Primary sclerosing cholangitis (PSC) is an autoimmune disease affecting the biliary tract. Chronic inflammation leads to a destruction of the biliary tract with recurrent bacterial cholangitis and the need of regular hospitalizations. So far, no causative therapies are available for PSC. Therapeutic approaches are limited to the treatment of bacterial infections and the optimization of bile flow by endoscopic interventions. The biliary tract was considered to be a sterile niche within the gastrointestinal tract. The isolation of bacteria from bile samples was equaled to bacterial infection. However, due to culture-independent methods like high-throughput sequencing, evidence is rising that the biliary tract is not sterile but harbors a bacterial community even in healthy individuals which introduces the concept of dysbiosis being relevant in the clinical course of PSC and not only infection.