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

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.

A Next-Generation Bacteria (Akkermansia muciniphila BAA-835) Presents Probiotic Potential Against Ovalbumin-Induced Food Allergy in Mice.

Next-generation microorganisms have recently gained prominence in the scientific community, mainly due to their probiotic and postbiotic potentials. However, there are few studies that investigate these potentials in food allergy models. Therefore, the present study was designed to evaluate the probiotic potential of Akkermansia muciniphila BAA-835 in an ovalbumin food allergy (OVA) model and also analyse possible postbiotic potential. To access the probiotic potential, clinical, immunological, microbiological, and histological parameters were evaluated. In addition, the postbiotic potential was also evaluated by immunological parameters. Treatment with viable A. muciniphila was able to mitigate weight loss and serum levels of IgE and IgG1 anti-OVA in allergic mice. In addition, the ability of the bacteria to reduce the injury of the proximal jejunum, the eosinophil and neutrophil influx, and the levels of eotaxin-1, CXCL1/KC, IL4, IL6, IL9, IL13, IL17, and TNF, was clear. Furthermore, A. muciniphila was able to attenuate dysbiotic signs of food allergy by mitigating Staphylococcus levels and yeast frequency in the gut microbiota. In addition, the administration of the inactivated bacteria attenuated the levels of IgE anti-OVA and eosinophils, indicating its postbiotic effect. Our data demonstrate for the first time that the oral administration of viable and inactivated A. muciniphila BAA-835 promotes a systemic immunomodulatory protective effect in an in vivo model of food allergy to ovalbumin, which suggests its probiotic and postbiotic properties.