Intestinal microbiota regulate xenobiotic metabolism in the liver.


Björkholm, B; Bok, CM; Lundin, A; Rafter, J; Hibberd, ML; Pettersson, S; (2009) Intestinal microbiota regulate xenobiotic metabolism in the liver. PLoS One, 4 (9). e6958. ISSN 1932-6203 DOI: https://doi.org/10.1371/journal.pone.0006958

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Abstract

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. 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. 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.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
PubMed ID: 19742318
Web of Science ID: 269622500019
URI: http://researchonline.lshtm.ac.uk/id/eprint/2869475

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