作者
Rina Odakura,Dai Ishikawa,Masashi Omori,Takashi Maruyama,Keiichi Haga,Kei Nomura,Mayuko Haraikawa,Qian Zhang,Tomoyoshi Shibuya,Taro Osada,Akihito Nagahara
摘要
Background: In recent years, rectifying imbalances of the gut microbiota with fecal microbiota transplantation (FMT) from healthy donors to patients suffering Ulcerative colitis (UC) have gained clinical interest. As several ongoing trials are exploring the possibility of using FMT to treat UC, discerning factors associated the long-term efficacy of FMT treatment becomes important. Our present study explored the factors related to the efficacy of FMT combined with triple-antibiotic therapy [amoxicillin, fosfomycin, and metronidazole (AFM); (A-FMT)] in patients with UC. Methods: Patients aged 16 years or older suffering from active UC with a Lichtiger’s clinical activity index (CAI) score ≥4 or Mayo endoscopic score (MES) ≥1 participated in the clinical study between March 2014 and October 2019. After rigorous screening, we selected relatives aged 20 years or older, or other volunteer donors. After 2 weeks of oral administration of 3 antibacterial agents, about 200ml of fresh or frozen stool solution of donor stool dissolved in saline solution was obtained by colonoscopy. CAI score at 4 weeks after treatment was defined as "response" if the CAI was ≤9 points and improved by ≥3 points, "remission" if the CAI further improved to ≤3 points, and "relapse" if the CAI increased or treatment was intensified at 48 weeks after treatment in the effective group. Results: Ninety-seven patients (68 males, 29 females, age 39.2 ± 12.9 years, disease duration 8.5 ± 8.0 years, CAI 10.7 ± 3.0, Mayo endoscopic subscore (MES) 1.8 ± 0.7) and 62 donors were included. 93 patients completed A-FMT, with an efficacy rate of 63.9% (ITT) at 4 weeks of treatment and a remission induction rate of 36.1%. The short-term efficacy was associated with pre-treatment Mayo endoscopic score (response P = 0.001, remission P < 0.001), history of corticosteroid treatment (response P = 0.04, remission P = 0.01), and history of tacrolimus treatment (response P = 0.04, remission P = 0.14). The cumulative non-relapse rate was significantly higher in the sibling donor group than in the parent-child donor group (P = 0.001). The age difference between patients and donors also affected the cumulative non-relapse rate (P = 0.01). Conclusion: In our study, the optimal timing for patients to receive A-FMT is before corticosteroid and tacrolimus treatments, and early-stage patients receive fecal transplants from siblings with the best clinical outcomes. While the short-term efficacy of A-FMT was related to the patient's own characteristics, the long-term efficacy was related to patient-donor matching.