Complete Microbiota Engraftment Is Not Essential for Recovery from Recurrent <named-content content-type="genus-species">Clostridium difficile</named-content> Infection following Fecal Microbiota Transplantation
ABSTRACT Bacterial communities from subjects treated for recurrent Clostridium difficile infection (rCDI) by fecal microbiota transplantation (FMT), using either heterologous donor stool samples or autologous stool samples, were characterized by Illumina next-generation sequencing. As previously rep...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2016-12-01
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| Series: | mBio |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.01965-16 |
| _version_ | 1818844470686253056 |
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| author | Christopher Staley Colleen R. Kelly Lawrence J. Brandt Alexander Khoruts Michael J. Sadowsky |
| author_facet | Christopher Staley Colleen R. Kelly Lawrence J. Brandt Alexander Khoruts Michael J. Sadowsky |
| author_sort | Christopher Staley |
| collection | DOAJ |
| description | ABSTRACT Bacterial communities from subjects treated for recurrent Clostridium difficile infection (rCDI) by fecal microbiota transplantation (FMT), using either heterologous donor stool samples or autologous stool samples, were characterized by Illumina next-generation sequencing. As previously reported, the success of heterologous FMT (90%) was superior to that of autologous FMT (43%) (P = 0.019), and post-FMT intestinal bacterial communities differed significantly between treatment arms (P < 0.001). Subjects cured by autologous FMT typically had greater abundances of the Clostridium XIVa clade and Holdemania bacteria prior to treatment, and the relative abundances of these groups increased significantly after FMT compared to heterologous FMT and pre-FMT samples. The typical shift to post-FMT, donor-like assemblages, featuring high relative abundances of genera within the Bacteroidetes and Firmicutes phyla, was not observed in the autologous FMT subjects. Autologous FMT patient bacterial communities were significantly different in composition than those for heterologous FMT patients and donors (P < 0.001). The SourceTracker program, which employs a Bayesian algorithm to determine source contributions to sink communities, showed that patients initially treated by heterologous FMT had significantly higher percentages of engraftment (i.e., similarity to donor communities, mean value of 74%) compared to those who suffered recurrence following autologous FMT (1%) (P ≤ 0.013). The findings of this study suggest that complete donor engraftment may be not necessary if functionally critical taxa are present in subjects following antibiotic therapy. IMPORTANCE This study provides a detailed characterization of fecal bacterial communities in subjects who participated in a previously published randomized clinical trial to treat recurrent C. difficile infection (rCDI). Bacterial communities were characterized to determine differences between subjects who received fecal bacteria either from healthy donor stool samples or their own stool samples as “placebo” in order to determine which groups of bacteria were most important in achieving a cure. The results of this study suggested that bacteria associated with secondary bile acid metabolism could potentially provide resistance to infection and that complete transfer of healthy donor microorganisms was not necessary to resolve CDI following unsuccessful antibiotic treatment. |
| first_indexed | 2024-12-19T05:14:17Z |
| format | Article |
| id | doaj.art-3310be38804c496a96615ccdd2b8da9d |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-19T05:14:17Z |
| publishDate | 2016-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-3310be38804c496a96615ccdd2b8da9d2022-12-21T20:34:44ZengAmerican Society for MicrobiologymBio2150-75112016-12-017610.1128/mBio.01965-16Complete Microbiota Engraftment Is Not Essential for Recovery from Recurrent <named-content content-type="genus-species">Clostridium difficile</named-content> Infection following Fecal Microbiota TransplantationChristopher Staley0Colleen R. Kelly1Lawrence J. Brandt2Alexander Khoruts3Michael J. Sadowsky4BioTechnology Institute, University of Minnesota, St. Paul, Minnesota, USADepartment of Medicine, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, USADepartment of Medicine, Division of Gastroenterology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York, USABioTechnology Institute, University of Minnesota, St. Paul, Minnesota, USABioTechnology Institute, University of Minnesota, St. Paul, Minnesota, USAABSTRACT Bacterial communities from subjects treated for recurrent Clostridium difficile infection (rCDI) by fecal microbiota transplantation (FMT), using either heterologous donor stool samples or autologous stool samples, were characterized by Illumina next-generation sequencing. As previously reported, the success of heterologous FMT (90%) was superior to that of autologous FMT (43%) (P = 0.019), and post-FMT intestinal bacterial communities differed significantly between treatment arms (P < 0.001). Subjects cured by autologous FMT typically had greater abundances of the Clostridium XIVa clade and Holdemania bacteria prior to treatment, and the relative abundances of these groups increased significantly after FMT compared to heterologous FMT and pre-FMT samples. The typical shift to post-FMT, donor-like assemblages, featuring high relative abundances of genera within the Bacteroidetes and Firmicutes phyla, was not observed in the autologous FMT subjects. Autologous FMT patient bacterial communities were significantly different in composition than those for heterologous FMT patients and donors (P < 0.001). The SourceTracker program, which employs a Bayesian algorithm to determine source contributions to sink communities, showed that patients initially treated by heterologous FMT had significantly higher percentages of engraftment (i.e., similarity to donor communities, mean value of 74%) compared to those who suffered recurrence following autologous FMT (1%) (P ≤ 0.013). The findings of this study suggest that complete donor engraftment may be not necessary if functionally critical taxa are present in subjects following antibiotic therapy. IMPORTANCE This study provides a detailed characterization of fecal bacterial communities in subjects who participated in a previously published randomized clinical trial to treat recurrent C. difficile infection (rCDI). Bacterial communities were characterized to determine differences between subjects who received fecal bacteria either from healthy donor stool samples or their own stool samples as “placebo” in order to determine which groups of bacteria were most important in achieving a cure. The results of this study suggested that bacteria associated with secondary bile acid metabolism could potentially provide resistance to infection and that complete transfer of healthy donor microorganisms was not necessary to resolve CDI following unsuccessful antibiotic treatment.https://journals.asm.org/doi/10.1128/mBio.01965-16 |
| spellingShingle | Christopher Staley Colleen R. Kelly Lawrence J. Brandt Alexander Khoruts Michael J. Sadowsky Complete Microbiota Engraftment Is Not Essential for Recovery from Recurrent <named-content content-type="genus-species">Clostridium difficile</named-content> Infection following Fecal Microbiota Transplantation mBio |
| title | Complete Microbiota Engraftment Is Not Essential for Recovery from Recurrent <named-content content-type="genus-species">Clostridium difficile</named-content> Infection following Fecal Microbiota Transplantation |
| title_full | Complete Microbiota Engraftment Is Not Essential for Recovery from Recurrent <named-content content-type="genus-species">Clostridium difficile</named-content> Infection following Fecal Microbiota Transplantation |
| title_fullStr | Complete Microbiota Engraftment Is Not Essential for Recovery from Recurrent <named-content content-type="genus-species">Clostridium difficile</named-content> Infection following Fecal Microbiota Transplantation |
| title_full_unstemmed | Complete Microbiota Engraftment Is Not Essential for Recovery from Recurrent <named-content content-type="genus-species">Clostridium difficile</named-content> Infection following Fecal Microbiota Transplantation |
| title_short | Complete Microbiota Engraftment Is Not Essential for Recovery from Recurrent <named-content content-type="genus-species">Clostridium difficile</named-content> Infection following Fecal Microbiota Transplantation |
| title_sort | complete microbiota engraftment is not essential for recovery from recurrent named content content type genus species clostridium difficile named content infection following fecal microbiota transplantation |
| url | https://journals.asm.org/doi/10.1128/mBio.01965-16 |
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