Certain Cancer Drugs May Need Gut Bacteria to Work

Gut Bacteria Large

Inside the human gut lives an expansive community of bacteria, which together with fungi, viruses, and other microscopic organisms makes up what is known as the gut microbiome. These trillions of microbes have been long-known to play an important role in certain bodily functions, like digestion.

But, modern technology is starting to reveal that gut bacteria are in fact responsible for much more. Scientists are discovering that this lively city of microorganisms is tied to everything from obesity to brain function.

Now, two studies suggest that intestinal bacteria may increase the effectiveness of certain types of cancer treatments. National Cancer Institute (NCI) researchers tested an immunotherapy and a platinum chemotherapy (one of the most widely used types of chemotherapy) and found that both were less effective in mice that had no bacteria in their guts. The therapies did a better job of attacking tumors in mice with normal gut bacteria. According to the study, this is because the gut microbiota helped to activate the “innate immune response against the tumors.”

A separate study from researchers at the French National Institute of Health and Medical Research (Inserm) found something similar in mice when testing the drug cyclophosphamide. As with the NCI study, these researchers discovered that the antitumor drug was less effective in mice lacking gut bacteria. The researchers say that this is because cyclophosphamide appears to affect the composition of the microbiota, which leads to an increase in the creation of immune cells that attack tumors.

The germ-free mice and mice that had been treated with antibiotics produced far fewer antitumor cells and “their tumors were resistant to cyclophosphamide.” The authors say their data suggests there could be risks associated with antibiotic medication during cancer treatments, though it’s not clear if such effects would also be seen in humans. On the positive side, they say their results also point to the potential to manipulate the gut microbiota in ways that could improve treatment.

Why Gut Bacteria is So Important

The results of these studies ultimately point to the important role bacteria play in the maturation of a proper immune system, according to Karen Guillemin, Ph.D., a researcher with the Institute of Molecular Biology at the University of Oregon. “A lot of cancer therapies – and the ones they were studying in these studies in particular – actually rely on the body’s immune system,” says Guillemin. “So when mice are reared germ free, then their immune systems don’t mature properly.” Therefore, she says, the mice immune systems don’t function normally, and so neither do the cancer therapies.

Karen Guillemin Lab PhotoGuillemin says that the takeaway from these studies for cancer patients is that they can be thinking about lifestyle changes that promote a healthy gut community. “There is evidence that shows that a diet that is really abundant in plants fosters a complex gut bacterial community that seems to be beneficial in a lot of ways including stimulating the immune system in a healthful way.” And, she says people should include lots of food in their diet that are rich in micronutrients, “which are also thought to be beneficial for cancer patients.”

Still, though these studies are important, Guillemin says a lot more research is needed. Extrapolating what the results mean for chemotherapy treatment in humans at this point is not really possible. “Every person has a different microbial community … so we have no way of predicting what any one person’s response to chemo would be.” She says that researchers now need to study different communities of gut bacteria, but this is a challenge as “we really don’t understand everything about how these communities function.”

That’s where Guillemin’s own research comes in. Studying different germ communities is complex, but in her lab, Guillemin is approaching the issue by looking at simple systems – those in zebra fish. “We want to figure out the rules of these simpler communities to understand more complex communities … to extrapolate to larger animals, such as people.”

When Gut Bacteria Goes Bad

One area that Guillemin says she and her lab partners are learning more about is how gut bacteria influence the rates of cell turnover in the lining of the gut. This work, which is funded by the American Cancer Society, is essentially exploring a connection between gut bacteria and the formation of cancer. “The bottom line the research is telling us is that gut bacteria play a role in regulating the program of cell proliferation and we know that program goes awry in colorectal cancers,” says Guillemin.
Indeed, another recent study, conducted by researchers at NYU Langone Medical Center, found that “colorectal cancer patients had fewer beneficial bacteria … than people without the disease.” One of the study’s authors said in a statement that “identification of these microbes may open the door for colorectal cancer prevention and treatment.”

Identifying the role of specific microbes is exactly what Guillemin and her team are now doing. They are looking at the effects of individual bacteria in the process of cell turnover to see what each member contributes to this process.

“Ultimately it might be that when a patient is diagnosed with risk for colorectal cancer because of inherited mutations or early polyps, maybe a clinician will also want to think about what is the compilation of gut bacteria in that person – is there too much of one member and should we maybe try to change that with probiotics.” What Guillemin is getting at is that better understanding gut bacteria may help in cancer prevention. “In thinking about the entire ecology of cancer development, we have to think not just about the cancer cells, but also all the cells and bacteria around them.”

Guillemin’s research along with the recent studies about the role gut bacteria play in chemotherapy treatment highlight an extremely complex and rapidly evolving area of cancer research. The composition of the human microbiome and the many ways – both good and bad – in which it affects health could increasingly play a leading role in how people think about and manage their health.

VIDEO: You are Your Microbes (by Karen Guillemin)

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