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BACKGROUND: The etiology of ulcerative colitis (UC), one of two forms of inflammatory bowel diseases (IBD), involves genetic and environmental components. Alterations in the composition and/or metabolic function of the colonic microbiota have been suggested by comparing IBD patients with healthy individuals. AIMS: Our aim was to study differences in fecal microbiota composition and proteolytic function in patients before and after onset of UC and in matched healthy controls. METHODS: Four individuals at risk for IBD were followed longitudinally and fecal samples were obtained before and after onset of UC. A cohort of sex/ age matched healthy volunteers (HV) also provided fecal samples. Microbial community structure was analysed by 16S sequencing and metabolic functional predictions were performed by PICRUSt using the 16S data. To obtain further insight into microbiota functions before and after onset of inflammation, shotgun metagenomics analysis was performed in the paired samples from UC patients. Proteolytic activities were measured in the feces. RESULTS: Increased relative abundance of Bacteroidetes phylum and decreased abundance of Firmicutes was observed in UC samples from before and after onset, compared to HV samples. When comparing the matched before and after UC onset samples, a further increase in Bacteroidetes phyla was detected after UC onset. At the genus level, Eubacterium, belonging to the Clostridium cluster XIII Incertae Sedis, and Subdoligranulum were lower after UC onset. The metagenomics analysis revealed lower Clostridiaceae and higher Lachnospiraceae families before, compared to after UC onset. Lower abundance of Roseburia hominis, a well-known butyrate producing bacteria of the Firmicutes phylum, was also detected after UC onset. Although predicted function analysis revealed that peptidases were increased in individuals after the onset of UC, measured proteolytic activity in fecal samples were higher both before and after UC onset, compared to HV. CONCLUSIONS: In this longitudinal follow-up of a small cohort of UC patients, differences in microbiota composition were present before development of clinically relevant inflammation. Of note, there was higher abundance of Bacteroidetes, a phylum with known proteolytic activity. After UC onset, higher pro-inflammatory capacity of the microbiota is further suggested by decreases in potentially anti-inflammatory species such as Roseburia hominis and increases in Clostridiaceae. Our results may help identify microbiota markers for risk of disease development and provide new targets for preventive therapies in individuals at risk for UC. FUNDING AGENCIES: CCC, CIHRHelmsley Charitable Trust and MBB received a MITACS Elevate PDF |
