Abstract
Exposure to a prolonged restraint stressor disrupts the colonic microbiota community composition, and is associated with an elevated inflammatory response to colonic pathogen challenge. Since the stability of the microbiota has been implicated in the development and modulation of mucosal immune responses, we hypothesized that the disruptive effect of the stressor upon the microbiota composition directly contributed to the stressor-induced exacerbation of pathogen-induced colitis. In order to establish a causative role for stressor-induced changes in the microbiota, conventional mice were exposed to prolonged restraint to change the microbiota. Germfree mice were then colonized by microbiota from either stressor-exposed or non-stressed control mice. One day after colonization, mice were infected with the colonic pathogen, Citrobacter rodentium. At six days post-infection, mice that received microbiota from stressor-exposed animals had significant increases in colonic pathology and pro-inflammatory cytokine (e.g. IL-1β) and chemokine (e.g. CCL2) levels after C. rodentium infection in comparison with mice that received microbiota from non-stressed mice. 16S rRNA gene sequencing revealed that microbial communities from stressed mice did not have any detectable Bifidobacterium present, a stark contrast with the microbial communities from non-stressed mice, suggesting that stressor-induced alterations in commensal, immunomodulatory Bifidobacterium levels may predispose to an increased inflammatory response to pathogen challenge. This study demonstrates that the commensal microbiota directly contribute to excessive inflammatory responses to C. rodentium during stressor exposure, and may help to explain why gastrointestinal disorders are worsened during stressful experiences.