Role of the Microbiota and Antibiotics in Primary Sclerosing Cholangitis

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.