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

Area of Science:

• Gastroenterology
• Cell Biology
• Pharmacology

Background:

• Endoplasmic reticulum (ER) stress and protein misfolding contribute to epithelial barrier dysfunction in inflammatory bowel disease.
• Tauroursodeoxycholic acid (TUDCA), a bile acid, functions as a chemical chaperone, mitigating ER stress and reducing colitis in preclinical models.

Purpose of the Study:

• To evaluate the safety and efficacy of oral TUDCA in patients with active ulcerative colitis (UC).
• To assess the impact of TUDCA on ER stress markers, mucosal healing, and clinical disease activity in UC patients.

Main Methods:

• An open-label trial involving patients with moderate-to-severe active UC receiving oral TUDCA (1.75 or 2 g/day) for 6 weeks.
• Primary outcome: change in ER stress markers. Secondary outcomes: safety, tolerability, and changes in clinical, endoscopic, and histologic disease activity.

Main Results:

• TUDCA was well-tolerated, with transient dyspepsia as the most common side effect.
• Significant reductions in ER stress and inflammation were observed in mucosal biopsies.
• Marked improvements in clinical, endoscopic, and histologic measures of UC disease activity were noted by week 6.

Conclusions:

• Oral TUDCA treatment for 6 weeks is safe and effective in active ulcerative colitis patients.
• TUDCA promotes mucosal healing, alleviates ER stress, and reduces clinical disease activity.
• A randomized controlled trial is recommended to further investigate TUDCA as an adjunctive therapy for UC.