Intestinal microbiota regulate xenobiotic metabolism in the liver
Björkholm B. Bok C.M. Lundin A. Rafter J. Hibberd M.L. Pettersson S.
Björkholm B.
Bok C.M.
Lundin A.
Rafter J.
Pettersson S.
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Alternative Title
Abstract
Background: The liver is the central organ for xenobiotic metabolism (XM) and is regulated by nuclear receptors such as CAR and PXR, which control the metabolism of drugs. Here we report that gut microbiota influences liver gene expression and alters xenobiotic metabolism in animals exposed to barbiturates. Principal findings: By comparing hepatic gene expression on microarrays from germfree (GF) and conventionally-raised mice (SPF), we identified a cluster of 112 differentially expressed target genes predominantly connected to xenobiotic metabolism and pathways inhibiting RXR function. These findings were functionally validated by exposing GF and SPF mice to pentobarbital which confirmed that xenobiotic metabolism in GF mice is significantly more efficient (shorter time of anesthesia) when compared to the SPF group. Conclusion: Our data demonstrate that gut microbiota modulates hepatic gene expression and function by altering its xenobiotic response to drugs without direct contact with the liver. © 2009 Björkholm et al.
Keywords
constitutive androstane receptor, cytochrome P450, farnesoid X receptor, pentobarbital, retinoid X receptor, barbituric acid derivative, pentobarbital, xenobiotic agent, article, circadian rhythm, controlled study, gene expression, genetic regulation, intestine flora, liver, liver function, liver size, liver weight, male, microarray analysis, mouse, nonhuman, xenobiotic metabolism, animal, biological model, cell nucleus, DNA microarray, gene expression profiling, gene expression regulation, intestine, metabolism, microbiology, multigene family, time, Animalia, Mus, Animals, Barbiturates, Cell Nucleus, Gene Expression Profiling, Gene Expression Regulation, Intestines, Liver, Male, Mice, Models, Biological, Multigene Family, Oligonucleotide Array Sequence Analysis, Pentobarbital, Time Factors, Xenobiotics
Source Title
PLoS ONE
Publisher
Series/Report No.
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Rights
Attribution 4.0 International
Date
2009
DOI
10.1371/journal.pone.0006958
Type
Article