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

Introduction

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.

Asthma Risk and Microbial Changes

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.

Project Hypothesis

Under the hypothesis that asthma risk from CS can be avoided by restoring the early gut microbiome, the proposed project will:

1. Identify key environmental, dietary, and host factors that help restore a CS-perturbed microbiome.
2. Map the compositional and functional potential of the CS microbial profiles.
3. Evaluate the role of the virome in the CS associations.
4. Perform co-cultures of key microbial consortia that may restore a healthy trajectory.

Experimental Validation

Finally, I will perform murine experimental models to validate the findings and conduct pilot studies on CS microbiota restoration by fecal microbiota transplantation (FMT) and fecal virome transplantation (FVT) in newborns.

Translational Research Potential

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, experimental models, and a pilot human trial to infer causal relationships with the perspective of developing a potential future intervention strategy.

Future Implications

If successful, this strategy will be groundbreaking for understanding the microbiome’s role in asthma development after CS and may potentially lead to novel prevention strategies and targeted, efficient microbiota manipulation in children with early microbial perturbations.