Antibiotic-Induced Alterations of the Murine Gut Microbiota and Subsequent Effects on Colonization Resistance against <named-content content-type="genus-species">Clostridium difficile</named-content>
ABSTRACT Perturbations to the gut microbiota can result in a loss of colonization resistance against gastrointestinal pathogens such as Clostridium difficile. Although C. difficile infection is commonly associated with antibiotic use, the precise alterations to the microbiota associated with this lo...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2015-09-01
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| Series: | mBio |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.00974-15 |
| _version_ | 1818835486963138560 |
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| author | Alyxandria M. Schubert Hamide Sinani Patrick D. Schloss |
| author_facet | Alyxandria M. Schubert Hamide Sinani Patrick D. Schloss |
| author_sort | Alyxandria M. Schubert |
| collection | DOAJ |
| description | ABSTRACT Perturbations to the gut microbiota can result in a loss of colonization resistance against gastrointestinal pathogens such as Clostridium difficile. Although C. difficile infection is commonly associated with antibiotic use, the precise alterations to the microbiota associated with this loss in function are unknown. We used a variety of antibiotic perturbations to generate a diverse array of gut microbiota structures, which were then challenged with C. difficile spores. Across these treatments we observed that C. difficile resistance was never attributable to a single organism, but rather it was the result of multiple microbiota members interacting in a context-dependent manner. Using relative abundance data, we built a machine learning regression model to predict the levels of C. difficile that were found 24 h after challenging the perturbed communities. This model was able to explain 77.2% of the variation in the observed number of C. difficile per gram of feces. This model revealed important bacterial populations within the microbiota, which correlation analysis alone did not detect. Specifically, we observed that populations associated with the Porphyromonadaceae, Lachnospiraceae, Lactobacillus, and Alistipes were protective and populations associated with Escherichia and Streptococcus were associated with high levels of colonization. In addition, a population affiliated with the Akkermansia indicated a strong context dependency on other members of the microbiota. Together, these results indicate that individual bacterial populations do not drive colonization resistance to C. difficile. Rather, multiple diverse assemblages act in concert to mediate colonization resistance. IMPORTANCE The gastrointestinal tract harbors a complex community of bacteria, known as the microbiota, which plays an integral role preventing its colonization by gut pathogens. This resistance has been shown to be crucial for protection against Clostridium difficile infections (CDI), which are the leading source of hospital-acquired infections in the United States. Antibiotics are a major risk factor for acquiring CDI due to their effect on the normal structure of the indigenous gut microbiota. We found that diverse antibiotic perturbations gave rise to altered communities that varied in their susceptibility to C. difficile colonization. We found that multiple coexisting populations, not one specific population of bacteria, conferred resistance. By understanding the relationships between C. difficile and members of the microbiota, it will be possible to better manage this important infection. |
| first_indexed | 2024-12-19T02:51:29Z |
| format | Article |
| id | doaj.art-a78c8b95ed514351b9363b3faade264b |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-19T02:51:29Z |
| publishDate | 2015-09-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-a78c8b95ed514351b9363b3faade264b2022-12-21T20:38:36ZengAmerican Society for MicrobiologymBio2150-75112015-09-016410.1128/mBio.00974-15Antibiotic-Induced Alterations of the Murine Gut Microbiota and Subsequent Effects on Colonization Resistance against <named-content content-type="genus-species">Clostridium difficile</named-content>Alyxandria M. Schubert0Hamide Sinani1Patrick D. Schloss2Department 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 Perturbations to the gut microbiota can result in a loss of colonization resistance against gastrointestinal pathogens such as Clostridium difficile. Although C. difficile infection is commonly associated with antibiotic use, the precise alterations to the microbiota associated with this loss in function are unknown. We used a variety of antibiotic perturbations to generate a diverse array of gut microbiota structures, which were then challenged with C. difficile spores. Across these treatments we observed that C. difficile resistance was never attributable to a single organism, but rather it was the result of multiple microbiota members interacting in a context-dependent manner. Using relative abundance data, we built a machine learning regression model to predict the levels of C. difficile that were found 24 h after challenging the perturbed communities. This model was able to explain 77.2% of the variation in the observed number of C. difficile per gram of feces. This model revealed important bacterial populations within the microbiota, which correlation analysis alone did not detect. Specifically, we observed that populations associated with the Porphyromonadaceae, Lachnospiraceae, Lactobacillus, and Alistipes were protective and populations associated with Escherichia and Streptococcus were associated with high levels of colonization. In addition, a population affiliated with the Akkermansia indicated a strong context dependency on other members of the microbiota. Together, these results indicate that individual bacterial populations do not drive colonization resistance to C. difficile. Rather, multiple diverse assemblages act in concert to mediate colonization resistance. IMPORTANCE The gastrointestinal tract harbors a complex community of bacteria, known as the microbiota, which plays an integral role preventing its colonization by gut pathogens. This resistance has been shown to be crucial for protection against Clostridium difficile infections (CDI), which are the leading source of hospital-acquired infections in the United States. Antibiotics are a major risk factor for acquiring CDI due to their effect on the normal structure of the indigenous gut microbiota. We found that diverse antibiotic perturbations gave rise to altered communities that varied in their susceptibility to C. difficile colonization. We found that multiple coexisting populations, not one specific population of bacteria, conferred resistance. By understanding the relationships between C. difficile and members of the microbiota, it will be possible to better manage this important infection.https://journals.asm.org/doi/10.1128/mBio.00974-15 |
| spellingShingle | Alyxandria M. Schubert Hamide Sinani Patrick D. Schloss Antibiotic-Induced Alterations of the Murine Gut Microbiota and Subsequent Effects on Colonization Resistance against <named-content content-type="genus-species">Clostridium difficile</named-content> mBio |
| title | Antibiotic-Induced Alterations of the Murine Gut Microbiota and Subsequent Effects on Colonization Resistance against <named-content content-type="genus-species">Clostridium difficile</named-content> |
| title_full | Antibiotic-Induced Alterations of the Murine Gut Microbiota and Subsequent Effects on Colonization Resistance against <named-content content-type="genus-species">Clostridium difficile</named-content> |
| title_fullStr | Antibiotic-Induced Alterations of the Murine Gut Microbiota and Subsequent Effects on Colonization Resistance against <named-content content-type="genus-species">Clostridium difficile</named-content> |
| title_full_unstemmed | Antibiotic-Induced Alterations of the Murine Gut Microbiota and Subsequent Effects on Colonization Resistance against <named-content content-type="genus-species">Clostridium difficile</named-content> |
| title_short | Antibiotic-Induced Alterations of the Murine Gut Microbiota and Subsequent Effects on Colonization Resistance against <named-content content-type="genus-species">Clostridium difficile</named-content> |
| title_sort | antibiotic induced alterations of the murine gut microbiota and subsequent effects on colonization resistance against named content content type genus species clostridium difficile named content |
| url | https://journals.asm.org/doi/10.1128/mBio.00974-15 |
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