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Bile acids and Barrett's oesophagus: a sine qua non or coincidence?

BACKGROUND: Barrett's oesophagus (BO), a premalignant condition associated with the development of oesophageal adenocarcinoma (OAC), is thought to be a consequence of chronic duodeno-gastro-oesophageal reflux. Of the refluxates, bile acids, either alone or in combination with acid, are probably the most important.

METHODS: Analysis of the literature on the role played by bile acids in inducing BO and/or progression to OAC.

RESULTS: Combined pH and Bilitec 2000 (as a measure of bile reflux) monitoring and oesophageal aspiration studies in humans suggest a combined role for bile acids, particularly taurine conjugated bile acids, in causing oesophageal mucosal injury. Evidence from animal models has demonstrated that duodenal juice alone is also able to induce BO and/or OAC. Likewise, ex vivo studies with biopsies from BO patients show that increased proliferation and cyclo-oxygenase-2 expression are present after a pulsed exposure to acid or conjugated bile acids, but not if acid and bile acids are combined. Proton-pump inhibitors (PPIs) have been shown to decrease the biliary component of the refluxate. There is some evidence that PPIs are able to reduce neoplastic progression in BO. On the other hand, chronic PPIs can also stimulate bacterial overgrowth, which can result in increased production of secondary bile acids, particularly deoxycholic acid, in the stomach. Deoxycholic acid has been demonstrated to have a tumour-promoting capacity.

CONCLUSIONS: It is unknown what factors of the refluxate (acid and/or bile) induce BO and/or promote carcinogenesis, but there is evidence that secondary bile acids play a role. A better understanding of the molecular steps involved in the induction of BO, and the role of bile acids herein, may identify targets at which preventive therapies can be directed.

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