Anxiety disorders comprise the single most common mental illness in the U.S. Anxiety develops from a complex set of mental, genetic and physical risk factors that are correlated with medical comorbidities attributable to pro-inflammatory pathophysiology. Recent evidence implicates profound involvement of gut microbiota in this and a novel concept of an impaired gut-brain communication is emerging for anxiety and other mental disorders. In fact, our preliminary data with patients support this concept. In addition, our studies have shown that global overexpression of angiotensin-converting enzyme 2 (ACE2) protects mice from anxiety disorder and these mice have unique gut microbiota. Together, this offers us a unique opportunity to address the most important question regarding the role of the gut-brain axis in anxiety: is altered gut microbiota responsible for anxiety disorder? The proposed study is designed to exploit the impact of ACE2 and microbiota by transferring their anxiolytic benefits from donor animals to affected animals by way of fecal microbiota transplant (FMT). Furthermore, Dr. Stevens of our team has discovered a unique gut microbiome dysbiosis profile in human anxiety patients, and studies show that FMT can improve mood. However, the anxiolytic mechanism is unknown.