Today’s post summarizes an intriguing study on the role Lactobacillus acidophilus (L. acidophilus) may play in inhibiting breast cancer development. (1) I need to emphasize the word “may” as this study was done with rodents and not people. Like any hypothesis pertaining to health, we won’t know if this has applicability until subjected to clinical trials in humans.
Breast cancer is one of the leading causes of death in women the world over. While modern medicine has made incredible strides against this killer, more remains to be done to eliminate this scourge from the planet.
The role of immunity in cancer prevention is a complicated subject and one that won’t be covered in this very brief post. Suffice it to say that cancer cells evade detection and destruction by the immune system at their inception and develop mechanisms that continually thwart immune defenses as they grow.
What complicates matters for researchers is that there are many different types of cancer cell lines and what is effective against one type of cancer can be ineffective or actually encourage growth in another. What follows studied only one particular breast cancer cell line—4T1—and may or may not be applicable for other breast cancer types.
This type of cancer spreads easily to distant organs. Death in rodents is typically due to cancer cells having spread to the lung. Because of this, this mouse model of breast cancer is considered the most challenging to control.
In this study, 4T1 cancer cells were transplanted into four to six week-old Balb/c mice with tumors developing on the 8th day. Tumors were allowed to grow for an additional eight days after which the mice were divided into four groups.
Group one was treated with L. acidophilus derived from yogurt and are identified in the following two illustrations by the SD designation. Group two was treated with L. acidophilus cultured from the stool of newborns (ST). Group three was treated with the chemotherapy drug cyclophosphamide (CYC) and group four served as the control group (CON). Treatment lasted 15 days.
During this period, tumor growth in all four groups was continually measured and is plotted in the graph below:
The greatest shrinkage in tumor size was unsurprisingly found in those mice receiving cyclophosphamide. No surprise here as this is an exceedingly powerful chemo drug, but with some very serious and toxic side effects that you can read about here.
As expected, the control group experienced the highest tumor growth rate. However, look at the two middle lines. In both cases, mice treated with L. acidophilus experienced reductions in tumor growth, especially in those mice given L. acidophilus derived from yogurt.
On day 16, blood was drawn and all mice were killed. Spleens and tumors were removed for evaluation, and an assessment of cytokine levels was conducted.
Here we see the various levels of cytokines found in the four groups. The bar in white represents levels of interferon gamma (IFN-γ). The highest levels among all four groups were in mice treated with L. acidophilus derived from yogurt (SD).
Why is this important? Because the precursors to this particular class of cytokines are natural killer cells which L. acidophilus has been shown to increase. Natural killer cells and interferon gamma are critical for immune regulation, fighting viral infections and inhibiting cancer growth.
IFN-γ shifts the immune response from Th2 to Th1. I covered what Th1 and Th2 immunity responses are and how gut flora impacts them here. Th1 is the arm of the immune system that provides protection from cancer development.
IFN-γ has other effects apart from shifting the balance away from Th2 immunity. It also inhibits angiogenesis. This is the process of forming new blood cells that tumors use to sustain themselves and grow. IFN-γ also increases natural killer cell activity which further fuels interferon gamma production in a feed-forward manner.
As with all things in life, however, too much interferon gamma ceases to be beneficial. It can increase intestinal permeability and lead to autoimmune disorders.
So tipping the scale towards Th1 immunity without counterbalancing effects from other beneficial bacterial is not ideal. Another reason having a diverse and healthy gut flora is the best insurance against a skewed immune response.
Moving on, we see that L. acidophilus had no impact on the production of the cytokine interleukin 4. However, it had pronounced effects on the Th2 cytokine tumor growth factor beta (TGF-β).
TGF-β is an anti-inflammatory cytokine that inhibits cell proliferation and cancer formation. When expressed by normal cells, it truly is a good thing.
However, once formed tumors also express this cytokine, and they do so to protect themselves from our immune system and extinction. TGF-β produced by cancer cells acts on surrounding cells to cause immune suppression and increase angiogenesis. (2)
The dramatic decreases in tumor growth factor beta seen in both L. acidophilus groups is extremely encouraging. While cyclophosphamide also reduced the levels of this cytokine, it was no match for what was seen in both probiotic groups.
I’ve always been of the opinion that many cancers, like so many chronic diseases, are the result of disturbed gut flora. That certainly appears to be the case in colon cancer. (3)
Long-term courses of antibiotics are associated with an increased risk of breast cancer. (4) Other behaviors that negatively impact gut flora like binge drinking are also strongly associated with elevated breast cancer risk. (5) Given what we know about how these microbes shape immune function, I don’t believe it’s unreasonable to implicate gut dysbiosis as a major player in breast cancer development.