Screening and construction of probiotic strains with enhanced protective properties against intestinal disorders

Abstract

16: 86 Á/95Within the scope of the DEPROHEALTH project, a range of wild-type strains of Lactobacillus were analysed for their ability to interact with the host immune system. While the studied isolates interacted in a strain-specific way with immune cells, they seemed to have little and non-discriminative effect on epithelial cells. However, they were shown to facilitate the cross-talk between intestinal and immune cells. Studies conducted in mouse colitis models confirmed that specific strains possess higher intrinsic anti-inflammatory properties. Two of these were further engineered to produce murine IL10 and are presently being evaluated for their protective effect in a TNBS colitis model. Cell wall mutants of Lactobacillus plantarum NCIMB8826 were analysed for their phenotypic traits, immune modulatory ability and capacity to act as live carriers. This led to the identification of mutants with increased anti-inflammatory or antigen delivery properties. Substantial work was invested in attempts to increase the immune response induced by recombinant lactobacilli producing Helicobacter or rotavirus antigens. In the course of these experiments, new methods to evaluate the load of Helicobacter in infected mice were developed. Novel targeting signals for cell surface presentation of therapeutic molecules were also identified. Finally, a safe biologically contained lactococcal strain secreting human IL10 was constructed, thus opening the way to a first clinical trial in patients suffering from inflammatory bowel disease (IBD).

Enhanced antiinflammatory capacity of a Lactobacillus plantarum mutant synthesizing modified teichoic acids

“…Recent studies have reported the positive effects of probiotics not only in the prevention of colitis in animal models (14)(15)(16) but also in the maintenance of remission after surgery in IBD (17)(18)(19). We established that the in vivo protective effect of LAB in a murine 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced model of colitis is strain-specific (20,21). Several LAB strains were reported to exert in vitro stimulatory properties on cells of the innate immune system, including macrophages and natural killer cells, and to induce the production of both proinflammatory cytokines, such as TNF-␣ and IL-12, and the antiinflammatory IL-10 cytokine (6,7,10,22).…”