The gut microbiota provides a wide range of beneficial functions for the host, and has an immense effect on the host's health status. The presence of microbiome in the gut may often influence the effect of an orally administered drug. Molecular mechanisms of this process are however mostly unclear. We investigated how the effect of a nonsteroidal drug nabumetone on expression of drug metabolizing enzymes (DMEs) in mice intestine and liver is changed by the presence of microbiota, here, using the germ free (GF) and specific pathogen free (SPF) BALB/c mice. First, we have found in a preliminary experiment that in the GF mice there is a tendency to increase bioavailability of the active form of nabumetone, which we have found now to be possibly influenced by differences in expression of DMEs in the GF and SPF mice. Indeed, we have observed that the expression of the most of selected cytochromes P450 (CYPs) was significantly changed in the small intestine of GF mice compared to the SPF ones. Moreover, orally administered nabumetone itself altered the expression of some CYPs and above all, in different ways in the GF and SPF mice. In the GF mice, the expression of the DMEs (CYP1A) responsible for the formation of active form of the drug are significantly increased in the small intestine and liver after nabumetone application. These results highlight the importance of gut microbiome in processes involved in drug metabolism in the both gastrointestinal tract and in the liver with possible clinical relevance.

• MeSH
• antiflogistika nesteroidní aplikace a dávkování   metabolismus   MeSH
• aplikace orální MeSH
• Bacteria metabolismus   MeSH
• cytochrom P-450 CYP1A1 metabolismus   MeSH
• dysbióza MeSH
• játra účinky léků   enzymologie   MeSH
• metabolická aktivace MeSH
• myši inbrední BALB C MeSH
• nabumeton aplikace a dávkování   metabolismus   MeSH
• střevní mikroflóra * MeSH
• systém (enzymů) cytochromů P-450 genetika   metabolismus   MeSH
• tenké střevo účinky léků   enzymologie   mikrobiologie   MeSH
• transkripční faktory genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• antiflogistika nesteroidní MeSH
• cytochrom P-450 CYP1A1 MeSH
• nabumeton MeSH
• systém (enzymů) cytochromů P-450 MeSH
• transkripční faktory MeSH