R Fedorak

263 Fecal Microbial Transplantation Can Modulate Increased Colitis Susceptibility Induced by High Sugar Diets

Background: Primary sclerosing cholangitis (PSC) is a cholestatic liver disorder very frequently associated with inflammatory bowel diseases (IBD). The intestinal microbiota seems to be essential in PSC as bacterial translocation is thought to play an important role in the pathogenesis of the disease. Given the association with IBD and the fact that patients with IBD have a well-documented intestinal dysbiosis, we hypothesized that dysbiosis would also play a role in PSC. Methods: Faecal samples from 52 PSC patients and 52 age, sex and BMI matched healthy controls were collected. Within the PSC cohort, 39 patients had concomitant IBD (17 Crohns disease (CD) and 22 ulcerative colitis (UC)). After bacterial DNA extraction, 16S rDNA paired-end sequencing was performed using Illumina MiSeq sequencer. Successfully combined reads were quality-filtered (30 QS over 90% of read length) and chimeric sequences filtered out (UCHIME). Sequencing depth was downsized to 10000 reads/sample by random selection. Reads were clustered at 97% sequence similarity for species-level de novo OTU picking (USEARCH). The Ribosomal Database Project classifier was used for taxonomic assignment. Statistical analyses were performed with R package phyloseq, using non-parametric Mann-Whitney U and Kruskal-Wallis tests, with multiple testing correction (FDR). Results: The overall microbiota diversity was significantly decreased in PSC patients compared to healthy controls (p<0.0001). This reduction was observed in each subgroup of PSC patients (PSC only, PSC+CD, PSC+UC) versus healthy controls (adjusted p<0.0001)(Figure 1). At genus level, five genera were consistently more abundant in PSC patients compared to healthy controls (adjusted p<0.02): Enterococcus, Fusobacterium, Lactobacillus, Veillonela and Morganella. PSC patients with IBD versus controls showed differences in the abundance of an additional 33 genera (adjusted p<0.05) including Faecalibacterium, Roseburia, Blautia and Butyricicoccus. Conclusion: The intestinal microbiota of PSC patients is clearly different from that of healthy controls, even in the absence of intestinal inflammation such as IBD. A unique microbial signature of five genera is observed in PSC patients, irrespective of the presence of IBD. In PSC patients with concomitant IBD, a dysbiosis involving previously described IBD-related genera is also observed in addition to the PSC specific microbial signature. Our data support the hypothesis that the intestinal microbiota plays an important role in the pathogenesis of this chronic cholestatic liver disease.