Hyperbaric oxygen augments susceptibility to C. difficile infection by impairing gut microbiota ability to stimulate the HIF-1α-IL-22 axis in ILC3
ABSTRACTHyperbaric oxygen (HBO) therapy is a well-established method for improving tissue oxygenation and is typically used for the treatment of various inflammatory conditions, including infectious diseases. However, its effect on the intestinal mucosa, a microenvironment known to be physiologicall...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2023.2297872 |
| _version_ | 1797368489848078336 |
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| author | José L. Fachi Laís. P. Pral Helder C. Assis Sarah Oliveira Vinícius R. Rodovalho Jefferson A. C. dos Santos Mariane F. Fernandes Valquíria A. Matheus Renata Sesti-Costa Paulo J. Basso Marina Flóro e Silva Niels O. S. Câmara Selma Giorgio Marco Colonna Marco A. R. Vinolo |
| author_facet | José L. Fachi Laís. P. Pral Helder C. Assis Sarah Oliveira Vinícius R. Rodovalho Jefferson A. C. dos Santos Mariane F. Fernandes Valquíria A. Matheus Renata Sesti-Costa Paulo J. Basso Marina Flóro e Silva Niels O. S. Câmara Selma Giorgio Marco Colonna Marco A. R. Vinolo |
| author_sort | José L. Fachi |
| collection | DOAJ |
| description | ABSTRACTHyperbaric oxygen (HBO) therapy is a well-established method for improving tissue oxygenation and is typically used for the treatment of various inflammatory conditions, including infectious diseases. However, its effect on the intestinal mucosa, a microenvironment known to be physiologically hypoxic, remains unclear. Here, we demonstrated that daily treatment with hyperbaric oxygen affects gut microbiome composition, worsening antibiotic-induced dysbiosis. Accordingly, HBO-treated mice were more susceptible to Clostridioides difficile infection (CDI), an enteric pathogen highly associated with antibiotic-induced colitis. These observations were closely linked with a decline in the level of microbiota-derived short-chain fatty acids (SCFAs). Butyrate, a SCFA produced primarily by anaerobic microbial species, mitigated HBO-induced susceptibility to CDI and increased epithelial barrier integrity by improving group 3 innate lymphoid cell (ILC3) responses. Mice displaying tissue-specific deletion of HIF-1 in RORγt-positive cells exhibited no protective effect of butyrate during CDI. In contrast, the reinforcement of HIF-1 signaling in RORγt-positive cells through the conditional deletion of VHL mitigated disease outcome, even after HBO therapy. Taken together, we conclude that HBO induces intestinal dysbiosis and impairs the production of SCFAs affecting the HIF-1α-IL-22 axis in ILC3 and worsening the response of mice to subsequent C. difficile infection. |
| first_indexed | 2024-03-08T17:33:12Z |
| format | Article |
| id | doaj.art-ed1e23da62434203b9437ffe3ad696db |
| institution | Directory Open Access Journal |
| issn | 1949-0976 1949-0984 |
| language | English |
| last_indexed | 2024-03-08T17:33:12Z |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj.art-ed1e23da62434203b9437ffe3ad696db2024-01-02T14:17:24ZengTaylor & Francis GroupGut Microbes1949-09761949-09842024-12-0116110.1080/19490976.2023.2297872Hyperbaric oxygen augments susceptibility to C. difficile infection by impairing gut microbiota ability to stimulate the HIF-1α-IL-22 axis in ILC3José L. Fachi0Laís. P. Pral1Helder C. Assis2Sarah Oliveira3Vinícius R. Rodovalho4Jefferson A. C. dos Santos5Mariane F. Fernandes6Valquíria A. Matheus7Renata Sesti-Costa8Paulo J. Basso9Marina Flóro e Silva10Niels O. S. Câmara11Selma Giorgio12Marco Colonna13Marco A. R. Vinolo14Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USADepartment of Genetics and Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, BrazilDepartment of Genetics and Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, BrazilDepartment of Genetics and Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, BrazilDepartment of Genetics and Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, BrazilDepartment of Genetics and Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, BrazilDepartment of Genetics and Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, BrazilDepartment of Genetics and Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, BrazilHematology and Hemotherapy Center, University of Campinas, Campinas, BrazilDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, BrazilDepartment of Animal Biology, Institute of Biology, University of Campinas, Campinas, BrazilDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, BrazilDepartment of Animal Biology, Institute of Biology, University of Campinas, Campinas, BrazilDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USADepartment of Genetics and Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, BrazilABSTRACTHyperbaric oxygen (HBO) therapy is a well-established method for improving tissue oxygenation and is typically used for the treatment of various inflammatory conditions, including infectious diseases. However, its effect on the intestinal mucosa, a microenvironment known to be physiologically hypoxic, remains unclear. Here, we demonstrated that daily treatment with hyperbaric oxygen affects gut microbiome composition, worsening antibiotic-induced dysbiosis. Accordingly, HBO-treated mice were more susceptible to Clostridioides difficile infection (CDI), an enteric pathogen highly associated with antibiotic-induced colitis. These observations were closely linked with a decline in the level of microbiota-derived short-chain fatty acids (SCFAs). Butyrate, a SCFA produced primarily by anaerobic microbial species, mitigated HBO-induced susceptibility to CDI and increased epithelial barrier integrity by improving group 3 innate lymphoid cell (ILC3) responses. Mice displaying tissue-specific deletion of HIF-1 in RORγt-positive cells exhibited no protective effect of butyrate during CDI. In contrast, the reinforcement of HIF-1 signaling in RORγt-positive cells through the conditional deletion of VHL mitigated disease outcome, even after HBO therapy. Taken together, we conclude that HBO induces intestinal dysbiosis and impairs the production of SCFAs affecting the HIF-1α-IL-22 axis in ILC3 and worsening the response of mice to subsequent C. difficile infection.https://www.tandfonline.com/doi/10.1080/19490976.2023.2297872Hyperbaric oxygenmicrobiotabutyrateclostridioides difficileinnate lymphoid cellsILC3 |
| spellingShingle | José L. Fachi Laís. P. Pral Helder C. Assis Sarah Oliveira Vinícius R. Rodovalho Jefferson A. C. dos Santos Mariane F. Fernandes Valquíria A. Matheus Renata Sesti-Costa Paulo J. Basso Marina Flóro e Silva Niels O. S. Câmara Selma Giorgio Marco Colonna Marco A. R. Vinolo Hyperbaric oxygen augments susceptibility to C. difficile infection by impairing gut microbiota ability to stimulate the HIF-1α-IL-22 axis in ILC3 Gut Microbes Hyperbaric oxygen microbiota butyrate clostridioides difficile innate lymphoid cells ILC3 |
| title | Hyperbaric oxygen augments susceptibility to C. difficile infection by impairing gut microbiota ability to stimulate the HIF-1α-IL-22 axis in ILC3 |
| title_full | Hyperbaric oxygen augments susceptibility to C. difficile infection by impairing gut microbiota ability to stimulate the HIF-1α-IL-22 axis in ILC3 |
| title_fullStr | Hyperbaric oxygen augments susceptibility to C. difficile infection by impairing gut microbiota ability to stimulate the HIF-1α-IL-22 axis in ILC3 |
| title_full_unstemmed | Hyperbaric oxygen augments susceptibility to C. difficile infection by impairing gut microbiota ability to stimulate the HIF-1α-IL-22 axis in ILC3 |
| title_short | Hyperbaric oxygen augments susceptibility to C. difficile infection by impairing gut microbiota ability to stimulate the HIF-1α-IL-22 axis in ILC3 |
| title_sort | hyperbaric oxygen augments susceptibility to c difficile infection by impairing gut microbiota ability to stimulate the hif 1α il 22 axis in ilc3 |
| topic | Hyperbaric oxygen microbiota butyrate clostridioides difficile innate lymphoid cells ILC3 |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2023.2297872 |
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