Abnormal intestinal milieu in posttraumatic stress disorder is not impacted by treatment that improves symptoms.

Posttraumatic stress disorder (PTSD) is a psychiatric disorder, resulting from exposure to traumatic events. Current recommended first-line interventions for the treatment of PTSD include evidence-based psychotherapies, such as cognitive processing therapy (CPT). Psychotherapies are effective for reducing PTSD symptoms, but approximately two-thirds of veterans continue to meet diagnostic criteria for PTSD after treatment, suggesting there is an incomplete understanding of what factors sustain PTSD. The intestine can influence the brain and this study evaluated intestinal readouts in subjects with PTSD. Serum samples from controls without PTSD ( = 40) from the Duke INTRuST Program were compared with serum samples from veterans with PTSD ( = 40) recruited from the Road Home Program at Rush University Medical Center. Assessments included microbial metabolites, intestinal barrier, and intestinal epithelial cell function. In addition, intestinal readouts were assessed in subjects with PTSD before and after a 3-wk CPT-based intensive treatment program (ITP) to understand if treatment impacts the intestine. Compared with controls, veterans with PTSD had a proinflammatory intestinal environment including lower levels of microbiota-derived metabolites, such as acetic, lactic, and succinic acid, intestinal barrier dysfunction [lipopolysaccharide (LPS) and LPS-binding protein], an increase in HMGB1, and a concurrent increase in the number of intestinal epithelial cell-derived extracellular vesicles. The ITP improved PTSD symptoms but no changes in intestinal outcomes were noted. This study confirms the intestine is abnormal in subjects with PTSD and suggests that effective treatment of PTSD does not alter intestinal readouts. Targeting beneficial changes in the intestine may be an approach to enhance existing PTSD treatments. This study confirms an abnormal intestinal environment is present in subjects with PTSD. This study adds to what is already known by examining the intestinal barrier and evaluating the relationship between intestinal readouts and PTSD symptoms and is the first to report the impact of PTSD treatment (which improves symptoms) on intestinal readouts. This study suggests that targeting the intestine as an adjunct approach could improve the treatment of PTSD.