• PRIMARY SCLEROSING CHOLANGITIS
• INFLAMMATORY BOWEL DISEASE
• BILE ACID METABOLISM

The pathogenesis of primary sclerosing cholangitis (PSC) remains enigmatic; genetic studies gave somehow disillusioning results, disease-modifying drugs are urgently awaited and therefore progress in PSC therapy is difficult to recognise. Nevertheless, there is continuous and increasing scientific and clinical interest in this clinical conundrum, which is fired by novel omics technologies and innovative animal model techniques. A possible pathogenetic gut–liver axis in patients with PSC suffering from concomitant IBD in 75% (increasingly referred to as PSC-IBD to discriminate it from the classic UC or Crohn’s disease) puzzled us for decades and there is increasing genetic and clinical evidence outdating the concept of PSC as an extrahepatic manifestation of IBD.1 There is accumulating evidence that patients with PSC show complex alterations in the gut microbiome and in addition in the microbiome’s metabolism.2 3 In a nutshell, however, most studies reported reduced diversity and shifts in the overall composition of the (faecal) microbiota, but did not point towards specific pathogens and so far did not point towards game-changing diagnostic or therapeutic avenues. Interestingly, specific antibiotics may have some beneficial effects in patients with PSC and numerous clinical studies are currently ongoing.4 Bile acid metabolism is modulated by intestinal bacteria and alterations of the gut microbiome, …