P863 Eradication of dysbiotic indigenous species by multiple antibiotic pre-treatment contribute to effective faecal microbiota transplantation

Abstract

Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection. To provide effective FMT protocol for ulcerative colitis (UC) has been desired. We previously reported that the combination therapy with multiple antibiotic therapy (AFM: amoxicillin, fosfomycin and metronidazole) and FMT (Antibiotic FMT: A-FMT) synergistically contributes to the recovery of the phylum Bacteroidetes composition, which is associated with high clinical response for UC. Here, we constructed further additional microbial analyses at the species level to confirm whether Bacteroidetes species from donors actually colonised and contribute to its effective transplantation. AFM therapy was administered to patients for 2 weeks until 2 days before FMT. Donor fecal samples were collected on the day of administration and transferred via colonoscopy within 6 h. Microbial analysis at the species level was performed by a method based on hsp60 sequences using next generation sequencing technique. We found that dysbiosis in UC was involved the loss of species diversity among Bacteroidetes, resulting in hyper- and hypoproliferation of particular species. (Simpson’s diversity index; UC vs. healthy donors; n = 27, 25; p = 0.0001). Moreover, in responders treated by A-FMT, the diversity significantly recovered up at 4 weeks after FMT (baseline vs. after A-FMT; n = 14, 14; p < 0.05) via transplantation of Bacteroidetes cells. In order to evaluate the influence of bacterial transplantation from donors to recipients, we calculated the similarities of species compositions among 86 samples from patients (A-FMT, AFM monotherapy, single FMT monotherapy; n = 17, 3, 3) at base line, patients after AFM, patients at 4 weeks post FMT and their donors. Among 14 clinical responders treated with A-FMT, species components in 9 responders at 4 weeks post A-FMT were most similar or second most similar to their individual donors, whose probability is 1/3655 or 1/1288. In contrast, in the clinical non-responders, patients treated with AFM monotherapy and patients treated with single FMT monotherapy, there were no cases that exhibited the most or second similarities with their individual donors. These results suggested that living cells of the Bacteroidetes were transplanted effectively from donor to recipient simultaneously with clinical improvement by A-FMT. This combination therapy alleviated intestinal dysbiosis, including loss of species diversity in UC. Eradication of dysbiotic indigenous species by AFM pre-treatment may promote the entry of living cells, improving the bacterial composition of the intestinal microbiota in UC.