P035 Anti-inflammatory Effect and Mechanism of Action of BMC333, a Rationally-Designed Live Bacterial Consortium Based on Microbiome Functional Genomic Analysis for Treating IBD

Abstract Background The mechanisms by which the intestinal microbiome drives inflammation and disease activity in IBD is not clear. Most of current efforts developing treatments targeting are focused on microbial taxa very few developed based functions this condition. Using high-resolution functional analysis we have designed a live bacterial consortium consisting four strains with anti-inflammatory (BMC333); demonstrated significant effects mouse model DSS-induced colitis improving index, colon length, histologic score fecal lipocalin (presented at DDW 2022). Aim To validate action BMC333 using IL10-reporter model. Methods Germ free mice bearing IL10-GFP reporter gene (B6. IL10-GFP) were orally gavaged 109 CFU/strain or vehicle/placebo (n=6 each group) experimental days 1 4. induction period was followed 10 without intervention animals sacrificed day 14. Immunologic assessed splenocytes lamina propria I. quantitating immune-suppressive cells flow cytometry. II. Comparing effect stimulation strains’ lysates IL10- IFNγ production from vehicle-treated mice. Results Treatment resulted in: Higher levels (IL10-expressing CD4 T B cells, regulatory T-cells) treated compared numbers IL10-expressing splenic immunocytes stimulated to non-stimulated cells. Additionally, secreted higher IL10 levels, whereas strain did induce secretion pro-inflammatory cytokine IFNγ, as measured ELISA. Conclusion These results indicate that beneficial is, least partially, mediated increasing IL-10 increased IL-10-producing after vivo colonization, producing lysate-stimulated splenocytes. stimulates immuno-suppressive cell populations propria, but no IFNγ. findings consistent our previously reported studies provide strong rationale for further development an effective treatment IBD.