The gut microbiome and cancer treatment: What we do and don’t know
Your body is home to trillions of microbes. These bacteria, viruses, fungi and other organisms impact everything from how you process food to your immune system response. They outnumber our human cells but mostly live in harmony. One of the most studied communities of microbes is the one that lives in our gastrointestinal tract — the gut microbiome.
MD Anderson surgical oncologist and researcher Jennifer Wargo, M.D., is studying the relationship between the gut microbiome and cancer, and trying to understand whether regulating the gut microbiome can promote health and treat cancer. Her perspective on the progress made in this area was recently published in the journal Science.
To learn more about the link between the gut microbiome and cancer, we spoke with Wargo and Nadim Ajami, Ph.D., executive director of MD Anderson’s Program for Innovative Microbiome and Translational Research (PRIME-TR).
Why are you interested in altering the gut microbiome?
Wargo: We’ve learned that bacteria, viruses, fungi and other microbes naturally found in the gut can influence treatment response either positively or negatively. In a recent study, our team found that the gut microbiome can shape how patients with cancer respond to immunotherapy. Now we’re working to find out if changing an individual’s microbiome could help them respond better to cancer treatment.
Ajami: Microbiomes vary greatly from person to person. That’s true in both healthy populations and in people living with specific diseases. There are favorable microbiomes in terms of response to therapies. That means certain communities of microbes are associated with a better response to cancer treatment. In cancer, we want to change the microbiome to make treatment more effective for more patients.
What strategies are being used to change the gut microbiome?
Wargo: Scientists are studying different approaches to modulate the gut microbiome. For example, using fecal microbiota transplants (FMT), we can literally take poop from a patient who had a complete response to therapy and give a “poop pill” to another patient. Or, we can manufacture a mixture, or consortia, of microbes, put it in a pill and give it to people.
Another strategy is to target and kill specific microbes in the gut using newer technologies. Changing diet can also change the microbiome. Finally, there are prebiotics and postbiotics that you can buy. We’re studying all of these strategies through pre-clinical models and clinical trials to see which approaches are the safest and most effective ways to regulate the gut microbiome in the context of cancer treatment.
Have any of these gut microbiome regulation strategies been successful in treating other diseases?
Ajami: Yes, there’s a clear example from the field of infectious diseases with Clostridioides difficile (C. diff) infection. This bug can take over the gut after someone receives antibiotics and cause life-threatening diarrhea. It can recur in one-third of patients. We know that the problem with recurrent C. diff is the lack of diversity in the gut microbiota. Until recently, there wasn’t an effective treatment for C. diff that continues to come back and doesn’t respond to other antibiotics. However, researchers found that fecal microbiota transplants, or “poop pills,” from healthy donors can restore the gut microbiome diversity in patients with C. diff and clear the infection. This treatment is now the standard of care for patients with recurrent C. diff.
Recently, an oral microbiome therapy, made from a consortia of microbes, was used in a Phase III trial to treat recurrent C. diff. Our group is applying a similar approach to modulate and improve the gut microbiome of melanoma patients.
What does current microbiome research say about probiotics?
Wargo: There was a lot of public enthusiasm for over-the-counter probiotics when we, and others, published papers about the importance of the gut microbiome in cancer patients. So we did a study where we asked our patients if they took over-the-counter probiotics. It was a small study, but we actually found that if people took probiotics, their microbiome was much less diverse and immunotherapy didn’t work as well for them.
Ajami: We don’t completely know how over-the-counter probiotics work. They’re considered safe products, but unlike the new oral microbiome therapies currently being studied, over-the-counter probiotics are one-size-fits-all and not designed to treat any specific disease or condition. They might give you temporary benefits, but we're not sure it’s the most efficient strategy to modulate the microbiome. Commercial probiotics may work for some people, some of the time, but they don't work for everyone, all the time.
What research is MD Anderson doing to study the gut microbiome?
Ajami: MD Anderson has many researchers working on microbiome science from different perspectives and in different diseases. For example, Dr. Wargo has studied the microbiome in the context of melanoma for many years, but we also have scientists like Florencia McAllister, M.D., actively researching the microbiome in pancreatic cancer, and others who are just starting to investigate the microbiome in preclinical models of HPV-related cancers and glioblastoma.
MD Anderson researchers have published more than 90 microbiome papers, and we currently have a dozen clinical trials examining how everything from diet to pre-surgery antibiotics affect the microbiome. Recently, we launched PRIME-TR, a new program to coordinate this emerging research and effectively translate it from the research labs to clinical trials.
What else do you want cancer patients and caregivers to know about the microbiome?
Wargo: Everyday things, like diet, antibiotic use or over-the-counter probiotics, can impact your microbiome and could impact your cancer treatment. So, it’s important to make sure your care team knows what you’re putting into your body. We want patients to be involved in research studies for the microbiome, but, as they say, don’t try this at home.
We're at the cutting-edge of microbiome research, and we’re working to best understand how these microbes that are so prevalent in our bodies and in our environment can shape overall health and cancer risk. It’s complex and we’ve made a lot of progress, but we still have a long way to go.