A potential role for stress-induced microbial alterations in IgA-associated irritable bowel syndrome with diarrhea

Stress is a known trigger for flares of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), yet this process is not well understood. Here, we found that restraint stress in mice leads to signs of diarrhea, fecal dysbiosis, and a barrier defect via opening of goblet-cell associated passages. Notably, stress increased host immunity to gut bacteria as assessed by immunoglobulin A (IgA)-bound gut bacteria. Stress-induced microbial changes were necessary and sufficient to elicit these effects. Moreover, similar to mice, many diarrhea-predominant IBS (IBS-D) patients from two cohorts displayed increased anti-bacterial immunity as assessed by IgA-bound fecal bacteria. This anti-bacterial IgA response in IBS-D correlated 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 disruption of the intestinal microbial community that alters gastrointestinal function and host immunity to commensal bacteria.