Intestinal microbiota regulate xenobiotic metabolism in the liver.
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.


RESULTS
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.


CONCLUSIONS
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.
Björkholm
Britta
B
Department of Microbiology, Tumor and Cell biology, Karolinska Institutet, Stockholm, Sweden.
Bok
Chek Mei
CM
Lundin
Annelie
A
Rafter
Joseph
J
Hibberd
Martin Lloyd
ML
Pettersson
Sven
S
D000818:Animals; D001463:Barbiturates / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007422:Intestines / Q000382:microbiology*; D008099:Liver / Q000378:metabolism / Q000382:microbiology*; D008297:Male; D051379:Mice; D008954:Models, Biological; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D010424:Pentobarbital / Q000494:pharmacology; D013997:Time Factors; D015262:Xenobiotics / Q000378:metabolism*
D001463:Barbiturates; D015262:Xenobiotics; D010424:Pentobarbital