The role of the microbiome and psychosocial stress in the expression and activity of drug metabolizing enzymes in mice

Autor:	Tomas Hudcovic, Pavel Anzenbacher, Lenka Jourova, Hana Kozakova, Nina Zemanová, Martin Vodička, Petra Hermanova, Jiří Pácha, Eva Anzenbacherova, Iveta Zapletalová
Jazyk:	angličtina
Rok vydání:	2020
Předmět:	0301 basic medicine Male medicine.medical_specialty lcsh:Medicine Endogeny Biology Gut flora digestive system Gene Expression Regulation Enzymologic Article Xenobiotics 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Cytochrome P-450 Enzyme System Internal medicine medicine Animals Chronic stress Microbiome RNA Messenger lcsh:Science chemistry.chemical_classification Regulation of gene expression Mice Inbred BALB C Multidisciplinary lcsh:R biology.organism_classification Gastrointestinal Microbiome Enzymes 030104 developmental biology Endocrinology Enzyme Metabolism chemistry Liver lcsh:Q Xenobiotic 030217 neurology & neurosurgery Drug metabolism Stress Psychological Transcription Factors
Zdroj:	Scientific Reports, Vol 10, Iss 1, Pp 1-8 (2020) Scientific Reports
ISSN:	2045-2322
Popis:	The gut microbiota is involved in a number of different metabolic processes of the host organism, including the metabolism of xenobiotics. In our study, we focused on liver cytochromes P450 (CYPs), which can metabolize a wide range of exo- and endogenous molecules. We studied changes in mRNA expression and CYP enzyme activities, as well as the mRNA expression of transcription factors that have an important role in CYP expression, all in stressed germ-free (GF) and stressed specific-pathogen-free (SPF) mice. Besides the presence of the gut microbiota, we looked at the difference between acute and chronic stress. Our results show that stress has an impact on CYP mRNA expression, but it is mainly chronic stress that has a significant effect on enzyme activities along with the gut microbiome. In acutely stressed mice, we observed significant changes at the mRNA level, however, the corresponding enzyme activities were not influenced. Our study suggests an important role of the gut microbiota along with chronic psychosocial stress in the expression and activity of CYPs, which can potentially lead to less effective drug metabolism and, as a result, a harmful impact on the organism.
Databáze:	OpenAIRE
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