Tauroursodeoxycholic Acid (TUDCA) Reduces ER Stress and Lessens Disease Activity in Ulcerative Colitis

ABSTRACT: Background and Aims: In inflammatory bowel disease, protein misfolding in the endoplasmic reticulum (ER) potentiates epithelial barrier dysfunction and impairs mucosal healing. Tauroursodeoxycholic acid (TUDCA), a naturally occurring bile acid, acts as a chemical chaperone to reduce protein aggregation and colitis severity in preclinical models. We conducted an open label trial evaluating oral TUDCA as therapy in patients with active ulcerative colitis (UC). Methods: Patients with moderate-to-severely active UC (Mayo score ≥6, endoscopic subscore ≥1) received oral TUDCA at 1.75 or 2 g/day for 6 weeks. Exclusion criteria included known hepatic disorders or change in UC therapy within 60 days. Clinical disease activity questionnaires, endoscopy with biopsy, blood, and stool were collected at enrollment and after 6 weeks. The primary outcome measure was change in ER stress markers while safety, tolerability and change in UC disease activity were secondary outcomes. Results: Thirteen participants completed the study with eleven evaluable for clinical response. TUDCA was well-tolerated with transient dyspepsia being the most common side effect. Mucosal biopsies revealed significant reductions in ER stress and inflammation as well as an increase in markers of epithelial restitution. Clinical, endoscopic, and histologic disease activity were significantly improved at week 6 (mean total Mayo Score: 9 to 4.5, p<0.001). Conclusions: Six weeks of oral TUDCA promoted mucosal healing, lessened ER stress, and reduced UC clinical disease activity. TUDCA was safe and well-tolerated in patients with active UC. A randomized controlled trial of adjunctive TUDCA therapy in patients with UC is warranted. ClinicalTrials.gov (NCT04114292).

ORGANISM(S): Homo sapiens

PROVIDER: GSE266963 | GEO | 2025/05/30

REPOSITORIES: GEO