Increased Fiber Intake May Improve Immunotherapy Responses in Patients With Skin Cancer Subtype

A high-fiber diet consisting of at least 20 grams per day may be associated with the longest survival without disease progression in patients with advanced melanoma who were treated with immunotherapy, according to recent study findings.

Results from the study, which were published in the journal Science, also demonstrated that patients with melanoma who consumed a high-fiber diet may have a better response to immunotherapy, but commercially available probiotic supplements may have unintended effects.

CURE® spoke with Carrie R. Daniel-MacDougall, director of the Bionutrition Research Core and an associate professor in the Department of Epidemiology at The University of Texas MD Anderson Cancer Center in Houston, to learn more about why the gut microbiome remains important for patients with cancer, how following a high-fiber diet may be easier than some may think and what further research is needed in this area before this becomes standard practice.

Why did you and your team find it so important to conduct this study?

In 2018, my collaborator, Dr. Jennifer A. Wargo, and a big team of us put together the first paper showing that the microbiome was important to immune and therapeutic responses to immunotherapy in melanoma patients. At the time, there were other groups doing those studies when that research came out. It's not just melanoma, its renal cell carcinoma, some other cancer patients that the microbiome is really important for immunotherapy responses. Then some of the preclinical data really showed how the mechanism was strongly linked to the gut microbiome for anti-tumor immunity.

While (we were) working on (that) manuscript, we saw that we had the signal for starch or fiber-degrading bacteria like faecalibacterium, and Ruminococceae, which there's lots of work done in healthy individuals who aren't on cancer therapy, saying that we can modulate those with fiber.

The first step for intervening with patients is to measure these behaviors in patients and see what we might see. So first, do no harm, measure and try to understand. We started giving patients these lifestyle questionnaires, which was not done at the time. People were not asking patients these questions in a quantitative way like we do in healthy groups. And so we asked them about their dietary habits, their supplement use and a range of other different things. And it took us about five years of collecting those data to have enough follow-up to really put together this paper.

What we observed is that dietary fiber is good and probiotics, maybe not so good, or at least not broadly beneficial. It's more complicated than maybe what people hope it would be. That's really what we saw here and how we landed on that. Then the preclinical models, again, give us the hint that patients who have insufficient fiber intake or patients who'd consume certain commercially available probiotics might actually have impaired anti-tumor immunity through its effect on the microbiome.

What are the major takeaways from your study?

The message is still that the microbiome is important. We found consistent findings with our first paper in a much larger set of new patients. We definitely can still say that, that is the case. We have a little bit better idea what that target is. It still seems to be that Ruminococceae family and faecalibacterium, these keystone species that are associated with fiber and starch degradation. But they also play a role in keeping the microbiome in a comfortable, homeostatic, ideal situation. A good, healthy microbiome has a lot of things going, not just one species or one bug problem. So those particular bacteria are gatekeepers that keep all that in check. So that's the message that is consistent with other cohorts, other cancer patient populations with the microbiome. I feel we just added more to that.

The new thing is that what patients do on their own — besides the drugs, besides coming to their appointments — matter. You can see that diet is something that a lot of patients are interested in changing on their own. It's something that their caregivers are really invested in. Every caregiver has a different idea for what their patient should eat. And diet is something that's approachable. It's something that we can all tweak on our own. We all have access to in the grocery store. It’s not a prescription drug, but the effects could be powerful. And the effects are not straightforward. It's really important that we start to study this in a very systematic and quantitative way because a lot of these decisions that patients and caregivers are making are not based on scientific data; they're based on our best guesses or what we know for cancer prevention.

The same goes for supplements. Cancer patients love to take supplements. There's actually quite a lot of data that cancer patients are more likely to take supplements than healthy populations. That makes sense. Anyone with a chronic disease is looking for something that's going to help them or make their health improve. We all want to do our best. But the thing is, dietary supplements, in general, are not always predictable in terms of what their effects are in an individual. That's because we all start at a different place. And then the efficacy of these supplements is also very variable in terms of what you're getting, what you think that you're getting and how it's going to have an impact outside of the food for the case of a dietary or nutritional supplement, or outside of the entire microbiome as a community. One particular bacteria dropped in to your microbial community may have a different effect than you may be hoped for or intend. That's what our research really specifically addresses: patient questions in a scientific way. And that's something that we want to be the source of valid, scientific-based evidence for these dietary, probiotic and other types of decisions that patients ask their physician and their care team about. We want to give them better answers.

What are some of the major aspects of this high-fiber diet that may improve immunotherapy responses in patients with melanoma?

From what we know now, which is admittedly still not a lot, this is one particular diet that may be effective in improving a patient's microbiome. That's not just based on our research; that's based on research in a lot of other settings outside of cancer therapy. It's actually not a diet that's very different than what's already recommended in our national dietary recommendations. That includes consuming (whole) grains, legumes, which are beans typically and (whole fruits and vegetables), the foods that we’ve always been told these are the healthy foods that you should eat instead of filling your plate with all the other delightful things that we like to eat; fill your plate with those things, and then make sure that you meet your dietary needs in terms of your protein needs, fat needs — you do actually need those things too with other healthy food sources — so lean meats, fish and healthy fats. It's not that different to follow that fiber-rich food pattern than what we already know.

Cancer patients may have other things going on, so they need to speak to their care team if they're going to make a dramatic dietary change. For example, sometimes cancer patients will have issues going on with kidney function, maybe they have to avoid certain leafy greens or they're taking medications that there's some interaction. It's always important to talk to your care team. But these are not necessarily dramatic changes to diet. Patients are still consuming the same foods that people consume but changing the proportions and trying to increase one particular group.

Sometimes patients are more likely to do the extreme version, which might be to go vegan or vegetarian, which is something they were not before. I would just caution that it's also important, again, that you meet your overall nutritional needs for protein, fat and carbohydrates in any dietary pattern that you meet because you want to have all the energy and all the strength to get through the journey that you're about to embark on, just not take it to the extreme. It’s an important message when we're trying our hardest to do our best.

What further research is needed in this area?

We are still continuing this research. We want to broadly collaborate with other groups around the country and look at this in other patient populations. We know that there's many more patients than those with melanoma who were really interested and want to know if this applies to them. We're actively collecting data in other cancer patient populations here at MD Anderson and with other colleagues around the country and working with international organizations as well to try to understand that.

The last step is with my melanoma oncology colleague, Dr. Jennifer L. McQuade, Dr. Wargo in surgical oncology, we are doing dietary intervention trials. So observational data and mouse and preclinical data are very promising, but it's not the definitive answer. We have ongoing trials in patients going on to immunotherapy treatment, and we are feeding patients either high-fiber, healthy diet or a healthy diet that has more like an American level of fiber and seeing if those patients do differently. We're really excited to see how that goes. There’s a lot of things in the pipeline. All the answers are not there right now, but the promise, the excitement and the motivation is certainly there.

This interview has been edited for clarity and conciseness.

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