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

Descripción del proyecto

Recuperación de la salud intestinal para prevenir el asma infantil

Los niños nacidos por cesárea corren un alto riesgo de sufrir asma y alergias a los seis años. Este mayor riesgo está relacionado con alteraciones considerables de la microbiota intestinal, sobre todo cuando la composición microbiana no se normaliza en el primer año de vida. En este contexto, el equipo del proyecto RestoreGut, financiado por el Consejo Europeo de Investigación, pretende abordar esta cuestión analizando formas de restaurar el microbioma intestinal en los recién nacidos por cesárea. Los investigadores identificarán los factores ambientales, alimentarios y del hospedador que favorecen una maduración microbiana saludable, estudiarán el papel del viroma y ensayarán el trasplante de microbiota fecal y viroma en recién nacidos. Si sus resultados son satisfactorios, RestoreGut podría allanar el camino a unas estrategias innovadoras para prevenir el asma y crear tratamientos específicos de la microbiota para niños con desequilibrios microbianos precoces.

Objetivo

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.