Lactobacillus Alleviates Colitis Caused by Chemotherapy Via Biofilm Formation

Background: Severe colitis is a common side effect of chemotherapy in cancer patients. A widely consumed probiotic, Lactobacillus, has been reported to alleviate colitis. However, the gastric acid has a powerful bactericidal effect, which restricts to clinical trial success. In this study, we attempted to enhance the viability of probiotics in a gastric acid environment and improve the colitis induced by dextran sulfate sodium (DSS) and chemotherapeutic docetaxel.Methods: We purified Lactobacillus from diverse brands of yogurt and estimated their growth at pH 6.8 and pH 2.0. In the further investigation, the bacterial biofilm formation was used to define the mechanism by which administration of LGG via oral gavage alleviates the colitis and intestine permeability of the mice induced by DSS and docetaxel. The potential benefit of probiotics on the treatment of breast cancer metastasis has been assessed as well.Results: Lactobacillus growth was unexpectedly faster in the pH 2.0 than in the neutral pH medium during the first hour. However, its growth was greatly reduced after the first hour in the pH 2.0 medium but was maintained at neutral pH. As expected, Escherichia coli (E. coli) could not grow well in an acidic medium. Lactobacillus rhamnosus (LGG) administered in the fasting state via oral gavage significantly improved the preventive effect in the colitis caused by DSS and docetaxel. Further mechanistic investigations suggested that LGG reduced the permeability of the intestine and decreased the expression of proinflammatory cytokines, TNFα, IL-1β, and IL-6, in colitis by biofilm formation. We examined the chemotherapeutic effect of docetaxel in a breast cancer model and found that increasing the docetaxel dose may reduce tumor growth and metastasis in the lung but did not benefit survival due to severe colitis. However, the LGG supplement significantly improved the survival of tumor-bearing mice following a high dose of docetaxel treatment. Conclusions: Our findings provide new insights into the potential mechanism of probiotic protection of the intestine and provide a novel therapeutic strategy to augment the chemotherapeutic treatment of tumors.