Anti-cancer effect of genetically modified lactic acid bacteria expressing antioxidant enzymes or il-10 in a colorectal cancer mouse model

Abstract

The association between inflammatory bowel diseases and colorectal cancer is well documented. The genetic modification of lactic acid bacteria as a tool to increase the anti-inflammatory potential of these microorganisms has also been demonstrated. Thus, the aim of the present work was to evaluate the anti-cancer potential of different genetically modified lactic acid bacteria (GM-LAB) producing antioxidant enzymes (catalase or superoxide dismutase) or the anti-inflammatory cytokine IL-10 (protein or DNA delivery) using a chemical induced colon cancer murine model. Colon carcinogenesis was induced in mice by a weekly subcutaneous injection of dimethylhydrazine (DMH, 20mg/mouse) during 10 consecutive weeks. For the feeding protocol, LAB cultures grown in specific culture media, washed in order to eliminate any remaining traces of antibiotics and resuspended in sterile nonfat milk were administered to mice orally by diluting in the rodent?s drinking water. Bacterial suspensions were prepared freshly every day and given to the mice starting on the day of the first DMH injection, during 6 months (until the end of the experiment). The animals received GM-LAB producing the anti-oxidant enzymes, IL-10 or a mixture of these GM-LAB. Intestinal damage, enzyme activities and cytokines were evaluated and compared to the results obtained from mice that received the wild type strains from which derived de GM-LAB. All the GM-LAB assayed showed beneficial effects against colon cancer as observed by decreased intestinal damage scores and the modulation of the immune system compared to the animals that received the wild-type progenitor strains. The importance to select LAB with innate beneficial properties as the progenitor strain was demonstrated with the GM-LAB producing anti-oxidant enzymes. In addition, the best effects were observed when mice received a mixture of GM-LAB that combined different anti-inflammatory mechanisms. Mixtures of selected LAB and GM-LAB could be used as an adjunct treatment to decrease the inflammatory harmful environment associated to colorectal cancer, especially for patients with chronic intestinal inflammation who have an increased risk to develop colorectal cancer.