A Potential Role for Stress-Induced Microbial Alterations in IgA-Associated Irritable Bowel Syndrome with Diarrhea
Sunaina Rengarajan, Kathryn A. Knoop, Arvind Rengarajan, Jiani Chai, Jose G. Grajales‐Reyes, Vijay K. Samineni, Emilie V. Russler-Germain, Prabha Ranganathan, Alessio Fasano, Gregory S. Sayuk, Robert W. Gereau, Andrew L. Kau, Dan Knights, Purna Kashyap, Matthew A. Ciorba, Rodney D. Newberry, Chyi‐Song Hsieh
Abstract
Stress is a known trigger for flares of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS); however, this process is not well understood. Here, we find that restraint stress in mice leads to signs of diarrhea, fecal dysbiosis, and a barrier defect via the opening of goblet-cell associated passages. Notably, stress increases host immunity to gut bacteria as assessed by immunoglobulin A (IgA)-bound gut bacteria. Stress-induced microbial changes are necessary and sufficient to elicit these effects. Moreover, similar to mice, many diarrhea-predominant IBS (IBS-D) patients from two cohorts display increased antibacterial immunity as assessed by IgA-bound fecal bacteria. This antibacterial IgA response in IBS-D correlates with somatic symptom severity and was distinct from healthy controls or IBD patients. These findings suggest that stress may play an important role in patients with IgA-associated IBS-D by disrupting the intestinal microbial community that alters gastrointestinal function and host immunity to commensal bacteria.