Antibiotics Trigger Host Innate Immune Response via Microbiota-Brain Communication in .

Besides their direct bactericidal effect, antibiotics have also been suggested to stimulate the host immune response to defend against pathogens. However, it remains unclear whether any antibiotics may stimulate the host immune response by affecting bacterial activity. In this study, reasoning that genetic mutations inhibit bacterial activities and, thereby, may mimic the effects of antibiotics, we performed genome-wide screening and identified 77 genes whose inactivation induces , representing an innate immune and detoxification response. Further analyses reveal that this host immune response can clearly be induced through either inactivating the respiratory chain via the bacterial mutation or using the antibiotic Q203, which is able to enhance host survival when encountering the pathogen . Mechanistically, the innate immune response triggered by both the mutation and Q203 is found to depend on the host brain response, as evidenced by their reliance on the host neural gene , which is required for neurotransmitter release in head neurons. Therefore, our findings elucidate the critical involvement of the microbiota-brain axis in modulating the host immune response, providing mechanistic insights into the role of antibiotics in triggering the host immune response and, thus, facilitating host defense against pathogens.