Galipeau HJ, Caminero A, Turpin W, et al. - This study was sought to present novel fecal biomarkers that precede clinical diagnosis of ulcerative colitis (UC). Researchers used 16S rRNA gene sequencing, shotgun metagenomic sequencing, in vitro functional assays, and gnotobiotic colonizations to characterize the microbial composition and function in fecal samples from a cohort of healthy individuals at-risk for inflammatory bowel diseases (IBD) (pre-UC) that later developed UC (post-UC), and matched healthy controls (HC). Researchers distinguished elevated fecal proteolytic activity that precedes the clinical diagnosis of UC and correlates with gut microbiota variations. This study’s findings indicate that this proteolytic signature may constitute a non-invasive biomarker of inflammation to monitor at-risk populations that can be targeted therapeutically with anti-proteases.