A121 DESIGNER PROBIOTICS AS A NOVEL THERAPEUTIC AGAINST INFLAMMATORY BOWEL DISEASE.

Inflammatory bowel disease is a major health burden in developed countries. Current pharmaceutical therapies are risky or ineffective for long-term use and are associated with severe side effects. Therefore, new alternative therapies for IBD are needed. Probiotic therapy, which is the ingestion of non-pathogenic microorganisms to provide health benefits, is considered a potential treatment option. However, clinical trials using probiotics for IBD treatment have yielded very inconsistent and difficult to interpret data. There is a lack of evidence to support the use of probiotic supplementation in IBD management. We have created genetically engineered probiotics that we hypothesize are more efficacious than current commercial probiotics. The overall aim is to determine if the novel designer probiotics will result in better efficacy of probiotic therapy against IBD. Post-weaned female C57BL/6 mice (n=8) were given either of the two designer probiotics (007A or 007B) or the unmodified parent strains with 1x109 CFU/ml via oral gavage for 1–3 days. The mice were challenged with 3.5% DSS via drinking water for 7 days to induce DSS-induced murine colitis. Weight change and clinical scores were assessed. Intestinal immune responses including histopathological scoring, immune cell infiltration, and cytokine analysis were performed. Both designer probiotics, 007A and 007B, were shown to be more efficacious during colitis compared to the unmodified parent strains. Macroscopic examination revealed modified designer probiotics have less bloody and loose stool in their colon and cecum compared to the unmodified parent strains. Both designer probiotic groups lost significantly less body weight and had lower clinical scores during the DSS-induced colitis period. The unmodified parent DSS group lost up to 15% of their initial starting body weight and had high clinical scores, indicating humane endpoint. Our designer probiotic supplementation showed significantly fewer gene expression levels of pro-inflammatory markers such as TNF-α, IFN-γ, IL-1β, and IL-17a. In contrast, the unmodified parent strains showed elevated expression of many pro-inflammatory markers, indicating no improvement during IBD. Our proprietary designer probiotics control inflammation and associated symptoms during colitis. This research could result in genetically improved probiotics leading to better efficacy and a potential alternative therapeutic option for IBD patients. CCC

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