Metabolomic and Microbiome Profiling Reveals the Protective Mechanism of Pyrrosia petiolosa Against Radiation-Induced...

Radiation-induced intestinal injury (RIII) is a common complication of tumor radiotherapy, significantly impacting patients' quality of life and posing challenges for developing effective medical countermeasures. This study investigated the reparative effects of the traditional Chinese medicine Pyrrosia petiolosa (Christ) Ching on radiation damage through in vivo and in vitro models. By integrating gut microbiota and untargeted metabolomics analyses, it elucidated the multidimensional mechanisms through which P. petiolosa regulates the microbiome as well as metabolic homeostasis. In vitro experiments demonstrated that P. petiolosa effectively suppressed radiation-induced inflammatory factors (IL-6, TNF-α, and IL-1β) and alleviated radiation-induced oxidative stress (MDA, GSH, and SOD). In vivo models further confirmed that P. petiolosa significantly alleviated radiation-induced intestinal inflammation and leukopenia, while protecting the structural and functional integrity of mouse small intestinal crypt villi. Mechanistic studies revealed P. petiolosa reshaped the gut microbiota by promoting enrichment of beneficial bacteria such as Bacteroides, concurrently restoring the homeostasis of key metabolic pathways, including glutathione, glycerophospholipids, and the tricarboxylic acid cycle. Analysis of the microbiome-metabolome interaction network revealed that treatment with P. petiolosa altered the correlation patterns between gut microbiota and fecal metabolites, including potentially beneficial bacteria and metabolites associated with inflammatory and oxidative stress responses. These findings suggest that microbiome-metabolome remodeling may contribute to the protective effects of P. petiolosa against radiation-induced intestinal damage. Overall, this study provides preliminary evidence that P. petiolosa may alleviate acute radiation-induced intestinal damage through anti-inflammatory and antioxidant effects accompanied by changes in gut microbiota and metabolic homeostasis, while identifying candidate targets for future functional validation.