Did you know?
While estrogen is essential for normal bodily functions, excessive or prolonged exposure to estrogen, especially in hormone-sensitive tissues like the breast or uterus, can increase the risk of developing breast or endometrial cancer.
Estrogen
Researched by:
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Karen Pendergrass
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Karen Pendergrass
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
Fact-checked by:
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Kimberly Eyer
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Kimberly Eyer
Kimberly Eyer, a Registered Nurse with 30 years of nursing experience across diverse settings, including Home Health, ICU, Operating Room Nursing, and Research. Her roles have encompassed Operating Room Nurse, RN First Assistant, and Acting Director of a Same Day Surgery Center. Her specialty areas include Adult Cardiac Surgery, Congenital Cardiac Surgery, Vascular Surgery, and Neurosurgery.
Estrogen is a steroid hormone primarily found in women, crucial for reproductive health, secondary sexual characteristics, and various physiological processes. It regulates menstrual cycles, supports pregnancy, and influences bone density and cardiovascular health. Dysregulation of estrogen levels can lead to various disorders and health complications.
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Karen Pendergrass
Researched by:
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Karen Pendergrass
ID
Karen Pendergrass
Fact-checked by:
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Kimberly Eyer
ID
Kimberly Eyer
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
Overview 
FAQs 
References Overview
Estrogen, a pivotal sex hormone in women, orchestrates several physiological functions. This includes the promotion of reproductive organ development to the maintenance of secondary sexual characteristics. Its influence extends to diverse realms, including metabolism, cardiovascular health, women’s health, and bone development. The regulation of estrogen levels within the body is tied to estrogen metabolism. Dysregulation of estrogen metabolism can precipitate a spectrum of estrogen-related disorders. Recent investigations have unveiled the human gut microbiota as a complex endocrine organ with profound implications for physiology. [1, 2]
What else should I know about Estrogen?
Estrogen is primarily produced in the ovaries, adrenal glands, and adipose tissue and consists of estrone (E1), estradiol (E2), and estriol (E3). The ovaries mainly synthesize E1 and E2, and E3 is the main metabolite of E1 and E2 degradation in the liver. Both free and conjugated forms of estrogen are circulating in the bloodstream, with the conjugated form predominating. E2 is the most biologically active estrogen in the female body and remains inactive in circulation mostly by binding to plasma proteins, primarily sex-binding globulin (SHBG). Once it is deconjugated, free-form estrogen will regain biological activity. By combining with estrogen receptors (ERs), estrogen plays a vital role in regulating physiological processes. Thus, stable estrogen levels are important for maintaining homeostasis.
Estrogen and the Microbiome
The gut microbiota significantly influences various physiological processes by producing metabolites, immunological signaling, and hormonal intermediates. Recent research has underscored the role of the gut microbiota in modulating estrogen metabolism, suggesting a bidirectional relationship between estrogen levels and gut microbiota homeostasis. At the center of this interaction lies the estrobolome, comprised of gut bacterial genes such as GUS, which encode gut microbial β-glucuronidase (gmGUS). The estrobolome plays a crucial role in regulating estrogen metabolism, thereby impacting the development and progression of estrogen-related diseases, such as endometriosis and breast cancer. [x,x,x] This intricate interplay between gut microbiota and estrogen metabolism presents promising avenues for the development of therapeutic interventions targeting estrogen-driven disorders.
What else should I know about the microbiome in estrogen-driven diseases?
The β-glucuronidase gene, or GUS gene, initially discovered in Escherichia coli and other Enterobacteriaceae in 1934, emerged as a pivotal player in estrogen metabolism following its elucidation in 1944 [x]. This enzyme, β-glucuronidase, holds particular significance in estrogenic metabolism and estrogen-driven diseases due to its ability to deconjugate estrogen molecules, thereby releasing them into their active, free form capable of exerting biological effects.[x] The activity of β-glucuronidase enzymes, facilitated by both an increased abundance of bacteria harboring the estrobolome and heightened expression of these gene-encoding enzymes, accelerates the deconjugation process, consequently elevating the levels of free estrogens circulating in the enterohepatic circulation. Thus, the estrobolome plays a pivotal role as a mediator in regulating estrogen levels within the body.
The intricate relationship between the gut microbiota and estrogen extends beyond estrogen metabolism to encompass broader physiological processes such as the modulation of inflammatory responses and carbohydrate metabolism. [x] Consequently, gut microbiota dysbiosis has been implicated in various gynecological diseases, underscoring the importance of maintaining microbial balance for overall health. Elevated activity of gut microbial β-glucuronidase, particularly gmGUS, has been observed in several pathological conditions, including endometriosis and malignant tumors affecting the breast, ovary, and gastrointestinal tract. This observation underscores the potential clinical implications of targeting the estrobolome in the management of estrogen-related disorders.
Moreover, advancements in microbiome research have led to the identification of a human intestinal β-glucuronidase atlas within the Human Microbiome Project GI database. This comprehensive atlas revealed the presence of 279 GUS genes, with the majority taxonomically classified as Bacteroidetes (52%), Firmicutes (43%), Verrucomicrobia (1.5%), and Proteobacteria (0.5%). [x, x] Such insights into the taxonomic distribution of GUS genes within the human gut microbiota provide valuable context for understanding the microbial contributions to estrogen metabolism and related physiological processes.
FAQs
Does a higher Bacteroidetes to Firmicutes ratio mean an estrogen-mediated condition?
Does a higher Bacteroidetes to Firmicutes ratio mean an estrogen-mediated condition?
While an association between the Bacteroidetes to Firmicutes ratio and estrogen-mediated conditions may exist in certain contexts, it would be overly simplistic to assert a direct causal relationship based solely on this ratio. Factors such as diet, genetics, lifestyle, and environmental influences can also significantly impact both gut microbiota composition and estrogen levels.
Women's Health
Women’s health, a vital aspect of medical science, encompasses various conditions unique to women’s physiological makeup. Historically, women were often excluded from clinical research, leading to a gap in understanding the intricacies of women’s health needs. However, recent advancements have highlighted the significant role that the microbiome plays in these conditions, offering new insights and potential therapies. MicrobiomeSignatures.com is at the forefront of exploring the microbiome signature of each of these conditions to unravel the etiology of these diseases and develop targeted microbiome therapies.
β-Glucuronidase
β-glucuronidase in the gut microbiome breaks down metabolites, drugs, and hormone conjugates like estrogen, aiding microbial energy use and nutrient cycling. Its activity influences drug efficacy and hormone levels, maintaining estrogen balance and impacting health. Disruption in this process can lead to estrogen-related diseases, such as gynecological cancers and menopausal syndrome, and increase colorectal cancer risks by reactivating carcinogens, highlighting its pivotal role in linking microbial actions to host physiological processes.
References
- Gut flora in health and disease.. Guarner F, Malagelada JR.. (Lancet. 2003)
- Gut microbiome and health: mechanistic insights.. de Vos WM, Tilg H, Van Hul M, Cani PD.. (Gut. 2022)