scholarly journals The Microbiome in Primary Sclerosing Cholangitis: Current Evidence and Potential Concepts

2017 ◽  
Vol 37 (04) ◽  
pp. 314-331 ◽  
Author(s):  
Johannes Hov ◽  
Tom Karlsen

AbstractThe close relationship between primary sclerosing cholangitis (PSC) and inflammatory bowel disease has inspired hypothetical models in which gut bacteria or bacterial products are key players in PSC pathogenesis. Several studies using high-throughput sequencing technology to characterize the gut microbiota in PSC have been published over the past years. They all report reduced diversity and significant shifts in the overall composition of the gut microbiota. However, it remains unclear as to whether the observed changes are primary or secondary to PSC development and further studies are needed to assess the biological implications of the findings. In the present article, we review the published data in perspective of similar studies in other diseases. We discuss aspects of methodology and study design that are relevant to interpretation of the data. Furthermore, we propose that interpretation and further assessments of findings are structured into conceptual compartments, and elaborate three such possible concepts relating to immune function (the “immunobiome”), host metabolism (the “endobiome”), and dietary and xenobiotic factors (the “xenobiome”) in PSC.

2020 ◽  
Vol 14 (7) ◽  
pp. 935-947 ◽  
Author(s):  
Mohammed Nabil Quraishi ◽  
Animesh Acharjee ◽  
Andrew D Beggs ◽  
Richard Horniblow ◽  
Chris Tselepis ◽  
...  

Abstract Background Although a majority of patients with PSC have colitis [PSC-IBD; primary sclerosing cholangitis-inflammatory bowel disease], this is phenotypically different from ulcerative colitis [UC]. We sought to define further the pathophysiological differences between PSC-IBD and UC, by applying a comparative and integrative approach to colonic gene expression, gut microbiota and immune infiltration data. Methods Colonic biopsies were collected from patients with PSC-IBD [n = 10], UC [n = 10], and healthy controls [HC; n = 10]. Shotgun RNA-sequencing for differentially expressed colonic mucosal genes [DEGs], 16S rRNA analysis for microbial profiling, and immunophenotyping were performed followed by multi-omic integration. Results The colonic transcriptome differed significantly between groups [p = 0.01]. Colonic transcriptomes from HC were different from both UC [1343 DEGs] and PSC-IBD [4312 DEGs]. Of these genes, only 939 had shared differential gene expression in both UC and PSC-IBD compared with HC. Imputed pathways were predominantly associated with upregulation of immune response and microbial defense in both disease cohorts compared with HC. There were 1692 DEGs between PSC-IBD and UC. Bile acid signalling pathways were upregulated in PSC-IBD compared with UC [p = 0.02]. Microbiota profiles were different between the three groups [p = 0.01]; with inferred function in PSC-IBD also being consistent with dysregulation of bile acid metabolism. Th17 cells and IL17-producing CD4 cells were increased in both PSC-IBD and UC when compared with HC [p < 0.05]. Multi-omic integration revealed networks involved in bile acid homeostasis and cancer regulation in PSC-IBD. Conclusions Colonic transcriptomic and microbiota analysis in PSC-IBD point toward dysregulation of colonic bile acid homeostasis compared with UC. This highlights important mechanisms and suggests the possibility of novel approaches in treating PSC-IBD.


2016 ◽  
Vol 150 (4) ◽  
pp. S583-S584
Author(s):  
Joana Torres ◽  
Carolina Palmela ◽  
Xiuliang Bao ◽  
Ana Paula Krieger ◽  
Sónia Velho ◽  
...  

2021 ◽  
Author(s):  
Samaneh Ostadmohammadi ◽  
Masoumeh Azimirad ◽  
Hamidreza Houri ◽  
Kaveh Naseri ◽  
Ehsan Javanmard ◽  
...  

Abstract Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease. Its aetiology remains largely unknown, although frequent concomitant inflammatory bowel disease (IBD) hints towards common factors underlying intestinal and bile duct inflammation. Herein, we aimed to explore the relative abundance of fecal microbiota in PSC-IBD patients compared to IBD-only subjects and healthy controls.We included 14 PSC-IBD patients, 12 IBD patients, and 8 healthy controls (HCs). A quantitative real-time PCR (qPCR) assay was to determine a selection of bacterial phyla, families, and genera.Relative abundance of taxa showed that Bacteroidetes was the most abundant phylum among the patients with PSC-IBD (29.46%) and also HCs (39.34%), whereas the bacterial species belonging to the phylum Firmicutes was the most frequent group in IBD-only subjects (37.61%). The relative abundance of Enterobacteriaceae family was higher among PSC-IBD (3%) than HCs (0.5%), and thus, could be used as a PSC-associated microbial signature.Our findings showed that intestinal microbiota composition in PSC-IBD patients was completely different from that of IBD-only patients. Further studies using large-scale cohorts should be performed to better describe the contribution of the gut microbiota to PSC pathogenesis with underlying IBD.


2017 ◽  
Vol 6 (1) ◽  
pp. 112-122 ◽  
Author(s):  
J Torres ◽  
C Palmela ◽  
H Brito ◽  
X Bao ◽  
H Ruiqi ◽  
...  

Background Patients with primary sclerosing cholangitis associated with inflammatory bowel disease (PSC-IBD) have a very high risk of developing colorectal neoplasia. Alterations in the gut microbiota and/or gut bile acids could account for the increase in this risk. However, no studies have yet investigated the net result of cholestasis and a potentially altered bile acid pool interacting with a dysbiotic gut flora in the inflamed colon of PSC-IBD. Aim The aim of this study was to compare the gut microbiota and stool bile acid profiles, as well as and their correlation in patients with PSC-IBD and inflammatory bowel disease alone. Methods Thirty patients with extensive colitis (15 with concomitant primary sclerosing cholangitis) were prospectively recruited and fresh stool samples were collected. The microbiota composition in stool was profiled using bacterial 16S rRNA sequencing. Stool bile acids were assessed by high-performance liquid chromatography tandem mass spectrometry. Results The total stool bile acid pool was significantly reduced in PSC-IBD. Although no major differences were observed in the individual bile acid species in stool, their overall combination allowed a good separation between PSC-IBD and inflammatory bowel disease. Compared with inflammatory bowel disease alone, PSC-IBD patients demonstrated a different gut microbiota composition with enrichment in Ruminococcus and Fusobacterium genus compared with inflammatory bowel disease. At the operational taxonomic unit level major shifts were observed within the Firmicutes (73%) and Bacteroidetes phyla (17%). Specific microbiota-bile acid correlations were observed in PSC-IBD, where 12% of the operational taxonomic units strongly correlated with stool bile acids, compared with only 0.4% in non-PSC-IBD. Conclusions Patients with PSC-IBD had distinct microbiota and microbiota-stool bile acid correlations as compared with inflammatory bowel disease. Whether these changes are associated with, or may predispose to, an increased risk of colorectal neoplasia needs to be further clarified.


2020 ◽  
Vol 158 (6) ◽  
pp. S-732-S-733
Author(s):  
Camilla A. Martins ◽  
Ana Elisa R. Caon ◽  
Marilia G. Cruz ◽  
Luísa L. Barros ◽  
Alexandre Carlos ◽  
...  

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