Agarwood essential oils alleviate hypoxia-induced gastric and small intestinal injury.

Agarwood, a traditional Chinese medicine, has been widely used in the treatment of gastrointestinal diseases. The antibacterial and antioxidant properties of agarwood essential oils (EOs) have been well documented. High-altitude (> 2500 m) regions attract tens of millions of visitors worldwide each year; however, the hypoxic environment poses a threat to the health of the body's organ systems, including the digestive system. Additionally, hypoxia has been reported to alter the gut microbiota and metabolites. Our previous study demonstrated that hypoxia exposure triggered ferroptosis in the gastric and small intestinal mucosa. This study aimed to explore the therapeutic effects and potential mechanisms of EOs in hypoxia-induced gastric and small intestinal mucosal injury. EO effects were evaluated based on clinical manifestations, histopathological assessments, and lipid peroxidation as determined by reactive oxygen species (ROS) and 4-hydroxynonenal (4-HNE) levels. We also assessed microbiota changes through 16 S rRNA gene amplicon sequencing and analyzed metabolites using untargeted liquid chromatography-mass spectrometry in the gastric and small intestinal contents of mice. EO treatment significantly alleviated hypoxia-triggered mucosal damage in the stomach and small intestine. Notably, EOs reduced hypoxia-induced lipid peroxidation and partially recovered the microbiota and metabolite disruptions induced by hypoxia. Specifically, Candidatus_Saccharimonas and Akkermansia may contribute to mucosal repair via regulating xanthoxic acid and aspartylglycosamine, and guanosine, respectively. EOs may provide a promising approach for treating hypoxia-induced gastric and small intestinal damage by repressing lipid peroxidation and regulating the microbiota and metabolites.