Fecal microbial determinants of fecal and systemic estrogens and estrogen metabolites: a cross-sectional study

Journal of Translational Medicine

Research

Jianxin Shi¹  Mitchell H Gail¹  Barbara Fuhrman²  James J Goedert³  Roberto Flores⁴  Jacques Ravel⁵  Pawel Gajer⁵  Timothy D Veenstra⁶  Xia Xu⁶ 

[1] Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 20852, Rockville, MD, USA;Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 20852, Rockville, MD, USA;Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Room 7068, 20852, Rockville, MD, USA;Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Room 7068, 20852, Rockville, MD, USA;Cancer Prevention Fellowship Program, National Cancer Institute, 20852, Rockville, MD, USA;Institute of Genome Sciences, University of Maryland School of Medicine, 21201, Baltimore, MD, USA;Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, SAIC-Frederick, 21702, Frederick, MD, USA;

关键词: Microbiome;    Feces;    Enterohepatic circulation;    β-glucuronidase;    β-glucosidase;    Postmenopausal estrogens;    Fecal estrogens;    Estrogen metabolites;   

DOI  :  10.1186/1479-5876-10-253

 received in 2012-10-03, accepted in 2012-12-17,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundHigh systemic estrogen levels contribute to breast cancer risk for postmenopausal women, whereas low levels contribute to osteoporosis risk. Except for obesity, determinants of non-ovarian systemic estrogen levels are undefined. We sought to identify members and functions of the intestinal microbial community associated with estrogen levels via enterohepatic recirculation.MethodsFifty-one epidemiologists at the National Institutes of Health, including 25 men, 7 postmenopausal women, and 19 premenopausal women, provided urine and aliquots of feces, using methods proven to yield accurate and reproducible results. Estradiol, estrone, 13 estrogen metabolites (EM), and their sum (total estrogens) were quantified in urine and feces by liquid chromatography/tandem mass spectrometry. In feces, β-glucuronidase and β-glucosidase activities were determined by realtime kinetics, and microbiome diversity and taxonomy were estimated by pyrosequencing 16S rRNA amplicons. Pearson correlations were computed for each loge estrogen level, loge enzymatic activity level, and microbiome alpha diversity estimate. For the 55 taxa with mean relative abundance of at least 0.1%, ordinal levels were created [zero, low (below median of detected sequences), high] and compared to loge estrogens, β-glucuronidase and β-glucosidase enzymatic activity levels by linear regression. Significance was based on two-sided tests with α=0.05.ResultsIn men and postmenopausal women, levels of total urinary estrogens (as well as most individual EM) were very strongly and directly associated with all measures of fecal microbiome richness and alpha diversity (R≥0.50, P≤0.003). These non-ovarian systemic estrogens also were strongly and significantly associated with fecal Clostridia taxa, including non-Clostridiales and three genera in the Ruminococcaceae family (R=0.57−0.70, P=0.03−0.002). Estrone, but not other EM, in urine correlated significantly with functional activity of fecal β-glucuronidase (R=0.36, P=0.04). In contrast, fecal β-glucuronidase correlated inversely with fecal total estrogens, both conjugated and deconjugated (R≤-0.47, P≤0.01). Premenopausal female estrogen levels, which were collected across menstrual cycles and thus highly variable, were completely unrelated to fecal microbiome and enzyme parameters (P≥0.6).ConclusionsIntestinal microbial richness and functions, including but not limited to β-glucuronidase, influence levels of non-ovarian estrogens via enterohepatic circulation. Thus, the gut microbial community likely affects the risk for estrogen-related conditions in older adults. Understanding how Clostridia taxa relate to systemic estrogens may identify targets for interventions.Trial registrationNot applicable.

【 授权许可】

Unknown   
© Flores et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.