Gut microbiota modualtes innate anxiety via the neuron activity of medial prefrontal cortex in mice
Anxiety disorders are the most common mental illness with a lifetime prevalence of up to 33.7%, the mechanisms of which have been only partially elucidated. Recent observations have revealed the gut microbiota contributes to the regulation of anxiety. However, little attention has been given to innate anxiety, which excluded genetic background and environmental factors. Herein, we investigate causal mechanisms of gut microbiota in modulating innate anxiety. First, specific pathogen-free (SPF) C57BL/6J mice were divided into high-anxiety (HA) and low-anxiety (LA) subgroups in the top or bottom 44%, respectively (ie, the middle 12% was excluded) in the elevated plus maze (EPM). We transplanted the microbiota from high or low anxiety mice, which was identified by 16S rRNA sequencing to be of a differential composition, to antibiotic (ABX)-treated C57 mice. Strikingly, ABX treatment produced anxiolytic effects and HA-FMT recipients exhibited anxiety-like behaviors. We moreover defined that the neuron activity of medial prefrontal cortex (mPFC) was activated identified by increased c-Fos expression and GCaMP6 signals in the HA-FMT recipients. Finally, RNA-seq suggested that transcriptional reprogramming, modification of proteins, and synaptic plasticity modulation were involved in the gut microbiota-brain axis mechanism. We conclude that the microbiota influences the innate anxiety-like behavior and affects the neuron activity of mPFC involving transcriptional reprogramming, modification of proteins, and synaptic plasticity modulation. Overall design: RNA-seq analysis of  medial prefrontal cortex from high- and low-anxiety mice