Hormones and the Gut Microbiome: A Guide to Connecting the Dots
Do your patients complain of hormonal symptoms? I would comfortably assume they also have gastrointestinal complaints. And this isn’t just a coincidence. But what might not be as obvious is how closely connected hormones are to the gut microbiome. While this may seem complex, it really can be simple.
To begin, let’s discuss how estrogen metabolism works
Estrogen metabolizes physiologically in numeric order—phase 1, phase 2, phase 3. But we need to address it in reverse – phase 3, phase 2, phase 1.
Phase 1 is the hydroxylation phase. It occurs in the liver, where estrogen has three metabolic pathways by which it can be metabolized: CYP1A1, CYP1B1, and CYP3A4. This process results in three forms of hydroxylated estrogens: 2-OH-E1, 4-OH-E1, and 16-OH-E1.1
Phase 2 is the conjugation step. This also takes place in the liver. Estrogens become deactivated, specifically through sulfation, glucuronidation, and methylation, so they can be eliminated. This requires certain nutrients and enzymes in the body, namely COMT and MTHFR.2
Phase 3 is the final stage – elimination. The deactivated estrogens from Phase 2 are packaged up and eliminated from the body through the stool. Bile is also necessary to facilitate this process. Things like inflammation, dysbiosis, and overall intestinal health can all impact how smoothly this process takes place. It is now clear that if Phase 3 is backed up or working inefficiently, estrogen metabolism backs up and even slows entirely.
This is why I address Phase 3 first
To better understand estrogen elimination, we must fully understand the gut microbiome. The gut microbiome is comprised of an estimated average of 39 trillion microbes.3 It is a diverse group of bacteria, fungi, protozoa, archaea, and viruses. Three phyla dominate the microbiome: Firmicutes (Gram-positive), Bacteroides (Gram-negative), and Actinobacteria (Gram-positive). Furthermore, the estrobolome is a specific collection of enteric bacterial genes whose products are capable of influencing estrogens. It serves to metabolize and modulate the body’s circulating estrogen, which in turn affects weight, mood, libido, and accumulation of lifetime exposure to estrogens.4
To better understand estrogen elimination, we must fully understand the gut microbiome. The gut microbiome is comprised of an estimated average of 39 trillion microbes.3 It is a diverse group of bacteria, fungi, protozoa, archaea, and viruses. Three phyla dominate the microbiome: Firmicutes (Gram-positive), Bacteroides (Gram-negative), and Actinobacteria (Gram-positive). Furthermore, the estrobolome is a specific collection of enteric bacterial genes whose products are capable of influencing estrogens. It serves to metabolize and modulate the body’s circulating estrogen, which in turn affects weight, mood, libido, and accumulation of lifetime exposure to estrogens.4
Studies also show that the estrobolome influences other sex hormones.5 In men, the increase in testosterone during puberty causes a greater microbial shift compared to the pre-pubescent microbiome. This increase in microbial diversity, increases short-chain fatty acid production, therefore increasing sex hormones. Lower microbial diversity resultsin lower sex hormone levels.
A disrupted microbiome is commonplace in today’s world. Frequent antibiotic use, chronic stress, chronic steroid use, the Standard American Diet, low fiber intake, lack of exercise, mold and toxic exposure, poor sleep, and food sensitivities are a few of the many causes of a disrupted microbiome.6 This leads to bacterial overgrowth, parasites, insufficiency dysbiosis, impaired digestion, leaky/inflamed tight junctions, elevated b-glucuronidase levels, and hormonal imbalance.
But how does gut dysbiosis specifically influence hormones?
Intestinal permeability leads to inflammation, which in turn suppresses ovarian hormone production. Additionally, elevated b-glucuronidase leads to estrogen excess.7 In Phase 3 of estrogen detoxification, the liver and intestines bind toxins and steroid hormones for elimination. These toxins and hormones are bound by glucuronic acid, allowing them to be excreted in the stool. B-glucuronidase is an enzyme that breaks that tight bond between glucuronic acid and toxins and hormones in the intestines.8
B-glucuronidase is produced by intestinal epithelium and certain intestinal bacteria.9 High levels (detected on most diagnostic stool studies) are not desirable. Higher levels have been associated with higher circulating estrogens and lower excretion in women. Lower levels are currently not of much clinical significance. High levels are commonly seen with an imbalanced microbiome. Major microbial producers of b-glucuronidase are: Bifidobacterium, Lactobacillus, Escherichia coli, Clostridium, Bacteroides species, Ruminococcus gnavus, Staphylococcus, and Eubacterium.10
B-glucuronidase is produced by intestinal epithelium and certain intestinal bacteria.9 High levels (detected on most diagnostic stool studies) are not desirable. Higher levels have been associated with higher circulating estrogens and lower excretion in women. Lower levels are currently not of much clinical significance. High levels are commonly seen with an imbalanced microbiome. Major microbial producers of b-glucuronidase are: Bifidobacterium, Lactobacillus, Escherichia coli, Clostridium, Bacteroides species, Ruminococcus gnavus, Staphylococcus, and Eubacterium.10
Common symptoms associated with elevated b-glucuronidase levels are similar to estrogen dominance: heavy periods, clotting, cramping, fibrocystic breasts, headaches, mood swings, weight gain, fatigue, anxiety, irregular periods, infertility, and brain fog.11
So now that I have complicated how you think about hormonal balance, let’s review how truly simple it can be to address this complex scenario with your patients.
We must first rebalance the microbiome!
In my private practice, my tried-and-true go-to for microbial balance is the Biocidin® line of botanicals. Due to Biocidin’s broad-spectrum activity, the diverse group of b-glucuronidase producing organisms are all susceptible. Add in the fact that it dismantles biofilms, and you have the assurance of its success. Additionally, it selectively enhances beneficial organisms. This aids in the robust diversity of the microbiome that is protective against bacterial overgrowth and dysbiosis. The feelings of emotional distress and brain fog often seen with estrogen dominance are also aided by Biocidin® as it helps improve vitality and mental clarity.
For complex cases or those with significant overgrowth, I add Olivirex®. This superior olive leaf combination offers additional broad-spectrum support. It supports drainage pathways through the liver and kidneys to assist in detoxification. Previously, we discussed the liver’s involvement in estrogen metabolism. Other detoxification pathways are involved as well, so adding Olivirex® can improve patient outcomes.
Biocidin’s spore-based probiotic Proflora®4R is another addition I make to my patients’ protocols. It helps support microbial balance in the GI tract, which keeps b-glucuronidase-producing bacteria in check. It also helps maintain intestinal health for improved digestion of food and absorption of nutrients and plays a primary role in the development of Gut-Associated Lymphoid Tissue (GALT). Promoting a healthy inflammatory response helps mitigate any excess inflammation that would lead to a sluggish Phase 3 detoxification process.
One Biocidin® product that provides nutritional support to the adrenals – which directly supports hormones – is Biotonic™. It is an adaptogenic tonic that helps restore vitality and energy while also targeting digestion and aiding in detoxification. Incorporating adaptogenic herbs allows you to subtly address your patient’s hormones, while first working on Phase 3 of estrogen detoxification. Additionally, efficiently breaking down and absorbing nutrients helps mitigate the growth of opportunistic bacteria, aiding in the production of b-glucuronidase.
Lastly, I always add in G.I.Detox™+. It is Biocidin’s full-spectrum binder. This assists in the “mop-up” of endotoxins and biofilm components. Without it, your patients will likely experience more “herxing” or “die-off” during their protocol. By mitigating these unpleasant symptoms, you will achieve more compliance from your patients and more successful outcomes.
By keeping your gut healing simple and effective with the help of Biocidin’s line of botanicals, your patients will not only balance their hormones but optimize their overall health and wellbeing.
1 T;, T. Y. (n.d.). Cytochrome P450-mediated metabolism of estrogens and its regulation in human. Retrieved September 15, 2021, from https:// pubmed.ncbi.nlm.nih.gov/16112414/
2 Yasuda, M.T., Sakakibara, H. & Shimoi, K. Estrogen- and stress-induced DNA damage in breast cancer and chemoprevention with dietary flavonoid. Genes and Environ 39, 10 (2017). https://doi.org/10.1186/s41021-016-0071-7
3 Barko, P., McMichael, M., Swanson, K., & Williams, D. (2017, November 24). The Gastrointestinal Microbiome: A Review. Retrieved August 20, 2021, from https://onlinelibrary.wiley.com/doi/pdf/10.1111/jvim.14875
4 Kho, Z. Y., & Lal, S. K. (0001, January 01). The Human Gut Microbiome – A Potential Controller of Wellness and Disease. Retrieved August 20, 2021, from https://www.frontiersin.org/articles/10.3389/fmicb.2018.01835/full
5 Beale, A. L., Kay e, D. M., & Marques, F. Z. (2019, April 25). The role of the gut microbiome in sex differences in arterial pressure. Retrieved August 20, 21, from https://bsd.biomedcentral.com/articles/10.1186/s13293-019-0236-8
6 Khosravi, A., & Mazmanian, S. K. (2013). Disruption of the gut microbiome as a risk factor for microbial infections. Current opinion in microbiology, 16(2), 221–227. https://doi.org/10.1016/j.mib.2013.03.009
7 Briden, D. L. (2020, February 24). How your gut affects your hormones. Retrieved August 20, 2021, from https://helloclue.com/articles/ cycle-a-z/how-your-gut-affects-your-hormones
8 Beta-Glucuronidase; stool. (n.d.). Retrieved August 20, 2021, from https://www.doctorsdata.com/beta-glucuronidase-stool/
9 B Ervin SM;Li H;Lim L;Roberts LR;Liang X;Mani S;Redinbo MR;. (n.d.). Gut microbial β-glucuronidases reactivate estrogens as components of the estrobolome that reactivate estrogens. Retrieved August 20, 2021, from https://pubmed.ncbi.nlm.nih.gov/31636122/’
10 Beta-Glucuronidase; stool. (n.d.). Retrieved August 20, 2021, from https://www.doctorsdata.com/beta-glucuronidase-stool/
11 Baker, J. M., Al-Nakkash, L., & Herbst-Kralovetz, M. M. (2017, June 23). Estrogen–gut microbiome axis: Physiological and clinical implications. Retrieved September 15, 2021, from https://www.sciencedirect.com/science/ article/abs/pii/S0378512217306503