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 colonized 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. Microbiome analysis at the species level was performed by a method based on hsp60 sequences using Miseq. 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 = .0001). Moreover, in responders treated by A-FMT, the diversity significantly recovered up at 4weeks after FMT (baseline vs after A-FMT; n = 14, 14; p < 0.05) via transplantation of Bacteroidetes cells as supported by the high similarities of bacterial compositions among patients and their donors, in contrast, in the patients treated with FMT monotherapy and AFM monotherapy, there were no cases that exhibited the high similarities with their donors. This combination therapy alleviated intestinal dysbiosis, including loss of species diversity in UC. Eradiation of dysbiotic indigenous species by AFM pretreatment may promote the entry of living cells, improving the bacterial composition of the intestinal microbiota in UC.
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