P5379 - Microbiota-Targeted Therapies in Biologic-Refractory Ulcerative Colitis: A Systematic Review and Meta-Analysis

Nayanika Tummala, MD¹, Hakim Wazir, MBBS², Rithish Nimmagadda, MBBS³, Amna Amir Jalal, MBBS⁴, Muhammad Haleem Nasar, MBBS⁵, Maryam Muzzafar, MBBS⁶, Syed Ibad Hussain, MBBS⁴, Kusalik Boppana, MBBS⁷, Ashish Chilakapati, MBBS⁸, Gurmanleen Singh. Sohi, MBBS⁹, Diya Rathi, MBBS¹⁰, Noora Inam, MBBS¹¹
1St. Mary's General Hospital, New York Medical College, Poughkeepsie, NY; 2Gajju Khan Medical College,Swabi Pakistan Medicine department, Shahmansor, Swabi, North-West Frontier, Pakistan; 3One Brooklyn Health-Interfaith Medical Center, Brooklyn, NY; 4Jinnah Sindh Medical University, Karachi, Sindh, Pakistan; 5Northwest School of Medicine, Peshawar, North-West Frontier, Pakistan; 6allama iqbal medical college, Lahore, Punjab, Pakistan; 7Kasturba Medical College of Manipal, Manipal, Karnataka, India; 8MBBS, Tampa, FL; 9Government Medical College,Patiala, Patiala, Punjab, India; 10Dow university of health sciences, Karachi, Pakistan, Karachi, Sindh, Pakistan; 11Gajju khan medical college, Swabi, North-West Frontier, Pakistan

Introduction: The safety and efficacy of microbiota-targeted therapies (MTT), including fecal microbiota transplantation (FMT), probiotics, and postbiotics, for ulcerative colitis (UC) have been investigated in adults (≥18 years) and have shown potential in restoring intestinal balance. However, their role in biologic-refractory UC is controversial. Biological refractory ulcerative colitis is a type of ulcerative colitis that doesn’t respond to biological treatment. We conducted this systematic review and meta-analysis to evaluate the safety and effectiveness of MTT in adult patients with biologic-refractory ulcerative colitis, incorporating the latest clinical trial evidence.

Methods: We conducted a systematic search up to May 2025 in PubMed, Cochrane Library, Scopus, Embase, and ClinicalTrials.gov, following PRISMA guidelines. Study selection was done using Rayyan, and data on clinical and endoscopic outcomes and adverse events were extracted into Excel. Meta-analysis was performed using RevMan 5.4 with a random-effects model. Heterogeneity was assessed using I² and p-values, with sensitivity analyses conducted to test the robustness of findings.

Results: We included 10 studies involving total of 491 patients. MTT significantly improved clinical remission compared to control (RR = 2.04; 95% CI: 1.18–3.54; P = 0.01) (figure 1), with results remaining robust after excluding a high-weight outlier (RR = 2.12; 95% CI: 1.43–3.15; P = 0.0002). Clinical response was also significantly higher in the MTT group (RR = 1.94; 95% CI: 1.29–2.90; P = 0.001) (figure 2), as was endoscopic remission (RR = 2.36; 95% CI: 1.39–4.03; P = 0.002) (figure 3). Total adverse events did not differ significantly between groups (RR = 0.92; 95% CI: 0.76–1.11; P = 0.39) (figure 4), suggesting a comparable safety profile. Heterogeneity was low to moderate across outcomes, except for initial clinical remission (I² = 68%), which improved notably in sensitivity analysis (I² = 10%).

Discussion: Our systematic review and meta-analysis shows that microbiota-targeted therapies are safe and effective in inducing clinical and endoscopic remission in patients with biologic-refractory ulcerative colitis, without increasing total adverse events. However, the heterogeneity of interventions and relatively small study populations warrant further large-scale trials to determine optimal treatment strategies and assess long-term outcomes.


Figure: Figure 1 - Meta-analysis of Microbiota Transplant Therapy versus Control in Ulcerative Colitis outcomes

Disclosures:
Nayanika Tummala indicated no relevant financial relationships.
Hakim Wazir indicated no relevant financial relationships.
Rithish Nimmagadda indicated no relevant financial relationships.
Amna Amir Jalal indicated no relevant financial relationships.
Muhammad Haleem Nasar indicated no relevant financial relationships.
Maryam Muzzafar indicated no relevant financial relationships.
Syed Ibad Hussain indicated no relevant financial relationships.
Kusalik Boppana indicated no relevant financial relationships.
Ashish Chilakapati indicated no relevant financial relationships.
Gurmanleen Sohi indicated no relevant financial relationships.
Diya Rathi indicated no relevant financial relationships.
Noora Inam indicated no relevant financial relationships.

Nayanika Tummala, MD¹, Hakim Wazir, MBBS², Rithish Nimmagadda, MBBS³, Amna Amir Jalal, MBBS⁴, Muhammad Haleem Nasar, MBBS⁵, Maryam Muzzafar, MBBS⁶, Syed Ibad Hussain, MBBS⁴, Kusalik Boppana, MBBS⁷, Ashish Chilakapati, MBBS⁸, Gurmanleen Singh. Sohi, MBBS⁹, Diya Rathi, MBBS¹⁰, Noora Inam, MBBS¹¹. P5379 - Microbiota-Targeted Therapies in Biologic-Refractory Ulcerative Colitis: A Systematic Review and Meta-Analysis, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.