Commensal gut bacteria wield secretion systems to tune human immunity

A large analysis of healthy human gut bacteria shows that about 80% of Pseudomonadota carry intact type III secretion systems, with over 90% possessing a host-directed secretion system. The researchers built a meta-interactome linking commensal effectors to human proteins, finding effector-target neighborhoods enriched for genetic variation tied to immune and metabolic diseases. Metagenomic data show effector enrichment in Crohn’s disease but depletion in ulcerative colitis. Functionally, commensal effectors can translocate into human cells and modulate NF-κB signaling and cytokine secretion in vitro, suggesting T3SS contribute to microbiome–host communication and may influence health and disease.