Crohn's disease (CD) is an inflammatory bowel disease linked to microbial and environmental factors, including psychological stress. This study demonstrates that stress-exposed mice exhibit ileal dysbiosis, dominated by Enterobacteriaceae expansion. Stress-induced glucocorticoids promote apoptosis of IL-22-producing CD45+CD90+ cells, crucial for ileal mucosal barrier integrity. Blocking glucocorticoid signaling or administering recombinant IL-22 restores mucosal immunity, prevents dysbiosis, and inhibits AIEC expansion. This suggests that psychological stress impairs IL-22-mediated gut immunity, creating a niche for Crohn's disease-associated pathobionts. Immunomodulation can counteract stress's negative effects on gut immunity and dysbiosis.

Christopher R. Shaler, Alexandra A. Parco, Wael Elhenawy, Jasmeen Dourka, Jennifer Jury, Elena F. Verdu, Brian K. Coombes