Abstract
BackgroundClostridium difficile is an opportunistic human intestinal pathogen, and C. difficile infection (CDI) is one of the main causes of antibiotic-induced diarrhea and colitis. One successful approach to combat CDI, particularly recurrent form of CDI, is through transplantation of fecal microbiota from a healthy donor to the infected patient. In this study we investigated the distal gut microbial communities of three CDI patients before and after fecal microbiota transplantation, and we compared these communities to the composition of the donor’s fecal microbiota. We utilized phylogenetic Microbiota Array, high-throughput Illumina sequencing, and fluorescent in situ hybridization to profile microbiota composition down to the genus and species level resolution.ResultsThe original patients’ microbiota had low diversity, was dominated by members of Gammaproteobacteria and Bacilli, and had low numbers of Clostridia and Bacteroidia. At the genus level, fecal samples of CDI patients were rich in members of the Lactobacillus, Streptococcus, and Enterobacter genera. In comparison, the donor community was dominated by Clostridia and had significantly higher diversity and evenness. The patients’ distal gut communities were completely transformed within 3 days following fecal transplantation, and these communities remained stable in each patient for at least 4 months. Despite compositional differences among recipients’ pre-treatment gut microbiota, the transplanted gut communities were highly similar among recipients post-transplantation, were indistinguishable from that of the donor, and were rich in members of Blautia, Coprococcus, and Faecalibacterium. In each case, the gut microbiota restoration led to a complete patient recovery and symptom alleviation.ConclusionWe conclude that C. difficile infection can be successfully treated by fecal microbiota transplantation and that this leads to stable transformation of the distal gut microbial community from the one abundant in aerotolerant species to that dominated by members of the Clostridia.
Highlights
Clostridium difficile is an opportunistic human intestinal pathogen, and C. difficile infection (CDI) is one of the main causes of antibiotic-induced diarrhea and colitis
Fecal microbiota obtained from a healthy donor is processed, standardized, and subsequently transplanted into patients suffering from the recurrent C. difficile infection
Samples were collected from each CDI patient a few days before the transplantation, on days 3 and 7 after transplantation, and periodically with gradually increasing time periods between sample collections based on patients’ availability and ability to provide a fresh stool sample (Figure 1A)
Summary
Clostridium difficile is an opportunistic human intestinal pathogen, and C. difficile infection (CDI) is one of the main causes of antibiotic-induced diarrhea and colitis. Fecal microbiota transplantation (FMT) is gaining a wider acceptance as treatment for recurrent CDI In this technique, fecal microbiota obtained from a healthy donor is processed, standardized, and subsequently transplanted into patients suffering from the recurrent C. difficile infection. Recent studies from our group showed that the eradication of the disease symptoms is accompanied by a dramatic shift in the microbial community as examined by TRFLP and gene sequencing analyses [8,9]. These methods were limited in the achieved taxonomic resolution and the ability to directly quantify microbiota members, and they could not reveal detailed microbiota composition before and after FMT treatment
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