Recently, a collaborative study between Professor Yongjun Lu's team from the School of Life Sciences at Sun Yat-sen University and Professor Hui Wang's team from the Sixth Affiliated Hospital of Sun Yat-sen University has revealed the pathogenesis of radiation proctitis mediated by radiation-induced gut microbiota and metabolic dysregulation. The related findings were published in "Advanced Science."
Radiation proctitis is a common side effect following radiotherapy for pelvic malignancies such as prostate, rectal, and uterine tumors, with a high incidence rate and a lack of effective clinical treatments. Radiation can lead to dysbiosis of the gut microbiota; however, the co-metabolites and regulatory network characteristics involved in the host-microbiota interaction in radiation proctitis have not been elucidated.
In this study, researchers used a radiation proctitis mouse model and multi-omics strategies to characterize the interaction between gut microbiota and their metabolites with the host immune system to reveal the mechanism by which gut microbiota participate in radiation protection through their co-metabolites. Metabolomic results showed a significant decrease in the concentration of the gut co-metabolite 3-hydroxybutyric acid (3HB) in the feces and serum of radiation proctitis mice and radiation therapy patients, which was negatively correlated with the expression levels of the pro-inflammatory cytokine IL6.
Furthermore, the researchers further elucidated the radiation-protective role and mechanism of 3HB in intestinal inflammation and tissue damage, showing that 3HB significantly improved radiation-induced injury by downregulating IL6 expression mediated by G protein-coupled receptor 43 (GPR43) in radiation proctitis mice. Additionally, microbial analysis revealed a significant decrease in the abundance of the potential probiotic Akkermansia muciniphila in the intestines of radiation proctitis mice and radiation therapy patients compared to the untreated control group; oral gavage of A. muciniphila significantly increased 3HB concentration, downregulated GPR43 and IL6 expression, and improved radiation damage.
The first author of the paper, Associate Researcher Zhenhuang Ge from the School of Life Sciences at Sun Yat-sen University, stated that the above results indicate the relevance of radiation-induced gut microbiota and metabolic dysregulation to the pathogenesis of radiation proctitis, and targeting the "gut-immune" axis pathway can significantly improve tissue damage following radiation. This study provides new preventive and therapeutic strategies for alleviating radiation-induced injuries in clinical practice.
For more information on the related paper, please visit: http://doi.org/10.1002/advs.202306217
