Supporting Hormonal Balance via the Gut Microbiome: Overview
Dysbiosis, characterized by an overgrowth of pathogenic bacteria and loss of beneficial species, can disrupt gut barrier integrity, allowing lipopolysaccharides (LPS) and other endotoxins to enter the bloodstream and drive systemic inflammation. This inflammation disrupts hormonal signaling pathways, such as through the HPA axis, and can potentially lead to hormonal imbalances that manifest as reproductive, adrenal, and/or thyroid dysfunctions. Furthermore, dysbiosis in the estrobolome, in particular, may directly impair estrogen metabolism and contribute to estrogen imbalance, specifically. With that, we will finish the conversation by going through an absolutely remarkable tool for supporting hormonal health via supporting both the estrobolome and overall intestinal microbiome.
The Estrobolome
The estrobolome refers to the aggregate of gut microbiota capable of metabolizing estrogens through the production of β-glucuronidase enzymes. These bacterial enzymes play a critical role in the enterohepatic recirculation of estrogens by deconjugating estrogen metabolites, such as estrone and estradiol, in the intestines. In more detail, Estrogens, such as estrone (E1) and estradiol (E2), undergo hepatic phase II detoxification in the liver, where they may be conjugated through glucuronidation. This conjugation involves attaching glucuronic acid to the estrogens, making them more hydrophilic, thus facilitating their excretion via bile into the intestines. Once in the intestines, β-glucuronidase within the estrobolome can deconjugate these estrogens, converting them back into their active, lipophilic forms, which can be reabsorbed into systemic circulation. This microbial community (estrobolome) is particularly involved in the regulation of estrogen homeostasis, as well as influencing systemic estrogen levels. The estrobolome’s activity thereby integrates gut microbial function with endocrine signaling, significantly affecting and supporting hormonal balance within the body.
Dysbiosis in the Estrobolome
Dysbiosis within the estrobolome, characterized by an imbalance in the composition of gut microbiota, disrupts estrogen metabolism and enterohepatic recirculation. When the microbial diversity is reduced, or pathogenic species proliferate, β-glucuronidase activity may either become excessive or insufficient, leading to altered estrogen deconjugation. For example, insufficient β-glucuronidase activity (due to a reduced abundance of gut microbiota capable of metabolizing estrogens through the production of β-glucuronidase enzymes) reduces the reactivation of conjugated estrogens, resulting in a decreased pool of bioavailable estrogens and potentially contributing to hypoestrogenic states. This, unfortunately, may exacerbate menopausal symptoms or contribute to conditions including bone density loss.
Regarding Menopause, Case Study: There was a remarkable study investigating the effect of specific probiotic strains on estrogen metabolism in women undergoing the menopausal transition. The research highlights the role of gut microbiota in estrogen modulation, particularly through the action of β-glucuronidase (GUS), an enzyme produced by certain bacteria that deconjugates estrogen glucuronides, allowing for the reabsorption of active estrogens. The study involved in vitro screening of 84 strains of lactic acid bacteria and bifidobacteria for GUS activity, identifying Levilactobacillus brevis KABP052 as the strain with the highest activity. The researchers conducted a randomized, double-blind, placebo-controlled trial in peri- and postmenopausal women, where participants received a probiotic formula containing GUS-positive strains, including L. brevis KABP052. After 12 weeks, the probiotic group showed significantly higher serum levels of estradiol (31.62 ± 7.97 pg/mL) and estrone (21.38 ± 8.57 pg/mL) compared to the placebo group - truly incredible findings!
How General Dysbiosis Can Contribute to Hormonal Imbalance:
Example Using LPS-Driven Chronic Inflammation
Dysbiosis refers to an imbalance in the gut microbiota, where the composition and function of microbial communities deviate from a healthy state. In a state of dysbiosis, there is often a loss of beneficial bacteria (such as Lactobacillus and Bifidobacterium) and a proliferation of opportunistic or pathogenic bacteria.
LPS is a major component of the outer membrane of Gram-negative bacteria and acts as a potent endotoxin in the body. In a healthy gut, LPS is largely confined to the lumen and prevented from entering circulation by a robust intestinal epithelial barrier and a well-functioning immune system. This barrier is composed of tight junction proteins, such as claudins, occludins, and zona occludens proteins, which regulate the permeability of the gut lining. In a dysbiotic state, increased intestinal permeability occurs due to the disruption of these tight junctions. Several factors contribute to this disruption, including microbial dysbiosis and the secretion of inflammatory cytokines, for instance.
When tight junctions are compromised, LPS can translocate across the intestinal epithelium into the lamina propria, where it is picked up by immune cells, such as macrophages and dendritic cells. From there, LPS can enter the mesenteric lymphatic system and bloodstream, leading to systemic exposure. Once in circulation, LPS may bind to Toll-like receptor 4 (TLR4) on immune cells, particularly macrophages, triggering a cascade of pro-inflammatory cytokine production, including TNF-α, IL-6, and IL-1β. This systemic endotoxemia promotes a state of chronic low-grade inflammation.
Inflammation and Hormonal Imbalance
Chronic inflammation, such as that which is driven by the entry of lipopolysaccharides (LPS) and other endotoxins into the bloodstream, can play a key role in disrupting hormonal balance. Inflammatory cytokines can directly affect the hypothalamic-pituitary-adrenal (HPA) axis, a central regulatory system for stress responses and hormonal homeostasis. Specifically, cytokines, such as IL-6 and TNF-α, stimulate the release of corticotropin-releasing hormone (CRH) from the hypothalamus, which in turn promotes the release of adrenocorticotropic hormone (ACTH) from the pituitary gland. ACTH may then increase the production of cortisol, a "stress" hormone, from the adrenal glands.
Likewise, chronic inflammation can influence reproductive hormones through various pathways. Inflammatory cytokines, such as IL-6 and TNF-α, can disrupt the hypothalamic-pituitary-gonadal (HPG) axis by affecting the hypothalamus, which regulates the secretion of gonadotropin-releasing hormone (GnRH). Changes in GnRH signaling can alter the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary gland, leading to downstream effects on the ovaries or testes and thus impacting the production of estrogen, progesterone, and testosterone.
Therefore, How Can We Support Hormone Balance via the Estrobolome & Overall Intestinal Microbiome?
Bacteriophages
Bacteriophages, such as LH01 (Myoviridae), LL5 (Siphoviridae), T4D (Myoviridae), and LL12 (Myoviridae), can specifically target certain pathogenic bacterial strains. These phages may attach to bacterial cells, inject their genetic material, and use the bacterial machinery to reproduce. As the phages replicate, they eventually can cause the bacterial cell to burst (lyse), releasing new phages.
Probiotics
Probiotics help by repopulating the gut with beneficial bacteria that can compete with harmful microorganisms, produce antimicrobial compounds, and enhance the gut's barrier function. In the context of the estrobolome, probiotics can play a critical role in regulating estrogen metabolism. As noted previously, the estrobolome is a collection of gut bacteria that produce enzymes like β-glucuronidase which reactivates estrogen that has been conjugated for excretion. An imbalance in these bacteria can lead to improper estrogen metabolism and hormonal imbalances. Levilactobacillus brevis KABP™-052, a strain studied for its β-glucuronidase activity, has been shown to support estrogen reactivation and modulate serum estrogen levels, helping to maintain hormonal balance in peri- and postmenopausal women.
Moreover, beneficial microbes / probiotics can compete with pathogenic bacteria for nutrients and binding sites on the gut mucosa, reducing the risk of pathogen colonization and subsequent dysbiosis.
Nouri Hormone Balance Probiotic with Prebiotics
All of these (LH01 (Myoviridae), LL5 (Siphoviridae), T4D (Myoviridae), LL12 (Myoviridae), and estrobolme-supporting probiotics) are formulated within Nouri Hormone Balance Probiotic with Prebiotics. It combines an array of remarkable probiotics, including Lactobacillus gasseri KABP™-064, Lacticaseibacillus rhamnosus IMC-501®, Lacticaseibacillus paracasei IMC-502®, Levilactobacillus brevis KABP™-052, Pediococcus acidilactici KABP™-021, Lactiplantibacillus plantarum KABP™-051, and Lacticaseibacillus rhamnosus SP1; and it was expertly designed to support both intestinal and hormonal health. Daily Nouri also utilizes capsule-in-capsule technology designed to facilitate remarkable probiotic delivery directly to the gut.
They recommend taking one capsule per day, with or without food, to support your gut microbiome and tackle everyday hormonal imbalance symptoms.
Nouri Hormone Balance Probiotic with Prebiotics is an absolutely remarkable supplement to support the estrobolome and beyond, and Nouri does such a wonderful job at making their products accessible to all. With that, go and check out Nouri Hormone Balance Probiotic with Prebiotics over at dailynouri.com, and use code CHLOE20 to get 20% off.
*Always consult with a licensed medical professional for all of your medical needs and before taking any nutritional supplement.
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