Breast cancer remains one of the most prevalent cancers globally, with over 2.3 million new cases diagnosed each year. It’s a disease that affects both men and women, though it is significantly more common in women. According to the American Cancer Society, breast cancer accounts for about 30% (or 1 in 3) of all new cancer cases in U.S. women, and less than 1% of all breast cancers occur in men. Less than 10% of breast cancer is caused by inherited genes mutation, and the remaining 90% is caused by environmental and lifestyle factors. This includes poor diet, age, dense breast tissues, hormonal imbalances, alcohol consumption, smoking, radiation, environmental toxins, obesity, physical inactivity, and stress.
In recent years, research has begun to explore the intricate connections between gut health and cancer. One fascinating area of study is the role of gut dysbiosis in breast cancer. But before diving into this relationship, let’s clarify what gut microbiota and gut dysbiosis mean.
What is Gut Microbiota?
The gut microbiota or microbiome refers to a diverse community of microorganisms, including bacteria, viruses, fungi, and protozoa, that reside in the intestines. A healthy microbiota plays a crucial role in maintaining overall health. These microorganisms are involved in various physiological functions, including digestion, metabolism, and immune regulation. They help break down complex carbohydrates (fiber), synthesize vitamins, and produce beneficial metabolites like short chain fatty acids (SCFAs). Therefore, maintaining a balanced microbiota is crucial for a healthy gut environment and overall health.
What is Gut Dysbiosis?
Dysbiosis refers to an imbalance in the gut microbiota. Dysbiosis occurs when harmful bacteria outnumber beneficial ones, and/or reduction in microbiome’s diversity. This imbalance has been linked to a range of health issues, including inflammatory diseases, metabolic disorders, and, intriguingly, cancer. Factors contributing to gut dysbiosis include poor diet (high in ultra-processed foods and sugar, and low in fiber), environmental toxins, stress, antibiotics and drugs.
How Gut Dysbiosis Impacts Breast Cancer?
Recent research highlights a compelling link between gut dysbiosis and breast cancer. Gut dysbiosis influences cancer development through mechanisms such as systemic inflammation, immune response alterations, and disrupted hormonal metabolism.
Here’s a detailed examination of these mechanisms:
Estrogen Metabolism
Estrogen plays a pivotal role in breast cancer, especially hormone receptor-positive types. The gut microbiota is crucial in metabolizing estrogens, and dysbiosis can disrupt this process. Estrogens are metabolized in the liver, where they get conjugated with glucuronic acid in preparation for elimination through urine and feces. In dysbiosis, bacteria produce beta-glucuronidases, an enzyme that deconjugates estrogens that have been destined for excretion via feces. So, instead of being eliminated, these estrogen metabolites are reabsorbed into the bloodstream to reach distant tissue, like breast, where elevated levels can fuel cancer growth. Elevated estrogen levels due to dysbiosis can increase the activation of estrogen receptors on breast cancer cells, promoting their growth and proliferation.
Impact on Hormonal Balance:
An imbalance in gut microbiota can lead to hormonal imbalances beyond estrogen alone. Dysbiosis can affect the levels of other hormones, such as androgens and progesterone, which can also impact breast cancer risk. This can further compound the effects of altered estrogen metabolism.
DNA Damage
Dysbiosis can cause damage to host DNA—a critical step in cancer development. Gut microbes release toxins into the host cells, causing DNA mutation, increasing reactive oxygen species, and altering cell proliferation and death.
Immune Response:
A balanced gut microbiota is essential for a properly functioning immune system. With 70-80% of immune cells being present in the gut, there is an intricate interplay between the gut microbiota, gut lining, and the immune system. Gut dysbiosis impacts immune system function and inflammation, which plays a critical role in cancer development and progression.
Altered Immune Cell Function:
Dysregulation of T-Cells: A healthy gut microbiota supports the development and function of various T-cells, including regulatory T-cells (Tregs), which help maintain immune tolerance and prevent autoimmune reactions. Dysbiosis can disrupt T-cell balance, leading to impaired immune regulation and increased susceptibility to chronic inflammation and cancer.
Macrophage Activation: Macrophages are essential immune cells involved in detecting and responding to pathogens. Dysbiosis can alter macrophage function, leading to an exaggerated inflammatory response. Macrophages may become hyperactive, producing excessive pro-inflammatory cytokines that contribute to a tumor-promoting environment.
Role of Lipopolysaccharides in Dysbiosis and Inflammation
Lipopolysaccharides (LPS) are large molecules found in the outer membrane of Gram-negative bacteria. They are potent endotoxins that play a key role in the inflammatory response. In the context of dysbiosis, the excessive presence of LPS due to an imbalanced gut microbiome can have significant effects on systemic inflammation. Dysbiosis often leads to increased intestinal permeability, commonly referred to as “leaky gut.” When the gut lining becomes compromised, LPS can translocate from the gut lumen into the bloodstream. The presence of LPS triggers the production of inflammatory cytokines, which create a pro-inflammatory environment that is conducive to cancer development. Low-grade inflammation can promote tumor cell proliferation, survival, and metastasis.
The Role of Diet in Supporting Gut Health
Diet significantly influences gut microbiota composition and function. Incorporating certain dietary components can help manage gut dysbiosis and potentially reduce cancer risk:
Fiber: Dietary fiber is crucial for a healthy gut microbiota. It serves as a prebiotic, feeding beneficial bacteria and promoting their growth. High-fiber diet helps maintain a balanced gut microbiota and lower gut bacteria that produce beta-glucuronidase. This reduces deconjugation and reabsorption of estrogens, increasing the fecal elimination of estrogen compounds and leading to a reduction in estrogen levels. Increased fiber intake has been associated with reduced inflammation and a lower risk of breast cancer.
High fiber diet also promotes the production a short chair fatty acid called butyrate by butyrate-producing bacteria. Butyrate has the anticancer activity of inducing cancer cell apoptosis (cell death). It also suppresses has anti-inflammatory effects. Butyrate also suppresses the formation of tumor blood vessels (angiogenesis) and inhibits tumor formation.
Fiber food sources include whole grains, nuts, seeds, fruits, vegetables, legumes and lentils. The daily recommended amount of fiber is 25 to 40 grams.
Polyphenols: These plant compounds found in fruits, vegetables, nuts, olive oil, and beverages like red wine, tea and coffee. They can reduce oxidative stress and inflammation, which are associated with cancer progression. Polyphenols also can influence gut microbiota composition by acting as prebiotics (food used by gut microbiome), and therefore promoting the growth of beneficial bacteria such as Bifidobacterium and Lactobacillus and inhibiting the harmful ones. Their consumption may reduce breast cancer risk by modulating gut health, reducing the production of harmful estrogen metabolites, inhibiting cancer cell proliferation, and inducing cancer cells apoptosis.
Calcium D-Glucarate: This compound is a natural substance found in highest amount in oranges, apples, grapefruit, and cruciferous vegetables. It is also found in a supplement form. It supports phase 2 liver detoxification and inhibits beta-glucuronidase enzyme. It prevents the body from reabsorbing and recycling hormones, such as estrogen, and harmful environmental toxins. Aiding in the elimination of excess estrogens, calcium D-glucarate helps maintain hormonal balance, potentially reducing the risk of estrogen-related breast cancer.
Conclusion
Understanding the link between gut dysbiosis and breast cancer underscores the importance of maintaining a balanced gut microbiota for overall health. Dysbiosis impacts cancer development through immune modulation, metabolic changes, systemic inflammation, and disrupted estrogen metabolism. Dietary components like fiber, polyphenols, and calcium D-glucarate play crucial roles in supporting gut health and reducing cancer risk. As research advances, integrating gut microbiota management into cancer prevention and treatment strategies could offer promising new pathways for improving health outcomes and reducing breast cancer risk.
Interested in exploring your gut health further? A comprehensive functional stool test can help detect imbalances and provide insights into digestion, inflammation, and immune function. Contact us to learn how you can support your gut health and overall well-being.
References
- Siegel RL, Giaquinto AN, Jemal A. Cancer Statisitcs, 2024, CA Cancer J Clin. 2024; 74:12-49
- Ruo SW, Alkayyali T, Win M, et al. Role of Gut Microbiota Dysbiosis in Breast Cancer and Novel Approaches in Prevention, Diagnosis, and Treatment. Cureus. Aug 2021;13(8):e17472. doi:10.7759/cureus.17472
- Zhang J, Xie Q, Huo X, et al. Impact of intestinal dysbiosis on breast cancer metastasis and progression. Front Oncol. 2022;12:1037831. doi:10.3389/fonc.2022.1037831
- Teng NMY, Price CA, McKee AM, Hall LJ, Robinson SD. Exploring the impact of gut microbiota and diet on breast cancer risk and progression. Int J Cancer. Aug 1 2021;149(3):494-504. doi:10.1002/ijc.33496