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Intestinal microbiota regulate xenobiotic metabolism in the liver.


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.

SUBMITTER: Bjorkholm B 

PROVIDER: S-EPMC2734986 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Intestinal microbiota regulate xenobiotic metabolism in the liver.

Björkholm Britta B   Bok Chek Mei CM   Lundin Annelie A   Rafter Joseph J   Hibberd Martin Lloyd ML   Pettersson Sven S  

PloS one 20090909 9


<h4>Background</h4>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.<h4>Principal findings</h4>By comparing hepatic gene expression on microarrays from germfree (GF) and conventionally-raised mice (SPF), we identified a cluster of 112 differentially exp  ...[more]

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