A210 ADLERCREUTZIA IS DEPLETED IN UC PATIENTS, EVEN BEFORE CLINICAL DIAGNOSIS, AND INVERSELY CORRELATES WITH FECAL ELASTOLYTIC ACTIVITY. (26th February 2020) - Santiago Badenas, A
Abstract: Background: A combination of genetics, environmental, and immune factors contribute to the development of ulcerative colitis (UC). Host proteolytic imbalance has been reported in active UC. Preliminary results from our lab suggest microbial proteolytic activity is increased before as well as after onset of UC, and transfer of this activity to mice contributes to inflammation. Aims: Our aim was to correlate the elastolytic activity of fecal samples from individuals at risk for IBD, before and after onset of ulcerative colitis, with their fecal microbiota profiles Methods: We first investigated proteolytic activity in fecal samples from individuals at risk to develop UC (pre-UC, n=12) prior to disease onset and after UC diagnosis (post-UC, n=7) and matched healthy controls (n=66). Microbial community analysis was performed by sequencing the V4 region of the 16S rRNA gene region using Illumina MiSeq platform. Sequences were analyzed with QIIMEv1.9.0. We measured bacterial proteolytic activity, using a FITC-elastin assay. Results: Microbial community analysis revealed that the overall diversity (both richness and evenness) in UC patients was decreased compared to healthy controls as well as pre-UC patients. The relative abundance of the genus Adlercreutzia was decreased by 3.1 fold in pre-UC patients compared to healthy controls and was further decreased in post-UC (3.8 fold). The presence of Adlercreutzia was also found to be negatively correlated (r=-0.47, p<0.0001) with elastolytic activity in stool supernatant, suggesting a possible protective role in the disease. Conclusions: We found novel potentially protective bacteria, Adlercreutzia, which was depleted in UC patients, even before clinical diagnosis and correlated negatively with proinflammatory elastolytic activity described previously in IBD. The protective mechanisms are under investigation. On behalf of the CCC-GEM Project consortiumand Supported by a CCC GIA to EFV Funding Agencies: CCC