β-Glucuronidase can inadvertently increase cancer risk by reactivating detoxified carcinogens in the gut, transforming them back into harmful compounds, highlighting its complex and potentially dangerous role in the body.
β-Glucuronidase
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.
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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.
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.
Research feed -
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 
Research Feed Overview
β-Glucuronidase plays a multifaceted and critical role in both microbial ecology and host health within the microbiome. This enzyme primarily breaks down liver-excreted glucuronides in the gut. These glucuronides include metabolites, drugs, and hormones. By breaking these down, β-glucuronidase enables gut bacteria to access and use these compounds as energy sources. This activity supports nutrient cycling and enhances the metabolic diversity of the microbial community. Additionally, β-glucuronidase affects host health by altering the bioavailability and effectiveness of medications. It also changes hormone levels by deconjugating hormone glucuronides. One key interaction is between β-glucuronidase and estrogen, which maintains essential physiological estrogen levels for homeostasis. Disruptions in this interaction can disturb estrogen metabolism, leading to estrogen-related diseases like gynecological cancers and menopausal syndrome. These conditions may worsen with gut microbial dysbiosis. Moreover, β-glucuronidase can reactivate carcinogens from their detoxified forms, increasing colorectal cancer risks linked to the microbiome. Therefore, β-glucuronidase is a crucial link between microbial metabolism and host physiological processes, highlighting the complex interplay between the microbiome and human health.
Function
β-Glucuronidase is a type of hydrolase enzyme that catalyzes the hydrolysis of β-D-glucuronic acid residues from the non-reducing end of mucopolysaccharides such as heparan sulfate and chondroitin sulfate. This reaction is crucial for the degradation and recycling of these complex carbohydrates in the body. One of the most shocking aspects of β-glucuronidase is its dual role in benefiting and potentially harming the host. While it facilitates essential metabolic processes in the gut microbiome, β-glucuronidase can also inadvertently increase cancer risk. This enzyme can reactivate carcinogens that have been detoxified by the liver and excreted into the gut as harmless glucuronides. Once reactivated by β-glucuronidase, these compounds regain their toxic and carcinogenic properties, potentially contributing to the development of cancers like colorectal cancer. This paradoxical effect underscores the complexity of the enzyme’s impact on health, demonstrating how a substance crucial for metabolic and digestive efficiency can pose a significant risk to the host.
Significance
The enzyme’s role extends beyond just metabolic functions; it is also implicated in various pathological conditions due to its influence on drug bioavailability and the behavior of hormones and carcinogens. Abnormal levels of β-glucuronidase have been associated with several diseases, including liver disease, certain types of cancer, and metabolic disorders. Furthermore, β-glucuronidase from bacterial sources in the gut can deconjugate estrogen back into its active form, potentially influencing estrogen-dependent conditions like breast cancer and endometriosis. This aspect highlights the enzyme’s role in modulating hormone-driven pathologies and underscores its importance in the microbiome-health axis.
Microbes that express β-Glucuronidase
Bacteria express β-glucuronidase for several reasons, primarily to enhance their survival and metabolic efficiency within host environments like the gastrointestinal tract. This enzyme aids in nutrient acquisition by breaking down complex molecules such as glucuronides—conjugated forms of substances excreted into bile or secreted into the gut—allowing bacteria to utilize the released sugars and other components. This capability is vital in the nutrient-variable environment of the gut. Additionally, β-glucuronidase facilitates environmental adaptation, giving bacteria a survival advantage by enabling them to exploit otherwise inaccessible sources of energy and carbon. The enzyme also plays a role in detoxification, helping bacteria manage or break down toxic substances, though it may also inadvertently activate procarcinogens, impacting host health. These diverse functions highlight the enzyme’s integral role in bacterial survival strategies and its significant effects on host interactions.
| Bacteria | Characteristics |
|---|---|
| Escherichia coli | An anaerobic bacterium known for its strong β-glucuronidase activity is often linked to various infections and diseases. |
| Streptococcus spp. | Includes several species in the gut flora; involved in the hydrolysis of glucuronides. |
| Bacteroides spp. | Major component of the gut microbiome; these anaerobic bacteria are significant producers of β-glucuronidase. |
| Clostridium perfringens | An anaerobic bacterium, known for its strong β-glucuronidase activity, often linked to various infections and diseases. |
| Staphylococcus spp. | Some species in this genus express β-glucuronidase, contributing to their pathogenic profile in some contexts. |
| Enterococcus faecalis | Part of the normal gut flora but can be pathogenic; expresses β-glucuronidase which may play a role in its virulence and the intestinal environment. |
| Lactobacillus spp. | Typically considered beneficial, some species in this genus can produce β-glucuronidase, affecting estrogen levels and potentially influencing hormone-dependent conditions. |
Implicated Conditions
Here are some of the conditions that β-glucuronidase has been implicated in, which illustrates the diversity of its potential clinical impacts:
| Condition | Role of β-Glucuronidase |
|---|---|
| Breast Cancer | Elevated levels can enhance estrogen activity, promoting the proliferation of estrogen-responsive breast cancer cells. |
| Endometriosis | Increases estrogen levels through deconjugation, potentially exacerbating the condition. |
| Liver Disease | High β-glucuronidase activity activity is often seen in liver dysfunction, affecting drug metabolism and toxin clearance. |
| Colorectal Cancer | Bacterial β-glucuronidase activity may influence the metabolism of carcinogens, contributing to colorectal carcinogenesis. |
| Gout | Impaired breakdown of glycosaminoglycans can contribute to uric acid accumulation. |
| Neonatal Jaundice | Elevated serum levels may indicate or exacerbate conditions like jaundice in newborns, as it affects bilirubin clearance. |
Research Feed
The role of gut and genital microbiota and the estrobolome in endometriosis, infertility and chronic pelvic pain
October 27, 2021
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Endometriosis
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Endometriosis
Did you know?
Gut microbiota predict endometriosis better than vaginal microbiota.
Chronic Pelvic Pain (CPP)
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Chronic Pelvic Pain (CPP)
Did you know?
Estimates suggest that 1 in 7 women in the United States is affected by Chronic Pelvic Pain (CPP).
Infertility
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Infertility
Did you know?
Despite common perceptions, male factors alone are responsible for about 30% of all infertility cases and contribute to another 20% when combined with female factors. This highlights the importance of evaluating both partners in infertility assessments.
This review highlights the gut and genital microbiome's roles in estrogen-driven conditions like endometriosis, infertility, and CPP, emphasizing dysbiosis' impact on inflammation and estrogen metabolism.
What was reviewed?
The reviewed manuscript explored the intricate relationship between the gut and genital microbiomes, the estrobolome, and their roles in the pathophysiology of endometriosis, infertility, and chronic pelvic pain (CPP). The authors critically examined 28 clinical and six preclinical studies to understand microbial dysbiosis's contributions to estrogen metabolism, inflammation, and symptomatology in these conditions. This review also identified methodological gaps in microbiome studies and proposed strategies to improve future research.
Who was reviewed?
The review included human and animal studies, examining women diagnosed with endometriosis, infertility, and CPP, alongside healthy controls. Specific focus was placed on microbial associations in the gut, cervicovaginal, and endometrial microbiomes, with emphasis on bacterial vaginosis-associated bacteria, Lactobacillus depletion, and microbial influences on estrogen-driven mechanisms.
What were the most important findings?
Key findings highlighted that dysbiosis in the gut microbiome disrupts the estrobolome, an essential modulator of estrogen metabolism. This disruption contributes to heightened systemic and local inflammation, potentially exacerbating endometriosis symptoms and infertility. Many studies noted an association between bacterial vaginosis-related bacteria and a reduction in Lactobacillus dominance in the cervicovaginal microbiome with the prevalence of endometriosis and infertility. Additionally, the review underscored a bidirectional relationship between gut microbiota and endometriosis progression in animal models, emphasizing the role of gut dysbiosis in increasing b-glucuronidase activity, leading to elevated circulating estrogen levels.
What are the greatest implications of this review?
This review underscores the need for rigorous, standardized methodologies to better delineate causal relationships between microbiota and gynecological conditions like endometriosis and CPP. The findings of this review suggest that targeting the microbiome could lead to novel diagnostics and therapeutics for estrogen-driven diseases. The review also highlights the potential of leveraging microbiome-based biomarkers for non-invasive diagnostics and monitoring of endometriosis progression, bridging a critical translational gap in gynecological health.
Breast Cancer
Traditionally linked to genetic predispositions and environmental exposures, emerging evidence highlights the microbiome as a critical and underappreciated factor influencing breast cancer progression, immune response, and treatment outcomes.
Endometriosis
Endometriosis involves ectopic endometrial tissue causing pain and infertility. Validated and Promising Interventions include Hyperbaric Oxygen Therapy (HBOT), Low Nickel Diet, and Metronidazole therapy.
Breast Cancer
Traditionally linked to genetic predispositions and environmental exposures, emerging evidence highlights the microbiome as a critical and underappreciated factor influencing breast cancer progression, immune response, and treatment outcomes.
Endometriosis
Endometriosis involves ectopic endometrial tissue causing pain and infertility. Validated and Promising Interventions include Hyperbaric Oxygen Therapy (HBOT), Low Nickel Diet, and Metronidazole therapy.