Recurrent urinary tract infections (UTI) have been considered potential triggers of primary biliary cirrhosis (PBC), an autoimmune cholestatic liver disease characterised by progressive destruction of intrahepatic bile ducts. Additional support for the link made between PBC and UTI was based on early observations of recurrent episodes of bacteriuria in female patients with PBC. A series of large epidemiological studies demonstrated a strong correlation between recurrent UTI and PBC, initiating a series of studies investigating the role of Escherichia coli (E. coli, the most prevalent organism isolated in women with UTI) as a trigger of PBC. Immunological evidence of B- and T-cell cross-reactive responses implicating PBC-specific autoantigens and E. coli mimics have been clearly demonstrated, adding support to the notion that E. coli is a potential infectious inducer of PBC in susceptible individuals. One of the major limitations in proving the E. coli/PBC association was the lack of reliable E. coli-infected animal models of PBC. This review provides an overview of the evidence linking this infectious agent with PBC and discusses the pros and cons of a recently developed E. coli-infected animal model of PBC. 1. Introduction Primary biliary cirrhosis (PBC) is an autoimmune cholestatic liver disease characterized by high-titre antimitochondrial antibodies (AMA), as well as disease-specific antinuclear antibodies (ANA) [1, 2]. The presence of AMA is considered pathognomonic for PBC, as serum AMA positivity predicts disease development in asymptomatic individuals [3]. The natural course of PBC is generally slow, although the disease course is unpredictable. Over the years, the progression of the disease leads to the inflammatory destruction of small intrahepatic bile ducts, which progresses to fibrosis, cirrhosis, and eventual liver failure [1]. As the disease overwhelmingly affects middle-aged females frequently complaining from recurrent urinary tract infections (UTI), Escherichia coli (E. coli) has been postulated as a potential trigger for the development of the disease [4, 5]. Epidemiological, immunological, and microbiological data have provided strong evidence in support of the pathogenic link between this bacterium and the disease [6–18]. These data are comprehensively discussed elsewhere and will not be mentioned in the present report. AMA are directed against components of the 2-oxoacid dehydrogenase complexes, which mainly recognise the E2 subunit of the pyruvate dehydrogenase complex (PDC) in 90% of cases [2, 19]. In 20–70% of cases, the E2
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