ABSTRACT
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 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.
Subject(s)
Clostridioides difficile , Clostridium Infections , Gastrointestinal Microbiome , Hyperbaric Oxygenation , Mice , Animals , Nuclear Receptor Subfamily 1, Group F, Member 3 , Immunity, Innate , Hyperbaric Oxygenation/adverse effects , Interleukin-22 , Dysbiosis/therapy , Lymphocytes , Butyrates/pharmacology , Fatty Acids, Volatile/pharmacology , Anti-Bacterial Agents/pharmacologyABSTRACT
BACKGROUND: The repair of burns in diabetic patients is a clinical problem. It is relevant to study alternative therapies that can improve the healing process. Our aim was to investigate the effects of Solidago chilensis associated or not with laser on burns in diabetic rats. METHODS: The animals were divided in four groups (n = 30): C- without treatment; S- S. chilensis extract; L-laser irradiated; LS- laser and S. chilensis. In 7, 14 and 21 days samples were collected after the injury to structural, morphometric and molecular analysis. RESULTS: Our results demonstrate the association of S. chilensis and laser reduced the inflammatory infiltrate and favored the angiogenesis. In the groups treated only with laser or with the plant extract showed higher levels of VEGF. The low-level laser therapy (LLLT) promoted higher collagen I and reduction of collagen III. It was also observed higher MMP-2 activation and a decreasing of the active isoform of MMP-9 in the S, L and LS groups. CONCLUSIONS: The treatments improved the repair of burns in diabetic rats, since it reduced the inflammatory infiltrate and favored the collagen organization presenting similar effects in the burn repair of the diabetics.