Effect of lactobacillus rhamnosus DY801 on methionine metabolism and Th17 cells in the treatment of acute radiochemotherapy induced bowel injury.

person Lu Yu Nanfang Hospital Southern Medical University, Guangzhou, China info_outline Lu Yu, Zhenhui Chen, Hongying Fan, Yi Ding

Authors person Lu Yu Nanfang Hospital Southern Medical University, Guangzhou, China info_outline Lu Yu, Zhenhui Chen, Hongying Fan, Yi Ding Organizations Nanfang Hospital Southern Medical University, Guangzhou, China, Southern Medical University, Guangzhou, China, Nanfang Hospital, Southern Medical University, Guangzhou, China Abstract Disclosures Research Funding National Natural Science Foundation of China Background: Radiation and chemotherapy are important treatments for patients with pelvic malignant tumors, and they will inevitably lead to the occurrence of radiochemotherapy-induced intestinal injury. Acute radiochemotherapy-induced intestinal injury reduces the quality of life and treatment compliance of patients, which ultimately affects overall survival. However, at present, the treatment of acute intestinal injury is limited. Therefore, alleviating acute radiochemotherapy-induced intestinal injury is an important scientific problem to be solved urgently in tumor treatment. Methods: The stool samples of patients before and after treatment were analyzed by 16S rRNA sequencing to explore the intestinal bacteria associated with radiochemotherapy-induced intestinal injury. The changes in intestinal bacteria and metabolism related to radiochemotherapy-induced intestinal injury were explored through mice in vivo experiments, metagenomics, and non-target metabolomics analysis. New strains of Lactobacillus were obtained from fresh human fecal samples. The molecular mechanism of the therapeutic effect of Lactobacillus rhamnosus DY801 was explored through in vivo experiments, RNA-sequencing, Crispr/cas9 gene knockout, immunohistochemistry, flow cytometry, LC/MS, and western blot. Results: 16S rRNA sequencing of stool samples from patients before and after treatment suggested that the abundance of Lactobacillus and Bacteroides decreased after radiotherapy and chemotherapy. In vivo experiments in mice showed that the decrease in abundance of Lactobacillus and Bacteroides, the decrease of methionine metabolism, and the increase of activated Th17 cells were related to the severity of radiochemotherapy-induced intestinal injury. Ten new strains of Lactobacillus were isolated, cultured, and identified from the feces of matched normal people. Among them, Lactobacillus rhamnosus DY801 had a resistance to acid and bile salt, and has the strongest ability to treat radiochemotherapy-induced intestinal injury. In vivo and in vitro experiments suggest that Lactobacillus rhamnosus DY801 inhibited the proinflammatory Th17 cells through methionine, a production of metB gene, and significantly improve acute intestinal injury. Conclusions: Lactobacillus rhamnosus DY801 regulated methionine metabolism and inhibited Th17 cells in the treatment of the acute radiochemotherapy-induced intestinal injury.