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.
