β-Glucuronidase

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:

  • Karen Pendergrass ID
    Karen Pendergrass

    User avatarKaren 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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Fact-checked by:

  • Kimberly Eyer ID
    Kimberly Eyer

    User avatarKimberly 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.

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January 3, 2025

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.

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Researched by:

  • Karen Pendergrass ID
    Karen Pendergrass

    User avatarKaren 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.

    Read More

Fact-checked by:

  • Kimberly Eyer ID
    Kimberly Eyer

    User avatarKimberly 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.

    Read More

Last Updated: 2024-04-22

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

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.

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.

BacteriaCharacteristics
Escherichia coliAn 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 perfringensAn 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 faecalisPart 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:

ConditionRole of β-Glucuronidase
Breast CancerElevated levels can enhance estrogen activity, promoting the proliferation of estrogen-responsive breast cancer cells.
EndometriosisIncreases estrogen levels through deconjugation, potentially exacerbating the condition.
Liver DiseaseHigh β-glucuronidase activity activity is often seen in liver dysfunction, affecting drug metabolism and toxin clearance.
Colorectal CancerBacterial β-glucuronidase activity may influence the metabolism of carcinogens, contributing to colorectal carcinogenesis.
GoutImpaired breakdown of glycosaminoglycans can contribute to uric acid accumulation.
Neonatal JaundiceElevated 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
Endometriosis

Did you know?
Gut microbiota predict endometriosis better than vaginal microbiota.

Chronic Pelvic Pain (CPP)
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
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.

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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.

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