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Sci Rep. 2018 May 25;8(1):8166. doi: 10.1038/s41598-018-26506-1.

Long-Term Administration of Conjugated Estrogen and Bazedoxifene Decreased Murine Fecal β-Glucuronidase Activity Without Impacting Overall Microbiome Community.

Author information

1
Division of Nutritional Sciences, University of Illinois, Urbana-Champaign, Urbana, IL, USA.
2
Department of Food Science and Human Nutrition, University of Illinois, Urbana-Champaign, Urbana, IL, USA.
3
Department of Pathobiology, University of Illinois, Urbana-Champaign, Urbana, IL, USA.
4
The Roslin Institute, University of Edinburgh, Edinburgh, Scotland, UK.
5
National Center for Supercomputing Applications, University of Illinois, Urbana-Champaign, Urbana, IL, USA.
6
Carl R. Woese Institute for Genomic Biology, University of Illinois, Urbana-Champaign, Urbana, IL, USA.
7
Carle Illinois College of Medicine, University of Illinois, Urbana-Champaign, Urbana, IL, USA.
8
Department of Chemistry, University of Illinois, Urbana-Champaign, Urbana, IL, USA.
9
Division of Nutritional Sciences, University of Illinois, Urbana-Champaign, Urbana, IL, USA. zmadake2@illinois.edu.
10
Department of Food Science and Human Nutrition, University of Illinois, Urbana-Champaign, Urbana, IL, USA. zmadake2@illinois.edu.
11
National Center for Supercomputing Applications, University of Illinois, Urbana-Champaign, Urbana, IL, USA. zmadake2@illinois.edu.
12
Carl R. Woese Institute for Genomic Biology, University of Illinois, Urbana-Champaign, Urbana, IL, USA. zmadake2@illinois.edu.
13
Cancer Center at Illinois, University of Illinois, Urbana-Champaign, Urbana, IL, USA. zmadake2@illinois.edu.
14
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA. zmadake2@illinois.edu.

Abstract

Conjugated estrogens (CE) and Bazedoxifene (BZA) combination is used to alleviate menopause-associated symptoms in women. CE+BZA undergo first-pass-metabolism in the liver and deconjugation by gut microbiome via β-glucuronidase (GUS) enzyme inside the distal gut. To date, the impact of long-term exposure to CE+BZA on the gut microbiome or GUS activity has not been examined. Our study using an ovariectomized mouse model showed that CE+BZA administration did not affect the overall cecal or fecal microbiome community except that it decreased the abundance of Akkermansia, which was identified as a fecal biomarker correlated with weight gain. The fecal GUS activity was reduced significantly and was positively correlated with the abundance of Lactobacillaceae in the fecal microbiome. We further confirmed in Escherichia coli K12 and Lactobacillus gasseri ADH that Tamoxifen-, 4-hydroxy-Tamoxifen- and Estradiol-Glucuronides competed for GUS activity. Our study for the first time demonstrated that long-term estrogen supplementation directly modulated gut microbial GUS activity. Our findings implicate that long-term estrogen supplementation impacts composition of gut microbiota and microbial activity, which affects estrogen metabolism in the gut. Thus, it is possible to manipulate such activity to improve the efficacy and safety of long-term administered estrogens for postmenopausal women or breast cancer patients.

PMID:
29802368
PMCID:
PMC5970144
DOI:
10.1038/s41598-018-26506-1
[Indexed for MEDLINE]
Free PMC Article

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