The impact on our health of the mutually beneficial relationship with the microbes in and on our body – called the microbiome – can’t be underestimated. Each gram of colon content contains a number of bacteria in the same order of magnitude as the stars present in the Milky Way galaxy. Naturally, these bacteria influence our metabolism, and which bacteria thrive is determined by factors such as genetics, diet, alcohol intake and medication. This paper summarizes the available research on how the microbiome affects estrogen levels in the body and influences the risk of developing estrogen receptor positive breast cancer.
Humans and microbes have come to a delicate and mutually advantageous equilibrium. However, some external influences can disturb this balance in favor of other bacteria, with a negative impact on health. This can lead to disease or potentially even oncogenesis and tumor progression. Perhaps the best-known example is Helicobacter pylori, a bacterium associated with ulcers and stomach cancer.
For hormone receptor positive breast cancer, high concentrations of estrogens are a proven risk factor. How these hormones are metabolized can thus influence cancer risk. Normally, they are chemically modified in the liver and excreted in the bile. However, in the gut, these chemical modifications can be undone by certain bacteria, leading to a reabsorption of the estrogens in the bloodstream.
A microbiome containing lots of bacteria capable of reversing estrogen modification would promote reabsorption, leading to higher concentrations and an increased risk of breast cancer. The bacterial composition in the gut is affected by a number of factors such as diet, alcohol and antibiotic use. Some of these have also been independently linked to breast cancer risk.
THE NUTS AND BOLTS
It has been known for several decades that antibiotics disturb bacterial gut populations. With regards to breast cancer risk some conflicting results have been found. In mouse models, antibiotics lead to a decrease of the enzymatic activities that enable estrogen reabsorption. Theoretically, antibiotics would thus prevent the reabsorption leading to higher estrogen concentrations, and lower breast cancer risk. In contrast, large-scale epidemiological studies on humans indicate a slightly increased risk of breast cancer caused by long-term antibiotic use. Overall, the effect is deemed very small.
Adiposity is associated with higher circulating estrogen levels in postmenopausal women, and thus an increased breast cancer risk. Changes in diet can not only impact weight, but can also influence the gut microbiome composition. Diets rich in fat and meat result in significantly higher estrogen levels in the blood. Indeed, in strict vegetarians, more estrogen was excreted in the feces than in non-vegetarians.
Alcohol consumption increases the risk of breast cancer, in particular ER-positive tumors in postmenopausal women. The precise effect is not clear, but alcohol consumption may lead to bacterial growth in the small intestine, where normally fewer microbes are present. It also affects the composition of the colonic microbiome in rats. Some hypotheses have been formulated, but the interactions between alcohol, estrogens and breast carcinogenesis in humans need to be investigated more thoroughly.
Finally, probiotics and fermented food are known to have a beneficial effect on gut microbiome composition. Foods containing lactic acid bacteria have been explored for anticancer properties. For example, in several epidemiological studies, consumption of fermented milk was associated with decreased risk of breast cancer.
HOW WILL THIS HELP ME?
Much work is still to be done in fully grasping the influence of the microbiome on health. A lot of studies are already ongoing, and researchers advocate the collection of fecal samples in future epidemiological studies. Despite the initial insights discussed here, the impact of the microbiome on the processing of estrogen also needs further investigation. Confirming its role in hormone-driven malignancies would allow using the bacterial composition in the gut as a biomarker in cancer risk prediction. Furthermore, products such as prebiotics, probiotics and antimicrobial agents, which impact this bacterial composition, could play an important role in cancer prevention and treatment.
The Intestinal Microbiome and Estrogen Receptor-Positive Female Breast Cancer – JNCI Journal of the National Cancer Institute (2016)