Colonization by non-pathogenic bacteria alters mRNA expression of cytochromes P450 in originally germ-free mice.
Gut microbiota provides a wide range of beneficial function for the host and has an immense effect on the host's health state. It has also been shown that gut microbiome is often involved in the biotransformation of xenobiotics; however, the molecular mechanisms of the interaction between the gut bacteria and the metabolism of drugs by the host are still unclear. To investigate the effect of microbial colonization on messenger RNA (mRNA) expression of liver cytochromes P450 (CYPs), the main drug-metabolizing enzymes, we used germ-free (GF) mice, lacking the intestinal flora and mice monocolonized by non-pathogenic bacteria Lactobacillus plantarumNIZO2877or probiotic bacteria Escherichia coli Nissle 1917 compared to specific pathogen-free (SPF) mice. Our results show that the mRNA expression of Cyp1a2 and Cyp2e1 was significantly increased, while the expression of Cyp3a11 mRNA was decreased under GF conditions compared to the SPF mice. The both bacteria L. plantarumNIZO2877and E. coli Nissle 1917 given to the GF mice decreased the level of Cyp1a2 mRNA and normalized it to the control level. On the other hand, the colonization by these bacteria had no effect on the expression of Cyp3a11 mRNA in the liver of the GF mice (which remained decreased). Surprisingly, monocolonization with chosen bacterial strains has shown a different effect on the expression of Cyp2e1 mRNA in GF mice. Increased level of Cyp2e1 expression observed in the GF mice was found also in mice colonized by L. plantarumNIZO2877; however, the colonization with probiotic E. coli Nissle 1917 caused a decrease in Cyp2e1 expression and partially restored the SPF mice conditions.
Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic.
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Jourová
Department of Pharmacology, Palacky University Olomouc, Olomouc, Czech Republic.|Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic.
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Anzenbacher
Department of Pharmacology, Palacky University Olomouc, Olomouc, Czech Republic.|Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic.
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Lišková
Department of Pharmacology, Palacky University Olomouc, Olomouc, Czech Republic.|Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic.
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Matušková
Institute of Microbiology, The Czech Academy of Sciences, Novy Hradek, Czech Republic.
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Hermanová
Institute of Microbiology, The Czech Academy of Sciences, Novy Hradek, Czech Republic.
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Hudcovic
Institute of Microbiology, The Czech Academy of Sciences, Novy Hradek, Czech Republic.
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Kozáková
Institute of Microbiology, The Czech Academy of Sciences, Novy Hradek, Czech Republic.
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Hrnčířová
Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic. eva.anzenbacherova@upol.cz.
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Anzenbacherová
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D005260:Female; D000069196:Gastrointestinal Microbiome; D005856:Germ-Free Life; D007778:Lactobacillus / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice / Q000235:genetics / Q000382:microbiology*; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System
Biotransformation Enzyme; Cyp2e1 Expression; Cyp3a11 mRNA; Intestinal Microbiota; Protease Inhibitor Cocktail Tablet