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Reestablishing the lung microbiome : preclinical evaluation of targeted probiotics for pneumonia treatment

Project description

Restoring the lung microbiome to treat pneumonia

Emerging evidence indicates that, similar to the gut, healthy lungs also contain their own microbiome, a diverse community of commensal microbes that supports respiratory health and immune function. Given that lungs are constantly exposed to microbes in the air and in the upper respiratory tract, this is to be expected. With the support of the Marie Skłodowska-Curie Actions programme, the RESTORE project focuses on hospital-acquired pneumonia and proposes to restore microbial balance in the lungs as a way of treating and preventing pneumonia more effectively. Researchers will test lung-specific probiotics and microbial metabolites to identify microbes capable of rebuilding the lung microbiome. Long-term this will mean less use of antibiotics for pneumonia treatment.

Objective

"Nosocomial pneumonia is the second most common and most frequently fatal hospital-acquired infection worldwide. Previous understanding of lung health depicted a dichotomous view of microbial status (sterile vs. infected), leading to ""one-size-fits-all"" treatments that primarily target pathogens but neglect the complex host-microbiome interaction. The RESTORE hypothesis is that re-establishing the healthy respiratory microbiome core using a probiotic composed of lung-specific commensal bacteria and/or their derived metabolites can mitigate pneumonia severity by modulating pathogens and mucosal immunity. My main objectives are: 1) define lung-specific bacterial consortium and their derived metabolites/peptides, whose elimination is associated with pneumonia severity; 2) test their effects in vitro on commensal bacteria and pathogens; and 3) evaluate their impact on pathogens multiplication, microbiome composition, and lung mucosal immunity. I will use data from existing cohorts to identify bacterial consortia with pneumonia severity and integrate multi-omics data to characterize these consortia and their metabolic products. Then, I will assess the interactions within the bacterial consortium and their effects on pathogens by analyzing the growth and transcriptional responses. Finally, I will investigate their therapeutic potential in pneumonia mice models, focusing on pathogen burden, microbiome composition, transcriptomic activity, and immune modulation using single-cell RNA sequencing and flow cytometry. RESTORE represents a pioneering approach by leveraging the lung microbiome to develop non-antibiotic, lung-specific strategies, addressing the complexity of pneumonia pathophysiology beyond pathogen eradication. By employing a multi-disciplinary integration of cutting-edge methodologies, this project could revolutionize pneumonia treatment and potentially extend to other infectious diseases."

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

NANTES UNIVERSITE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 242 260,56
Address
1 QUAI DE TOURVILLE
44000 Nantes
France

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Region
Pays de la Loire Pays de la Loire Loire-Atlantique
Activity type
Higher or Secondary Education Establishments
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Total cost

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