Estrogen and the Gut Microbiome

We live along with several million microbes in our body. In fact we have more microbial cells than human cells! Scientific studies in the last several years have shown that these microbes play a huge role in deciding whether we are healthy or ill!

Few Important Facts :

• Microbes are present in your skin, mouth, gut, vagina, eyes , breasts and even possibly the brain!
• The term microbiome includes the microbes along with their genetic material.
• The gut microbiome has been studied more than the microbiome of the other areas and therefore you hear more about it.
• The microbiome includes bacteria, viruses and fungi present in the body.
• The gut microbiome has co-evolved with humans and therefore anything that affects the microbiome in turn affects your health.
• Microbes do not function in isolation. Therefore it is not just
• who is present (Not just “good” and “bad” bacteria) but
• who are their friends
• what are they eating and
• what are they doing together.
• Gut dysbiosis is imbalances in the composition and function of intestinal microbes.Good gut health is much like an Amazon rainforest while gut dysbiosis is like an ill-maintained lawn.
• Food has the biggest impact on your gut microbiome!

What Do The Gut Microbes Do For You?

Your gut microbiome influences the following areas of health:

• Immune system: A pregnant mother’s gut microbes impact the development of the immune and nervous systems in the baby! Therefore, a healthy microbiome means a healthy baby and a healthy adult!
• Your gut is the biggest immune organ in your body. Not only autoimmune diseases but most diseases are immune system problems.
• Helps in making neurotransmitters like GABA, serotonin , dopamine, norepinephrine.
• Make some vitamins.
• Affect mood and cognition.
• Energy metabolism: Gut microbes decide how much of your food is stored as fat and how much is used up in different body processes. For example, human genes do not have the full complement of carbohydrate processing enzymes ,(CAZyme Carbohydrate Active Enzymes) required to process complex carbohydrates in the gut.Therefore, we need help from gut microbes that have the additional enzymes. In fact studies have shown that some CAZymes processing bacteria are associated with body weight—the “thin” bugs and “fat” bugs!
• Inflammation: Your gut bacteria decide the levels of inflammation in your body.

   High inflammation= More disease.

• Hormone metabolism: The variety of your gut microbes will decide how well you metabolise estrogens in your body. High levels of estrogen are related to a higher risk for cancers like breast and endometrial cancers.

ESTROGEN AND GUT MICROBIOME

Estrogens, of which there are three types, E1, E2 and E3 are produced mainly in the ovaries (before menopause), fat tissue, adrenal glands and placenta. (However, estrogen is made in other areas like the brain , liver, heart , muscles and bones. To know more about Hormone Therapy in Women stay tuned to hormone webinar to be announced later).

After menopause the ovary stops producing estrogen but other tissue, like fat and adrenal glands still produce some estrogen.

Estrogens have numerous beneficial effects in your body. ( To know more, stay tuned to hormone webinar).

The estrogen in your blood is metabolised through your liver. In the liver the estrogen undergoes various processes ( with scien-cy names like methylation, glucuronidation, or sulfonation ) and gets excreted in the bile.

The estrogen in the bile is conjugated. They have to be deconjugated or made active. (Apologies for these terms!)

Conjugated estrogen=not active.

Deconjugated estrogen=active estrogen.

How are the gut microbiome and estrogen related?

The conjugated estrogen in the bile reach the intestine and have to be deconjugated by enzymes from gut bacteria. The estrogen processing bacteria along with their genetic material are called the Estrobolome (Plottel,2011)

The Estrobolome are usually a combination of different bacteria which produce enzymes that have long names like β-glucuronidase and β-glucuronides.

The variety of estrogen-metabolising bacteria will decide how well your body deals with estrogen and this in turn, will decide how much of active estrogen is present in your tissue.

Gut Barrier Dysfunction or “Leaky Gut”

Your gut is lined by a single layer of cells. In a healthy gut this layer works like a gatekeeper , keeping away the ‘bad” stuff from causing mayhem. Gut barrier dysfunction or more commonly known as “leaky gut” is a condition when the barrier doesn’t work efficiently. “Leaky gut” is associated with many illnesses including obesity, autoimmune diseases, cancer, heart disease and diabetes.

LPS, estrogen and “leaky gut”

LPS (Lipopolysaccharides) are substances derived from bacterial cell walls. Higher levels of LPS in the blood are related to higher inflammation and “leaky gut”. Estrogen regulates the level of LPS in your body. Chronic inflammation drives many diseases like diabetes, heart disease, cancer, autoimmune diseases and mood disorders.

Healthy gut bacteria and no “leaky gut” =>healthy estrogen metabolism => lower health risk.

Conditions affected by Estrogens and Gut Microbiome Interactions.

• Weight gain, belly fat:
• Breast cancer, Endometrial cancer
• Polycystic Ovarian Syndrome (PCOS)

Weight gain, belly fat

Women tend to gain weight around the time of menopause. Scientific studies have shown that women who were already insulin resistant (pre-diabetic, diabetic) tended to gain more weight and most of the weight gain was around the middle.Being insulin resistant may be a reason why you are struggling with weight loss.

Menopause is a time when your body stops producing estrogen and progesterone. (Testosterone is important in women too! We will discuss on the webinar).

People with pre-diabetes or diabetes have different types of gut microbiome in comparison to healthy people. Estrogens regulate fat hormones (adipokines) and the pancreas, which produces insulin, has estrogen receptors too!

Therefore, an imbalance in estrogens and gut dysbiosis, along with “leaky gut” may be why you have a challenge losing weight.

Breast cancer, Endometrial cancer:

High level of estrogens and an imbalance in the levels of different estrogen metabolites are related to a higher risk for hormone-dependant cancers like breast and endometrium (lining of the uterus). However, low estrogen levels are associated with weaker bones, dementia, heart disease and diabetes.Therefore, it is a Goldilocks situation! Too much and of the “bad”type of estrogens, you are at higher risk for some cancers. Too little, and you have weak bones, poor brain function and heart disease and diabetes! Hormonal balance is the key!

How will you know if you have high estrogens?

• You can measure hormone levels in blood or saliva. Blood levels do not always reflect levels in the tissue, but as a general rule, high hormone levels in blood have been associated with higher risk for some cancers. (It is more nuanced than that :-))
• You can measure hormone metabolites in urine. (Stay tuned to upcoming webinar).

Polycystic Ovarian Syndrome (PCOS)

Polycystic Ovarian Syndrome (PCOS) is one of the commonest hormonal abnormality seen in young women. The main features of PCOS are weight gain, abnormal hair growth (hirsutism), high male hormones (androgens), low estrogen ,insulin resistance and infertility.

Studies have shown that women with PCOS have a lower diversity of gut microbes compared to health women. Interestingly, laboratory studies have shown that some bacteria can make testosterone! Guys, no, you can’t just have a probiotic containing those bacteria and increase your levels of testosterone…….at least not yet 🙂

Studies have also shown that improvement in PCOS symptoms change gut bacteria to a healthy variety.

 

WHAT AFFECTS THE MICROBIOME

As you can see in the graphic above, the list of factors that you can control (to a great extent) is longer than the list of things that you can’t control!

The Most Important Factors Affecting the Gut Microbiome are

• Food
• Antibiotics (and other medications)

Food and Estrogen

• Phytoestrogens, soy.
• Vegetarian versus non-vegetarian diet.

Phytoestrogens, soy:

Phytoestrogens are plant-derived food compounds that are similar to the estrogen produced in your body. Soy is one of the commonest sources of phytoestrogens available. 

The  important questions are

• • • How does soy affect the gut microbiome?
    • Can phytoestrogens work as “natural” hormones in menopausal women? (We will answer this question on the webinar)

Soy and gut microbiome:

Studies have shown that the presence of bacteria producing a substance called “equol” affect how you process soy.Some of you are  good “equol-producers” and some of you are not. The jury is still out about the beneficial effects of soy on overall health.It is possible that the effects of soy on traditional soy-eating Asian people is different from “recent soy eaters” . Additionally, traditional soy food is fermented soy products like tempeh, miso, versus the highly processed soy milk and other soy derivatives available in the market today.

Vegetarian versus non-vegetarian diet

What is the truth about eating meat? Will it kill you? The answer, as always , is not simple. Many of you are vegetarians from birth and some of you think it is unethical to eat meat. I respect your choice and  cultural heritage.I am not here to take a stand either for or against eating meat,(I am non-vegetarian) but I am highlighting some information from research papers.

A small study in the British Journal of Nutrition (Karelis 2010), started with the hypothesis that vegetarians would have a more favourable sex hormonal profile compared to omnivores (those who eat meat and plants).They found that vegetarians had lower levels of estrogen, free testosterone and DHEA-s compared to omnivores. Lower estrogen levels favour a lower risk for hormone-dependant cancers. But as I had mentioned before, hormonal balance is more important than just the levels of individual hormones.

Interestingly, though this was a small study , the favourable hormonal profile in vegetarians was also related to their fibre intake!

Though this study did not look at the gut microbiome, fibre from vegetables provide food for the gut microbes (prebiotics).

Antibiotics and Estrogen:

Antibiotic use has one of the biggest impact on your gut microbiome. Sometimes the post-antibiotics change in gut microbiome can last a for along time! I am not suggesting that you should not take antibiotics when necessary, but using antibiotics willy nilly for just about any condition cannot be justified.

A very small study (Martin,1975) done on 3 pregnant women taking the antibiotic ampicillin showed changes in the products of estrogen and progesterone metabolism in the stool. Their conclusion was that ampicillin reduced the gut flora.

WHAT CAN YOU DO?

Eat “real” food to feed your gut microbes.

Eat enough vegetables to get adequate fibre.

Do not take antibiotics unless absolutely necessary.

Look at hormonal balance AFTER addressing gut health.

Attend Free Hormone Webinar!

Shabnam Das Kar
Functional Medicine Consultant
Director Medical Education,
Better Medical Centre, Calgary, AB

 

REFERENCES

 

• • 1. Plottel, Claudia S., and Martin J. Blaser. “Microbiome and malignancy.” Cell host & microbe4 (2011): 324-335.
    2. Ridlon, Jason M., et al. “Clostridium scindens: a human gut microbe with a high potential to convert glucocorticoids into androgens.” Journal of lipid research9 (2013): 2437-2449.
    3. María Insenser, Mora Murri, Rosa del Campo, M Ángeles Martínez-García, Elena Fernández-Durán, Héctor F Escobar-Morreale, Gut Microbiota and the Polycystic Ovary Syndrome: Influence of Sex, Sex Hormones, and Obesity, The Journal of Clinical Endocrinology & Metabolism, Volume 103, Issue 7, July 2018, Pages 2552–2562
    4. Harmon, Brook, et al. “Estrogen levels in serum and urine of vegetarian and omnivore premenopausal women.” Public health nutrition9 (2014): 2087.
    5. Karelis, Antony D., et al. “Comparison of sex hormonal and metabolic profiles between omnivores and vegetarians in pre-and post-menopausal women.” British journal of nutrition2 (2010): 222-226.
    6. Atkinson, Charlotte, et al. “In vitro incubation of human feces with daidzein and antibiotics suggests interindividual differences in the bacteria responsible for equol production.” The Journal of nutrition3 (2004): 596-599.
    7. Maskarinec G, Ju D, Morimoto Y, Franke AA, Stanczyk FZ. Soy Food Intake and Biomarkers of Breast Cancer Risk: Possible Difference in Asian Women?. Nutr Cancer. 2017;69(1):146–153. doi:10.1080/01635581.2017.1250924
    8. Martin, F., et al. “Excretion of progesteone metabolites and estriol in faeces from pregnant women during ampicillin administration.” Journal of steroid biochemistry9 (1975): 1339-1346.