Gut microbiota maintains FXR activation and protects from fatal liver damage in a murine model of primary sclerosing cholangitis

2020 ◽  
Vol 73 ◽  
pp. S81
Author(s):  
Kai Markus Schneider ◽  
Lena Candels ◽  
Antje Mohs ◽  
Carsten Elfers ◽  
Annika Wahlström ◽  
...  
2020 ◽  
Vol 174 (5) ◽  
pp. 104-107
Author(s):  
A. V. Nikitin ◽  
A. I. Khavkin ◽  
T. A. Skvortsova ◽  
G. V. Volynets ◽  
A. O. Atameeva

A clinical case of a combination of ulcerative colitis with cirrhosis in the outcome of primary sclerosing cholangitis in a twelve-year-old child is presented. The uniqueness of the clinical observation lies in the atypical onset of ulcerative colitis in the form of complaints of weakness and headache, as well as detected anemia of 3 severity. It is important that the child lacked diarrhea, blood in the stool, tenesmus, weight loss, and fever. Of the most characteristic signs of liver damage, only itching of the skin of the lower extremities was noted. As a result, the child was diagnosed with cirrhosis of the liver at the end of the extraintestinal manifestation of ulcerative colitis — primary sclerosing cholangitis.


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.


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.


Sign in / Sign up

Export Citation Format

Share Document