The composition of the fecal microbiota of UC patients differs from that of healthy individuals: we found a reduction in R hominis and F prausnitzii, both well-known butyrate-producing bacteria of the Firmicutes phylum. These results underscore the importance of dysbiosis in IBD but suggest that different bacterial species contribute to the pathogenesis of UC and CD.
ObjectivePrimary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease often leading to end-stage liver disease. Its pathogenesis remains largely unknown, although frequent concomitant IBD hints towards common factors underlying gut and bile duct inflammation. Considering the mounting evidence on the involvement of the intestinal microbiota in initiating and determining IBD phenotype, we investigated intestinal microbiota composition in patients with PSC.DesignStool samples were collected from 147 individuals (52 patients with PSC, 52 age, gender and body mass index-matched healthy volunteers, 13 UC and 30 patients with Crohn's disease). An independent validation cohort of 14 PSC and 14 matched controls was recruited. 16S rDNA sequencing of faecal DNA was performed (Illumina MiSeq).ResultsThe microbiota of patients with PSC was characterised by decreased microbiota diversity, and a significant overrepresentation of Enterococcus (p=3.76e-05), Fusobacterium (p=3.76e-05) and Lactobacillus (p=0.0002) genera. This dysbiosis was present in patients with PSC with and without concomitant IBD and was distinct from IBD, and independent of treatment with ursodeoxycholic acid. A decision tree based on abundances of these three genera allowed reliable classification in the validation cohort. In particular, one operational taxonomic unit belonging to the Enterococcus genus was associated with increased levels of serum alkaline phosphatase (p=0.048), a marker of disease severity.ConclusionsWe here present the first report of PSC-associated faecal dysbiosis, independent from IBD signatures, suggesting the intestinal microbiota could be a contributing factor in PSC pathogenesis. Further studies are needed to confirm these findings and assess causality.
SUMMARY BackgroundThe general increased life expectancy is reflected in the age of patients with inflammatory bowel disease (IBD). The knowledge about efficacy and safety of anti-tumour necrosis factor (TNF) therapy in elderly is scarce and conflicting.
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