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Primary sclerosing cholangitis is characterised by intestinal dysbiosis independent from IBD

Joao Sabino, Sara Vieira-Silva, Kathleen Machiels, Marie Joossens UGent, Gwen Falony, Vera Ballet, Marc Ferrante, Gert Van Assche, Schalk Van der Merwe, Severine Vermeire, et al. (2016) GUT. 65(10). p.1681-1689
abstract
Objective: Primary 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. Design: Stool 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). Results: The microbiota of patients with PSC was characterised by decreased microbiota diversity, and a significant overrepresentation of Enterococcus (p=3.76-e05), 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. Conclusions: We 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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
ALKALINE-PHOSPHATASE, LIVER-CIRRHOSIS, DISEASE, RISK, MICROBIOME, EPIDEMIOLOGY, ENTEROCOCCUS
journal title
GUT
Gut
volume
65
issue
10
pages
1681 - 1689
Web of Science type
Article
Web of Science id
000384456500014
JCR category
GASTROENTEROLOGY & HEPATOLOGY
JCR impact factor
16.658 (2016)
JCR rank
2/79 (2016)
JCR quartile
1 (2016)
ISSN
0017-5749
1468-3288
DOI
10.1136/gutjnl-2015-311004
language
English
UGent publication?
no
classification
A1
id
8540902
handle
http://hdl.handle.net/1854/LU-8540902
date created
2017-12-08 11:14:15
date last changed
2018-01-22 15:13:46
@article{8540902,
  abstract     = {Objective: Primary 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. 
Design: Stool 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). 
Results: The microbiota of patients with PSC was characterised by decreased microbiota diversity, and a significant overrepresentation of Enterococcus (p=3.76-e05), 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. 
Conclusions: We 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.},
  author       = {Sabino, Joao and Vieira-Silva, Sara and Machiels, Kathleen and Joossens, Marie and Falony, Gwen and Ballet, Vera and Ferrante, Marc and Van Assche, Gert and Van der Merwe, Schalk and Vermeire, Severine and Raes, Jeroen},
  issn         = {0017-5749},
  journal      = {GUT},
  keyword      = {ALKALINE-PHOSPHATASE,LIVER-CIRRHOSIS,DISEASE,RISK,MICROBIOME,EPIDEMIOLOGY,ENTEROCOCCUS},
  language     = {eng},
  number       = {10},
  pages        = {1681--1689},
  title        = {Primary sclerosing cholangitis is characterised by intestinal dysbiosis independent from IBD},
  url          = {http://dx.doi.org/10.1136/gutjnl-2015-311004},
  volume       = {65},
  year         = {2016},
}

Chicago
Sabino, Joao, Sara Vieira-Silva, Kathleen Machiels, Marie Joossens, Gwen Falony, Vera Ballet, Marc Ferrante, et al. 2016. “Primary Sclerosing Cholangitis Is Characterised by Intestinal Dysbiosis Independent from IBD.” GUT 65 (10): 1681–1689.
APA
Sabino, Joao, Vieira-Silva, S., Machiels, K., Joossens, M., Falony, G., Ballet, V., Ferrante, M., et al. (2016). Primary sclerosing cholangitis is characterised by intestinal dysbiosis independent from IBD. GUT, 65(10), 1681–1689.
Vancouver
1.
Sabino J, Vieira-Silva S, Machiels K, Joossens M, Falony G, Ballet V, et al. Primary sclerosing cholangitis is characterised by intestinal dysbiosis independent from IBD. GUT. 2016;65(10):1681–9.
MLA
Sabino, Joao, Sara Vieira-Silva, Kathleen Machiels, et al. “Primary Sclerosing Cholangitis Is Characterised by Intestinal Dysbiosis Independent from IBD.” GUT 65.10 (2016): 1681–1689. Print.