Intestinal flora induces the expression of Cyp3a in the mouse liver

T. Toda, N. Saito, N. Ikarashi, K. Ito, M. Yamamoto, A. Ishige, K. Watanabe, K. Sugiyama

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

In order to determine the effects of intestinal flora on the expression of cytochrome P450 (CYP), the mRNA expression of CYP was compared between specific pathogen-free (SPF) and germ-free (GF) mice. Most of the major CYP isozymes showed higher expression in the livers of SPF mice compared with GF mice. Nuclear factors such as pregnane - receptor (PXR) and constitutive androstane receptor (CAR), as well as transporters and conjugation enzymes involved in the detoxification of lithocholic acid (LCA), also showed higher expression in SPF mice. The findings suggest that in the livers of SPF mice, LCA produced by intestinal flora increases the expression of CYPs via activation of PXR and CAR. Drugs such as antibiotics, some diseases and ageing, etc. are known to alter intestinal flora. The present findings suggest that such changes also affect CYP and are one of the factors responsible for individual differences in pharmacokinetics.

Original languageEnglish
Pages (from-to)323-334
Number of pages12
JournalXenobiotica
Volume39
Issue number4
DOIs
Publication statusPublished - 2009 Nov 6

Keywords

  • Cyp3a
  • Germ-free
  • Intestinal flora
  • Lithocholic acid
  • Nuclear transcription factors
  • Pregnane X receptor (PXR)

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis

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    Toda, T., Saito, N., Ikarashi, N., Ito, K., Yamamoto, M., Ishige, A., Watanabe, K., & Sugiyama, K. (2009). Intestinal flora induces the expression of Cyp3a in the mouse liver. Xenobiotica, 39(4), 323-334. https://doi.org/10.1080/00498250802651984