COMMENTARY

Liver Disease and the Gut Microbiome

Rowen K. Zetterman, MD

Disclosures

February 03, 2017

In This Article

Sclerosing Cholangitis

Sclerosing cholangitis is a biliary tract disorder that results in inflammation and fibrosis of intra- and extrahepatic bile ducts. There is a strong association between sclerosing cholangitis and inflammatory bowel disease, especially ulcerative colitis, but the clinical severity of colitis associated with sclerosing cholangitis is often mild, more likely to be right-sided, and coupled with a greater risk for the development of colon carcinoma.[52]

Early studies of a rat model of small-intestinal bacterial overgrowth produced biliary inflammation and bile duct fibrosis with radiographic changes similar to that seen in sclerosing cholangitis of humans.[33] An animal model of sclerosing cholangitis has also suggested that the absence of the intestinal microbiome will increase the severity of biochemical and histologic biliary injury compared with animals with normal microbiota.[53]

In human studies, the mucosa-associated microbiota throughout the colon in patients with sclerosing cholangitis is similar,[54] containing a reduced diversity of bacteria.[55,56] This variation in patients with sclerosing cholangitis is observed regardless of whether they have associated ulcerative colitis.

Enrichment of Veillonella species in patients with sclerosing cholangitis[55] is also seen in other inflammatory conditions.[57] Barnesiellaceae and Blautia species are increased independent of the clinical severity of associated sclerosing cholangitis,[54] and enrichment of enterococci, fusil bacteria, and lactobacilli in the microbiome of patients with sclerosing cholangitis occurs regardless of whether inflammatory bowel disease is present.[56]

Studies of the mucosa-associated microbiome in patients with sclerosing cholangitis suggest that it is distinct,[58] with a twofold reduction in Clostridiales compared with controls with ulcerative colitis and a reduction in Bacteroides species, an increase in Escherichia species, and a reduction in Prevotella and Roseburia species compared with controls. Increased intestinal permeability has also been described in patients with sclerosing cholangitis,[20] coupled with an increased likelihood of finding Escherichia coli or Candida species in the bile.[59] Not surprisingly, treatment with antibiotics (including vancomycin in children[60]) can significantly improve liver tests in patients with sclerosing cholangitis compared with administration of ursodeoxycholic acid alone.[61]

Still More to Learn

These studies raise interesting questions about the role of the intestinal microbiome, and perhaps individual species of organisms in the microbiome, in the development of liver injury and end-stage liver disease. As we develop more detailed methodologies for characterization of the intestinal microbiome, our knowledge of the microbiome and the liver will improve.

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