in the future potentially lead to novel prevention strategies and targeted, efficient microbiota manipulation in children with early microbial perturbations.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/101125482
Start date: 01-05-2024
End date: 30-04-2029
Total budget - Public funding: 1 999 934,00 Euro - 1 999 934,00 Euro
Cordis data

Original description

Associations between caesarean section (CS) and childhood asthma may be mediated through microbial changes. In 700 children followed prospectively from birth, I recently showed that microbial perturbations after delivery by CS explain the delivery mode-associated risk of developing asthma in the first 6 years of life. CS was associated with more than a doubled risk of later asthma and allergic sensitization as well as immense compositional changes in the gut microbiota. An increased asthma risk was only found in children born by caesarean section, if their microbiome did not normalize by age 1 year, suggesting that a healthy microbial maturation can alleviate the child’s increased asthma risk.
Under the hypothesis that asthma risk from CS can be avoided by restoring the early gut microbiome, the proposed project will identify key environmental, dietary and host factors that help restoring a CS perturbed microbiome, map the compositional and functional potential of the CS microbial profiles, evaluate the role of the virome in the CS associations and perform co-cultures of key microbial consortia that may restore a healthy trajectory. Finally, I will perform murine experimental models to validate the findings and perform pilot studies on CS microbiota restoration by fecal microbiota transplantation (FMT) and fecal virome transplantation (FVT) in newborns.
This will be a truly translational research project, with the potential to go from clinical observations to mechanisms based on bioinformatics and microbiological laboratory work and experimental models and a pilot human trial to infer causal relationships with the perspective of developing a potential future intervention strategy.
If successful, this strategy will be groundbreaking for understanding the microbiome’s role in asthma development after CS and in the future potentially lead to novel prevention strategies and targeted, efficient microbiota manipulation in children with early microbial perturbations.

Status

SIGNED

Call topic

ERC-2023-COG

Update Date

22-11-2024
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Horizon Europe
HORIZON.1 Excellent Science
HORIZON.1.1 European Research Council (ERC)
HORIZON.1.1.0 Cross-cutting call topics
ERC-2023-COG ERC CONSOLIDATOR GRANTS
HORIZON.1.1.1 Frontier science
ERC-2023-COG ERC CONSOLIDATOR GRANTS