Researchers led by Helmholtz Munich report that some gut-dwelling bacteria — including strains not typically considered harmful — possess syringe-like molecular machinery that can deliver bacterial proteins into human cells, affecting immune and metabolic signaling. The work also links these bacterial “effector” genes to Crohn’s disease–associated microbiome patterns, though the authors say more studies are needed to determine how the mechanism influences disease.
Scientists at Helmholtz Munich, working with collaborators including Ludwig Maximilian University of Munich (LMU), Aix-Marseille University and France’s Inserm, have identified a mechanism by which some gut bacteria can directly deliver proteins into human cells.
In a study published in Nature Microbiology (2026, volume 11, issue 2, page 442), the team reports that many gut-associated, non-pathogenic or commensal bacterial strains carry type III secretion systems — microscopic, syringe-like structures known for injecting “effector” proteins into host cells. The authors say this challenges a long-standing view that such systems are largely confined to classic pathogens such as Salmonella.
Our goal was to better characterize some of the underlying processes of how gut bacteria affect human biology.
Veronika Young, a first author of the study alongside Bushra Dohai, said the researchers aimed to move beyond broad microbiome–disease correlations by systematically mapping direct molecular contacts between bacterial proteins and human proteins.
To probe what these injected proteins do, the researchers mapped more than 1,000 protein–protein interactions between bacterial effector proteins and human proteins. Follow-up experiments reported by the team suggest the bacterial proteins can influence immune and metabolic signaling — including NF-κB signaling and cytokine responses, pathways central to regulating inflammation.
This fundamentally changes our view of commensal bacteria. It shows that these non-pathogenic bacteria are not just passive residents but can actively manipulate human cells by injecting their proteins into our cells.
That assessment came from Prof. Pascal Falter-Braun, director of Helmholtz Munich’s Institute for Network Biology and a corresponding author of the study.
The researchers also report that genes encoding these effector proteins are more common in the gut microbiomes of people with Crohn’s disease. They suggest that direct protein transfer from bacteria to human cells could contribute to long-term intestinal inflammation, while emphasizing that future work will be needed to test causality and to determine when and where these secretion systems are activated in the body.
The team said future studies will examine how specific bacterial effector proteins act in different tissues and disease contexts — work that could eventually inform more targeted approaches to prevention or treatment.
