Deciphering the mechanisms underlying phage-bacterial coexistence in the gut

Description du projet

Les mécanismes de la coexistence des phages et des bactéries dans l’intestin

Les phages jouent un rôle essentiel dans la diversité microbienne intestinale et la santé humaine. Leurs mécanismes d’interaction avec les bactéries sont toutefois encore mal compris, ce qui entrave les études sur les microbiomes et les thérapies basées sur les phages. Soutenu par le programme Actions Marie Skłodowska-Curie, le projet COEXIGUT va se pencher sur les mécanismes qui sous-tendent la coexistence des phages et des bactéries dans l’environnement intestinal. Avec Escherichia coli, Enterococcus faecalis et leurs phages comme systèmes modèles, le projet va développer des systèmes in vitro pour explorer les effets de la composition chimique des nutriments et/ou de la diversité des populations sur la coexistence. Il analysera également les signatures protéomiques et génomiques associées à la résistance et à la persistance des phages et des bactéries.

Objectif

Bacteriophages (phages) are major drivers of microbial diversity and ecosystem function in many habitats. In the human gut, they play a crucial role in shaping bacterial populations, influencing host health and microbiome stability. While several studies have revealed that phages and their bacterial hosts can coexist for extended periods, the mechanisms underlying this long-term coexistence remain largely unknown. Understanding how such stability is maintained is essential for both fundamental microbiome research and the development of phage-based therapies.
This project aims to dissect some of the molecular and ecological mechanisms that sustain stable phage-bacterial coexistence in the gut. Using Escherichia coli and Enterococcus faecalis (two commensal species commonly found in the intestinal microbiota) and their corresponding phages, I will establish controlled in vitro systems to study how factors such as nutrient composition, community complexity, and culture conditions influence coexistence dynamics. Combining these assays with deep sequencing, metabolomics and proteomics, genomic changes and molecular pathways involved in resistance and phage persistence will be decoded. The functional role will be validated through the knockdown of the identified pathways and, ultimately, tested in gnotobiotic mice colonized with the OMM12 synthetic microbial community.
The expected outcome is a detailed mechanistic understanding of how phages and their hosts coexist over time in the gut environment. By uncovering the key genetic and ecological factors involved, this project will provide fundamental insights into microbiome resilience and control. This knowledge will also help inform the rational design of microbiome-targeted interventions and improve the predictability and safety of phage therapy in clinical settings.