The Gut Microbiota Is Associated with Clearance of <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Independent of Adaptive Immunity
ABSTRACT Clostridium (Clostridioides) difficile, a Gram-positive, anaerobic bacterium, is the leading single cause of nosocomial infections in the United States. A major risk factor for Clostridium difficile infection (CDI) is prior exposure to antibiotics, as they increase susceptibility to CDI by...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2019-02-01
|
| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mSphereDirect.00698-18 |
| _version_ | 1818836585339158528 |
|---|---|
| author | Jhansi L. Leslie Kimberly C. Vendrov Matthew L. Jenior Vincent B. Young |
| author_facet | Jhansi L. Leslie Kimberly C. Vendrov Matthew L. Jenior Vincent B. Young |
| author_sort | Jhansi L. Leslie |
| collection | DOAJ |
| description | ABSTRACT Clostridium (Clostridioides) difficile, a Gram-positive, anaerobic bacterium, is the leading single cause of nosocomial infections in the United States. A major risk factor for Clostridium difficile infection (CDI) is prior exposure to antibiotics, as they increase susceptibility to CDI by altering the membership of the microbial community enabling colonization. The importance of the gut microbiota in providing protection from CDI is underscored by the reported 80 to 90% success rate of fecal microbial transplants in treating recurrent infections. Adaptive immunity, specifically humoral immunity, is also sufficient to protect from both acute and recurrent CDI. However, the role of the adaptive immune system in mediating clearance of C. difficile has yet to be resolved. Using murine models of CDI, we found that adaptive immunity is dispensable for clearance of C. difficile. However, random forest analysis using only two members of the resident bacterial community correctly identified animals that would go on to clear the infection with 66.7% accuracy. These findings indicate that the indigenous gut microbiota independent of adaptive immunity facilitates clearance of C. difficile from the murine gastrointestinal tract. IMPORTANCE Clostridium difficile infection is a major cause of morbidity and mortality in hospitalized patients in the United States. Currently, the role of the adaptive immune response in modulating levels of C. difficile colonization is unresolved. This work suggests that the indigenous gut microbiota is a main factor that promotes clearance of C. difficile from the GI tract. Our results show that clearance of C. difficile can occur without contributions from the adaptive immune response. This study also has implications for the design of preclinical studies testing the efficacy of vaccines on clearance of bacterial pathogens, as inherent differences in the baseline community structure of animals may bias findings. |
| first_indexed | 2024-12-19T03:08:57Z |
| format | Article |
| id | doaj.art-d5acd46ecdab471fabdd0ee27a9c43c3 |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-12-19T03:08:57Z |
| publishDate | 2019-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-d5acd46ecdab471fabdd0ee27a9c43c32022-12-21T20:38:03ZengAmerican Society for MicrobiologymSphere2379-50422019-02-014110.1128/mSphereDirect.00698-18The Gut Microbiota Is Associated with Clearance of <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Independent of Adaptive ImmunityJhansi L. Leslie0Kimberly C. Vendrov1Matthew L. Jenior2Vincent B. Young3Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USADivision of Infectious Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USADepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USADepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USAABSTRACT Clostridium (Clostridioides) difficile, a Gram-positive, anaerobic bacterium, is the leading single cause of nosocomial infections in the United States. A major risk factor for Clostridium difficile infection (CDI) is prior exposure to antibiotics, as they increase susceptibility to CDI by altering the membership of the microbial community enabling colonization. The importance of the gut microbiota in providing protection from CDI is underscored by the reported 80 to 90% success rate of fecal microbial transplants in treating recurrent infections. Adaptive immunity, specifically humoral immunity, is also sufficient to protect from both acute and recurrent CDI. However, the role of the adaptive immune system in mediating clearance of C. difficile has yet to be resolved. Using murine models of CDI, we found that adaptive immunity is dispensable for clearance of C. difficile. However, random forest analysis using only two members of the resident bacterial community correctly identified animals that would go on to clear the infection with 66.7% accuracy. These findings indicate that the indigenous gut microbiota independent of adaptive immunity facilitates clearance of C. difficile from the murine gastrointestinal tract. IMPORTANCE Clostridium difficile infection is a major cause of morbidity and mortality in hospitalized patients in the United States. Currently, the role of the adaptive immune response in modulating levels of C. difficile colonization is unresolved. This work suggests that the indigenous gut microbiota is a main factor that promotes clearance of C. difficile from the GI tract. Our results show that clearance of C. difficile can occur without contributions from the adaptive immune response. This study also has implications for the design of preclinical studies testing the efficacy of vaccines on clearance of bacterial pathogens, as inherent differences in the baseline community structure of animals may bias findings.https://journals.asm.org/doi/10.1128/mSphereDirect.00698-18Clostridium difficileadaptive immunitycolonization resistanceintestinal colonizationmicrobiota |
| spellingShingle | Jhansi L. Leslie Kimberly C. Vendrov Matthew L. Jenior Vincent B. Young The Gut Microbiota Is Associated with Clearance of <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Independent of Adaptive Immunity mSphere Clostridium difficile adaptive immunity colonization resistance intestinal colonization microbiota |
| title | The Gut Microbiota Is Associated with Clearance of <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Independent of Adaptive Immunity |
| title_full | The Gut Microbiota Is Associated with Clearance of <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Independent of Adaptive Immunity |
| title_fullStr | The Gut Microbiota Is Associated with Clearance of <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Independent of Adaptive Immunity |
| title_full_unstemmed | The Gut Microbiota Is Associated with Clearance of <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Independent of Adaptive Immunity |
| title_short | The Gut Microbiota Is Associated with Clearance of <named-content content-type="genus-species">Clostridium difficile</named-content> Infection Independent of Adaptive Immunity |
| title_sort | gut microbiota is associated with clearance of named content content type genus species clostridium difficile named content infection independent of adaptive immunity |
| topic | Clostridium difficile adaptive immunity colonization resistance intestinal colonization microbiota |
| url | https://journals.asm.org/doi/10.1128/mSphereDirect.00698-18 |
| work_keys_str_mv | AT jhansilleslie thegutmicrobiotaisassociatedwithclearanceofnamedcontentcontenttypegenusspeciesclostridiumdifficilenamedcontentinfectionindependentofadaptiveimmunity AT kimberlycvendrov thegutmicrobiotaisassociatedwithclearanceofnamedcontentcontenttypegenusspeciesclostridiumdifficilenamedcontentinfectionindependentofadaptiveimmunity AT matthewljenior thegutmicrobiotaisassociatedwithclearanceofnamedcontentcontenttypegenusspeciesclostridiumdifficilenamedcontentinfectionindependentofadaptiveimmunity AT vincentbyoung thegutmicrobiotaisassociatedwithclearanceofnamedcontentcontenttypegenusspeciesclostridiumdifficilenamedcontentinfectionindependentofadaptiveimmunity AT jhansilleslie gutmicrobiotaisassociatedwithclearanceofnamedcontentcontenttypegenusspeciesclostridiumdifficilenamedcontentinfectionindependentofadaptiveimmunity AT kimberlycvendrov gutmicrobiotaisassociatedwithclearanceofnamedcontentcontenttypegenusspeciesclostridiumdifficilenamedcontentinfectionindependentofadaptiveimmunity AT matthewljenior gutmicrobiotaisassociatedwithclearanceofnamedcontentcontenttypegenusspeciesclostridiumdifficilenamedcontentinfectionindependentofadaptiveimmunity AT vincentbyoung gutmicrobiotaisassociatedwithclearanceofnamedcontentcontenttypegenusspeciesclostridiumdifficilenamedcontentinfectionindependentofadaptiveimmunity |