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

Autor: Walsh J; APC Microbiome Ireland, University College Cork, Cork, Ireland.; School of Pharmacy, University College Cork, Cork, Ireland., Gheorghe CE; APC Microbiome Ireland, University College Cork, Cork, Ireland.; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland., Lyte JM; APC Microbiome Ireland, University College Cork, Cork, Ireland.; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland., van de Wouw M; APC Microbiome Ireland, University College Cork, Cork, Ireland.; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland., Boehme M; APC Microbiome Ireland, University College Cork, Cork, Ireland.; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland., Dinan TG; APC Microbiome Ireland, University College Cork, Cork, Ireland.; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland., Cryan JF; APC Microbiome Ireland, University College Cork, Cork, Ireland.; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland., Griffin BT; APC Microbiome Ireland, University College Cork, Cork, Ireland.; School of Pharmacy, University College Cork, Cork, Ireland., Clarke G; APC Microbiome Ireland, University College Cork, Cork, Ireland.; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland., Hyland NP; APC Microbiome Ireland, University College Cork, Cork, Ireland.; Department of Physiology, University College Cork, Cork, Ireland.
Jazyk: angličtina
Zdroj: The Journal of pharmacy and pharmacology [J Pharm Pharmacol] 2020 Aug; Vol. 72 (8), pp. 1072-1081. Date of Electronic Publication: 2020 Apr 26.
DOI: 10.1111/jphp.13276
Abstrakt: Objectives: 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.
(© 2020 Royal Pharmaceutical Society.)
Databáze: MEDLINE
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