Open AccessGut microbiome‐mediated modulation of hepatic cytochrome P450 and P‐glycoprotein: impact of butyrate and fructo‐oligosaccharide‐inulin
Author(s) -
Walsh Jacinta,
Gheorghe Cassandra E.,
Lyte Joshua M.,
Wouw Marcel,
Boehme Marcus,
Dinan Timothy G.,
Cryan John F.,
Griffin Brendan T.,
Clarke Gerard,
Hyland Niall P.
Publication year - 2020
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/jphp.13276
Subject(s) - prebiotic , butyrate , inulin , cytochrome p450 , biology , microbiome , gut flora , gene expression , drug metabolism , downregulation and upregulation , metabolism , pharmacology , medicine , sodium butyrate , endocrinology , gene , biochemistry , bioinformatics , fermentation
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.