Rethinking the bile acid/gut microbiome axis in cancer

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dc.contributor.authorPhelan, John P.
dc.contributor.authorReen, F. Jerry
dc.contributor.authorCaparros-Martin, Jose A.
dc.contributor.authorO'Connor, Rosemary
dc.contributor.authorO'Gara, Fergal
dc.contributor.funderTeagasc
dc.contributor.funderMarine Institute
dc.contributor.funderIrish Thoracic Society
dc.contributor.funderHealth Research Board
dc.contributor.funderIrish Research Council for Science, Engineering and Technology
dc.contributor.funderDepartment of Agriculture, Food and the Marine
dc.contributor.funderScience Foundation Ireland
dc.contributor.funderEuropean Commission
dc.date.accessioned2018-02-20T13:24:12Z
dc.date.available2018-02-20T13:24:12Z
dc.date.issued2017
dc.description.abstractDietary 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 cohortsen
dc.description.sponsorshipDepartment of Agriculture, Food and the Marine (FIRM/RSF/CoFoRD; FIRM 08/RDC/629; FIRM 1/F009/MabS; FIRM 13/F/516); Irish Research Council for Science, Engineering and Technology (PD/2011/2414; GOIPG/2014/647); Health Research Board/Irish Thoracic Society (MRCG-2014-6); Marine Institute (Beaufort award C2CRA 2007/082); Teagasc (Walsh Fellowship 2013)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationPhelan, J. P., Reen, F. J., Caparros-Martin, J. A., O'Connor, R. and O'Gara, F. (2017) 'Rethinking the bile acid/gut microbiome axis in cancer', Oncotarget, 8(70), pp.115736-115747. doi:10.18632/oncotarget.22803en
dc.identifier.doi10.18632/oncotarget.22803
dc.identifier.endpage115747
dc.identifier.issn1949-2553
dc.identifier.issued70
dc.identifier.journaltitleOncotargeten
dc.identifier.startpage115736
dc.identifier.urihttps://hdl.handle.net/10468/5503
dc.identifier.volume8
dc.language.isoenen
dc.publisherImpact Journals LLCen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Technology and Innovation Development Award (TIDA)/14/TIDA/2438/IE/Next Generation Antibiotics: anti-biofilm, anti-pathogenic natural bioactives from marine microorganisms./
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Technology and Innovation Development Award (TIDA)/12/TIDA/B2405/IE/Optimised detection of key biomarkers of Pseudomonas aeruginosa towards a clinical application/
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Technology and Innovation Development Award (TIDA)/12/TIDA/B2411/IE/Development of small molecule therapeutics for medical intervention: anti-biofilm inhibitors for the medical device sector./
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Technology and Innovation Development Award (TIDA)/13/TIDA/B2625/IE/Small molecule inhibitors of HIF-1: a new class of anti-cancer therapeutics./
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2275/IE/Synthesis and Solid State Pharmaceutical Centre (SSPC)/
dc.relation.projectinfo:eu-repo/grantAgreement/EC/H2020::IA/634486/EU/Industrial Applications of Marine Enzymes: Innovative screening and expression platforms to discover and use the functional protein diversity from the sea/INMARE
dc.relation.projectinfo:eu-repo/grantAgreement/EC/FP7::SP3::PEOPLE/256596/EU/Dissecting the role of a novel transcriptional regulator in microbial-host interactomes./MEXT REGULATION
dc.relation.projectinfo:eu-repo/grantAgreement/EC/FP7::SP1::KBBE/287589/EU/Marine Microbial Biodiversity, Bioinformatics and Biotechnology/MICRO B3
dc.relation.projectinfo:eu-repo/grantAgreement/EC/FP7::SP1::KBBE/311975/EU/Marine Microorganisms: Cultivation Methods for Improving their Biotechnological Applications/MACUMBA
dc.relation.projectinfo:eu-repo/grantAgreement/EC/FP7::SP1::KBBE/312184/EU/Increasing Value and Flow in the Marine Biodiscovery Pipeline/PHARMASEA
dc.relation.projectinfo:eu-repo/grantAgreement/EC/FP7::SP3::PEOPLE/607786/EU/BluePharmTrain/BLUEPHARMTRAIN
dc.relation.urihttp://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=22803&path[]=71990
dc.rights© 2017, Phelan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/
dc.subjectBile acidsen
dc.subjectMicrobiomeen
dc.subjectGut-axisen
dc.subjectCanceren
dc.subjectDysbiosisen
dc.titleRethinking the bile acid/gut microbiome axis in canceren
dc.typeArticle (peer-reviewed)en
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