Immune modulation effects and safety of Lactobacillus casei variety rhamnosus in a chemotherapy-induced intestinal mucositis mouse model

Background: Intestinal mucositis remained one of the most deleterious side effects in cancer patients undergoing chemotherapy. 5-Fluorouracil (5-FU) treatment was reported to affect the abundance of gut microbiota. In this study, we hypothesize that the probiotics could preserve gut ecology, ameliorate inflammation and protect epithelium by maintaining the tight junction integrity via immune modulations of enterocytes and intestinal stem cells. Our aim is to characterize these changes and to investigate the immune modulation effects and safety of probiotic via a 5-FU-induced intestinal mucositis mouse model.Methods 5-FU-injected BALB/c mice were used. They were either orally administrated saline or probiotic suspension of Lactobacillus casei variety rhamnosus (Lcr35). Diarrhea score, serum pro-nflammatory cytokines, intestinal histology and T-cells subtypes were assessed. Immunostaining analysis for intestinal stem cells CD44 and Ki67 proliferation were processed. Samples of blood and internal organs were investigated for bacteria translocation.Results Diarrhea was attenuated significantly after oral Lcr35 administration. Serum pro-inflammatory cytokines were significantly increased in 5-FU group and were reversed by Lcr35. There was a tremendous rise of CD3+/CD8+ count in the 5-FU group. The CD8+ count was reversed in the 5-FU+Lcr35 group. 5-FU caused a significant decrease of CD3+CD4+/CD3+CD8+ ratio and was reversed by Lcr35. 5-FU significantly stimulated the expression of CD44 stem cells and was restored by Lcr35. We also found 5-FU could increase the number of Ki67 proliferative cells. No bacterial translocation was found in this study.Conclusions Our results showed 5-FU caused intestinal inflammation via Th1 and Th17 responses. 5-FU could stimulate stem cells and proliferation cells in a mouse model. We demonstrated chemotherapy could decrease immune competence. Probiotics were shown to modulate immune response. This is the first study to analyze the immune modulation effects and safety of Lactobacillus strains on enterocytes and intestinal stem cells in a 5-FU-induced mucositis mouse model. The model therefore seems well suited to study the effects of different probiotics on chemotherapy-induced mucositis, prior to performing clinical human studies.