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Bacterial infection has been investigated most intensively, both epidemiologically and experimentally, as a prime environmental aetiology in PBC. The association of recurrent history of urinary tract infection (UTI) with PBC has been frequently confirmed by several large-scale, case\u2013control studies, despite variation in geographic area or case-finding methods. Escherichia coli is a predominant pathogen in most cases with UTI. Animal studies and molecular mimicry analysis between the human and E. coli E2 subunit of the 2-oxo-acid dehydrogenase complexes demonstrated that E. coli infection is a key factor in breaking immunological tolerance against the mitochondria, resulting in the production of anti-mitochondrial autoantibodies (AMA), the disease-specific autoantibodies of PBC. Novosphingobium aromaticivorans, a ubiquitous xenobiotic-metabolizing bacterium, is another candidate which may be involved in the aetiology of PBC. Meanwhile, improved environmental hygiene and increased prevalence of PBC, especially in males, may argue against the aetiological role of bacterial infection in PBC. Multiple mechanisms can result in the loss of tolerance to mitochondrial autoantigens in PBC; nonetheless, bacterial infection is probably one of the dominant pathways, especially in female patients. Notably, there is a rising prevalence of male patients with PBC. With increasing exposure to environmental xenobiotics in both genders, studies directed towards identifying the environmental culprit with systematically designed case\u2013control studies are much needed to further determine the environmental factors and role of bacterial infections in PBC.<\/jats:p>","DOI":"10.1111\/cei.13198","type":"journal-article","created":{"date-parts":[[2018,8,12]],"date-time":"2018-08-12T00:49:30Z","timestamp":1534034970000},"page":"25-34","source":"Crossref","is-referenced-by-count":76,"title":["Pathogen infections and primary biliary cholangitis"],"prefix":"10.1093","volume":"195","author":[{"given":"A","family":"Tanaka","sequence":"first","affiliation":[{"name":"Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P S C","family":"Leung","sequence":"additional","affiliation":[{"name":"Division of Rheumatology Allergy and Clinical Immunology, University of California 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