The role of bile acids in the development of Barrett’s Oesophagus and Oesophageal Adenocarcinoma: a systematic review

Abstract

Oesophageal adenocarcinoma (OAC) and its precursor, Barrett’s oesophagus (BO), have overlapping risk factors, including gastro-oesophageal reflux disease. Refluxed contents contain bile acids (BAs) in an acidic environment. The aim of the current study was to investigate, in human subjects, tissues and cell-lines, potential associations of BAs with development or progression of BO to OAC, and to identify mechanisms underlying these effects. A systematic review of six computerised databases was conducted on original articles involving oesophageal tissue from human subjects or oesophageal cell-lines. All articles retrieved for inclusion examined effects of BAs, at neutral pH, on development or risk reduction of BO or OAC. Key findings from the 25 studies included were that deoxycholic acid exerted effects on BA-induced BO and OAC through several potentially co-operating mechanisms, including oxidative stress, DNA damage, inflammation, proliferation, apoptosis, enhanced clonogenicity and angiogenesis. In BO, taurodeoxycholic acid was associated with oxidative-stress, DNA damage and increased proliferation. Ursodeoxycholic acid prevented deoxycholic-acid-induced inflammation in non-malignant human oesophageal cells and BO. Lithocholic acid increased levels of SMAD4, promoting apoptosis in BO. In conclusion, BAs are associated with biological features linked to cancer development, which could be targeted therapeutically, through medication, bacterial supplementation, or lifestyle modifications.