Hyperbaric oxygen improves combined drug-induced hyperuricemia model in rats by remodeling gut microbiota and regulating host metabolism

This study aimed to investigate the ameliorative effect of hyperbaric oxygen (HBO) on a rat model of hyperuricemia induced by combined drugs and its underlying mechanism. A rat model of drug-induced hyperuricemia (HUA)was established by using a combination of yeast, potassium oxonate (PO) and hypoxanthine (Hx). During the modeling process, hyperbaric oxygen therapy was also administered. Serum uric acid (UA), creatinine (Cr)and blood urea nitrogen (BUN)levels were measured, and HE staining was used to evaluate the histopathological damage of small intestine and kidney tissues. Serum non-targeted metabolomics analysis was conducted, and 16 S rRNA gene sequencing was used to analyze the changes in intestinal flora structure, to evaluate the therapeutic effect of hyperbaric oxygen therapy. The results showed that HBO therapy could significantly reduce the UA, Cr and BUN levels and alleviate the histopathological damage of small intestine and kidney tissues in model rats. At the same time, HBO therapy could regulate the imbalance of intestinal flora, reduce potential pathogenic bacteria, and reduce the endogenous production of UA by decreasing the relative abundance of Bacteroides and Alistipes. Further serum metabolomics analysis indicated that HBO therapy could improve the differential metabolites in HUA rats, and the pathways of these differential metabolites were mainly related to glutathione metabolism, as well as d-glutamine and d-glutamate metabolism. HBO therapy could regulate key pathways such as purine metabolism and amino acid metabolism, and promote the generation of UA excretion-related metabolites. This study confirmed that HBO could improve combined drug-induced HUA by remodeling the intestinal flora structure and regulating the host metabolic pathways, providing new experimental evidence and potential targets for non-pharmacological treatment of HUA.