Intestinal Microbiota Regulate Xenobiotic Metabolism in the Liver

被引：185
作者：
Bjorkholm, Britta
Bok, Chek Mei
Lundin, Annelie
Rafter, Joseph
Hibberd, Martin Lloyd
Pettersson, Sven
机构：
[1] Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm
[2] Genome Institute of Singapore, Singapore
[3] Department of Biosciences and Nutrition, Karolinska University Hospital, Stockholm
[4] Swedish Institute for Infectious Disease Control Smittskyddsinstitutet, Solna
来源：
PLOS ONE | 2009年 / 4卷 / 09期
关键词：
CONSTITUTIVE ANDROSTANE RECEPTOR; PREGNANE-X-RECEPTOR; GERM-FREE; NEUROTROPHIC FACTOR; MICROSOMAL METABOLISM; CONDITIONAL DELETION; NUCLEAR RECEPTORS; DRUG-METABOLISM; INNATE IMMUNITY; BILE-ACIDS;
D O I：
10.1371/journal.pone.0006958
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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.
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页数：8
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