Gut Bacteria Actively Inject Proteins Into Human Cells to Control Immune Function

Researchers from Helmholtz Munich and international collaborators have made a groundbreaking discovery about how gut bacteria communicate with human cells. The study reveals that many common, non-pathogenic gut bacteria possess type III secretion systems—tiny injection mechanisms previously thought to exist only in harmful bacteria like Salmonella. These microscopic syringes allow friendly bacteria to actively inject their proteins directly into human cells, fundamentally changing our understanding of the microbiome.

The research team mapped over 1,000 interactions between bacterial effector proteins and human proteins, creating a comprehensive network showing how these injected proteins influence human biology. The bacterial proteins primarily target pathways involved in immune regulation and metabolism, including NF-κB signaling and cytokine responses—critical systems that coordinate immune activity and prevent autoimmune reactions.

Experimental validation confirmed that these bacterial proteins can significantly influence immune signaling. Cytokines like Tumor Necrosis Factor (TNF), which is commonly targeted in Crohn's disease treatment, are among the pathways affected by bacterial protein injection. This discovery provides a molecular mechanism explaining how gut bacteria influence human health beyond simple correlations.

Crucially, the researchers found that genes encoding these bacterial injection systems are more prevalent in the gut microbiomes of people with Crohn's disease. This suggests that direct protein transfer from bacteria to human cells may contribute to chronic intestinal inflammation and autoimmune conditions, offering new therapeutic targets for inflammatory bowel diseases and other microbiome-related disorders.