Microbiota as a cornerstone in the development of primary sclerosing cholangitis: paving the path for translational diagnostic and therapeutic approaches

In the last decades, the proportion of host–microbiota interaction studies in biomedical research continuously increased, mainly driven by the quest for a better understanding of microbiota-associated human diseases. Among the numerous medical conditions the courses of which have been shown to be influenced by the microbiota, GI disorders and especially IBDs have been studied extensively, either in experimental murine models or in clinical studies (reviewed in ref 1). Among the plethora of immune pathways impacted and dysregulated by the microbiota and thus leading to pathologies, inflammasome signalling has been shown to severely affect the progression of GI disorders2 and to be associated with microbiota composition.3 Primary sclerosing cholangitis (PSC) represents a rare disease characterised by chronic inflammation and concomitant fibrosis of the biliary tree with a poor outcome. A microbiota-dependent pathogenesis of PSC, similar to that of IBD, has been suggested.4 However, the number of clinical and experimental studies addressing host–microbiota interactions in PSC remains limited. Rederivation of PSC models into germ-free conditions caused either attenuation or aggravation of the phenotype,5 emphasising the microbiota-dependent character of this pathology and …