Gut bacterial membrane components as pathogenic signalling molecules in PSC-IBD

Abstract

Section snippets

Background and context

Primary sclerosing cholangitis (PSC) is an immune-mediated sclerosing cholangiopathy characterized by stricturing of the biliary tree and a strong association with inflammatory bowel disease (IBD).¹ This is emphasized by the observations of a higher recurrence rate of PSC after liver transplantation in individuals with active IBD and a protective effect of colectomy on PSC progression. “Gut-liver axis” signalling includes microbiota-related molecules passing an impaired intestinal barrier with

Objectives, methods, and findings

The authors isolated OMVs from intestinal bacteria and studied the migratory capacity of OMVs to the liver and their hepatic inflammatory and fibrogenic effects. They used the Mdr2^-/- mouse model to resemble PSC and an additional model of PSC-IBD by crossing Mdr2^-/- and Casp8^ΔIEC mice.¹¹ Bacterial OMV transport was visualized in vivo in the Rosa26.tdTomato mouse model inoculated by oral gavage with E. Coli^Cre or E. Coli^GFP.¹² For the proof-of-concept experiment, OMVs isolated from K. pneumoniae

Significance of findings

Dorner et al. elegantly show that in models for PSC-IBD, OMVs from PSC-associated bacterial strains, as opposed to the bacteria themselves, translocate to the liver. The OMVs elicit pathogenic effects in PSC-IBD, mainly through pro-inflammatory and pro-fibrotic hepatic and bile duct changes. Similarities in the phenotype between Mdr2^-/- mice injected with OMVs and Casp8^ΔIECxMdr2^-/- mice suggests that intestinal microbial and inflammatory signaling molecules both contribute to hepatobiliary

Financial support

The author did not receive any financial support to produce this manuscript.

Conflict of interest

The author declares no conflict of interest with regard to this work.Please refer to the accompanying ICMJE disclosure forms for further details.