Class blog for sharing and commenting on current events in biology.

Tuesday, November 26, 2013

Gut Microbes Affect Cancer Treatment Outcome in Mice



No author listed. (November 26, 2013). NIH mouse study finds gut microorganisms may determine cancer treatment outcome.  National Institutes of Health. Retrieved from: http://www.nih.gov/news/health/nov2013/nci-21.htm

Background

            The term “microbiome” has become a buzz word lately in the fields of biology. Your microbiome consists of the native bacteria and other microorganisms that live in your gastrointestinal tract, on your skin, or around bodily orifices. For some time now scientists have understood that these microfauna are not merely harmless commensals, but actually provide many benefits to their human hosts. One such benefit is that they make it difficult for harmful microbes to invade, by crowding them out and altering the microenvironment, making it less hospitable. Our microbes also may play a role in helping us to digest certain foods. Scientists think that these microbes have a complex role with our immune system, but the relationship is poorly understood. Only recently have scientists begun to uncover the staggering numbers of microbes that live within us, and their remarkable diversity. 

Summary

This press release from the NIH describes a study conducted on mice in microbe-free, or nearly microbe free environment, and the negative impact that a lack of commensal gut microorganisms has on cancer treatment in mice. The “germ-free” mice were created using two different methods. One group of mice was raised in sterile conditions from birth, so they did not have any bacteria living within or on them. The other group of “germ-free” mice were born and raised in normal lab conditions, but then given a powerful antibiotic cocktail that results in a greater than 10,000 fold reduction in bacteria.
The next step was to give the mice cancer. Cancerous cells from tumors from lymphoma, melanoma, and colon cancers at similar stages of tumor progression. These cancers were selected based on their known ability to be transplanted and similar susceptibility to drug treatments. Tumors were inject subcutaneously, and allowed to grow to diameters of 0.2 inches or more. The mice were then treated with either an immunotherapy drug, which normally functions to ramp up the immune system and attack the tumors, or by traditional chemotherapy drugs oxaliplatin and cisplatin.
The germ-free mice (both groups) did not respond well to either immunotherapy or chemotherapy treatments demonstrating that the normal microbiota plays a significant role in the ability to respond to cancer treatment. The mechanisms underlying this are not yet well understood. However in this experiment scientists did measure cytokines production in the mice, and found them to be reduced. Cytokines are proteins secreted by cells and regulate cell activity and immune responses such as inflammation. So there may be some complex interaction between immune cells and the microbiome, that is necessary for drug-therapy effectiveness, and this signaling is interfered with when the microbes are not present.

Relevance

            When antibiotics were first discovered, they were heralded as wonder-drugs capable of eradicating infectious disease and curing many illnesses. And antibiotics have saved millions of lives, stopping simple infections from turning lethal, and curing people of prolonged illnesses from the likes of gonorrhea and tuberculosis. However, there is an increasing concern that use of antibiotics is permanently altering our microbiome, killing off the good bacteria along with the bad. Ironically the result could be an impaired ability to fight off future infections, making people more disease-prone.
            The revelation that taking antibiotics could actually decrease your body’s ability to respond well to cancer drug therapies is a startling one. Because many cancer patients have a suppressed immune system and tend to get sick, they are precisely more likely than the average person to have received multiple rounds of antibiotics. The idea that taking antibiotics could make it harder to fight cancer is very worrisome. Understanding this could have huge implications for cancer-treatments. Perhaps we should be inoculating patients with good bacteria from healthy people before subjecting them to drug therapy treatments. Perhaps doctors should be more wary about prescribing antibiotics to cancer patients, or the public in general. This study should have a direct impact on oncologists and families coping with cancer. 

Critique & Conclusions

            This article was meant as brief overview and summary of a recently published scientific peer reviewed journal article. Since brevity was its aim, I found it acceptable that it glossed over many of the more complex details of the study. The article defined terms for the public such as “immunotherapy,” “cytokines,” and “tumor microenvironment,” which I found helpful. However, there were a lot of variables in this study: two types of “germ-free” mice, three types of cancer tested, two different types of therapies (immunotherapy and chemotherapy), with a total of three different drugs used. I would have liked to maybe see a data table or flow chart that listed out all these variables. Were the two groups of mice each given the three different types of cancer? (Thus creating essentially six experimental groups?) Which cancers were treated with which therapies? I am assuming there were control groups as well, but I would like the article to have mentioned the control groups and how great was the difference between the “germ-free” and the control? Although the article need not be too technical, one or two statistics or numbers would have strengthened the main points.  
            Because I do research on the role of immune cells in the tumor microenvironment of mice with pancreatic cancer, I believe this article may have a direct link to my own research. Perhaps the lack of microbes impacts the presence of macrophages and T-cells, which are known to play a role in tumor progression and immune response. I spent the last summer identifying macrophages and T-cells and reading this article is motivating me to look into this issue more deeply. I plan to read the full journal article on which this summary was based, and look into other recent publications that explore the role between the microbiome and immune cells in cancer.

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