First, distinct gut microbiota compositions differentiate HA and LA phenotypes; Second, microbial depletion via antibiotics exerts anxiolytic effects; Third, HA-FMT recipients display increased anxiety-like behaviors compared to LA-FMT mice; Fourth, elevated c-Fos expression in HA-FMT mice within the mPFC, basolateral amygdala (BLA), and central amygdala (CeA); Fifth, transcriptomic profiling identifies microbiota-dependent regulation of brain function in mPFC; Last, In vivo GCaMP recordings demonstrate heightened mPFC neuronal activity during innate anxiety states. The gene discussed is FOS; the disease is Anxiety.