Diluted Fecal Community Transplant Restores Clostridioides difficile Colonization Resistance to Antibiotic-Perturbed Murine Communities
ABSTRACT Fecal communities transplanted into individuals can eliminate recurrent Clostridioides difficile infection (CDI) with high efficacy. However, this treatment is only used once CDI becomes resistant to antibiotics or has recurred multiple times. We sought to investigate whether a fecal commun...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2022-08-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mbio.01364-22 |
| _version_ | 1797999707593637888 |
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| author | Nicholas A. Lesniak Sarah Tomkovich Andrew Henry Ana Taylor Joanna Colovas Lucas Bishop Kathryn McBride Patrick D. Schloss |
| author_facet | Nicholas A. Lesniak Sarah Tomkovich Andrew Henry Ana Taylor Joanna Colovas Lucas Bishop Kathryn McBride Patrick D. Schloss |
| author_sort | Nicholas A. Lesniak |
| collection | DOAJ |
| description | ABSTRACT Fecal communities transplanted into individuals can eliminate recurrent Clostridioides difficile infection (CDI) with high efficacy. However, this treatment is only used once CDI becomes resistant to antibiotics or has recurred multiple times. We sought to investigate whether a fecal community transplant (FCT) pretreatment could be used to prevent CDI altogether. We treated male C57BL/6 mice with either clindamycin, cefoperazone, or streptomycin and then inoculated them with the microbial community from untreated mice before challenge with C. difficile. We measured colonization and sequenced the V4 region of the 16S rRNA gene to understand the dynamics of the murine fecal community in response to the FCT and C. difficile challenge. Clindamycin-treated mice became colonized with C. difficile but cleared it naturally and did not benefit from the FCT. Cefoperazone-treated mice became colonized by C. difficile, but the FCT enabled clearance of C. difficile. In streptomycin-treated mice, the FCT was able to prevent C. difficile from colonizing. We then diluted the FCT and repeated the experiments. Cefoperazone-treated mice no longer cleared C. difficile. However, streptomycin-treated mice colonized with 1:102 dilutions resisted C. difficile colonization. Streptomycin-treated mice that received an FCT diluted 1:103 became colonized with C. difficile but later cleared the infection. In streptomycin-treated mice, inhibition of C. difficile was associated with increased relative abundance of a group of bacteria related to Porphyromonadaceae and Lachnospiraceae. These data demonstrate that C. difficile colonization resistance can be restored to a susceptible community with an FCT as long as it complements the missing populations. IMPORTANCE Antibiotic use, ubiquitous with the health care environment, is a major risk factor for Clostridioides difficile infection (CDI), the most common nosocomial infection. When C. difficile becomes resistant to antibiotics, a fecal microbiota transplant from a healthy individual can effectively restore the gut bacterial community and eliminate the infection. While this relationship between the gut bacteria and CDI is well established, there are no therapies to treat a perturbed gut community to prevent CDI. This study explored the potential of restoring colonization resistance to antibiotic-induced susceptible gut communities. We described the effect that gut bacterial community variation has on the effectiveness of a fecal community transplant for inhibiting CDI. These data demonstrated that communities susceptible to CDI can be supplemented with fecal communities but that the effectiveness depended on the structure of the community following the perturbation. Thus, a reduced bacterial community may be able to recover colonization resistance in patients treated with antibiotics. |
| first_indexed | 2024-04-11T11:09:00Z |
| format | Article |
| id | doaj.art-d4a208c06efb4caf9f8cee2be1e4516a |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-04-11T11:09:00Z |
| publishDate | 2022-08-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-d4a208c06efb4caf9f8cee2be1e4516a2022-12-22T04:28:05ZengAmerican Society for MicrobiologymBio2150-75112022-08-0113410.1128/mbio.01364-22Diluted Fecal Community Transplant Restores Clostridioides difficile Colonization Resistance to Antibiotic-Perturbed Murine CommunitiesNicholas A. Lesniak0Sarah Tomkovich1Andrew Henry2Ana Taylor3Joanna Colovas4Lucas Bishop5Kathryn McBride6Patrick D. Schloss7Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USADepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USADepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USADepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USADepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USADepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USADepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USADepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USAABSTRACT Fecal communities transplanted into individuals can eliminate recurrent Clostridioides difficile infection (CDI) with high efficacy. However, this treatment is only used once CDI becomes resistant to antibiotics or has recurred multiple times. We sought to investigate whether a fecal community transplant (FCT) pretreatment could be used to prevent CDI altogether. We treated male C57BL/6 mice with either clindamycin, cefoperazone, or streptomycin and then inoculated them with the microbial community from untreated mice before challenge with C. difficile. We measured colonization and sequenced the V4 region of the 16S rRNA gene to understand the dynamics of the murine fecal community in response to the FCT and C. difficile challenge. Clindamycin-treated mice became colonized with C. difficile but cleared it naturally and did not benefit from the FCT. Cefoperazone-treated mice became colonized by C. difficile, but the FCT enabled clearance of C. difficile. In streptomycin-treated mice, the FCT was able to prevent C. difficile from colonizing. We then diluted the FCT and repeated the experiments. Cefoperazone-treated mice no longer cleared C. difficile. However, streptomycin-treated mice colonized with 1:102 dilutions resisted C. difficile colonization. Streptomycin-treated mice that received an FCT diluted 1:103 became colonized with C. difficile but later cleared the infection. In streptomycin-treated mice, inhibition of C. difficile was associated with increased relative abundance of a group of bacteria related to Porphyromonadaceae and Lachnospiraceae. These data demonstrate that C. difficile colonization resistance can be restored to a susceptible community with an FCT as long as it complements the missing populations. IMPORTANCE Antibiotic use, ubiquitous with the health care environment, is a major risk factor for Clostridioides difficile infection (CDI), the most common nosocomial infection. When C. difficile becomes resistant to antibiotics, a fecal microbiota transplant from a healthy individual can effectively restore the gut bacterial community and eliminate the infection. While this relationship between the gut bacteria and CDI is well established, there are no therapies to treat a perturbed gut community to prevent CDI. This study explored the potential of restoring colonization resistance to antibiotic-induced susceptible gut communities. We described the effect that gut bacterial community variation has on the effectiveness of a fecal community transplant for inhibiting CDI. These data demonstrated that communities susceptible to CDI can be supplemented with fecal communities but that the effectiveness depended on the structure of the community following the perturbation. Thus, a reduced bacterial community may be able to recover colonization resistance in patients treated with antibiotics.https://journals.asm.org/doi/10.1128/mbio.01364-22Clostridioides difficilecolonization resistancemicrobial ecologymicrobiomefecal transplantmice |
| spellingShingle | Nicholas A. Lesniak Sarah Tomkovich Andrew Henry Ana Taylor Joanna Colovas Lucas Bishop Kathryn McBride Patrick D. Schloss Diluted Fecal Community Transplant Restores Clostridioides difficile Colonization Resistance to Antibiotic-Perturbed Murine Communities mBio Clostridioides difficile colonization resistance microbial ecology microbiome fecal transplant mice |
| title | Diluted Fecal Community Transplant Restores Clostridioides difficile Colonization Resistance to Antibiotic-Perturbed Murine Communities |
| title_full | Diluted Fecal Community Transplant Restores Clostridioides difficile Colonization Resistance to Antibiotic-Perturbed Murine Communities |
| title_fullStr | Diluted Fecal Community Transplant Restores Clostridioides difficile Colonization Resistance to Antibiotic-Perturbed Murine Communities |
| title_full_unstemmed | Diluted Fecal Community Transplant Restores Clostridioides difficile Colonization Resistance to Antibiotic-Perturbed Murine Communities |
| title_short | Diluted Fecal Community Transplant Restores Clostridioides difficile Colonization Resistance to Antibiotic-Perturbed Murine Communities |
| title_sort | diluted fecal community transplant restores clostridioides difficile colonization resistance to antibiotic perturbed murine communities |
| topic | Clostridioides difficile colonization resistance microbial ecology microbiome fecal transplant mice |
| url | https://journals.asm.org/doi/10.1128/mbio.01364-22 |
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