セミナー情報

Clostridium difficile-associated disease (CDAD) is the major known cause of antibiotic-induced diarrhea and colitis, and the disease is thought to result from persistent disruption of commensal gut microbiota. Bacteriotherapy, by way of fecal microbial transplantation (FMT), can be used to treat recurrent CDAD, which is thought to reestablish the normal colonic microflora. However, limitations of conventional microbiologic techniques have, until recently, precluded testing of this idea. We have used terminal-restriction fragment length polymorphism and 16S rRNA gene sequencing approaches to characterize the bacterial composition of the colonic microflora in patients suffering from recurrent CDAD before and after treatment by FMT from a healthy donor. Although the patient's residual colonic microbiota, prior to therapy was deficient in members of the bacterial divisions-Firmicutes and Bacteriodetes, transplantation had a dramatic impact on the composition of the patient's gut microbiota. By 14 days post-transplantation, the fecal bacterial composition of the recipient was highly similar to that of the donor and was dominated by Bacteroides spp. strains and an uncharacterized butyrate producing bacterium. The change in bacterial composition was accompanied by resolution of the patient's symptoms. The striking similarity of the recipient's and donor's intestinal microbiota following after bacteriotherapy suggests that the donor's bacteria quickly occupied their requisite niches resulting in restoration of both the structure and function of the microbial communities present. We sought to overcome many of the barriers in our clinical FMT program by using standardized frozen fecal material from a screened standard donor. Standardization of material preparation significantly simplified the practical aspects of FMT without loss of apparent efficacy in clearing recurrent CDI – the overall success rate was 93%. Current studies using large-scale 16S-based pyrosequencing showed rapid engraftment of donor microbiota and flexibility in microbial diversity leading to healthy patients.