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P766 Combination therapy of fresh fecal microbial transplantation and antibiotics for ulcerative colitis

Ishikawa D., Takahashi M., Haga K., Shibuya T., Osada T., Watanabe S.

Juntendo University, Department of Gastroenterology, Tokyo, Japan

Background

Fecal microbiota transplantation (FMT) is a potential therapeutic approach to restore normal intestinal microbiota in patients with ulcerative colitis (UC), which is associated with dysbiosis; however, treatment efficacy remains unclear. Hence, we studied the impact of antibiotic pretreatment with amoxicillin, fosfomycin, and metronidazole (AFM therapy) and FMT versus AFM alone.

Methods

Patients with mild-to-severe active UC (n=21 combination-therapy group; n=20 AFM monotherapy group) were included. AFM therapy was administered to patients for 2 weeks until 2 days before FMT. 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. Microbiome analysis was performed by 16S rRNA next-generation sequencing.

Results

Thirty-six patients completed this assessment (n=17 combination-therapy group; n=19 AFM monotherapy group). At 4 weeks after treatment with FMT, clinical responses were observed in 14 patients (82.3%), and the Lichtiger's CAI score decreased from 10.1±3.2 to 5.1±3.7 (mean ± standard deviation; p<0.001). Nine of 14 responders achieved clinical remission (53.0%). A higher clinical response was observed following combination therapy compared to AFM monotherapy. The relative abundance of Bacteroidetes decreased significantly from 20.4% ± 11.1% before treatment to 0.3% ± 0.5% after 2 weeks of AFM pretreatment (p<0.0001). Among 17 cases treated with combination FMT and AFM therapy, the proportion of Bacteroidetes in 14 cases recovered was 27.4% ± 10.8% at 4 weeks after FMT therapy following AFM. We also observed improvements in patients' clinical symptoms scores in all responders. The Bacteroidetes proportion recovered in clinical responders at 4 weeks after FMT was not observed in the AFM monotherapy group. Persistent antimicrobial-associated dysbiosis found in the AFM monotherapy group was reversed by FMT. Furthermore, in endoscopic findings, a highly negative linear correlation was observed between the proportion of Bacteroidetes and the endoscopic sum score in patients treated with combination therapy with AFM and FMT (n=17, r=−0.74, p=0.001). In patients with severe clinical symptoms based on endoscopic scores, the relative abundance of Bacteroidetes did not increase, and improvement of UC symptoms was not observed.

Conclusion

FMT following antimicrobial bowel cleansing synergistically contributes to the recovery of the Bacteroidetes composition, which is associated with clinical response and UC severity. Thus, this therapeutic protocol may be useful for managing UC.