(OR22-04-26) The Effects of Psychological Stress on Gut Health in Mice Fed Either a Healthy Diet or the Total Western Diet

Objectives: Western dietary patterns and chronic psychological stress commonly co-occur and may interact to influence gut inflammation. We previously demonstrated that mice fed the Total Western Diet (TWD), which models Western macro- and micronutrient intake, exhibit exacerbated colitis compared with mice fed the AIN-93G diet. This study tested whether chronic psychological stress synergistically worsens colitis outcomes in mice consuming TWD.

Methods: Male C57BL/6 mice (n = 18/group) were fed either AIN-93G or TWD for 4 weeks and assigned to one of four treatment conditions per diet: diet alone, diet plus psychological stress (PS), diet plus azoxymethane/dextran sodium sulfate–induced colitis (DSS), or diet plus DSS plus PS (8 total groups). Colitis was induced on day 14 using azoxymethane injection followed by 1% DSS in drinking water for 10 days. Psychological stress was induced on days 18–24 using the social disruption (SDR) model (2 h/day exposure to an aggressor mouse). Primary outcomes included disease activity index (DAI), colon length, and histopathologic inflammation and epithelial regeneration scores.

Results: Diet strongly influenced colitis severity. TWD-fed mice exhibited higher disease activity and greater colon shortening compared with AIN-93G–fed controls (diet effect P < 0.0001). Psychological stress did not significantly increase DAI (P = 0.7352), but did have a significant main effect on colon shortening (P=0.0093). Histopathology confirmed increased mucosal inflammation in TWD-fed animals (diet effect P = 0.001). A significant diet × stress interaction was observed for epithelial regeneration scores (P = 0.01), suggesting stress may influence mucosal repair processes rather than acute inflammatory burden.

Conclusions: Consumption of a Western-pattern diet was the primary determinant of colitis severity in this model. Chronic psychological stress did not substantially exacerbate clinical disease activity but modestly influenced epithelial regeneration. These findings suggest that Western dietary patterns establish a pro-inflammatory baseline that dominates colitis susceptibility, while stress may modulate tissue repair rather than initiating disease pathology.

Funding Sources: USDA NIFA, Utah Agricultural Experiment Station