Evaluation of the biosafety of recombinant lactic acid bacteria designed to prevent and to treat colitis

摘要

Inflammatory Bowel Diseases or IBD affect the gastrointestinal tract and are characterized by recurrent inflammation that requires lifelong therapies. Probiotics such as lactic acid bacteria (LAB) have been proposed to complement current treatment protocols for these patients; however, their characteristics are strain dependent. In this regard certain novel characteristics are only possible through the genetic modification of these beneficial microorganisms. Different delivery systems, such as protein delivery of anti-oxidant enzymes and the anti-inflammatory cytokines such as IL-10 and DNA delivery have been shown to be effective for preventing and treating IBD in animal models. In this study, the safety of the recombinant LAB (recLAB) Streptococcus thermophilus (S.) CRL807:CAT, S. thermophilus CRL807: SOD, Lactococcus (L.) lactis NCDO2118 pXILCYT:IL-10, L. lactis MG1363 pValac:IL-10 and L. lactis MG1363 pGroESL:IL-10 with proven beneficial effects were compared to their progenitor strains S. thermophilus CRL807, L. lactis NCDO2118 or L. lactis MG1363. The prolonged administration of genetically modified strains evaluated in the present work showed that they were just as safe as the administration of the native strains from which they derive as demonstrated by normal animal growth and relative organ weights, absence of microbial translocation, altered blood parameters and modifications of intestinal histology. The results show the potential use of these recLAB in future therapeutic formulations; however, the use of modern bio-containment systems is required for the future acceptance of these recLAB by the medical community and patients suffering IBD.