P0624Antibiotic-Fecal Microbiota Transplantation for Ulcerative Colitis: Clinical Outcomes and Temporal Microbiota Dynamics in a Multicenter Prospective Study

Abstract

Abstract Background Gut microbiota dysbiosis contributes to ulcerative colitis (UC). Antibiotic-fecal microbiota transplantation (Antibiotic FMT), combining broad-spectrum antibiotics with FMT, has emerged as a strategy to restore microbial balance. We conducted a multicenter prospective study to evaluate its efficacy, safety, and temporal microbiota dynamics after FMT. Methods This trial (jRCTs031220542) was conducted from January 2023 to August 2025. Patients with active left-sided or extensive UC were enrolled. FMT products were prepared by Metagen Therapeutics using two donors from the Juntendo University stool bank. Patients received a 2-week regimen of amoxicillin, fosfomycin, and metronidazole, followed by three donor FMT administrations via colonoscopy and enema. Clinical remission was defined by MMDAI criteria, and week-8 remission was the primary endpoint. Stool samples collected at multiple timepoints underwent 16S rRNA sequencing to evaluate microbial shifts and donor–recipient similarity. Results Thirty-seven patients were enrolled; 33 completed treatment. Median age was 38 years; 26 were male. Baseline MMDAI was 7.1 ± 1.1. At week 8, 45.9% (17/37, p = 0.0012) achieved remission—significantly higher than historical controls (20.5%, p = 0.0183). All MMDAI subscores improved significantly (p 0.0001). Higher remission odds were observed in patients with left-sided colitis, disease duration ≥5 years, or prior steroid exposure. Adverse events were mild and self-limited, and no serious events occurred.Microbiota analysis showed increasing Shannon diversity and observed ASVs after FMT, with donor-shared ASVs rising to 46.5% at week 8 (p 0.05). Moreover, microbiota composition progressively approached donor profiles at 1, 2, and 8 weeks after FMT, accompanied by steady recovery of diversity. This donor convergence pattern was not observed in non-responders, suggesting that early microbiota trajectories may predict therapeutic outcomes. These temporal patterns provide insight into the mechanisms by which Antibiotic FMT induces durable microbial and clinical improvement. Conclusion Antibiotic FMT was effective and safe for inducing remission in active UC. Disease extent, duration, and steroid history may influence response. The temporal dynamics of microbiota restoration after FMT may clarify how microbial shifts contribute to therapeutic efficacy and could serve as biomarkers for treatment response. Antibiotic FMT represents a promising therapeutic option for UC. References: Ishikawa D* et al. Patient-donor similarity and donor-derived species contribute to the outcome of fecal microbiota transplantation for ulcerative colitis. J Crohns Colitis. 2025;19(4):jjaf054. Ishikawa D* et al. Anti-inflammatory effects of Bacteroidota strains derived from outstanding donors of fecal microbiota transplantation for the treatment of ulcerative colitis. Inflamm Bowel Dis. 2024;30(11):2136-2145. Nomura K, Ishikawa D* et al., Bacteroidetes species Are correlated with disease activity in ulcerative colitis. J Clin Med., 2021. Corridoni D, Ishikawa D et al., Single-cell atlas of colonic CD8+ T-cells in ulcerative colitis. Nat Med., Sep;26(9):1480-1490, 2020. Conflict of interest: Dr. Ishikawa, Dai: Dr. Ishikawa is a co-founder of Metagen Therapeutics and has received salary support as well as research funding from the company. Nomura, Kei: No conflict of interest Odakura, Rina: No conflict of interest Koma, Masao: No conflict of interest Maruyama, Takafumi: No conflict of interest Mizutani, Sayaka: No conflict of interest Nakato, Gaku: No conflict of interest Katsumata, Ryo: No conflict of interest Zhang, Xiaochen: No conflict of interest Fukuda, Shinji: No conflict of interest Yamada, Takuji: No conflict of interest Shibuya, Tomoyoshi: No conflict of interest Nagahara, Akihito: No conflict of interest