Gut microbiome-mediated modulation of hepatic cytochrome P450 and P-glycoprotein: impact of butyrate and fructo-oligosaccharide-inulin

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dc.contributor.authorWalsh, Jacinta
dc.contributor.authorGheorghe, Cassandra Elise
dc.contributor.authorLyte, Joshua M.
dc.contributor.authorvan de Wouw, Marcel
dc.contributor.authorBoehme, Marcus
dc.contributor.authorDinan, Timothy G.
dc.contributor.authorCryan, John F.
dc.contributor.authorGriffin, Brendan T.
dc.contributor.authorClarke, Gerard
dc.contributor.authorHyland, Niall P.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderYakult Bio-Science Foundationen
dc.contributor.funderJoint Programming Initiative A healthy diet for a healthy lifeen
dc.date.accessioned2020-04-28T14:21:48Z
dc.date.available2020-04-28T14:21:48Z
dc.date.issued2020-04-26
dc.date.updated2020-04-28T13:08:48Z
dc.description.abstractObjectives: Our objective was to demonstrate microbial regulation of hepatic genes implicated in drug metabolism and transport using germ‐free (GF) mice and to explore the impact of a microbial metabolite, butyrate, and a prebiotic dietary intervention on hepatic gene expression in mice. Methods: Using reverse‐transcriptase PCR, we investigated cytochrome P450 (CYP) and multidrug‐resistance protein 1 (MDR1) expression in conventional, GF and colonised GF mice. To investigate the effects of butyrate, sodium butyrate (3 g/l) was administered for 21 days to conventional or GF mice. In the prebiotic study, young adult and middle‐aged mice received diet enriched with 10% fructo‐oligosaccharide (FOS)‐inulin for 14 weeks. Key findings: Colonisation of GF animals normalised expression of Cyp3a11 and Mdr1b to conventional levels. Butyrate upregulated Cyp2b10 in conventional mice (P < 0.05) but overall did not induce widespread changes in hepatic genes. FOS‐inulin increased Cyp3a13 expression and had the opposite effect on Mdr1a expression in young adult mice (P < 0.05). Age, on the other hand, influenced the prebiotic effect on Cyp2a4 expression (P < 0.01). Conclusion: The expression of hepatic genes implicated in drug metabolism and transport displays sensitivity to the microbiome, microbiome‐derived metabolites and a microbial‐targeted intervention. Our study may provide the impetus to explore microbiota‐targeted interventions in normalising host metabolic activity and reducing inter‐individual variability in drug pharmacokinetics.en
dc.description.sponsorshipNature Research-Yakult (The Global Grants for Gut Health; Ref No. 626891); Joint Programming Initiative-a healthy diet for a healthy life ((JPI-HDHL) award, ‘A Menu for Brain Responses Opposing Stress-Induced Alternations in Cognition’ (AMBROSIAC; 15/JPHDHL/3270))en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationWalsh, J., Gheorghe, C.E., Lyte, J.M., van de Wouw, M., Boehme, M., Dinan, T.G., Cryan, J.F., Griffin, B.T., Clarke, G. and Hyland, N.P. (2020) 'Gut microbiome‐mediated modulation of hepatic cytochrome P450 and P‐glycoprotein: impact of butyrate and fructo‐oligosaccharide‐inulin', Journal of Pharmacy and Pharmacology, doi: 10.1111/jphp.13276en
dc.identifier.doi10.1111/jphp.13276en
dc.identifier.endpage10en
dc.identifier.issn2042-7158
dc.identifier.journaltitleJournal of Pharmacy and Pharmacologyen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/9885
dc.language.isoenen
dc.publisherWileyen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/en
dc.rights© 2020 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology. This is the peer reviewed version of the following article: (2020), Gut microbiome‐mediated modulation of hepatic cytochrome P450 and P‐glycoprotein: impact of butyrate and fructo‐oligosaccharide‐inulin. J Pharm Pharmacol., which has been published in final form at https://doi.org/10.1111/jphp.13276 This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.en
dc.subjectCytochromeen
dc.subjectHepaticen
dc.subjectMetabolismen
dc.subjectMicrobiomeen
dc.subjectTransporteren
dc.titleGut microbiome-mediated modulation of hepatic cytochrome P450 and P-glycoprotein: impact of butyrate and fructo-oligosaccharide-inulinen
dc.typeArticle (peer-reviewed)en
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