Bactérias Ácido Láticas Geneticamente Modificadas na Prevenção da Doença Inflamatória do Cólon

LEBLANC, J.G.

Sao Paulo

Congreso; Brazilian Conference of Prebiotics, Probiotics and Symbiotics ? PREPROSIM; 2013

Lactic acid bacteria (LAB) represent a heterogeneous group of microorganisms that are naturally present in many foods and possess a wide range of therapeutic properties since they are able to prevent the development of some diseases, such as shown using animal models for cancer, infections and gastrointestinal disorders such as intestinal inflammation. Although probiotic effects are a strain dependent trait, using modern genetic engineering techniques it is theoretically possible to obtain strains that can exert a variety of beneficial properties or provide them with the capability to produce new compounds with health promoting effects. LAB have been shown to regulate mucosal immune responses by modulating the production and liberation of regulatory agents such as cytokines by the host. Some of these cytokines, such as the anti-inflammatory interleukin-10 (IL-10), modulate the inflammatory immune response, thus immunomodulation is a mechanism by which LAB can prevent certain inflammatory bowel diseases (IBD). However, LAB cannot produce IL-10, reason for which different strategies for the expression of IL-10 gene by LAB or the use of LAB as a vehicle of this gene for its expression by eukaryotic cells have been developed. Using intestinal inflammation animal models of Crohn's Disease, it has been shown that IL-10 producing LAB were able to lower damage scores in their large intestines (at both macroscopic and microscopic levels), lower microbial translocation to liver, and increased anti-inflammatory / pro-inflammatory cytokine ratios. Oxidative stress also participates in the inflammatory processes and in the appearance of damages in pathologies of the gastrointestinal tract of humans such as IBD due to an imbalance in reactive oxygen species (ROS) concentrations and a decrease of antioxidant enzymatic activities in the intestines. LAB have been genetically engineered to produce antioxidant enzymes (such as catalases and superoxide dismutases) and these novel strains have been able to significantly decrease intestinal inflammation through a non-immune mechanism and helped in the prevention of induce Crohn's disease and colon cancer in mice. Thus the introduction of cytokine producing capabilities or antioxidant enzyme genes in current probiotic strains that have natural anti-inflammatory properties, such as the ability to modulate the immune dependent processes, could generate very useful strains that could be applied in the treatment of a variety of inflammatory diseases. These strains could also be included in treatment protocols since it has been shown that probiotics can enhance the effectiveness of traditional IBD treatments.