IDDF2023-ABS-0063 Lactobacillus rhamnosus DY801 regulates methionine metabolism and inhibits TH17 cells in the treatment of acute radiochemotherapy-induced bowel injury

Background

During chemoradiotherapy of colorectal cancer, acute chemoradiotherapy-induced bowel injury occurs frequently. Acute injury leads to decreased quality of life, poor treatment compliance and affects overall survival. However, the current treatment for acute injury is limited. Therefore, treating acute chemoradiotherapy-induced bowel injury needs to be addressed in oncology treatment.

Methods

Clinical fecal specimens, mice experiments, and metagenomics were used to explore whether gut microbiome is associated with acute chemoradiotherapy-induced bowel injury. New strains of Lactobacillus were selectively cultured and isolated from human feces. The characteristics and safety of the new strains were accessed using acid and bile salt resistance assay, adhesion assay, acute toxicity test, antibiotic resistance assay, and whole genome sequencing. Mice gavage assay, hybrid strain colonization assay, tumour-bearing experiment, and B-NDG mice were used to investigate whether dominant Lactobacillus can treat acute bowel injury in vivo and whether it affects the efficacy of radiochemotherapy. RNA-sequencing, untargeted metabolomics, metagenomics, CRISPR/Cas9, mass spectrometry, and in vivo mice experiments were conducted to explore the molecular mechanism of the Lactobacillus rhamnosus DY801 treating acute chemoradiotherapy-induced bowel injury. ELISA and LC-MS were used to evaluate the IL-17A, IL-17F and methionine levels in clinical blood specimens.

Results

The gut microbiome, especially Lactobacillus, was closely associated with acute chemoradiotherapy-induced bowel injury. Ten new strains of Lactobacillus were obtained, and three strains were found to have gastric colonization ability, controllable overall safety, and potential therapeutic effects. Lactobacillus could treat an acute injury, among which Lactobacillus rhamnosus DY801 can significantly inhibit the proinflammatory cytokines, treat the injury with the best effect and do not affect the efficacy of chemoradiotherapy of tumours. Specifically, Lactobacillus rhamnosus DY801 treats acute chemoradiotherapy-induced bowel injury through inhibiting Th17 cells in intestinal tissues by the metB gene, increasing methionine metabolism. Clinical specimens tentatively verified that the more severe the acute injury in patients, the lower the methionine level and the higher the IL-17A and IL-17F levels in the blood.

Conclusions

Lactobacillus rhamnosus DY801 regulated methionine metabolism and inhibited Th17 cells in the treatment of the acute radiochemotherapy-induced intestinal injury.