How Gut Health Regulates Oestrogen Metabolism: Exploring The Estrobolome
Meet the Estrobolome: Your Gut’s Role in Oestrogen Metabolism
Oestrogen is an important sex hormone produced by the ovaries, adrenal glands, and adipose tissue. Three different types of oestrogens play important roles throughout a woman’s life, including a healthy menstrual cycle, fertility and pregnancy, bone and cardiovascular health, mood regulation, and skin and hair health.
Oestrogen is excreted through a series of metabolic degradations via the liver, gut microbiota, and kidneys. Oestrogen metabolism is central to maintaining balanced circulating oestrogen levels. When this process is disrupted, it can lead to hormonal imbalances and contribute to oestrogen-related conditions such as endometriosis, premenstrual syndrome (PMS) and pre-menstrual dysphoric disorder (PMDD).
Emerging research shows that gut health plays a critical role in regulating systemic oestrogen levels. The collection of gut bacteria and their genes that are capable of metabolising oestrogens is referred to as the estrobolome. The gut bacteria produce enzymes such as β-glucuronidase which can negatively impact the recirculation and reabsorption of oestrogen in the body, and therefore impact oestrogen related conditions.
Beta-Glucuronidase: The enzyme that can hinder oestrogen metabolism
High levels of β-glucuronidase can convert conjugated (inactive) oestrogens back into their active, free forms. This increases the amount of free oestrogen re-entering circulation via the enterohepatic pathway, helping to maintain systemic estrogen at physiological levels or in some cases, contributing to oestrogen dominance.
Oestrogen dominance can exacerbate conditions such as endometriosis, PMS, and PMDD. In cases of endometriosis, oestrogen can stimulate the growth and proliferation of endometrial-like tissue outside of the uterus via angiogenesis. This phenomenon is supported by a complex interplay between oestrogen, cytokines, growth factors, and angiogenic factors that aid in establishing and progressing endometriotic implants which advance the disease. Supporting oestrogen metabolism is important for both symptom management and disease progression.
In relation to PMS and PMDD, higher levels of oestradiol during the luteal phase have been linked to more severe premenstrual symptoms. Women with PMDD have been shown to have differences in the expression of a group of estrogen-sensitive genes, specifically, genes from the epigenetic ESC/E(Z) complex, meaning their expression changes depending on oestrogen levels leading to altered brain chemistry and mood symptoms. In addition to this, increasing levels of oestrogen during the luteal phase increases the activity of Na-K-2Cl co-transporter, a transporter that pulls chloride into the neuron. This raises intracellular chloride levels making GABA’s calming effect flip to excitatory, contributing to mood instability in sensitive individuals.
“Elevated Oestradiol levels (specifically >600-800 pmol/L) are considered excess when testing seven days after ovulation.”
Supporting the Estrobolome: Gut-based strategies for hormonal balance
Assessing both serum oestrogen levels and oestrogen detoxification, via the estrobolome is the first step in supporting clients with endometriosis, PMS, and PMDD. It’s estimated that 60 different bacterial genera, classified into four main phyla including Bacteroidetes (52%), Firmicutes (43%), Verrucomicrobia (1.5%), and Proteobacteria (0.5%), encode for β-glucuronidase. Completing a quality microbiome test, such as the MetaXplore GI Plus from Co-Biome by Microba, which includes markers of β-glucuronidase activity is crucial for understanding if interventions for this enzyme are required as part of a comprehensive treatment plan.
Top 20 species known to produce β-glucuronidase
When there are elevated levels of β-glucuronidase producing bacteria, there are several key supplements that can help to reduce β-glucuronidase enzyme activity and therefore oestrogen levels. These include lactulose, oligofructose-enriched inulin, and calcium-d-glucorate.
Lactulose is a disaccharide (sugar) that is not digested in the upper gastrointestinal tract, while oligofructose-enriched inulin is a prebiotic fibre that selectively stimulates the growth of beneficial gut bacteria. Both lactulose and oligofructose-enriched inulin reach the colon undigested, where they act as prebiotic substrates. Glucomannan is a type of prebiotic fibre which has been shown to reduce faecal beta-glucuronidase activity. Once in the colon, they are selectively fermented by beneficial bacteria, particularly Bifidobacteria. This can lead to a shift in the gut microbial composition leading to a reduction in β-glucuronidase activity, as Bifidobacteria typically do not produce high levels of this enzyme. The result is a less favourable environment for β-glucuronidase-expressing bacteria, contributing to lower overall enzyme activity in the colon, and lower oestrogen levels.
Calcium-D-glucarate is the calcium salt of D-glucaric acid, a compound naturally produced in small amounts by the body and is also found in fruits and vegetables such as oranges, apples, grapefruit, and cruciferous vegetables. Supplementation with calcium-D-glucarate has been shown to inhibit β-glucuronidase activity. By reducing β-glucuronidase activity, calcium-D-glucarate can support healthy estrogen metabolism.
Clinical insight:
Lactulose dosage recommendations are for 10–15 ml, twice daily.
Oligofructose-enriched inulin dosage recommendations are 4 to 8g daily, and it’s suggested to increase the dosage slowly over time to minimise side effects
Glucomannan dosage recommendation 2 to 4g daily.
Calcium-D-glucarate dosage recommendations is from 1500 mg to 3000 mg daily.
Take home message on how gut health regulates oestrogen metabolism
While oestrogen is an important sex hormone, oestrogen dominance can contribute to conditions such as endometriosis, PMS, and PMDD. Assessing the role gut health plays in oestrogen metabolism and recirculation is important, and a quality microbiome test which gives insights into gut bacteria and β-glucuronidase activity is crucial. If there are high levels of β-glucuronidase activity in people with these conditions lactulose, glucomannan, oligofructose-enriched inulin, and calcium-d-glucorate are four supplements which can help to improve gut bacteria, reduce enzyme activity, and manage disease progression and associated symptoms.
Lesley O’Connor
Lesley O’Connor is a qualified Naturopath (BHSc) with a postgraduate certificate in Human Nutrition, who has a clinical interest in women’s health, fertility, IVF support, pregnancy, and post-partum health. Lesley adopts a food-as-medicine approach and emphasises a holistic view by assessing dietary, lifestyle, and environmental factors that impact women’s health.
With a client-centred approach, Lesley ensures women feel heard and validated, guiding them to work with their bodies for optimal health outcomes. As an educator and mentor, Lesley empowers women with the knowledge and tools to take control of their health, offering a fresh perspective in a system often lacking in these essential resources.
If you want to learn more about Lesley you can visit her website here.