TREATMENT OF INFLAMMATORY BOWEL DISEASE WITH GENETICALLY ENGINEERED K. LACTIS

Abstract

Inflammatory bowel disease (IBD) is an aggravating disorder characterized by mucosal inflammation of the intestinal lining. The two main forms of IBD, Crohn's disease and ulcerative colitis, can be triggered by a variety of factors, but are mostly distinguished by immunological abnormalities, among which the CCR5/CCL5 axis has a profound role in the initiation of immune response because of its upregulated activity. IBD can tremendously worsen patients' quality of life and require a comprehensive approach to treatment. This study aimed to evaluate the therapeutic potential of the CCR5 antagonist expressed in K. lactis in the restoration of intestinal barrier function and reduction of IBD-associated symptoms in the C57BL/6 mouse model. The experiment was performed using control and experimental subgroups with an acute form of disease, where mice received DSS-only treatment or DSS plus yeasts transformed with CCR5 antagonist, respectively. Inflammatory marker RORγ levels, mainly produced by Th17 cells, were estimated for both subgroups after 11 days. The mice getting the CCR5 inhibitor demonstrated a statistically significant decrease in RORγ-expressing cells in the small intestine. However, no significant differences were identified for the colon. These findings indicate that delivering a CCR5 inhibitor directly to the intestine via a vector could have some beneficial effects, but further studies are required to obtain reliable and statistically relevant results.