Genetic Variation in Gut Microbes as a Key Regulator of Host Social Behavior
The gut-brain axis allows gut microbes to influence host social behavior, yet the specific role of microbial genetic variation in this process and its potential transgenerational effects remains poorly understood. Using C. elegans as a model, we identified 77 E. coli strains among 3,983 mutants that markedly enhanced C. elegans aggregation behavior. Our findings reveal that mutant bacteria modulate C. elegans social behavior through distinct neurobehavioral pathways, demonstrating a synergistic regulatory mechanism between microbial genetics and host heredity. Mechanistically, ycgJ mutant bacteria were found to impact C. elegans social behavior via the mitochondrial pathway. Additionally, even F2 offspring of parent C. elegans exposed to these mutant bacteria exhibited enhanced social behavior within their populations. These insights underscore the significance of investigating microbial genetic variation in relation to host behavior, particularly for the development of genetically engineered probiotics, aimed at promoting well-being across generations. Overall design: C. elegans mRNA profiles of  wild type C. elegans (N2) fed BW25113 and  mutant bacteria