P052 Combination therapy of fresh fecal microbial transplantation and triple-antibiotic therapy for ulcerative colitis
Authors: Dai Ishikawa , Takashi Sasaki , Masahito Takahashi , Koki Okahara , Shoko Ito , Keiichi Haga , Tomoyoshi Shibuya , Taro Osada , Akihito Nagahara 
Published: July 2019

BACKGROUND:
Fecal microbiota transplantation (FMT) has proved its efficacy for treating recurrent Clostridium difficile infection, but an effective FMT protocol is still yet to be found for treating ulcerative colitis (UC). We previously demonstrated that fresh fecal-microbiota transplantation (FMT) following triple-antibiotic therapy [amoxicillin, fosfomycin, and metronidazole (AFM); A-FMT] induced dramatic changes in the phylum Bacteroidetes, which constitutes a critical factor correlated with clinical responses. Furthermore, we also reported that A-FMT combination therapy contributed to the microbiological improvement of intestinal dysbiosis in UC patients via successful transplantation of live Bacteroidetes cells from donors. Eradication of dysbiotic indigenous Bacteroidetes species by AFM pretreatment may promote the entry of living Bacteroidetes cells, thereby improving the dysbiosis of intestinal microbiota induced by UC. Here, we evaluated the efficacy of A-FMT compared to AFM monotherapy and examined factors correlated with clinical response.

METHODS:
This was an open label, non-randomized, prospective control study of the use of FMT in treating UC, following AFM pre-treatment. This clinical study included participants above 20 years of age. These patients were diagnosed with active UC, with a Lichtiger's Clinical Activity Index (CAI) of 5 or more, or with an endoscopic Mayo clinic score of 1 or more, between July 2014 and March 2017. Patients' spouses or relatives were selected as donor candidates. Donor fecal samples were collected on the day of administration and transferred into the patient's colon via colonoscopy within 6 h. The clinical features of UC were judged using CAI scores before treatment and 4 weeks after treatment. Clinical responses were defined as a CAI of less than 10 points and a decrease of 3 or more points, and clinical remission was defined as a CAI of 3 points or less.

RESULTS:
Patients with mild-to-severe active UC (n = 55 A-FMT group; n = 37 AFM monotherapy group) were included in this assessment. Seventy-nine patients completed this assessment (n = 47 A-FMT group; n = 32 AFM monotherapy group). Although the Mayo score was slightly higher in the A-FMT group, no significant difference was observed between the 2 treatment groups. No serious adverse events were observed during the study. At 4 weeks after treatment with FMT, the clinical responses were observed in 31 patients {Per Protocol Set (PPS): 66.0%) in the A-FMT group, resulting higher than of the AFM monotherapy group (PPS: 56.3%). In A-FMT group, the clinical remission rate was observed to be significantly higher than AFM monotherapy (A-FMT group 40.4%, AFM monotherapy 18.6%; P = 0.04). The endoscopic sum score was associated with clinical responses (Responders 7.5 ± 3.2, Non-responders 5.1 ± 3.6; P = 0.03) in A-FMT.

CONCLUSION(S):
A-FMT combination therapy exhibited reassuring clinical outcomes in comparison to AFM monotherapy. Further follow-up studies are required to evaluate the long-term efficacy of this FMT protocol, and it is possible that this protocol may become a useful strategy for the management of patients with UC.