Gut Bacteria Could Affect How We Respond to Immunotherapy

Did you know that your gut bacteria might predict whether or not you will respond to immunotherapy? Three different studies have found that responders and non-responders can be predicted based on the composition of their intestinal microbiota.¹

What do the studies show?

One of the studies, conducted by Laurence Zitvogel at the Institut Gustave Roussy, Villejuif, Paris, looked specifically at immunotherapy response by those with non-small cell lung cancer and renal cell carcinoma. The study found that patients with more bacteria from the species Akkermansia muciniphila had the best response to anti-PD-1 therapy.

The other two studies focused on patients with late-stage melanoma. Each identified different microbiota that seems to drive patient response to immunotherapy.

Zitvogel's group discovered that patients who had received antibiotics within two months of beginning their immunotherapy treatments relapsed sooner than those who had not received any recent antibiotics. In fact, patients who had not received antibiotics lived twice as long as those who had been given antibiotics before anti-PD-1 therapy.

There is still work to do

If you're like me, you got pretty excited when you read this. But, we are cautioned by a number of medical experts, including  Giorgio Trinchieri, Director of the Cancer and Inflammation Program at the US National Institutes of Health about getting ahead of ourselves. The studies present important findings, but there is still much work to do.

First, scientists still need to define how the gut bacteria is impacting response to immunotherapy. Trinchieri notes that the tumors that are responding to the immunotherapy are not in the colon, so, therefore, they are not in direct contact with the bacteria. "The microbiota most likely primes cells in the patients for an effective immune response," he says.

Furthermore, scientists need to determine the types of bacteria that are beneficial. All three studies identified microbiota that seemed to drive response, but each study identified different species.

Reasons different bacteria was found

Dr. Trinchieri gives some possible reasons different bacteria was found. “The microbiota are influenced by external variables, with large geographical differences," he said. "Food, for example, influences the microbiota. So while the microbiota affects anti-PD-1 therapy, which bacteria are actually involved could differ in different places. Also, which bacteria are important could differ according to patients and tumor.”

Results might also be skewed because of the small population sizes in the various studies. In addition, each study used different criteria for therapy response.

Some even question whether the findings have scientific relevance yet. Trinchieri warns that more data is required before results can be accurately predicted. Bertrand Routy, lead author of the Zitvogel study agrees. "Of course, the ultimate goal is to arrive at an intervention, but we are not there yet. We still have a few steps to validate before we can start to manipulate the gut microbiota of cancer patients," he said.

Turning to clinical trials

Clinical trials are needed so that researchers can answer questions like:

• Which bacteria should be given to patients?
• How should bacteria be given to patients?
• How often should it be given?
• In what form should the bacteria be given?

Routy, who now oversees the Laboratory of Immunotherapy / Oncomicrobiome, at the University of Montreal, Canada, hopes to begin enrolling patients in a clinical trial to try to find answers to these questions within the next year or two. “We need to validate the importance of the gut microbiota in a larger international cohort, and develop novel biomarkers in the microbiome," he explains. "But eventually, when a patient is newly diagnosed, along with a biopsy of the cancer, the microbiome will also be addressed.”

Where does this leave us?

So, where does all of this information leave us, you and me the patient? I never have been one for taking antibiotics for every little thing. I will definitely think twice in the future before I will agree to take them.

On the other hand, Dr. Routy reminds us, "Antibiotics save lives, and my biggest fear is that patients will not take antibiotics. As use of antibiotics affects the immune response, doctors should only prescribe antibiotics when they are really needed."

Stay tuned! It is exciting to realize that more breakthroughs are being made and that scientists are coming up with even more predictors of when immunotherapy will be most effective. In the not so distant future, doctors may be able to give us something to help raise our odds of responding to anti-PD-1 therapy. In the meantime, we are advised to help strengthen our immune systems the old-fashioned way: by eating a healthy, balanced diet and getting regular exercise.