Rethinking the bile acid/gut microbiome axis in cancer
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John P. Phelan1, F. Jerry Reen1, Jose A. Caparros-Martin3, Rosemary O’Connor2 and Fergal O’Gara1,3
1BIOMERIT Research Centre, School of Microbiology, University College Cork - National University of Ireland, Cork, T12 YN60, Ireland
2School of Biochemistry and Cell Biology, University College Cork, National University of Ireland, Cork, T12 YN60, Ireland
3Human Microbiome Programme, School of Biomedical Science, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6102, Australia
Fergal O’Gara, email: [email protected]
Keywords: bile acids; microbiome; gut-axis; cancer; dysbiosis
Received: June 21, 2017 Accepted: October 27, 2017 Published: December 01, 2017
Dietary factors, probiotic agents, aging and antibiotics/medicines impact on gut microbiome composition leading to disturbances in localised microbial populations. The impact can be profound and underlies a plethora of human disorders, including the focus of this review; cancer. Compromised microbiome populations can alter bile acid signalling and produce distinct pathophysiological bile acid profiles. These in turn have been associated with cancer development and progression. Exposure to high levels of bile acids, combined with localised molecular/genome instability leads to the acquisition of bile mediated neoplastic alterations, generating apoptotic resistant proliferation phenotypes. However, in recent years, several studies have emerged advocating the therapeutic benefits of bile acid signalling in suppressing molecular and phenotypic hallmarks of cancer progression. These studies suggest that in some instances, bile acids may reduce cancer phenotypic effects, thereby limiting metastatic potential. In this review, we contextualise the current state of the art to propose that the bile acid/gut microbiome axis can influence cancer progression to the extent that classical in vitro cancer hallmarks of malignancy (cell invasion, cell migration, clonogenicity, and cell adhesion) are significantly reduced. We readily acknowledge the existence of a bile acid/gut microbiome axis in cancer initiation, however, in light of recent advances, we focus exclusively on the role of bile acids as potentially beneficial molecules in suppressing cancer progression. Finally, we theorise that suppressing aggressive malignant phenotypes through bile acid/gut microbiome axis modulation could uncover new and innovative disease management strategies for managing cancers in vulnerable cohorts.
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