P741. The gut microbiota in primary sclerosing cholangitis and inflammatory bowel disease: correlations with disease and diet

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.

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Characterization of the gut microbiota in patients with primary sclerosing cholangitis compared to inflammatory bowel disease and healthy controls

Molecular Biology Reports ◽

10.1007/s11033-021-06567-8 ◽

2021 ◽

Author(s):

Samaneh Ostadmohammadi ◽

Masoumeh Azimirad ◽

Hamidreza Houri ◽

Kaveh Naseri ◽

Ehsan Javanmard ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Gut Microbiota ◽

Primary Sclerosing Cholangitis ◽

Bowel Disease ◽

Sclerosing Cholangitis ◽

Healthy Controls ◽

Inflammatory Bowel

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Su1903 The Gut Microbiota in Primary Sclerosing Cholangitis (PSC) and Inflammatory Bowel Disease (IBD): Correlations With Disease and Diet

Gastroenterology ◽

10.1016/s0016-5085(16)32002-9 ◽

2016 ◽

Vol 150 (4) ◽

pp. S583-S584

Author(s):

Joana Torres ◽

Carolina Palmela ◽

Xiuliang Bao ◽

Ana Paula Krieger ◽

Sónia Velho ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Gut Microbiota ◽

Primary Sclerosing Cholangitis ◽

Bowel Disease ◽

Sclerosing Cholangitis ◽

Inflammatory Bowel

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Characterization of the Gut Microbiota in Patients with Primary Sclerosing Cholangitis Compared to Inﬂammatory Bowel Disease and Healthy Controls

10.21203/rs.3.rs-431119/v1 ◽

2021 ◽

Author(s):

Samaneh Ostadmohammadi ◽

Masoumeh Azimirad ◽

Hamidreza Houri ◽

Kaveh Naseri ◽

Ehsan Javanmard ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Gut Microbiota ◽

Primary Sclerosing Cholangitis ◽

Relative Abundance ◽

Bowel Disease ◽

Sclerosing Cholangitis ◽

Bacterial Species ◽

Cholestatic Liver Disease ◽

Healthy Controls ◽

Inflammatory Bowel

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.

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The gut microbiota, bile acids and their correlation in primary sclerosing cholangitis associated with inflammatory bowel disease

United European Gastroenterology Journal ◽

10.1177/2050640617708953 ◽

2017 ◽

Vol 6 (1) ◽

pp. 112-122 ◽

Cited By ~ 23

Author(s):

J Torres ◽

C Palmela ◽

H Brito ◽

X Bao ◽

H Ruiqi ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bile Acid ◽

Gut Microbiota ◽

Bile Acids ◽

Primary Sclerosing Cholangitis ◽

Bowel Disease ◽

Sclerosing Cholangitis ◽

Colorectal Neoplasia ◽

Bile Acid Pool ◽

Inflammatory Bowel

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.

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