P463 Combination therapy of fresh faecal microbial transplantation and antibiotics for ulcerative colitis
D. Ishikawa*, T. Osada, K. Haga, T. Kodani, T. Shibuya, S. Watanabe
Juntendo University, Department of Gastroenterology, Tokyo, Japan
Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI). However, the efficacy of FMT for ulcerative colitis (UC) is controversial. There are no established standard practices for FMT therapy; therefore, it is not known whether fresh or frozen FMT is better as transplanted stool. Bacteriologically, many bacterial taxonomic groups other than spore-forming bacteria, such as species within the Bacillus and Clostridium genera, are susceptible to death at temperatures of -20°C, indicating that the composition of living bacterial cells would be different for fresh and frozen FMT. Previous studies have reported that frozen FMT has high efficacy for CDI, which may be explained by transplantation of spore-forming or freeze-tolerant bacteria.
In the present study, we hypothesised that pretreatment with amoxicillin, fosfomycin, and metronidazole (AFM therapy), which can also induce improvement and remission in UC patients, could act synergistically with fresh FMT. Of 25 patients enrolled, 4 received FMT alone, and 21 were treated AFM therapy for 2 weeks as pretreatment before FMT.
After pretreatment antibiotics, the relative abundance of Bacteroidetes decreased significantly. Bacteroidetes recovery at 4 weeks after FMT was dependent on endoscopic severity and correlated with clinical response. To identify the key species related to UC amongst the Bacteroidetes phylum, we constructed a microbiome analysis method based on Bacteroidetes hsp60 sequences using Miseq. We found dysbiosis in intestinal flora resulting from UC primarily involved the loss of species diversity and evenness amongst Bacteroidetes, resulting in hyper- and hypoproliferation of a particular species. Moreover, this combination therapy alleviated intestinal dysbiosis, including loss of species diversity amongst Bacteroidetes. Fresh FMT following AFM pretreatment contributed to the improvement of intestinal dysbiosis in patients with UC via transplantation of living Bacteroidetes cells from donors. Suppression of the indigenous bacteria with the system of commensal colonisation factor or antagonistic abilities by AFM pretreatment before FMT may have promoted the new entry of living Bacteroidetes cells derived from donors by FMT, thereby improving the bacterial composition of the intestinal microbiota in patients with UC at 4 weeks after fresh FMT.
To the best of our knowledge, this is the first report on combination therapy with fresh FMT and AFM pretreatment in patients with UC. The strategy presented in this study may serve as a basis for further investigations of the mechanisms through which the intestinal microbiota is altered following this therapy.