Phage-Bacteria-Host Tripartite Interactions in Gut Health and Disease – VENTRIS

The intestinal tract is home to a densely populated microbial community, or microbiota. A growing body of evidence suggests that this commensal relationship strongly defines the health state of humans. Within this community, the richness and diversity of bacteria are shaped by the intestinal physiology (metabolism, immunity...) and by external factors (nutrients, drugs…) and are often described as crucial for maintaining a healthy state, while deviating from such situation may result in transient or chronic disorders.
But the gut microbiota is composed of other microbial fractions, notably of bacteriophages (phages), the specific viruses of bacteria. Viromic studies have identified that gut phages are highly diverse and stable over time as well as very specific to single individuals. Metagenomic signatures of phage abundance and diversity were reported as associated to several diseases, such as inflammatory bowel disease (IBD). Also, increasing data suggest that the transfer of intestinal phages is crucial for the success of faecal material transplant (FMT) in resolving the recurrence of Clostridioides difficile infections.
Although of invaluable significance, these studies remain largely descriptive and limited in resolving the nature and extent of the interactions taking place between the intestinal organ and its microbiota. Thus, many are the standing questions regarding their putative role in determining or contributing to a healthy or a disease state. VENTRIS is a research project aimed at characterising the ecological and molecular mechanisms governing the tripartite interaction between phages, bacteria and the intestinal tract during healthy and inflammatory conditions. This objective will be achieved by understanding (i) the impact of phages on the intestinal barrier and its inflammatory state, using in vitro and ex vivo model, including clinical samples; (ii) the mechanisms of long term phage-bacteria stable coexistence in a murine model of controlled microbiota in the presence and absence of intestinal inflammation; (iii) the potential of gut phages in controlling or reverting intestinal inflammation by modulating the gut microbiota. This project is set to have an impact on the understanding of the dynamics regulating the homeostasis of the gut microbiota. Such knowledge will open the door to deciphering the metagenomics data associated to healthy and diseased states and to designing the targeted preservation and restoration of gut health using bacteriophage-based therapeutic options.