Is the biogeography of the mucosa-associated microbiota a key factor affecting primary sclerosing cholangitis disease course and treatment?

Abstract

We have read with interest the contribution by Bedke et al ,1 reporting changes in the stool microbiota associated with primary sclerosing cholangitis (PSC) in human and murine models of the disease. These changes coincide with an expansion of FoxP3+T reg cells, a response also linked with luminal butyrate concentrations and/or other goods and services arising from select commensal bacteria.2 Furthermore, the authors find patients with PSC with an associated IBD (PSC-IBD) as well as mice receiving faecal transfer from such patients experience a milder form of IBD, or attenuation of colitis, respectively. Their findings expand on those from Awoniyi et al , linking bile acid ecology and select stool bacteria deemed protective or pathogenic in a murine model of PSC, as well as an association of these microbial signatures with disease severity in patients with PSC.3 Attribution of the beneficial effects to the luminal/stool microbiota in both these studies was strengthened by their abrogation in mice following antibiotic administration. Interestingly, recent studies suggest that antibiotic treatment, and vancomycin administration in particular, can promote positive clinical benefits in both subjects with PSC and/or PSC-IBD regardless of age.4 Given the distinctive clinical features and epidemiology of PSC-IBD compared with IBD5 and the dichotomous impacts from antibiotics on disease course in different scenarios, …