Role of the microbiota and antibiotics in primary sclerosing cholangitis

James H Tabibian, Jayant A Talwalkar, Keith D Lindor, James H Tabibian, Jayant A Talwalkar, Keith D Lindor

Abstract

Primary sclerosing cholangitis (PSC) is an idiopathic, progressive, cholestatic liver disease with considerable morbidity and mortality and no established pharmacotherapy. In addition to the long-recognized association between PSC and inflammatory bowel disease, several lines of preclinical and clinical evidence implicate the microbiota in the etiopathogenesis of PSC. Here we provide a concise review of these data which, taken together, support further investigation of the role of the microbiota and antibiotics in PSC as potential avenues toward elucidating safe and effective pharmacotherapy for patients afflicted by this illness.

Figures

Figure 1
Figure 1
Proposed conceptual model of primary sclerosing cholangitis (PSC) etiopathogenesis. Cholangiocytes exist in a microenvironment abundant in potential etiologic mediators of cellular insult and activation, including microbial as well as nonmicrobial molecules. Whether PSC etiopathogenesis is related to increased exposure to constitutive molecular mediators of injury (e.g., through the enterohepatic circulation), alterations in the types of these mediators (e.g., due to enteric microbial dysbiosis), and/or an aberrant resident (e.g., cholangiocyte, hepatocyte) or recruited (e.g., lymphocyte) hepatic cell response remains uncertain. Immunogenetic factors can modify these variables and thus play a role in modulating initiation and progression of biliary injury in PSC. CCA: cholangiocarcinoma; HLA: human leukocyte antigen; NOD: nucleotide-binding oligomerization domain receptor; TLR: toll-like receptor.

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