Can the Microbiome Affect The Effectiveness of Cancer Treatment?

According to National Cancer Institute, approximately 38.4% of people will be diagnosed with cancer at some point in their lives. The overall cancer mortality rate in the U.S. fell 25% between 1990 and 2014, according to the National Cancer Institute. Scientists are constantly discovering new ways to make cancer treatments more effective and to increase patients’ quality of life.

One of the most promising areas of research has to do with the gastrointestinal (GI) microbiome. Research indicates that the bacteria in your gut can affect your response to chemotherapy, immunotherapy, and other anti-cancer drugs. These interactions can be positive (certain gut bacteria making a cancer drug work better) or negative (resulting in treatment challenges), depending on your microbiome and the type of cancer you have. These discoveries could have a major impact on how we treat cancer in the future.

 

Healthy gut bacteria can make immunotherapy more effective

In February 2018, the National Cancer Institute blog featured three studies that found that the types and diversity of bacteria in the gut influence whether a patient will benefit from a type of immunotherapy, called checkpoint inhibition, used to treat cancer. This type of immunotherapy, which leverages the immune system to fight cancer cells, is a cocktail of drugs that help the immune system respond more strongly to tumors.

The three 2018 studies, each published in Science, identified groups of gastrointestinal bacteria that were either “good” or “bad” influencers on the body’s response to checkpoint inhibitors. Patients who had lots of “good” bacteria responded more positively to the drugs. People with fewer “good” bacteriaor lots of “bad” bacteriadidn’t have as positive of a response to immunotherapy.

The first of the three studies found that tissue samples from lung and kidney cancer patients who didn’t respond well to immunotherapy had low levels of the bacterium Akkermansia muciniphila. When antibiotic-treated mice received supplemental A. muciniphila orally, their response to immunotherapy improved. While these results don’t mean that A. muciniphila is universally beneficial for all types of cancer, they do signal a path forward for future research.

The second and third studies found that melanoma patients with plenty of healthy gut bacteria responded well to immunotherapy. In contrast, the patients who didn’t have success with immunotherapy had imbalanced gut flora, which also was correlated with lower immune cell activity. The researchers in both studies concluded that cancer patients who maintain healthy gut flora are more likely to have positive results from immunotherapy.

 

Healthy gut bacteria can fight tumors

A May 2018 study, also published in Science, found that altering commensal (helpful) gut bacteria in mice could fight liver tumors. Researchers observed that Clostridium bacteria modified bile acids in the body, which signaled certain liver cells to produce the protein CXCL16. This, in turn, increased the number of natural killer T-cells (white blood cells that play a central role in immune response) in the liver, which attacked the tumors. Researchers concluded that the findings “not only have possible implications for future cancer therapeutic studies but also provide a link between the gut microbiome, its metabolites, and immune responses in the liver.”

 

Dangerous gut bacteria can cause chemotherapy failure and cancer recurrence

Scientists have also uncovered negative effects of “bad” gut bacteria on cancer patients. In 2017, researchers looked at how the gut microbiota could contribute to chemotherapy failure in colorectal cancer patients. They found that patients who had a recurrence of colorectal cancer following chemotherapy treatment also had a large amount of the inflammation-causing bacteria Fusobacterium nucleatum in their GI tracts. The study also found that F. nucleatum promoted colorectal cancer resistance to chemotherapy by targeting specific immune-signaling pathways in the body.

 

Healthy gut bacteria can alleviate chemotherapy symptoms

Another study in colorectal cancer patients from 2017 focused on patients treated with the chemotherapy drug irinotecan. After irinotecan is metabolized in the liver, it becomes inactive and is excreted through the intestine. Many patients who take irinotecan experience severe diarrhea when microbial enzymes called beta-glucuronidases re-activate the drug while it’s inside the digestive tract.

Currently, patients who take irinotecan are also prescribed oral antibiotics, in the hope that reducing the overall bacterial population in the gut will also improve this uncomfortable side effect. These researchers, however, thought they could find a better way.

They treated fecal samples from 20 healthy people with irinotecan. They found that in four of those samples, the bacteria present metabolized the drug especially quickly—fast enough to reactivate it while it was still in the body. That would potentially make the four people those samples were taken from vulnerable to a toxic response. The bacteria in the remaining 16 samples metabolized the drug more slowly.

The researchers also genetically sequenced the bacteria in all 20 samples, and found that the four “high metabolizer” samples also had higher levels of the gene for beta-glucuronidase compared to the rest of the group. Therefore, it might be possible to use GI microbiome sequencing tests to predict whether a given patient would have a toxic response.

Doctors would no longer need to prescribe oral antibiotics to every patient they put on irinotecan, only those at risk. In an article published by the Albert Einstein College of Medicine, the researcher who led the study also raised the possibility of prescribing prebiotics to patients to prep their gut microbiome for cancer treatment.

A 2017 study in esophageal cancer patients found that those who took synbiotics (a combination of probiotics and prebiotics) during chemotherapy had more beneficial bacteria and less harmful bacteria in their guts on the tenth day of chemotherapy. The patients with the healthier microbiomes also experienced fewer negative side effects from chemotherapy.

 

A healthy gut may benefit cancer patients

There is ample evidence to suggest that a healthy microbiome may help the body fight certain types of malignant tumors, make immunotherapy more effective, and make chemotherapy more comfortable for many cancer patients. As scientists learn more about ways to leverage the gut microbiota to make cancer treatment more successful and less painful, oncologists and other health care providers—not to mention their patients—can incorporate these findings into patient treatment plans.