Microbiome: What It Is and Why It's Important to Your Health

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Microbiome: What it Is and Why It’s Important to Your Health.

Presenter: Urvi A. Shah, M.D., Assistant Attending Physician, Myeloma Service, Memorial Sloan Kettering Cancer Center and Assistant Professor of Medicine at Weill Cornell Medicine.

Summary: The microbiome plays a crucial role in our overall health and our response to cancer treatment. In her lecture, Dr. Shah discusses studies that highlight the significance of dietary diversity and a high-fiber diet. She also offers advice on how to implement these changes before, during, and after cancer treatment.

Key Points:

• The microbiome refers to the collection of bacteria, viruses, and other microorganisms that live in and on our bodies. A healthy microbiome is associated with improved overall health and improved survival in many cancer patients.
• Dietary diversity is vital to a healthy microbiome. Eating a wide variety of plant-based foods can achieve this.
• Eating a plant-forward diet high in fiber improves the microbiome, improves the gut lining, and helps support the immune system. A high-fiber diet should include at least 25-30gm of fiber daily.

Highlights:

(00:04:32): The human body has more bacteria cells than human cells. We can impact overall health by improving an unhealthy microbiome that has insufficient healthy bacteria, which can lead to inflammation and gut dysfunction. 

(00:07:45): Studies have associated microbial diversity with improved survival.

(00:08:51): Dietary diversity, such as eating 30 or more different types of plants, is associated with improved microbiome health.

(00:13:29): Many people do not get enough fiber in their diets. A fiber-rich diet improves the microbiome and the gut lining and helps support the immune system. Studies show that patients who follow high-fiber, plant-forward diets have a 15-20% reduced risk of being diagnosed with cancer.

(00:19:49): In a clinical trial, overweight patients with MGUS (monoclonal gammopathy of undetermined significance) were given a high-fiber plant-based diet and nutrition coaching. The patients lost 8-9% weight and improved their health overall.

(00:22:44) By adopting a plant -forward, high fiber diet, patients were able to increase the biodiversity of their microbiome and decrease inflammation.

(00:23:12): It is possible that improving the microbiome improves the immune system enough to slow down the progression of cancer.

(00:25:46): A diet that does not allow fresh fruits and vegetables, has not been shown to reduce infection. It may cause additional unwanted weight loss and lower quality of life.

(00:27:39): A plant-based, high-fiber diet may also contribute to better outcomes, including remission rates and sustained MRD (minimal residual disease) negativity.

(00:32:24): Diet changes can be made slowly over time and should be individualized to each patient, taking into consideration disease state, symptoms, comorbidities and willingness to make changes.

Transcript of Presentation

(00:00:01): [Michael Riotto]:   Welcome to our workshop, Microbiome: What It Is and Why It's Important to Your Health. My name is Michael Riotto and I will be your moderator for this workshop.

(00:00:10): It is my absolute pleasure to introduce today's speaker, Dr. Urvi Shah. Dr. Shah is an Assistant Attending Physician on the Myeloma Service at Memorial Sloan Kettering Cancer Center and Assistant Professor of Medicine at Weill Cornell Medicine. Her research studies the effect of modifiable risk factors such as nutrition, obesity, and diabetes on cancer development and progression and how dietary interventions and supplements influence insulin resistance, body composition, gut biome, and the immune system. Please join me in welcoming Dr. Urvi Shah.

(00:00:52): [Dr. Urvi Shah]: Thank you so much, Michael, for that introduction. I'm really glad to be here with you all. I'm excited to talk about this topic, which I think is an up-and-coming topic because there's a lot of research going into this field. I think we're learning a lot, and we'll see a lot in the years to come. We are just scratching the surface.

(00:01:16): Introduction to the microbiome. In terms of the microbiome, I'll first explain to you what that is, and then we'll go into some studies that have shown changes in the microbiome. We will also look at nutrition tips that could affect the microbiome.

(00:01:35): As patients with myeloma and lymphoma are living longer, it is necessary to improve their quality of life with dietary and lifestyle interventions. We developed a program studying nutrition, microbiome and metabolism in myeloma and other cancers at Memorial Sloan Kettering. We know now that patients with blood cancer are living longer than maybe a decade ago.

(00:01:53): For instance, in myeloma and lymphoma, even looking at these, there has been significant progress made in terms of the number of treatment options available. With that, the good news is that patients now have an opportunity to live longer.

(00:02:10): It should not just be living longer, but we should also focus on outcomes that improve quality of life for living better. How do we look at dietary and lifestyle interventions to help patients tolerate the treatments and respond better?

(00:02:27): So, just to bring home that point and understand why this is important, this is an example of a 66-year-old patient that I'd seen a few years ago who had multiple comorbidities and multiple medical issues. Because of these issues, I was not able to do many of the treatments that mattered such as stem cell transplantation, CAR-T cell therapy and clinical trials. Because of this, the patient had a decreased overall survival.

(00:03:00): I’ve highlighted in green the things that I think could have been avoided, improved or reduced with lifestyle changes over time. I know it's challenging when someone develops cancer and tries to focus on lifestyle changes, but we're just going to discuss and think about some small tips and small changes we can make.

(00:03:21): This is a case of a patient of mine a few years ago who had myeloma. Compared to the prior patient, this patient is overall pretty healthy but still has cardiovascular disease. What you can see in this case is that the patient responded to chemotherapy and went on maintenance therapy. From the time he came in, he was in a wheelchair. Now he's really well and walking around. He felt like he had gotten back to his life. However, he did develop a cardiac arrest and died of that while his myeloma was in remission.

(00:03:54): As patients live longer with improved therapies, it is important to address their comorbidities. So, what I'm trying to say is that our therapies have gotten so good, not for all patients but for some patients, that patients are living very long, which is a great thing. But then we have to deal with the other lifestyle comorbidity issues that could affect outcomes, such as cardiovascular disease, diabetes, nutrition, physical activity, strength and things like that.

(00:04:21): Some of the things I'll talk about are the microbiome, different dietary patterns, some trials that we and others have done, as well as some nutrition tips.

(00:04:32): We have more bacteria cells in our body than human cells. One question for you all, and maybe you already know this, but do we have more human or bacterial cells in our body? We would assume it's human cells, but actually that's not the case. We have more bacterial cells than human cells. It's 38 trillion compared to 30 trillion. I think it just makes sense that we should be thinking about what the bacteria that live inside us want to eat, not just what we want to eat.

(00:05:03): An unhealthy microbiome has a reduction in healthy bacteria which can lead to inflammation and gut dysfunction.  So, thinking about the microbiome, there's a lot that's been done in healthy individuals and in disease. What you see is that with gut dysbiosis or unhealthy microbiome, there are things like reduced diversity and reduction in the healthy bacteria or good bacteria. This leads to a problem with the mucus layer - the barrier that's between the intestines and the immune system. There's more inflammation and more dysfunction. What you can also see here is another figure from a paper showing how the microbiome is central to health and disease. We're just cracking the surface but a lot of different things that could affect it.

(00:05:55): Age, gender, race, genetics and medical conditions are non-modifiable risk factors that can negatively influence the microbiome. What are factors that influence the microbiome? There are things that are non-modifiable, meaning we're born with them, or we live in a certain way. There is nothing we can do about it. How old we are, whether we are male or female, our age, genetics, infections, some of those things. Medical, some disorders that we can't control.

 (00:06:16): Nutrition, weight, diabetes, physical activity, sleep, stress and medications are all risk factors we have some control of. But what we can control are things that also affect the microbiome and immune system, such as nutrition, our body composition, diabetes, physical activity, sleep, stress, drugs and medications. I'll focus on the top three in this list, but I think we can talk about the others as well. One concept I want you all to understand is what is microbiome diversity? The reason I bring this up is that diversity is commonly talked about in most papers and studies, so if you understand what diversity means, I think you will understand a lot of the studies around microbiome and what they're trying to say

(00:07:03): Diversity in the microbiome refers to many different varieties of bacteria. So, think about a healthy forest, like a rainforest, that has many varieties of flora, fauna, animals, plants, species, so many different kinds, big and small. That is a healthy ecosystem.

(00:07:21): Then think about a plantation where there are only banana trees or coconut trees for miles on end. That is not a diverse or healthy ecosystem compared to the rainforest. When we think about diversity, we're thinking about a healthy rainforest in the gut microbiome where we want many kinds of species and variety.

(00:07:45): Microbiome diversity has been associated with improved survival in many studies. There have been numerous studies looking at this diversity and correlating it with cancer outcomes. Microbiome diversity has been associated with survival in many studies. What you can see here on the left is the red line, which is high diversity. has a better progression-free survival after transplant compared to low diversity. Then on the right, you see a box plot where the patients who had higher diversity were more likely to be in complete remission from their myeloma, or sustain their MRD-negativity. The figure on the left was from patients with lymphoma, myeloma as well.

(00:08:33): How do we improve gut microbiome diversity, and is that possible? Now, not a lot of studies have been done on cancer patients. A lot of this data that I will show you is in healthy individuals, with some in cancer patients, but I think a lot needs to be done.

(00:08:51): Dietary diversity, such as eating 30 or more different types of plants, is associated with improved microbiome health. Dietary patterns are a modifiable factor that can affect the gut microbiome and probably one of the most important ones as well. One study looked at hundreds of patients and asked them to fill out a dietary survey that asked, "How many plant foods do you eat in a week?" And what they meant by different plant foods, is if you're eating broccoli 10 times a week, that counts as one, but if you eat broccoli, potato, green beans, oranges and apples, that will count as five or six.

(00:09:29): So, how many different plant foods do you eat in a week? I would encourage you to go back and count this for yourself and think about it. Are you eating the same things because you just like it and you're in your comfort zone, or are you really trying different things? Maybe in the same meal, you have a stew with many types of beans. That would count as many instead of one. Every type of bean would be different.

(00:09:53): What they showed in this study was that those who ate more than 30 plant foods per week had more microbiome diversity, less antibiotic-resistant genes in the bacteria and more polyunsaturated fatty acids with anti-cancer and fat-reducing properties. This study said yes. Again, it's not an interventional study where we gave patients food and looked at what happened, but we looked at large populations and see what is associated. We do see that patients who eat a variety of 30 or more plant foods seem to have better microbiome health.

(00:10:35): Increased dietary fiber and fermented foods can improve microbiome function.  This is another study in healthy populations. Now this is an interventional study. They took 18 participants and told them , "Let's increase your fiber intake or increase the consumption of fiber in your diet." So, they added 20 grams per day of dietary fiber for four weeks. What you can see is the microbiome function, like short-chain fatty acids improved.

(00:10:58): I didn't really talk about short-chain fatty acids yet, but short-chain fatty acids are metabolites that are made by these bacteria. So, short-chain fatty acids like butyrate, acetate, propionate have been shown to have healthy effects on the immune system. Sometimes potentially anti-cancer and anti-inflammatory effects, too.

(00:11:22): They did see an improvement in microbiome function. And then another part of the study was to have these patients eat six servings per day of fermented foods over their baseline. They showed that there was a reduction in inflammation and increased microbiome diversity, suggesting high fiber and maybe fermented foods in healthy individuals did affect their microbiome in a good way.

(00:11:51): In some studies, patients with more plant based, high fiber diets had decreased risk of moderate to severe covid infections.  What about the immune system? So, I showed you how dietary patterns affect the immune system in healthy individuals. There have been three studies that have looked at dietary patterns in COVID-19 severity. I know it's not as relevant as it was before, but I think still relevant for us in terms of thinking about infections.

(00:12:13): I'm showing you only one of the studies. There are a few others that show very similar finding. What they showed was that patients who had improved the quality of their diet, meaning they followed more of plant-forward, fiber-rich diet, actually lowered their odds of developing moderate to severe COVID by 73%, suggesting that this anti-inflammatory property may have an effect.

(00:12:41): Now, again, these are population studies, not interventional studies so we have to understand that there are some limitations to these data, but if three studies are showing the same thing, I think we should think about it and not ignore it.

(00:12:57): I encourage you all to think about how much fiber you get in your diet. Sometimes, I know, it's not easy to suddenly go from a very low-fiber diet to a very high-fiber diet because the microbiome needs time to adjust. You can count and look at how much fiber you are getting in your diet. Remember, fiber only comes from plant foods, so if you are eating enough plant sources, you will get fiber. Beans, seeds, nuts, grains, fruits and vegetables all have fiber.

(00:13:29): Many people do not get enough fiber in their diets. A Fiber-rich diet improves the microbiome, the gut lining and helps support the immune system. This was a study that surveyed the U.S. population and asked them, "Do you get enough fiber in your diet?" 67% of them said, "Yes, I get enough fiber." But when they actually checked, only 5% did. So, we really live in a situation where most people are fiber-deficient and are not getting enough fiber. That's why I encourage you to think about whether you are getting enough in your diet. Like we talked about, a fiber-rich diet has major implications on the microbiome and the gut lining, as well as the immune system, as shown in multiple studies.

(00:14:13): Also, patients and doctors often think, "Okay. The patient has cancer. They've gone through a lot. Are they really going to make dietary changes? Should we bother with even telling them about this?"

(00:14:26): I agree that it may not be the right time all the time. If you've gone through a really intense period of treatment, now is not the time to suddenly try to change everything because you are just focused on recovering from those symptoms. But making gradual and slow changes can be helpful.

(00:14:42): Patients are interested in learning about what kind of diet changes they can make. We surveyed over 400 patients with plasma cell disorders, meaning myeloma and the pre-cancer states of myeloma. What you see is that most of these patients had questions about nutrition. Most felt their oncologist did not address it, and if their oncologist gave them recommendations, the patients did attempt to follow them.

(00:15:06): What was most interesting to me was that patients also actually made changes on their own. Of course, this is what they reported to us in the survey, but you can see that they started eating more of the healthier food and reduced the unhealthy food. Patients are making changes whether the doctor tells them to or not. So, I think these conversations, like the one we're having today, are extremely important to talk about what the changes could be, and how we go about making them.

(00:15:39): Another good website is the American Institute of Cancer Research or the World Cancer Research Fund. They have 10 cancer prevention guidelines, and six out of those 10 are actually related to diet and nutrition.

(00:16:00): They also have a section on their website on foods that fight cancer and foods you should limit. If you look at the section on foods that fight cancer, you will see that all of those foods are fiber-rich plant foods. Foods to limit include sugary processed drinks and meat. This is something that you can go to anytime.

(00:16:25): What do we know about pre-diagnosis dietary patterns and cancer? Now again, these are population studies. I'm not saying that this is for everybody, or this is why each person got cancer, because there can be vegans and vegetarians and plant-based eaters who also get cancer. And it could be the other way. Somebody could be eating a really unhealthy diet and doesn't get cancer. But what these studies try to tell us is what increases our risk for cancer, and what reduces our risk.

(00:16:58): Studies show that patients who have high fiber, plant-based diets have a 15-20% reduced risk of being diagnosed with cancer. There is one study from the UK and one from USA and one from France, showing that people who ate more fiber-rich foods, plant-forward foods, seem to have about a 15-20% reduced risk of cancer, overall. As cancer patients and survivors, I think it's important for us also to think about future risk, so I think this applies to us as well.

(00:17:26): Here I'm showing you some mechanisms on how diet may affect the risk. The fiber in the intestine actually moves the food through the intestine faster, which reduces the time of contact in the intestine. This is actually beneficial in reducing the risk of colon cancer and is also thought to be potentially beneficial for other cancers.

(00:17:55): Then butyrate, is a short-chain fatty acid. The fiber leads to healthier bacteria that make these short-chain fatty acids and reduces inflammation.

(00:18:05): We also have flavonoids or phytochemicals which have anti-cancer, anti-inflammatory effects. And fiber is also very good at maintaining weight, keeping us within the normal body weight , and reducing insulin resistance.

(00:18:27): Some studies that have looked at diet in combination with standard cancer treatment, or alone to prevent a cancer from developing, or to prevent the next cancer from developing. In the treatment setting in combination with therapies, and then in the survivorship setting after we finished the chemotherapy, and now in the maintenance or in the remission setting.

(00:18:53): There is an opportunity in the prevention setting, where we have these pre-cancer states bin myeloma, lymphoma, leukemia. There are genetic alterations that progress over time, telling us that as the disease progresses, there are more genetic changes in the cancer, but there is also a change in the immune function. The immune function gets more and more impaired with time.

(00:19:23): So, one of the studies that we did recently was looking at whether we can help tilt the scale for myeloma development. If we help patients reduce inflammation, have a better diet, improve insulin resistance, can we tilt the scale for myeloma development in patients who have the pre-cancer state of MGUS or smoldering myeloma or myeloma?

(00:19:49): In a clinical trial, overweight patients with MGUS (monoclonal gammopathy of undetermined significance) were given a high-fiber plant-based diet and nutrition coaching. The patients had 8-9% weight loss and overall improvement in their health. In this trial, we had patients who had a BMI or body mass index over 25, so in the category of overweight or obese. They also had the diagnosis of MGUS or monoclonal gammopathy or smoldering myeloma which has a pre-cancerous state. We gave them three months of a plant-based diet, which is a high-fiber diet. We gave them six months of coaching, and we followed them for one year on the study.

(00:20:22): Overall, most of the patients were able to follow it and continue it. Only three patients dropped out, two for medical reasons unrelated to the study, and one patient said they could not continue with the diet. But the rest, 20 patients were able to do this.

(00:20:40): What we saw was that patients' adherence to the diet, when we calculated how much of their diet was unprocessed plant food intake, improved from a baseline of 20% before they went on the study to 90%. It improved even a year later.

(00:20:58): We also saw that patients had an improvement in their weight with a reduction of about 8-9%. We saw their quality of life improve. Even though we were having them make lifestyle changes, it actually helped them have a better quality of life, with less fatigue and less shortness of breath.

(00:21:19): We also surveyed the patients and asked them, "Did you have any improvement in any other symptoms?" The green bars are patients who had improvement in things like cholesterol, hypertension, diabetes, energy, joint pain, and even GI (gastrointestinal) symptoms.

(00:21:39): All patients said they were able to do this diet, and most said they would be happy to do it again. What was nice was we had four patients who were able to actually stop prescription medications because they no longer needed it. One patient was on insulin for diabetes for over 30 years before going on this study, and then after a few months of being on the study was able to stop insulin. That also leads to savings in terms of money when you don't have to take as many prescriptions.

(00:22:15): Then we also looked at whether we were able to bring down the insulin levels, and if their adiponectin/leptin ratio or insulin resistance levels improved. We did see an improvement in insulin levels and an improvement in insulin sensitivity. We know that these things have been associated with cancer progression in different studies, so being able to improve that could potentially be a benefit,.

(00:22:44) By adopting a plant-forward, high-fiber diet, patients were able to increase the biodiversity of their microbiome and decrease inflammation. We also looked at the gut microbiome. Remember we talked about how diversity is a good thing? We were able to show in this study that after they changed their dietary pattern to a higher fiber, plant-forward diet, they were actually able to improve the gut microbiome diversity. You can see from the blue bar to the green bar, this has improved over time.

(00:23:12): It is possible that improving the microbiome improves the immune system enough to slow down the progression of cancer. There was also a reduction in inflammation. So, the C-reactive protein for those that had it elevated, that level did come down. Two patients in this study had their cancer markers, or their pre-cancer state, rising. The blue line shows you before they went on the study. The red line shows you that after they went on the study, the progression of their pre-cancer state to cancer slowed, suggesting that maybe improving weight, improving insulin resistance, improving the microbiome as well as the immune system ... I didn't show you the data on the immune system, but we saw improvements in that too ... could maybe affect the trajectory of the cancer for these patients.

(00:24:00): This is with patient permission. This was one of our patients on the study, before the study, and then after the study. He felt like the study really helped him. He's in his 70s and still feels very much like this helped him live a better life.

(00:24:19): We are now enrolling a much larger study for pre-cancer patients to try to understand not only the effect of diet, but also supplements such as Omega-3 and curcumin.

(00:24:31): The next part I wanted to talk about is patients who are on treatment. Can lifestyle and dietary changes really make a difference? Unfortunately, there is not a lot of data on this. I'll just show you a few small studies that have been done.

(00:24:51): This is one study done in acute lymphoblastic leukemia (ALL). They asked 40 newly diagnosed patients to improve the quality of their diet by following the USDA MyPlate guidelines and Traffic Light. This meant eating healthier foods and reducing unhealthy foods. Then, they compared whether there was a change in their disease before and after compared to a historical control, a group that never made these changes.

(00:25:25): You can see of course that insulin resistance improved. When they compared the rate of complete remission of patients on this study with a historical control, they saw an improvement in remission rates.

(00:25:46):  A diet that does not allow fresh fruits and vegetables, has not been shown to reduce infection, and it may cause additional unwanted weight loss and lower quality of life. Another study that was done in patients undergoing transplant was this Neutro-Diet study. I think the study is interesting and important because often patients who go through transplant are told to avoid fresh fruit and vegetables because of the infection risk. This study shows you why that's not necessary. It was a large, randomized Phase 3 study. They had 222 patients. They randomized them, meaning half of them got a protective diet where they could only eat cooked foods and food that had thick peels that they would peel. The other half got a diet which was basically hospital hygiene standard, but they could eat a salad if it was made and washed and prepared well, and they could eat fresh fruit that didn't have a thick skin.

(00:26:43): What you can see is that infection risk was the same between the two. The number of infections was no different. There was more reduction in weight in those on the protective diet, compared to those that were able to eat the fresh fruits and vegetables.

(00:27:04): Quality of life also may have been a little bit different between these groups and slightly more negative impact with the restrictive diet, suggesting, I think, that it's important for us not to restrict healthy fresh fruits and vegetables, but just make sure we are using caution by not eating food from outside where preparation may be unhygienic.

(00:27:39): A plant-based, high-fiber diet may also be contributing to better outcomes, including remission rates and sustained MRD (minimal residual disease) negativity. What about in the survivorship setting? Can dietary interventions help with that? Can it really prolong the time in remission for patients? We looked at this study, Dr. Lesokhin and me, as a group at Memorial Sloan Kettering. What we looked at were patients on maintenance therapy, lenalidomide maintenance. We looked at their microbiome.  They got myeloma treatment. Then they got a transplant or no transplant, and then they were on maintenance therapy, so after their initial cancer treatment and now on maintenance treatment.

(00:28:20): We collected microbiome through stool samples, and we collected dietary information. You can see that in the teal bar, the patients who had complete remission. They were more likely to have higher stool diversity, healthier bacteria and higher levels of the short-chain fatty acids I talked about.

(00:28:43): Then we surveyed these patients and asked, "What is it that you are eating?" We saw a correlation between healthier sources of protein, such as plant protein and seafood protein, as well as dietary flavonoids which are plant chemicals with anti-cancer and anti-inflammatory effects. These were linked to markers, such as butyrate and sustained MRD negativity. We think that diet may be affecting the microbiome, which I've shown you in multiple studies, and through that effect, potentially long-term control of their cancer. We are now studying this in a number of patients who are getting the diet while they're on maintenance, so it's an interventional study.

(00:29:46): There have been studies in lymphoma, leukemia, and myeloma looking at obesity as well as diabetes. An elevated BMI has been associated, probably, with a slightly worse survival compared to a normal BMI as well as with diabetes. So, I think it's important to think about these factors as something we can work toward that are in our control.

(00:30:21): Diet changes can be made slowly over time and should be individualized to each patient, taking into consideration disease state, symptoms, comorbidities and willingness to make changes. I want to shift gears a little bit to a few tips on how we think about fiber, and how we think about adding some of these recommendations in small ways? It doesn't have to be everything all at once.

(00:30:35): Remember I told you that fiber intake requirement is about 30 grams, on average, 25 for females, and it depends on what age group you fall in. You can look that up online. Look at a Western diet and look at a high-fiber diet. In general, Western diets have very little fiber content.

(00:30:57): This is just an example. I'm not saying this is a perfect meal on either side, but I'm just showing you an example of where fiber comes from. You can see that the Western diet is only getting the fiber from that bag of broccoli and the potato and the white rice and the bread. None of the other foods have fiber. Whereas the high-fiber diet is getting enough from all foods.

(00:31:22): Then you might ask. What about their protein because maybe they're not getting enough protein if they are eating so much fiber. But one thing to remember is that the recommended daily intake is 0.8 grams per kilo. I think if a person is older or if a person has more requirements because they've just gone through cancer treatment or they're losing weight, then maybe a little higher protein intake, 1.2 grams per kilo. If we think about a person who is 60 kilos, and we use that exact same example of the same foods, you can see that even the high-fiber diet is meeting the protein requirements of 72 grams because even oatmeal has protein and so does brown rice and so do lentils and avocados. So, most foods have all three building blocks. It's important to understand when we balance this out, we get enough. We need to plan out any meal, but here is what you see as an example.

(00:32:24): I just want to say, of course we need to individualize it, and since I'm giving the talk to everybody, I cannot guide individual patients, but I think you should think about your disease state? Is it something you feel receptive to hearing about and empowered by or does this feels very overwhelming and you don't want to hear about it. You don't feel it's going to help you?

(00:32:48): Also, whether there are medical issues. Do you have diarrhea, nausea or other things and can only tolerate certain foods, and you just cannot eat the other food? Then you have to focus on what you can eat because that's also important because we don't want significant weight loss unnecessarily.

(00:33:07): Also, think about whether you have any of these other things like diabetes, cardiovascular disease, high cholesterol? How do we reverse these things? There's enough data that lifestyle and dietary changes could improve those outcomes.

(00:33:20): Also, people are different. Some like to make changes overnight, and some like to do it gradually. So, know what's good for you. It's better not to overburden yourself and make all the changes at once if you're not the kind of person who likes that.

(00:33:36): A practical tip to consider is incorporating three servings of whole grains. Remember, carbohydrates are not bad. A lot of people think carbohydrates mean sugar. When it's complex carbohydrates, like whole grains, they are actually healthy and associated with reduced cancer risk. What we don't want are the sugary drinks and refined carbs such as cakes and cookies. Of course, we all enjoy them once in a while, but we don't want that to be a regular part of our meal.

(00:34:10): Fiber should be about at least 25 to 30 grams and we should have 5-6 servings of fruits and vegetable. Prioritize plant sources of protein such as beans, tofu and tempeh.

(00:34:24): Your fiber intake should be 25gms per day. If there's one thing you want to change, and if you have the average U.S. fiber intake of about 10 grams, you'll want to increase this to 25 grams. If you just add one cup of beans to your diet every day, you will go from 10 grams to 25 grams because one cup of beans has 15 grams protein and 15 grams fiber. It's possible to make just a small change like that and improve diet quality. Then we want to prioritize unsaturated fats, as well.

(00:35:00): It's important not to be calorie counting unless you feel that that's beneficial. If people are trying to lose weight with just calorie counting, sometimes that is very restrictive. I think just prioritizing the healthy foods and foods that are lower in calories such as fruits, vegetables and fiber-rich foods can help with that.

(00:35:22): If you need to gain weight, prioritize healthy fats such as nuts and seeds, avocados, olive oil and healthy proteins such as beans and tofu. Even frozen fruits and vegetables are healthy. It doesn't have to be raw salads all the time.

(00:35:41): This is a good example. I just wanted to bring home the point. Okay, you might think, "I'm eating honey toasted pecans. That's healthy." It's not. Look at the food labels if you can understand them. You'll see that this has about 19 grams of carbohydrates. Not a problem, but the problem is that the fiber is only one gram, and all the rest of it is sugar; 18 grams of added sugar.

(00:36:07): When you think about sugars, about four grams of sugar is one teaspoon. The average American takes in 17 teaspoons of sugar per day. Many people are above that 17 teaspoons. I encourage you to think about how many teaspoons you get per day. In this one serving of pecans, which is 18 grams of carbohydrates, you are getting four and a half teaspoons of sugar already. I would encourage you to keep the teaspoons of sugar per day to maybe less than nine or 10 teaspoons. A lot of sugar is in hidden things like cereal and things like that which you wouldn't know about.

(00:36:51): Eating healthy doesn't have to be boring. It doesn't have to impair quality of life or affect it. Often it can be things that can be cooked and it doesn't have to be raw foods and vegetables and salads alone. It could be exactly the same thing you like to eat, just a healthier version of it.

(00:37:10): If you like a hamburger maybe substitute a black bean burger. If you like a curry with meat in it, maybe next time it could be the same curry with tofu in it. Small changes like that can go a long way.

(00:37:24): Here are some goals I just put in case this has inspired you to make some changes. Maybe you could think about one of these that you could start with.  Think about the one that could be feasible for you. Each patient and person are different.

(00:37:44): With that, I'd like to conclude that it's important to focus on cancer not just from the perspective of living longer but living better and longer. By incorporating fitness and nutrition and improving our overall health, we can also improve our quality of life.

(00:38:03): I just wanted to thank the patients who've taken part in these studies we are doing, my mentors, collaborators and also funding sources without which this wouldn't be possible. If you want more information about the work I do, I do post a little bit on social media and you can follow Urvi Shah, MD. I'm happy to answer any questions that come up.

Question and Answer Session

(00:38:34): [Michael Riotto]:   All right. Thank you, Dr. Shah, for that incredible presentation. Much appreciated. We'll now begin the question-and-answer session. The first question, "If I'm on chronic medications like acid reflex, metformin or antibiotics, what does that do to my microbiome, and how can I improve it or help it?"

(00:39:17): [Dr. Urvi Shah]: It's a really good question, and it is a challenge because as you can see, each study is complicated and takes years to do, so if we had to do one study with each medication, it would be hard to do all of them and know exactly what happens. But I can tell you overall for things like antibiotics, there was a study done using mouse models last year. It was published in Nature Communications. What they showed was that fiber supplementation protects from antibiotic-induced gut microbiome dysbiosis in mice. Now that's different than humans, but they are already able to see this, and we already see it in healthy individuals and also in cancer. Those that have better diversity of their microbiome and healthier microbiome have better outcomes. I think maybe with antibiotics, it may be a little harder to achieve that level compared to without, but it's not all in waste; just because you're on antibiotics, you shouldn't even try.

(00:40:18): I think it's important to make these changes, maybe even more so important, but I think it's a good area we need to study much better. In terms of other medications, I have even less data. I think with antibiotics, there is data that some antibiotics affect the microbiome more than others. We are just getting to know a little bit of this, so if your doctor thinks you need antibiotics, I wouldn't just say stop it. I would say continue to do that but think about some of these dietary changes such as fiber-rich foods, fermented foods, things like that in your diet.

(00:40:59): [Michael Riotto]:   All right. Thank you, Dr. Shah. Next question. "If I have frequent bouts of diverticulitis, how can I be able to eat more fiber like corn or nuts which aggravate it?"

(00:41:13): [Dr. Urvi Shah]:  Good question. What I have understood from the GI data is that doctors admit previously that patients with diverticulitis should not eat nuts or seeds because they could get lodged in the diverticulosis, but this is no longer something that they recommend anymore. However, if that is really the case, I think it's still possible to make sure that it's ground or chewed properly so it's not a piece that's there, but the point was that it was thought that these small nuts and seeds could lodge into the diverticula and cause more inflammation, but that has not been proven to be true, so I would actually encourage you to eat more fiber. Another reason is the reason diverticulosis develops for many patients, maybe not all, but there is some data that a diet for long-term, many years and decades without enough fiber leads to periods of constipation. This high pressure from the constipation leads to these outpouches in diverticulosis formation, so a fiber-rich diet actually reduces diverticulosis risk.

(00:42:31): [Michael Riotto]:   All right. Thank you, Dr. Shah. Next question. "I have chronic GvHD. Would a high fiber or plant-based diet help reduce the inflammation?"

(00:42:42): [Dr. Urvi Shah]:  

Great question. I actually realized that I couldn't include these slides in the talk because of time, but there is a study. You might want to look at this, but it was a paper published in Blood from some of my colleagues in 2020. This study looked at the micro-derived short-chain fatty acids, butyrate and propionate, and showed that they are associated with protection from chronic GvHD. They didn't look at diet in this. They only looked at the short-chain fatty acids and said, "You people who have higher levels of these fatty acids have protection from GvHD." What they did show is that yes, more of these good short-chain fatty acids means protection or less GvHD.

(00:43:33): What we do know from the study that I already showed you is that eating a diet that is rich in fiber leads to more of these short-chain fatty acids, and when there are more of these short-chain fatty acids, maybe there is a potential that this could affect chronic GvHD. Nobody has yet ever studied it by providing a diet like that and seeing if we could improve GvHD, but based on the information we have from different studies, I believe that it could potentially help patients. Also, through the immune system, these short-term fatty acids affect the immune system in a positive way which could affect the GvHD in a positive way.

(00:44:17): [Michael Riotto]:  All right, next question. "What is a good source of information on different beneficial probiotics and prebiotics? Where can I find help?"

(00:44:29): [Dr. Urvi Shah]:   It's a good question. Unfortunately, I don't know of a good source. What I will say is that I don't generally recommend that people take a probiotic after transplant or any time in general. A couple of reasons. One is that there are small case reports or a few case reports of patients taking a probiotic and then getting a bloodstream infection because of a strain from the probiotic. I think that risk is higher in somebody post-transplant who is immune compromised. Second reason would be that there was a study done in melanoma, so this is different. This is not myeloma. This is skin cancer. These patients were getting an immune therapy called a checkpoint inhibitor, and they looked at what their diet was like in terms of how much fiber were they taking in. They showed that the patients who had high-fiber diets had the longest time in remission or probably the best progression-free survival compared to those who had a low-fiber diet or a diet high in fiber with taking probiotics, so the probiotics actually seemed to be detrimental in that study instead of being beneficial.

(00:45:55): I think that may be because probiotics cannot have the number and variety of strains that we need and will have a few, so maybe we need to study this better and understand it. We are doing a study through Health Foundation looking at the effect of probiotics on the gut microbiome in smoldering myeloma patients to see if this improves diversity and how patients do. I would say that post-antibiotics if you need it for a short-term to improve symptoms or it's beneficial, directly you're having benefits, then I think it's okay to take for a while, but I wouldn't recommend it to everybody and all the time just because you think it's healthy.

(00:46:40): [Michael Riotto]:   All right. Thank you. Next question. "You mentioned the American Cancer Society. Are there any other resources that you would recommend for nutritional guidance?"

(00:46:51): [Dr. Urvi Shah]:   American Cancer Society is great. I didn't actually mention that one. I mentioned the American Institute of Cancer Research, so you can look up the American Institute of Cancer Research. You can look at the American Cancer Society. In terms of herbs and supplements, MSK or Memorial Sloan Kettering has an app on their site called About Herbs. If you put in the herb or supplement you are thinking of taking, it will give you information on drug interactions and things like that and also potential uses or side effects. I think that's a good source for understanding some of that. Then I post a little bit about this kind of education and information on Instagram, Twitter or social media as well. I think those would be some sources.

(00:47:47): [Michael Riotto]:   Okay. "What are fermented foods exactly, and can you expand on why fermented foods are helpful to you?"

(00:47:55): [Dr. Urvi Shah]:   Sure, so fermented foods are things like sauerkraut, kombucha, kimchi, yogurt. Any food that has been cultured or fermented overnight or for a long period of time develops increased bacteria that improve the quality of that food. With that, mostly these bacteria are also live in the food, so when we eat these foods, we get some of these bacteria into our gut that have anti-inflammatory effect, so you can see a reduction in inflammation.

(00:48:49): [Michael Riotto]:   Okay, thank you. This one is an interesting one, especially for me. "Does physical fitness and daily exercise improve your gut biome and improve digestion and your uptake of nutrients?"

(00:49:03): [Dr. Urvi Shah]:   I love that question because I actually came across a study just last week looking at this. That study, again, it's not an interventional study, but what they looked at is thousands of people. They looked at their diet and their lifestyle and other factors. Then they associated it with microbiome diversity. They showed all of these dietary things that I already talked about, but they also showed that increased physical activity was associated with increased diversity. I think it helps, and I think, if possible, depending on what part of your cancer treatment you are in. I would strongly recommend doing some of it, even if it's just a walk for 15 minutes a day. Even if you're not able to get out of bed but just moving in bed or things like that, so maybe small goals that we can set for ourselves. Each person is different, so we have to decide on a day-to-day basis what's possible, but I think these things help.

(00:50:15): [Michael Riotto]:   Okay, thank you. Next question. "How can we eat a plant-based diet when so much of us are protein and calorie deficient because we're grossly underweight? How much fat is healthy, et cetera? Can you comment about that?"

(00:50:27): [Dr. Urvi Shah]:   A great question and a couple of things. One is when I talk about a plant-based diet, I think every person needs to decide what that percentage looks like for themselves. What I'm trying to say is it's important to get a majority of your calories or at least 30 grams of fiber in your diet. If you feel like you're not able to do that fully, and there are certain amounts of non-plant-based foods that you are going to eat, I think that is okay, but it's just a matter of the percentage.

(00:51:08): I think that sometimes people will think when I'm talking about plant based, I'm saying everybody needs to be vegan and vegetarian but remember, diet quality is more important than these labels we give it. Somebody can be vegan or vegetarian and eat Oreo cookies and French fries which are plant-based, and that is not healthy. That could be a junk food eater, and that's not a healthy diet. Whereas somebody could be an omnivore where they're eating meat a little bit, but they're mostly getting enough fiber from their diet, and that's probably healthier. I think a vegan diet can be extremely healthy if it is done right or planned well. It all depends on how you are thinking about it. I think it's important to make the changes gradually.

(00:51:54): That's one thing, and the second thing is a plant-based diet, because they are high in fiber, they tend to be lower in calorie density. Meaning that for the same amount of food you eat, you might be getting less calories unless you are eating things like nuts, seeds, and cooked food. If you eat a cup of spinach and a salad, you're really not getting much because it takes time to chew, and it's not a lot, but if you really cook that spinach, you will probably eat three cups of spinach without knowing it because once you've cooked the spinach, it becomes much easier to eat.

(00:52:31): Same thing with smoothies, so if your goal is to gain weight, think about how can we get more calories in? It's all a matter of just how we can eat more. What you can do is make smoothies which are healthy with a lot of fruits, vegetables, nuts, seeds, things like that. You could eat a lot more cooked foods than salads because you'll automatically eat more calories that way. You could be eating more frequently in terms of every few hours. That way you're getting enough calories. When you're snacking, think about things like nuts which are again rich in calories.

(00:53:10): Yes, in general, if you look at the same foods, plant foods have less calories than animal foods, which is why patients or people more likely stay within a normal weight if they're eating more plant foods. I think the opposite is where you're worried about losing weight, try to ensure you're getting enough calories. A big mistake people make when they suddenly go plant-based is they're not used to eating that much, so they just eat the same amount in terms of quantity, and then they're losing weight. If you want to gain weight, you probably just need to eat more in terms of quantity because plant foods, like I said, are lower in calories, so you need to eat much more. Think about beans, beans are a great source, so maybe eating bowls of things that are cooked with things like that.

(00:54:01): [Michael Riotto]:   All right. Thank you, Dr. Shah. Next question is, "How can I improve chronic anemia or low iron with my diet without eating red meat? Can you offer some suggestions on what types of food that I can do that?"

(00:54:14): [Dr. Urvi Shah]:  

Sure, so there are two types of iron. There is heme iron and non-heme iron. Heme iron comes from animal food, so what we have in our blood is also heme iron. What beef, pork all of that will have is heme iron and chicken. What plants have is non-heme iron, but that is still a good source of iron. There is some data to say that actually the non-heme iron is less inflammatory than the heme iron, so it will be a better source of iron in some ways. It may be a little harder to absorb in terms of quantity, but when you do get that iron, it is a less inflammatory kind of iron. Foods that are rich in iron that are plant-based are leafy greens, beans, things like that.  If you just Google plant-based sources of iron or plant-based diet iron sources, you will find foods that are rich in that. Then you can think about adding them daily or regularly into your diet.

(00:55:25): Unfortunately, I think that also when we have something like a blood cancer, there is also the possibility sometimes that the hemoglobin is low. It may not be due to an iron deficiency, but a lot of people assume that because they have anemia they have iron deficiency. That may not be the case and the anemia may be from the chemotherapy or the actual blood cancer or from another deficiency. So, I think that just because somebody has anemia doesn't mean that they need to eat red meat or they need iron. I think it's important for us to get your levels checked. If the iron is really that low, then it may be worth just taking an iron supplement to get the levels up and then trying to maintain it by eating healthy foods that are rich in iron. If it is not low, then you have more time, and you could just eat iron-rich foods like I talked about.

(00:56:23): [Michael Riotto]: Okay. Here's a combination question. "On your chart where you did the Western versus high-fiber diet chart, if you're post-chemo and transplant and you have bone density issues, can the chart be modified to include more calcium intake and/or do you recommend calcium supplement?"

(00:56:45): [Dr. Urvi Shah]:   It's a great question, and it's one that actually has gotten a lot of recent attention. The challenge with calcium supplements is we assume okay, bones have calcium, so if we eat more calcium, we're going to have stronger bones. This has been drilled into all of us from the time we're young in our youth, but there's a very good paper in the New England Journal of Medicine by Walter Willett, who's a top nutritional scientist. The title is Milk and Health. If you look at that paper and the evidence around calcium supplementation and bone health, there isn't data to actually show that calcium supplements improve bone density. There is some data also that calcium supplements may increase cardiovascular disease because they deposit into the blood vessels, so I would not recommend very high doses of calcium supplements. If you do take a supplement, it should be something about 500 or less per time that you take it, so if you're taking 1,000 or 1,500 grams, divide it into doses, not just one dose of 1,500 because otherwise, you're going to have this deposition issue. In terms of bone health, like I said, there is no data showing that actually increasing calcium supplements was associated with greater bone density.

(00:58:24): What I think is also very important to remember is that bone health comes from improved diet quality, so eating good sources of protein, healthier sources including the calcium, the Vitamin D, Vitamin K and all of these things together, and it's not just one thing. Also, physical activity and resistance training is very important for bone health. Another thing is calcium is not going to be absorbed if you don't have enough Vitamin D, so even if you're going to take calcium supplements, but your Vitamin D levels are extremely low, there is no point in taking it. So, I think it's important to make sure that your Vitamin D levels are within the normal range, maybe somewhere between 20 or 30 to 50 so that you can absorb the calcium that you are taking in your diet and if you end up on a supplement, too.

(00:59:24): [Michael Riotto]:   Okay, Dr. Shah, one last question. "How can I get enough high fiber when I have chronic diarrhea from my lenalidomide and other chemotherapy treatments?"

(00:59:36): [Dr. Urvi Shah]:  

That's a good question, and I think the gut adjusts over time. I think that one is for lenalidomide and diarrhea, there is some thought that maybe high fatty foods actually worsen the diarrhea, so high fiber foods are generally not fatty foods, and they might actually help with the diarrhea, not worsen it. Now we are studying this to understand the effects in our study, and hopefully I'll have more data for you in a few years, but I think you can make slow changes. I don't know how many grams of fiber you are eating now, but suppose it's 5 or 10. Then maybe you add a small amount like maybe a quarter cup of beans a day, or maybe you add one fruit per day or something and see how your gut handles it because also a microbiome needs to change to be able to digest these new foods that we're eating and get used to it, so we need to do it gradually and slowly and see if that can help you handle it. That could be one way.

(01:00:43): [Michael Riotto]:   Okay. We are almost out of time. On behalf of BMT InfoNet and our partners, I'd like to thank Dr. Shah for her very helpful presentation. Thank you, the audience, for your excellent questions. A short reminder that there's another workshop on Microbiome in GvHD this coming Thursday on this symposium. Please contact BMT InfoNet if we can help you in any other way. Enjoy the rest of the symposium and have a great afternoon and evening. Thank you very much.