Gut Microbiome Alters the Activity of Liver Cytochromes P450 in Mice With Sex-Dependent Differences

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F20%3A00535227" target="_blank" >RIV/61388971:_____/20:00535227 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15110/20:73605109

Výsledek na webu

<a href="https://www.frontiersin.org/articles/10.3389/fphar.2020.01303/full" target="_blank" >https://www.frontiersin.org/articles/10.3389/fphar.2020.01303/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fphar.2020.01303" target="_blank" >10.3389/fphar.2020.01303</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Gut Microbiome Alters the Activity of Liver Cytochromes P450 in Mice With Sex-Dependent Differences

Popis výsledku v původním jazyce

Sexual differences and the composition/function of the gut microbiome are not considered the most important players in the drug metabolism field, however, from the recent data it is obvious that they may significantly affect the response of the patient to therapy. Here, we evaluated the effect of microbial colonization and sex differences on mRNA expression and the enzymatic activity of hepatic cytochromes P450 (CYPs) in germ-free (GF) mice, lacking the intestinal flora, and control specific-pathogen-free (SPF) mice. We observed a significant increase in the expression ofCyp3a11in female SPF mice compared to the male group. However, the sex differences were erased in GF mice, and the expression ofCyp3a11was about the same in both sexes. We have also found higherCyp2c38gene expression in female mice compared to male mice in both the SPF and GF groups. Moreover, these changes were confirmed at the level of enzymatic activity, where the female mice exhibit higher levels of functional CYP2C than males in both groups. Interestingly, we observed the same trend as with CYP3A enzymes: a diminished difference between the sexes in GF mice. The presented data indicate that the mouse gut microbiome plays an important role in sustaining sexual dimorphism in terms of hepatic gene expression and metabolism.

Název v anglickém jazyce

Gut Microbiome Alters the Activity of Liver Cytochromes P450 in Mice With Sex-Dependent Differences

Popis výsledku anglicky

Sexual differences and the composition/function of the gut microbiome are not considered the most important players in the drug metabolism field, however, from the recent data it is obvious that they may significantly affect the response of the patient to therapy. Here, we evaluated the effect of microbial colonization and sex differences on mRNA expression and the enzymatic activity of hepatic cytochromes P450 (CYPs) in germ-free (GF) mice, lacking the intestinal flora, and control specific-pathogen-free (SPF) mice. We observed a significant increase in the expression ofCyp3a11in female SPF mice compared to the male group. However, the sex differences were erased in GF mice, and the expression ofCyp3a11was about the same in both sexes. We have also found higherCyp2c38gene expression in female mice compared to male mice in both the SPF and GF groups. Moreover, these changes were confirmed at the level of enzymatic activity, where the female mice exhibit higher levels of functional CYP2C than males in both groups. Interestingly, we observed the same trend as with CYP3A enzymes: a diminished difference between the sexes in GF mice. The presented data indicate that the mouse gut microbiome plays an important role in sustaining sexual dimorphism in terms of hepatic gene expression and metabolism.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Frontiers in Pharmacology

ISSN

1663-9812

e-ISSN

—

Svazek periodika

11

Číslo periodika v rámci svazku

OCT 2 2020

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

6

Strana od-do

01303

Kód UT WoS článku

000577726800001

EID výsledku v databázi Scopus

2-s2.0-85092776545