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Despite heterogeneity, an increased prevalence of psychological comorbidity and an altered pronociceptive gut microenvironment have repeatedly emerged as causative pathophysiology in patients with irritable bowel syndrome (IBS). Our aim was to study these phenomena by comparing gut-related symptoms, psychological scores, and biopsy samples generated from a detailed diarrhea-predominant IBS patient (IBS-D) cohort before their entry into a previously reported clinical trial. Data were generated from 42 patients with IBS-D who completed a