Decoding the neuronal and microbial basis of stress-induced colitis.

The etiology of Inflammatory Bowel Disease (IBD) is complex and incompletely understood, with interactions between various genetic risks and environmental factors such as the gut microbiome contributing to disease. Further, psychological stress often precedes flare-ups, is associated with colitis severity and stress changes gut microbiome profiles. However, a mechanistic link between stress, the microbiome and IBD remains unexplored. Accordingly, we propose to investigate a largely unappreciated aspect of IBD, the gut-brain axis. In this project, we pursue an innovative research strategy integrating immunologic, behavioral, neurologic and microbiome analyses to determine the mechanisms by which psychological stress interacts with the gut microbiome to increase colitis susceptibility in mice. Our central hypothesis is that stress reshapes the gut microbiome via vagus nerve signaling, which subsequently exacerbates intestinal inflammation, GI dysfunction and abdominal pain. The long-term objectives of this research are to understand the etiology of stress-induced colitis and leverage these discoveries to develop safe and effective new therapeutics for IBD by targeting gut-brain interactions.