Lactobacillus salivarius CPU-01 Ameliorates Temozolomide-Induced Intestinal Mucositis by Modulating Gut Microbiota, Maintaining Intestinal Barrier, and Blocking Pro-inflammatory Cytokines

Abstract

Chemotherapy-induced intestinal mucositis is one of the major toxic side effects in the treatment of cancer patients. The purpose of this study is to screen lactic acid bacteria which could alleviate intestinal inflammation and damage induced by chemotherapeutic agents and explore the possible underlying mechanisms. Lactobacillus salivarius CPU-01 was selected from traditional Chinese fermented foods due to its protective effects on the toxicity of temozolomide in Caenorhabditis elegans. Eighteen ICR mice were randomly divided into 3 groups including control group, temozolomide-induced intestinal mucositis group, and temozolomide + L. salivarius CPU-01 group, and were used to investigate the effect of L. salivarius CPU-01 on chemotherapy-induced intestinal mucositis. It has been demonstrated that the administration of L. salivarius CPU-01 can prevent colon shortening and alleviate colon tissue damage caused by temozolomide-induced intestinal mucositis in mice. L. salivarius CPU-01 relieved the intestinal microbiota disorders caused by temozolomide and contributed to the growth of beneficial bacteria, such as Lactobacillus, Clostridia UCG - 014_norank, and Akkermansia. In vivo experiments also indicated that L. salivarius CPU-01 can suppress the level of temozolomide-induced pro-inflammatory cytokines in serum and mRNA expression in the small intestine tissues. It was also found that L. salivarius CPU-01 significantly increased the expressions of intestinal tight junction (TJ) proteins, ZO-1, and Occludin proteins in mice treated with temozolomide. These findings suggest that L. salivarius CPU-01 can ameliorate temozolomide-induced intestinal mucositis by modulating gut microbiota, blocking pro-inflammatory cytokines, and repairing the intestinal barrier. These findings suggest probiotics may serve as a potential alternative therapeutic strategy for the prevention of chemotherapy-induced intestinal mucositis in the future.

Keywords: Gut microbiota; Intestinal barrier; Lactobacillus salivarius; Pro-inflammatory; Temozolomide.