Role of viral dark matter in drug-induced alterations of microbiome-immunity homeostasis
Responsible for the project: Lejla Imamovic
Coordinating institution: Inserm Regional Delegation Paris-IDF North Central
Virome
Phage
Host-microbe interactions
Antibiotics
- Total cost: 910k€
- Starting date: 01/02/2026
- Duration: 3,5 years
- Reference: 23-PESA-0001
- Overall objectives
Bacteriophages, viruses that infect bacteria, are the most abundant biological entities in the human gut, but remain largely unknown. Often referred to as the “viral dark matter” of the microbiome, they are believed to influence the organization and stability of microbial communities. However, research has mainly focused on bacteria, leaving major gaps in our understanding of the role of viral components in immunity and disease susceptibility.
Antibiotics, which are essential in medicine, profoundly disrupt the gut microbiome and are increasingly associated with long-lasting immune and inflammatory disorders. Although bacteriophages do not infect human cells, they are abundant on mucosal surfaces. The modalities of their interaction with mucosal immune environments, as well as the impact of antibiotics on these processes, remain poorly characterized.
The VIROMUNE project aims to analyze the relationships between intestinal bacteriophages, microbiota, and mucosal immune responses, to assess the impact of antibiotics on these interactions, and to understand how their disruption contributes to persistent imbalances in the microbiome and immunity.
- Scientific and societal issues
Antibiotics are used extensively, but their long-term effects on immune health remain poorly understood. Alterations in the microbiota-immunity axis are associated with chronic diseases, reduced vaccine efficacy, and increased vulnerability to infections, generating significant health and societal costs. These phenomena are still largely interpreted from a bacterial perspective.
As regulators of bacterial populations, bacteriophages could play a decisive role in the persistence of antibiotic-induced imbalances. The lack of knowledge about virus-immunity interactions currently limits our ability to predict the long-term risks associated with microbiome disruption.
By providing an integrated view of phage-bacteria-immunity interactions, VIROMUNE will contribute to the identification of phage markers of microbiome disruption and recovery, and to the development of more predictive and sustainable microbiome-centered approaches.
- Project focuses
The VIROMUNE project focuses on three main axes:
- Characterization of the immunologically active intestinal phageome and its influence on phage and bacterial dynamics.
- Analysis of the impact of antibiotics on phage-bacteria interactions and the stability of the intestinal microbiome.
- Exploration of phage-based microbiotic approaches to promote microbiome recovery after antibiotic disruption.
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- Coordinating institution: Inserm-DR Paris IDF Centre Nord

