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The relationship between the gut and the liver in primary sclerosing cholangitis (PSC) has puzzled researchers since the relationship was established almost 50 years ago.1 ,2 In Northern European populations, the prevalence of IBD in PSC ranges between 60% and 80%,3 and even in populations where the relationship is less apparent (eg, Asia) typical PSC patients (young males) show similar frequencies.4 It is by now reasonably well established that the type of IBD occurring in PSC differs from UC or Crohn's disease.5 From the clinical perspective, PSC-IBD is typically extensive yet quiescent, and shows a right-sided predominance often with subtle ileal inflammation and rectal sparing. From the genetic perspective, PSC-IBD appears more so an autoimmune condition than apparent for IBD.6 ,7
Only about 8.1% of the patients with IBD develop sclerosing cholangitis.8 The mechanisms are unknown and several explanatory models have been proposed over the years. The earliest hypotheses were built on a ‘leaky gut concept’, in which the mucosal injury in IBD would lead to ‘leakage’ of bacteria and bacterial products into the portal circulation.9 Later, a gut–liver T-cell trafficking axis emerged in which gut-derived T cells would contribute to biliary inflammation.10 A more recent hypothesis relates to the possibility of an antigen deriving from colonic content driving biliary inflammation,11 along the same logic dietary gluten drives small intestinal inflammation in coeliac disease.12 Common to all hypotheses is the gut is to blame for what happens to the bile ducts. So what is actually found there—in the gut?
There have been rapid advances in our knowledge on the composition and physiology of the gut microbiota in health and disease over the last 5 years.13 …