The Lactic Acid Bacteria (LAB) are well-known for their extensive use in the preparation of fermented food products. In addition, the potential health benefits they may exert in humans have been intensively investigated during the last century. However, the mechanisms underlying the health promoting traits attributed to LAB, especially lactobacilli, remain vastly unknown, which has impaired the rational design of probiotic screening methods with accurate predictive value. This project first aims at establishing a correlation between in vitro tests and mouse models mimicking important human intestinal disorders such as Inflammatory Bowel Disease, Helicobacter pylori- and Rotavirus-infections. As these diseases correspond to major public health problems, second generation probiotic strains with enhanced prophylactic or therapeutic properties will also be designed during the project. These designed strains and the isogenic parental ones will be used to unravel mechanisms involved in the immunomodulation capacity of specific lactobacillus strains.
The general purpose of this project is to acquire knowledge about the molecular factors affecting the immunomodulation and/or immunogenicity of selected probiotic lactobacilli so that, in the future, isolates with enhanced protective or therapeutic effect can be screened for or engineered. The objectives of the proposal are on one hand, to unravel mechanisms and identify key components of the immunomodulation capacity of probiotic lactobacilli; and on the other hand, to design "second generation" probiotic strains with enhanced properties against gastro-intestinal disorders.
Two types of gastro-intestinal diseases are targeted: inflammations such as Inflammatory Bowel Disease (IBD) and infections such as those caused by H. pylori and Rotavirus. For each of them, "therapeutic" or "prophylactic" (i.e. vaccine) recombinant probiotic strains will be constructed and tested in relevant animal models (i.e. mimicking the human disease) to evaluate their capacity to induce or modulate the immune response in the proper way. This data will be correlated to in vitro testing of the immunomodulation capacity with the hope to identify/develop screening methods that, in the future, will allow isolating efficient probiotic strains targeted to specific applications. Recombinant DNA technology will also be used to assess the importance of specific cell wall components and adhesion factors in immunomodulation.
Two types of modified probiotic strains will be constructed: mutant strains affected in their cell wall composition and adhesion proteins as well as recombinant strains with enhanced therapeutic or protective properties, focusing on gastrointestinal diseases of inflammatory (IBD) or infectious (H. pylori and Rotavirus) origin. The final goal would be to prove that designed probiotic strains could be used as original therapeutic agents as, if successful, they would lead to novel anti-inflammatory treatments or oral vaccines against Helicobacter pylori and rotavirus, respectively. It is also expected that, by the end of the study, major progress will have been achieved towards the rational design of simplified probiotic screening methods with accurate predictive value.