Microbial genetic variation drives host social traits via agmatine and NO-mediated cGMP-PKG pathways

The gut microbiota plays a vital role in regulating host physiology and behavior through its influence on the microbiota-gut-brain axis. Despite extensive research linking gut microbiota diversity to host behaviors, the genetic and molecular mechanisms underlying microbial regulation of social behaviors remain poorly understood. In this study, a screening for E. coli single-gene knockout mutants that increased social behaviors of C. elegans identified speB and narG as key E. coli genes regulating C. elegans aggregation. speB mutant increased the production and secretion of agmatine, while narG mutant E. coli reduced NO levels in C. elegans . Mechanistically, this study found that agmatine and NO regulated C. elegans aggregation via cGMP-PKG pathway. These findings deepen our understanding of the molecular basis of host-microbe interactions and provide new insights into the regulation of social behaviors by gut microbiota.