Microbial genetic composition regulates host social behavior

The co-evolutionary relationship between gut microbiota and their hosts is influenced by microbial genetic variation, which enables adaptation to host environmental changes, modifies metabolic processes, and refines host-microbiota interactions. Investigating how gut microbial genetic variations influence host neurobehavior can provide insights into the pathogenesis of neurological disorders. In this study, we screened a comprehensive single-gene knockout library of Escherichia coli (E. coli) and identified 370 mutant strains that reduced social behavior in Caenorhabditis elegans (C. elegans). Notably, five mutations in the L-tyrosine biosynthesis pathway significantly alter the social aggregation behavior of C. elegans via the TGF-β signaling pathway. These findings highlight the importance of considering both microbial genetic variation and community composition in the examination of gut microbe-host neurobehavioral interactions. The establishment of this relationship provides a reference and experimental basis for the development of genetically engineered probiotics aimed at regulating host behavior.