Carrie Daniel-MacDougall, Ph.D. (Host) Hi, I'm Dr. Carrie Daniel-MacDougall, associate professor in Epidemiology at MD Anderson Cancer Center. And this is part two of my conversation with Dr. Jennifer Wargo, professor of Surgical Oncology. Welcome to the Cancerwise Podcast.  

Jennifer Wargo, M.D. And I think, you know, just to highlight to our podcast audience that we had a paper published in Science in 2018 on the role of gut microbes in shaping response to cancer immunotherapy treatment. And then in 2021 had a follow-up paper showing that if patients consume at least 20 grams of fiber per day, that they're much more likely to respond to cancer immunotherapy treatment. And it's really important, right, because this is something that patients can do on their own. You know, patients come in, they have a cancer diagnosis. What can I do to help myself? And diet is a clear answer here. Having a better diet, right? Now, tell us a little bit, is it a threshold or is it, is this a more is more case for fiber or is this a threshold? And can you talk about other diets? Keto, you know, people are, sugar, processed, you know, you know, kind of the processed foods. 

Carrie Daniel-MacDougall, Ph.D. (Host) So, actually I think 20 grams is, is a starting point. And really being below that, you're probably at a level that's insufficient, right?  

Jennifer Wargo, M.D. What do most people get? Just, yeah, in the United States? 

Carrie Daniel-MacDougall, Ph.D. (Host)  The dietary recommendations for fiber in adults is about 14 grams per every thousand kilocalories. So, if you consume a 2,000 calorie diet, which is the standard amount on any food label, that's 28 grams per day for the average adult. And in the U.S., most people are getting somewhere in the range of 10 to 15 on a daily basis. Now, of course, that varies day-to-day and we see that in our patients. We did actually try to test this by having a control diet in our clinical trial studies. That control diet is an equally healthy diet, but with fiber restricted to less than 20 grams per day. And that, what is a healthy diet? We can we can talk a little bit about that, is that we're following the cancer prevention guidelines, dietary guidelines for cancer prevention. Those are always a good place to start for cancer patients. We know that these are also incredibly important for cancer survivorship. And so, it's a good thing to, kind of, start from there, stay there and maintain that. And that is limiting consumption of red and processed meats. Although, I will say that it is also important to talk with your care team and your clinical nutrition team. You may have certain protein needs and other things that might be important. So, I do hesitate for people to go fully vegan or something like that without additional support. Same with ketogenic diets. They probably have very appropriate places and specific conditions of certain types of therapy or certain types of patients who need to lose a large amount of weight. But patients need to follow those very strict diets with support, or they can develop nutrient deficiencies. In the case of keto, they can develop keto flu, which is definitely something that a patient would need support through. So, I think there are places for these very extreme and exciting diets, whether it's 50 grams of fiber a day or ketogenic diet or even intermittent fasting, which is another area of interest, particularly in the setting of chemotherapy and, sort of, managing different side effects with that. But it all has to be, you know, I really want to bring it back to the science and let's understand exactly what conditions these are the most effective as opposed to just throwing all of these things at a dartboard without really thinking about what the patient needs and what the patient is taking in terms of specific types of therapies or classes of therapies or even what they're dealing with in terms of the tumor itself. So, patients with colorectal cancer, for example, could never eat a 50-gram-a-day fiber because they'd have a very high risk of bulking in terms of getting too much fiber in the colon and not being able to pass stool. So, there are real, it is something that all patients can do, but I'd really like to be sure that, you know, we're starting from a place of, sort of, a healthy overall diet and some of the more extreme things I think need to be discussed with a care team, whether that's the most appropriate thing for the patient.  

Jennifer Wargo, M.D. Can you talk a little bit about the sample menus and, you know, what types of foods are high value with regard to fiber?  

Carrie Daniel-MacDougall, Ph.D. (Host) Sure. So, one of the most popular things that we have on the menu is a black bean brownie with a raspberry chia seed jam. We always have patients asking for a lot of those. Those are a little bit more difficult to pull off in your own kitchen. But, we also do a lot of sort of mixed dishes where we replace, kind of, low fiber foods with high-fiber foods. So, again, I hate to harp on beans, but they're just something that we sneak into a lot of our foods because we're trying to keep protein high, but also introduce fiber. So, one of the things we do is we may cut mashed potatoes and add in different amounts of white beans. And you really can't tell. It's very similar to, you know, cauliflower rice versus white rice, these kinds of things. But I think the easiest thing that we can do at home is keep a bowl of fruit, and, you know, on our counters, cucumbers in the refrigerator, cherry tomatoes on the counters so when we're like, just kind of wandering around looking for a snack, that that's what we grab for instead of the little pack of Cheez-Its or whatever it is that we eat in a hurry. And nuts are phenomenal in terms of fat, healthy fatty acids and fiber.  

Jennifer Wargo, M.D. But I think it takes intention, right? I think if you actually, we have a chart.  

Carrie Daniel-MacDougall, Ph.D. (Host) I was going to say, you have this down.  

Jennifer Wargo, M.D. Yes at home.  

Carrie Daniel-MacDougall, Ph.D. (Host) I just do everything for my children. You teach them how to fish for themselves.  

Jennifer Wargo, M.D. Well, I'm trying, but, you know, basically you have a chart on the refrigerator with different food types with its fiber content. And, you know, I urge everyone to take the fiber challenge, see how much fiber you eat in a day, and then be intentional about increasing your fiber. I think, you know, trying to get up to 20, 30, you know, kind of 28, as you've said, is is where everyone should be. Most people are well below 20. And, you know, can you actually get up to 30, 40, 50 grams a day, you know, just to improve your overall health? Let alone, you know, if you've been diagnosed with cancer, if you're undergoing cancer treatment, the stakes are very high. But I think the stakes are high for everyone. You know, to promote our overall health.  

Carrie Daniel-MacDougall, Ph.D. (Host)  And I personally, with my children, I hit it at breakfast because that's before you leave the house for the day and you don't know what's going to be available to you throughout the rest of the day. So, like every morning it's a bunch of different berries and nuts and oatmeal, and then they get to have some little treats and stuff too. But I try and pack them up with fiber early in the morning. It helps them stay full and focused throughout the day. And then, of course, one of the other strategies is to really build a plate at dinner where at least half of it is covered with those fiber rich foods, whether it's different types of whole grains and vegetables and fruit for dessert, like if you can just make those simple changes and make those snack foods, those high-fiber snack foods, throw those in your bag for the day. I think that's that's one way for people to achieve it. But, if you're trying to achieve it kind of without intention and you're counting on restaurants or different types of off-the-shelf foods, a lot of them will say,  I'm plant-based or I'm high-fiber or whatever. It is not the same. A Fiber One bar, for example, is not the same as consuming the fiber in the form that it was originally intended by nature. And that's where I think there's there's quite a lot of confusion and really where we're trying to go with these interventions and getting people to eat the whole food sources, even though the food supply is throwing a lot of different processed versions at us that may not necessarily be so great for our gut microbiome.  

Jennifer Wargo, M.D. Right. Yeah. And so I think, you know, the question is, you know, can we change our gut microbiome to improve our overall health and response to cancer treatment? The answer is absolutely yes. We can do that in a couple of ways. Diet is one way because, you know, you can change kind of the bugs that are there and you can partially do that through diet, but you can also change their function. And so you could have the same bugs there. And if you're feeding at McDonalds, they're not going to perform so well. But if you're feeding at a good plant-based, whole food-based, high-fiber diet, they're going to perform like gangbusters and really help your immune system and help your cancer treatment. So, I think that's really important. Now, I'll go ahead and talk about some other ways that we can change the microbiome. You know, so one way we know that negatively changes the microbiome is antibiotics, right? And so, broad spectrum antibiotics can actually harm your gut microbiome and potentially harm your response to cancer treatment. And so, I think avoiding overuse of antibiotics is really important. That's something we're working on. And then how can you actually favorably change the microbiome to help patients respond better? And so, we and others have studied this. And can you actually, you know, like transplant for blood cancers, can you actually do a transplant of the gut microbiome? It turns out you can. It's called a fecal microbiota transplant or an FMT. And people have actually shown that if you take a cancer patient who has actually gotten immunotherapy but hasn't responded, you wipe out their inherent microbiome and give them a fecal transplant, believe it or not, from a patient who's had a

complete response to therapy, that you can actually help them respond to that cancer treatment. And that is really remarkable. And how do you do that? Sometimes by colonoscopy and sometimes by pills. It's not yet FDA-approved, but it's being used in clinical trials. And so, using fecal transplant can actually help improve response to cancer treatment. Now, can we do anything short of a fecal transplant? I think that's an important question. And this has been a hot topic for several years now. There have been people who have tried to engineer different consortia or communities of bacteria that you can actually put back into the gut of patients with cancer to actually help them respond to cancer treatment. And, and this is being studied in clinical trials. We are actually working with a company, Kanvas Bio, with PRIME-TR at MD Anderson, where we've actually taken a patient's sample who's had a complete response to their cancer treatment and actually engineered a synthetic community of bacteria from that patient's sample. That's actually, we're hoping to use in clinical trials within the next year or two, and it's actually performing incredibly well in preclinical studies. And so, I think that's an exciting way to potentially change the microbiome to help patients respond better. Another way is that, can we actually it's not only having the right bugs there that matters, it's not having the wrong bugs. And can we use selective antibiotic approaches to get rid of the bad guys, if you will, and let the good guys flourish and really respond to the cancer treatment?  

Carrie Daniel-MacDougall, Ph.D. (Host) So, kind of, just thinking about all these things that we've talked about, it seems like, again, we have to come back to this concept of what does the particular patient need versus right now is, kind of, the Wild West out there, right? Like, over-the-counter probiotics or these different things that people are trying.  

Jennifer Wargo, M.D. The diet fun wheel.  

Carrie Daniel-MacDougall, Ph.D. (Host) The diet fun wheel is something I always talk about, like the patients get on the internet and spin the fun wheel and see what the most popular diet on the internet is today and try that. And I really hope that, you know, MD Anderson and others can really be the voice behind, how do we understand what the patient actually needs by doing the research to understand what's working, what's not working, in these observational and preclinical studies. And then we can build these clinical trials and other intervention studies where we try more than one thing based on what the patient actually needs. That's what I'm really excited. Of course, we have to write all the grants and show that each thing works alone. But I think that's what I'm the most excited about working with you on, is starting to bring these different strategies together. And so, I was just going to ask you, I mean, what do you think is on the horizon in that space for changing the gut microbiome?  

Jennifer Wargo, M.D. I've been so encouraged with the results from these clinical trials using diet to actually improve response to cancer treatment. I think it's very promising. We've seen some really encouraging results. And, you know, I think it's not just about patients with cancer. I think it's that, you know, certainly we can, you know, optimize our diets and really optimize the health of our gut microbiome to improve our own immune system, to promote our overall health, right, and response to vaccines, or just our overall health in general. And so, I think that's a really important metric. Now, can you speak a little bit to rising rates of cancer in younger individuals?  

Carrie Daniel-MacDougall, Ph.D. (Host) Maybe what's going on there?  

Jennifer Wargo, M.D. What's going on there? How can we combat it?  

Carrie Daniel-MacDougall, Ph.D. (Host) Yeah. 

Jennifer Wargo, M.D. What can we do here at MD Anderson and then globally to really make substantial changes to reduce that?  

Carrie Daniel-MacDougall, Ph.D. (Host) Right. So, kind of, thinking of, you know, where does all this fit in the space of cancer prevention? So, our family members and you know, this is obviously true for our cancer patients. They want to know what their family should be doing to prevent cancer as well. And so, there are some very clear things that we can modify in terms of our behavior, in terms of cancer prevention, that we actually do know have effects on the gut microbiome. So becoming physically active, maintaining a healthy weight, of course, eating the diet that we discussed before, where you're avoiding red and processed meats and added sugars and just in particular, anything that can survive on a shelf that has a long list of ingredients and things that you don't understand typically contains multiple unhealthy things that are not good for the gut microbiome, and not good for cancer prevention, and not good for cardiovascular disease prevention. Because I think, you know, one point that you had that I often bring up about diet is it's about adopting a healthier lifestyle to prevent a multitude of diseases. So, we shouldn't just be concerned about whether or not we're going to get cancer. One of the other killers in this country is cardiovascular disease or do we want to live a life where we don't have to deal with diabetes or these other chronic conditions that people are living with? And these particular behaviors that we can modify are at the basis of all those things.  

Jennifer Wargo, M.D. Right? So going forward, I think there's a multi-pronged approach. I

think education, I think, you know, providing patients with good fiber, you know, really highquality foods or even prebiotics and maybe even symbiotics, can we have a probiotic that's, you know, that's actually very useful, an engineered community of bugs that we could give to patients to help them respond to cancer treatment? I think that's on the the horizon using that in conjunction with diet. I don't think there's any replacement for diet, a good, healthy diet, what our moms all told us.  

Carrie Daniel-MacDougall, Ph.D. (Host) We all have to eat.   

Jennifer Wargo, M.D. Right? Exactly. We all have to eat and we have to eat healthy. And you know what? We need to get sleep. We need to reduce stress. All these things matter, you know, but, it makes a difference and it's like, it's obtainable.  

Carrie Daniel-MacDougall, Ph.D. (Host) Alright. Thanks for being here today. For more information or to request an appointment at MD Anderson, call 1-877-632-6789 or visit MDAnderson.org. And thanks for listening to the Cancerwise Podcast from MD Anderson Cancer Center.