Hyperbaric oxygen augments susceptibility to C. difficile infection by impairing gut microbiota ability to stimulate the HIF-1α-IL-22 axis in ILC3

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Fachi, Jose L. ; Pral, Lais. P. ; Assis, Helder C. ; Oliveira, Sarah ; Rodovalho, Vinicius R. ; dos Santos, Jefferson A. C. ; Fernandes, Mariane F. ; Matheus, Valquiria A. ; Sesti-Costa, Renata ; Basso, Paulo J. ; Floro e Silva, Marina ; Camara, Niels O. S. ; Giorgio, Selma ; Colonna, Marco ; Vinolo, Marco A. R.

• Tipo de documento: Artigo Científico
• Fonte: GUT MICROBES; v. 16, n. 1, p. 26-pg., 2024-12-31.

Resumo

Hyperbaric 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 ROR gamma t-positive cells exhibited no protective effect of butyrate during CDI. In contrast, the reinforcement of HIF-1 signaling in ROR gamma t-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-1 alpha-IL-22 axis in ILC3 and worsening the response of mice to subsequent C. difficile infection. (AU)

• Processo FAPESP: 17/06577-9 - Mecanismos envolvidos no efeito protetor dos ácidos graxos de cadeia curta frente à colite associada ao Clostridium difficile
• Beneficiário: José Luís Fachi
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 18/15313-8 - Análise dos mecanismos moleculares envolvidos na interação de metabólitos da microbiota e células do hospedeiro durante a inflamação
• Beneficiário: Marco Aurélio Ramirez Vinolo
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores - Fase 2