Structural and functional alterations in the gastrointestinal mucosa of rats in a PTSD model

Chronic stress contributes to mental disorders, including post-traumatic stress disorder (PTSD) and gastrointestinal (GI) diseases, which frequently exhibit comorbidity. However, PTSD can also develop following severe acute stress, such as life-threatening stress The associated GI tract damage remains poorly understood. Aim. To investigate long-term changes in the digestive tract mucosa following a single life-threatening stress exposure. Materials and Methods. On day 16 post-stress, rat behavioral activity was assessed using the Open Field test (evaluating general locomotion, exploratory behavior, anxiety-like responses). Histological analysis of the digestive tract included morphometric measurements of villus length and crypt depth, quantification of goblet cells (Alcian blue staining), and assessment of proliferative activity (immunohistochemical detection of phosphorylated histone H3). Results. In the long-term period following a single life-threatening stress exposure, rats developed PTSD-like manifestations characterized by increased anxiety and decreased exploratory behavior, accompanied by morphological alterations in the intestinal mucosa. The small intestine showed increased villus length, while the large intestine displayed deeper crypts. Small intestinal crypts demonstrated an elevated number of goblet cells and a reduced count of phosphorylated histone H3-immunopositive cells. Ultrastructural analysis revealed microvilli and mitochondrial damage in enterocytes and colonocytes, along with bacterial translocation into the epithelial layer. These findings collectively suggest impaired goblet cell maturation and migration against a background of suppressed epithelial proliferation, indicating substantial intestinal barrier compromise. Conclusion. PTSD development following acute life-threatening stress induces both structural and functional reorganization of the intestinal mucosa with barrier integrity disruption, underscoring the clinical need for therapeutic strategies targeting intestinal barrier restoration in post-stress disorder management.