Impact of Gut Microbiota on Intestinal and Hepatic Levels of Phase 2 Xenobiotic-Metabolizing Enzymes in the Rat


By jpeza - Posted on 05 Noviembre 2010

Fecha Publicación: 
1 Ene 2009
Datos del paper
Autor Principal: 
Walter Meinl
Volumen: 
37
Issue: 
6
Página Inicial: 
1179
Página Final: 
1186
Abstract: 

Using immunoblotting, we compared levels of phase 2 enzymes in
liver, small intestine, cecum, and colon of germ-free and control
rats (reassociated with rat intestinal microbiota). In addition, colonic
levels were studied after association with human intestinal
microbiota. The glutathione transferases (GSTs) studied, gastrointestinal
glutathione peroxidase (GPX2), both epoxide hydrolases
(EPHXs), and N-acetyltransferase (NAT) 1, were detected in all
tissues. GPX2 and GSTP1 were highest in large bowel; the other
enzymes of this group were highest in liver. NAT2 was found in the
large bowel but not in the liver or small bowel. Sulfotransferases
(SULTs) were detected in liver but were absent in small intestine;
two forms were present at moderate levels in the large intestine.
Strong gender-dependent differences were observed for several
enzymes in liver but not in gut. Colonic levels in germ-free animals
differed from those in control animals (* indicates statistical significance)
for GSTA1/2 (4.0*- and 5.0*-fold in males and females,
respectively), GSTA4 (1.5*/1.9*-fold), GSTM1 (1.1/1.5*-fold), EPHX1
(3.5*/2.4*-fold), EPHX2 (1.4/2.1*-fold), SULT1B1 (0.4*/0.6*-fold),
SULT1C2 (1.3/1.6*-fold), and NAT2 (1.4/1.5*-fold). Smaller effects
were observed when rats were colonized with human, compared
with rat, intestinal bacteria. Cecal enzyme levels in germ-free rats
were changed similarly to those in colon. No effects were seen in
small intestine. In liver, SULT1A1, SULT1C1, and SULT1C2 were
elevated in germ-free animals of both genders (1.5- to 2.6-fold);
hepatic EPHX2 was elevated 1.6-fold in females. In conclusion,
intestinal microbiota can affect levels of xenobiotic-metabolizing
enzymes in large intestine and liver, but the effects observed
were moderate compared with tissue-dependent expression
differences.

Dirección del Autor: 

Departments of Nutritional Toxicology (W.M., H.G.), Gastrointestinal Microbiology (S.S., M.B.), and Biochemistry of
Micronutrients (R.B.-F.), German Institute of Human Nutrition Potsdam-Rehbru¨ cke, Nuthetal, Germany

Keywords: 
immunoblotting ; small intestine
Coautores: 

Silke Sczesny,Regina Brigelius-Flohe ,Michael Blaut,Hansruedi Glatt

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