P568 Alterations of Intestinal Microbiota in Ulcerative Colitis Patients Treated with Sequential Antibiotic Combination and Faecal Microbiota Transplantation
D. Ishikawa*1, T. Osada1, T. Sasaki2, K. Kuwahara-Arai2, K. Haga1, T. Shibuya1, T. Kodani1, K. Hiramatsu2, S. Watanabe1
1Juntendo University, Department of Gastroenterology, Tokyo, Japan, 2Juntendo University, Department Bacteriology, Tokyo, Japan
Currently, the aetiology of ulcerative colitis (UC) is not understood well. Increasing evidence suggests that the intestinal microbiota is an important component of UC aetiology. Based on this knowledge, faecal microbiota transplantation (FMT), also known as faecal bacteriotherapy is emerging as a new therapeutic approach to restore normal function in the intestinal microbiota. In recent years, we have been interested to improve the efficacy of FMT in UC patients (Am J Gastroenterol 2010;105:1820-9). We have undertaken FMT with the aim of reconstituting an intestinal microbial environment that promotes remission in UC patients.
An antibiotic combination therapy with oral amoxicillin 1500mg/day, fosfomycin 3000mg/day and metronidazole 750mg/day followed by FMT was undertaken. The antibiotic combination was administered to UC patients for two weeks prior to FMT. A family member was selected as donor, and then blood and faecal samples were screened for pathogens according to "Amsterdam protocol for FMT" (Gastroentrology 2013;145:946-953). The donor faecal suspension was transplanted to the patient's caecum as a single application via a colonoscope. Faecal microbiota of the donors and the patients after or before treatment (6 samples from each group, total 24 samples) were processed by sequencing and analysis of the 16S rRNA gene using a Next-generation sequencer MIseq (Illmina). Up to 8,277,985 reads (average 306,592 reads per sample) were obtained, and 17 bacterial phyla 27 strains were identified.
A 100% stacked bar chart was prepared. After a two-week-antibiotics therapy, the proportion of phylum Bacteroidetes significantly decreased from 29.2 ± 19.3% before treatment to 1.0 ± 1.2% (P<0.01), while the proportion of phylum Proteobacteria significantly increased from 9.1% ± 11.7% to 78.6 ± 20.2% (P<0.001). In half of the post-FMT patients, the proportion of phylum Bacteroidetes increased up to the level of donor (average 42.4 ± 10.9%). Further, along with the recovery of the Bacteroidetes strains after FMT, a trend toward an improvement in patients' clinical symptoms score was noted.
FMT carries a promise for a natural and toxicity free intervention to replenishing the large intestine with therapeutically relevant strains of bacteria, and achieve disease remission. To our knowledge, this is the first clinical study of a sequential therapy involving FMT following a combination of antibiotics. We hope that the strategy we have applied may serve as the basis for further progress in understanding how alterations of the intestinal microbiota may become an effective therapeutic strategy for UC patients.