Key takeaways:

• The gut microbiome impacts female reproduction at every stage, thyroid disorders, bone mass and obesity, among other health concerns.
• Oral contraceptives, hormone therapy and stress can alter the gut microbiome.

Susan Weiner, MS, RDN, CDCES, FADCES, continues her conversation with Audrey Fleck, MS, RDN, about associations between gut dysbiosis — an unhealthy imbalance of microbes in the gut — and diseases associated with reproductive hormones.

See part 1 of the conversation here .

Weiner: In our last conversation, you described how gut health — the gut microbiome — can influence general health and also women’s hormonal health. How does that translate to some specific women’s health concerns?

Fleck: The gut microbiome impacts estrogen through the estrobolome, the part of the microbiome that modulates women’s hormones. There is evidence that the estrobolome affects fertility, thyroid function, obesity and metabolism, breast cancer and postmenopausal osteoporosis, among other conditions that affect women.

The connection between fertility and the gut is an interesting one. Our gut microbiome impacts female reproduction at every stage from egg cells, fertilization, implantation, pregnancy and even childbirth. By correcting abnormal microbiomes, reproductive outcomes may improve.

A small study, published in the Journal of Clinical Biochemistry and Nutrition in 2020, showed differences in the abundance of gut microbiota between fertile and infertile groups of women. The researchers demonstrated that adding a prebiotic fiber supplement (partially hydrolyzed guar gum, or PHGG) was associated with improved gut dysbiosis and pregnancy success among women with infertility. Further and larger studies are needed to provide more solid evidence.

Thyroid disorders are also highly prevalent and impact fertility among other women’s concerns, like energy level, metabolism and mental well-being. You bet there’s a thyroid-gut connection. There is a high prevalence of the coexistence of thyroid and gut-related diseases, such as Hashimoto’s disease and celiac disease/non-celiac gluten sensitivity. The correlation is likely the effect of gut bacteria on the immune system and thyroid function. Our microbiota also affects the uptake of critical thyroid nutrients: iodine, selenium, iron and zinc. Lastly, deiodinase activity — enzymes that convert thyroxine to its active form triiodothyronine (T₃) — has been found in the intestinal wall and can influence total T₃ body levels.

As for breast cancer, excess estrogen is recognized as a contributing factor in the development of hormone-receptor positive breast cancer and promotion of tumor growth. Through our knowledge of how the estrobolome influences the metabolism and circulation of estrogen, it is hypothesized that the microbiome can influence estrogen levels and increase risk for breast cancer.

A study published in the Journal of the National Cancer Institute in 2016 investigating differences in gut microbiome composition among postmenopausal women showed a less diverse fecal microbiome and a significantly altered composition in newly diagnosed patients with breast cancer (87% had ER-positive tumors) compared with healthy controls. At present, observational, large-scale human studies are needed to confirm associations while also controlling for other variables, like genetics, environmental factors and diet, among others.

Finally, estrogen protects bone mass, so once women enter menopause, there is a greater risk for development of osteoporosis. Gut microbes have been associated with increased bone mass by inhibiting osteoclast proliferation and differentiation, inducing apoptosis, reducing bone resorption, or promoting osteoblast proliferation and maturation. There are some studies that suggest specific probiotics can be helpful for enhancing bone health in postmenopausal osteoporosis. However, the therapeutic effect of gut microbes on osteoporosis remains to be further proven.

Weiner: What about obesity?

Fleck: People often think of obesity as a problem that needs to be addressed with just diet and exercise. You don’t know how many times I’ve had clients share that their doctor told them to eat less and move more and that’s it. Obesity is more complex than that.

A growing amount of evidence suggests that one means of treating overweight and obesity is through modulating the ecology of the gut microbiome. Certain types of gut microbes influence how many calories we can extract from ingested food. This is observed in human and mouse studies where microbial composition differs between lean individuals, who tend to have more Bacteroidetes, vs. individuals with obesity, who tend to have more Firmicutes.

Type 2 diabetes is common among people with excess fat. Gut dysbiosis is present in people with type 2 diabetes accompanied by a leaky gut. At present, the gut microbiota is considered a potential target for diabetes drugs, and how to reverse the imbalance of gut microbiota has become a therapeutic strategy for type 2 diabetes.

Since chronic inflammation is a big component of obesity and insulin resistance, having a leaky gut is fuel to the inflammation fire. Help reduce leaky gut and you will start to cool the chronic inflammation.

Gut dysbiosis is linked to the development of other chronic lifestyle conditions like heart disease, atherosclerosis, hypertension, cancer and gastrointestinal disorders. Just like diet is an important modifiable risk factor for developing chronic conditions, we should also be addressing gut health and promoting balanced gut microbiota to prevent or reduce progression of these diseases.

Weiner: We’ve talked about how the gut microbiome can affect women’s hormones. Can hormones in contraceptives and menopausal hormone therapies affect the gut?

Fleck: Yes, one thing important to mention is that oral contraceptives and hormone replacement therapy may alter our gut microbiome and promote inflammatory bowel disease.

A study published in Drug Safety in 2016 suggested that women who take oral contraceptives for 5 years and who have a family history of Crohn’s disease have a threefold increased risk of developing the condition. There are also studies linking menopausal hormone therapy and risk for ulcerative colitis.

Weiner: What should women be doing and eating — or not doing and not eating — to ensure a healthy gut? Women are constantly pitched nutritional supplements. Are any of these helpful?

Fleck: The food we eat has a direct impact on the diversity and richness of our microbiome. The more plant foods you eat, the more diverse your gut microbiome. Fruits, vegetables, whole grains, nuts, seeds, and even herbs and spices can positively influence our biome.

On the other hand, it takes only a few days following a change in diet for the microbe population in the gut to change. Alcohol; processed foods containing white flour, added sugar and vegetable oils; and decreased plant food intake can result in decreased microbe diversity and richness. Alcohol in particular promotes a leaky gut.

For gut health, there is enough evidence to suggest that probiotic and prebiotic supplements can be helpful.

Probiotic supplements can be used to help repopulate your gut bacteria with beneficial species. It’s important to know how to select the right probiotic for you.

The health benefits of probiotics are strain specific. What does that mean? Imagine walking into a pet store looking for a Great Dane, but instead they sold you a Chihuahua. That’s quite the difference.

Each probiotic strain is like a different breed of dog — no strains are the same and each has its own unique characteristics, so we have to pay close attention to the properties of the probiotics we select. Equally important is choosing a high-quality probiotic that contains live bacteria and that does not get destroyed by stomach acid on its journey into the colon.

Two probiotic strains — Lacticaseibacillus rhamnosus GR-1 and Limosilactobacillus reuteri RC-14 — are effective for treating some women’s genitourinary conditions, such as bacterial vaginosis, vaginal yeast infections and vaginal strep B infection.

Part of my nutritional advice to most clients is to consume a fermented food each day to obtain probiotic benefits from your diet. Fermented foods contain live bacteria and examples include yogurt, kefir, lacto-fermented vegetables like pickles and sauerkraut (not to be confused with vegetables that are “pickled”), miso and kombucha.

Prebiotics are “food” for your gut bacteria. They promote healthy gut flora, improve normal bowel function and provide fuel for colon cells to maintain a healthy gut barrier. Prebiotics are naturally occurring in many plant-containing foods as they are components of nondigestible fibers. Onions, asparagus, garlic, plantains, chicory and artichokes are examples of prebiotic foods. Polyphenol-rich foods feed butyrate-producing bacteria. Polyphenols are antioxidants found highest in blueberries, dark chocolate, grapes and tea.

I would argue that prebiotics are just as important, if not more important, than probiotics. If your goal is to maintain a balanced microbiome, rich in diverse beneficial species, then prebiotics are vital to their continued flourishing. I recommend my clients to take prebiotic supplements if they do not consume prebiotic foods daily.

Weiner: Finally, so many women lead stressful lives. What is the role of stress on a healthy gut?

Fleck: Stress negatively influences our gut microbiome composition quickly and significantly. This is why building stress resilience to nurture that gut-brain axis is a big part of how I help people. Stress increases cortisol levels and turns on our “fight or flight” state. Living in a chronic state of stress makes it impossible for your body to digest food optimally. Overall stress makes us more prone to bloating, gas and irregular bowel movements.

Part of building stress resilience is getting off the diet merry-go-round. Undereating sounds the alarm that our body is under threat from famine and we need to survive. Cortisol levels increase as our fight or flight system is triggered. As a result, the dial for digestion gets turned down.

References:

For more information:

Audrey Fleck, MS, RDN, is a registered and licensed dietitian-nutritionist specializing in integrative and functional nutrition for women. She can be reached at [email protected].

Susan Weiner, MS, RDN, CDN, CDCES, FADCES, is the owner of Susan Weiner Nutrition PLLC and the Healio | Women’s Health & OB/GYN Nourish to Flourish column editor. She can be reached at [email protected]; X (Twitter): @susangweiner.