A consortium led by researchers from the Institute of Network Biology (Helmholtz Munich) and TAGC (Inserm, Aix Marseille University) in collaboration with international partners has identified a previously unknown communication mechanism between intestinal bacteria and human cells. Bacteria present in the human intestine can directly deliver proteins into human cells, thereby actively influencing immune responses. These findings reveal a new way in which the gut microbiome acts on the human body and could contribute to a better understanding of how changes in gut bacteria contribute to the development of inflammatory diseases, such as Crohn's disease.
Although the human gut microbiome has long been associated with immune, metabolic, and inflammatory disorders, most of the evidence is correlative, and the molecular mechanisms underlying these links remain largely unexplored.
The study shows that many common and harmless gut bacteria possess type III secretion systems, microscopic syringe-like structures that can inject bacterial proteins directly into human cells. Until now, it was thought that these systems existed only in pathogenic bacteria such as Salmonella.
To understand the role of these bacterial proteins in human cells, the researchers mapped more than a thousand interactions between bacterial effector proteins and human proteins, creating a large-scale interaction network. Their analyses showed that bacterial proteins preferentially target human pathways involved in immune regulation and metabolism.
The researchers also discovered that the genes encoding these bacterial effector proteins are enriched in the gut microbiome of patients with Crohn's disease.
By identifying a previously unknown molecular link between gut bacteria and the human immune system, this study advances our understanding of how the microbiome affects human cells, moving research from correlation to causation.
Several TAGC researchers contributed significantly to this project: Jaime Fernandez-Macgregor, Deeya Saha, Mégane Boujeant, Sébastien Choteau, Lou Bergogne, Jérémie Perrin, Christine Brun, and Andreas Zanzoni (co-corresponding author of the article).
Press release (Inserm):
https://presse.inserm.fr/un-nouveau-lien-moleculaire-entre-les-bacteries-intestinales-et-le-systeme-immunitaire-humain/71813/
Original publication
Young et al., 2026: Effector–host interactome map links type III secretion systems in healthy gut microbiomes to immune modulation. Nature Microbiology. DOI: 10.1038/s41564-025-02241-y. https://www.nature.com/articles/s41564-025-02241-y