Your Gut is the Gateway to Good Health: Understanding Your Microbiome

Transcription:

[00:00] Moderator: It is now my great pleasure to introduce our speaker today, Dr. Christopher Damman.

Dr. Damman is a board-certified gastroenterologist at the Digestive Health Center at the University of Washington Medical Center and an Associate Professor of Gastroenterology and Medicine at the University of Washington. He previously led the Food and Microbiome Initiative at Bill & Melinda Gates Foundation. 

Dr. Damman is also editor-in-chief of Gut Bites MD, a website that features the latest research on the relationship between the gut microbiome, metabolism, immunity, the mind, and it's all presented in easy-to-understand language. The site also features Smart Bites, a science-based nutrition app designed to help simplify healthy food choices.

Please all join me in welcoming Dr. Damman.

[00:52] Dr. Damman: Thanks, Penina.

Gosh, what an honor to be part of this mission. And thank you so much to the organizers for the invitation to speak today.

Reporting from Seattle, super happy to talk about a topic that's really near and dear to my heart. It's a topic I'm quite passionate about.

It's the intersection of food, microbiome, and health, and it begs the question, why is a gastroenterologist talking about nutrition? Truth be told, in medical school, we actually received very, very little training formally on nutrition. I can quite literally count the number of lectures on my fingers and toes, maybe even just fingers, and it really wasn't until my time at the Gates Foundation that my mind was opened to the possibility of the power of nutrition in medicine, both in treating disease, but even more powerfully in preventing disease.

In traveling the world, meeting with children and mothers and fathers in Africa and Asia, treating malnutrition, it became very clear to me that many of the approaches that we were taking in treating disease there could be used in treating disease right back home. And we were taking a very microbiome-focused approach and nutrition-focused approach.

[02:18] So, that launched a second stage in my career, and that was really how nutrition can impact chronic disease, not just non-nutrition diseases that we struggle with here at home.

That is the topic of the presentation today. The gut is the gateway to health and nutrition in your microbiome.

And so just some disclosures. I consult for different food companies. These are companies that are developing next-generation products like Oobli and Supergut and BCD Biosciences with some of the key things that have been removed from foods restored.

 I'll begin with this curious question. Is a calorie a calorie? And is nutrition as simple as an accounting practice? Calories in, calories out.

[03:16] As I used to tell my daughters when they used to ask me, Dad, what do you do for a job? I would explain to them, well, I help people with their gut. And the gut is what helps them digest food. And I'd put things in simple terms like the food goes in, the food comes out. And yes, that is true.

We are, in some ways, very complicated tubes with a mouth and the other end. But there's a lot that happens to that nutrition as it passes through our gut, and it's not just the nutrients, not just the calories and the vitamins and minerals.

There's other elements to that food that's incredibly important, the bioactives, and it's those bioactives that we've missed. Those bioactives that are relevant to the trillions of organisms, the little microbes that live in our gut, the microbiome, and their brethren, the mitochondria that live within each and every one of our cells.

Mitochondria are actually anciently evolved from bacteria, amazingly. They're the powerhouses of our cell. They're what help translate the nutrition into useful energy that our cells can use.

[04:37] Well, these bioactives are incredibly important as instructions for how to do that. This is really a missing part of our nutrition story, so then lastly, I'll talk about some of the approaches that we're taking in order to embrace these new lessons in nutrition, functional foods, and how smart tech can help us measure whether food is quality or healthy or not.

[05:05] Well, let's start first with the problem, and this is a big problem, and it's a mounting problem. Some ways, it's an epidemic.

The epidemic of obesity, diabetes, and chronic disease at large. These are some of the outdated statistics from 2017. Statistics are even more remarkable now.

But you can see three quarters of people in the United States as of 2017 are either overweight or obese, and 45% either have prediabetes or diabetes. It's quite staggering. It's higher than that now.

This has led to a drop in life expectancy. We can see here in the United States, there are these inflection points in the red line relative to the average of other countries, which is in the dark gray line.

Inflection point that seems to happen around 1982. Another inflection point, maybe around 2008, and then a very clear inflection point when COVID hit.

What's remarkable is there's a similar inflection point, but not as deep. And there's a relatively quick rebound in other countries. So there's something very different about the baseline health in the United States.

[06:31] Now, what's contributing to that life expectancy and increase in death? This is a chart from the Journal of the American Medical Association, again, a little bit outdated, 2020, and it basically breaks down the causes of death across all the different diseases. What's remarkable looking at this is most of these diseases you can trace pretty immediately back to nutrition. For example, heart disease, cancer, even stroke, Alzheimer's disease, certainly diabetes.

By some estimates, upwards of 50% of disease is attributable to nutrition, maybe more, and if we look at what maybe caused this inflection point, which occurred sometime, you know, between 1970 and 1980, an increase pretty dramatic in chronic disease. This predates the death inflection point in the 80s.

[07:31] But what is it that caused this? And this inflection point hasn't been being seen across the world. There are parts of the world, pockets within the world, where people live very healthily until senior years. You know, parts of the world where disproportionately people live to 100 plus years.

These are the so-called blue zones, popularized by National Geographic; certain parts of the world where people do disproportionately live longer. So, places like Nicoya Peninsula in Costa Rica, in the Mediterranean, are Sardinia, Italy, and Ikaria, Greece, Okinawa, Japan, and Loma Linda, California, of all places. It's a pocket of Seventh-day Adventists and population that eats largely vegetarian.

[08:34] Dan Buettner is the National Geographic correspondent that popularized the blue zones, and he identified nine key factors that are contributing as common denominators in lifestyle across these different populations.

Now, nine factors is a lot to keep track of, and I like to keep things simple. So, I've condensed these into four different factors. social factors, movement or exercise, mindfulness, and diet.

[09:04] I call these the four pillars or the four Ms. It's a rebranding of pillars of health that probably seen in different contexts, and you'll see that these four Ms stands on a firm base of community. Those are our relationships with people, community at large that give many of us meaning.

[09:31] Now, the four Ms are movements, mind, molecules, and microbes.

Movement would be exercise, and the flip side would be being sedentary, couch potato, watching screens too much, for example.

Mind would be being mindful, maybe meditating or various practices that develop the mind sleep. Flip side would be insomnia and stress.

Molecules that would be eating healthy foods. Flip side would be ingesting toxins, additives.

And then lastly, microbes. Our microbiome would be the positive side of microbes. And then certainly pathogens would be the negative.

[10:23] And I'd like to focus on the diet. By some estimates, nutrition, the molecules, contributes as much as 40% to health and probably have a disproportionate impact.

There are tons of studies now looking at the Mediterranean diet, and this is one of the best study diets and its contribution to health across all dimensions and preventing various diseases and promoting neurocognitive health, preventing cancer even. 

Now there's mounting studies around these so-called ultra-processed foods. These are the foods that come in flashy packages in the grocery store. And these foods have been increasingly connected in epidemiological studies to poor health, whether that be metabolic health, cancer, longevity, the list is growing there.

These are just some of the studies linking ultra-processed foods to, at the top here, diabetes, showing a 10% increase in ultra-processed foods leads to a 15% higher risk of type 2 diabetes. And also in obesity, as households have relative availability of ultra-processed foods of increasing percentage across different countries, the prevalence of obesity increases as well. And then lastly, all-cause mortality. As ultra-processed food consumption and servings per day increases, all-cause mortality has been shown to increase.

[12:11] Now, this is epidemiological studies, meaning it's correlation, it's not causation.

But there are now some key studies that have actually looked at interventional trials where processed foods versus non-processed foods have been given to the very same individual in a crossover trial. So, they started with a diet of processed foods and then switched over to ultra-processed foods.

This is a landmark study that was done by Kevin Hall and colleagues at the National Institutes of Health (NIH), and they had about actually 20 subjects that were living at the facility for two weeks straight. So really well-controlled study. And they were given all their foods and had everything that you could imagine measured over the course of those two weeks.

[13:10] These two different diets, the ultra-processed and the minimally processed, were controlled as best they could for things like the number of calories, the types of nutrients that were present there.

They looked at the A, energy intake, so how many calories were consumed on these two different diets when people were left to eat as much as they really wanted. It's called ad libitum.

Then also what their body weight did even over the course of just two weeks. The results are quite stunning. The energy intake and the ultra-processed food consumption was significantly higher. You can see here on the top graph on the right. And not only that, but body weight increased just over two weeks. Now, a lot of this body weight was probably water weight due to the sodium, but the energy intake difference stands. And over time, it is possible that weight would also reflect not just water weights, but fat mass as well.

[14:18] So this begs the question, what are ultra-processed foods? ultra-processed foods is a label that can be traced to a paper out of Brazil that first coined the term the NOVA classification, and it broke foods down into four different groups.

The first group is what we would consider as whole foods or minimally processed foods. And you can see a picture in the orange on the left here. Things like fish and meat and fruits and vegetables, nuts and seeds, milk. Then we get into group two. These are processed foods, but not ultra-processed foods. So things like olive oil or honey or salt or butter. Group three would be even more processed foods, things like bread, canned foods, cheese, wine. And then lastly are these ultra-processed foods, group four. Foods that have added sugars, added components.

They're almost like frankenfoods where you take a fat, carbohydrates, and a protein, and you kind of put it all together as powders and create these foods.

But what are ultra-processed foods really? And let's dive a little bit deeper. And so one way of thinking about ultra-processed foods is they're really just concentrations of the things that we already get a lot of and probably too much of and shouldn't be eating as much of.

Michael Moss has a wonderful book titled Salt, Sugar, Fat, and this encapsulates this idea. We're just eating too much of sugar, salt, fat, and additives.

[16:25] That's one possibility. Another idea around ultra-processed foods is it's not just that we're getting too much of these things, but in processing the foods, turning them into the powders, creating these frankenfoods, we are creating hyperpalatable foods.

So, we're creating very specific combinations of these components of the sugar, the salt and the fat. And these very specific combinations actually are triggering our reward system in the brain. And there's a number of studies now that show these ultra-processed foods actually do have some addictive-like properties.

[17:07] And then there's this idea, well, maybe it's more about we take these whole foods, which are composed of cells, just like every plant is or every living being is, and we grind it up. In grinding it up, you're basically getting rid of that structure. You're disrupting the matrix, and you can see up on the top here, kind of the blue picture, this is a grain that's been ground up into flour. And you can see these tiny little particles.

Those particles never make their way down into the lower GI tract. They don't make their way to the colon where the microbes are. Microbes end up missing out.

[17:52] But in an unprocessed food, the cell structure is intact, and there's less digestion that happens in the upper gut, and more of that food actually makes it down to the colon. Less gets absorbed into the body, and so the relative number of calories that are available to you are less.

All right, well, that all seems very plausible.

[18:19] Now here's a fourth idea I'd like to introduce. We've had the added, we've had the hyperpalatability, we've had the disrupted matrix, but there's this concept that when we process foods, we're taking things out as well. We're not just concentrating for salt, sugar, and fat, but we're removing these things which traditionally haven't been considered nutrients.

But as it turns out, are really important, as alluded to in the very beginning, as instructions for how to process the nutrients. These are things like fibers and phytonutrients in the bioactives, bioactive fats. Proteins actually have bioactive components as well.

[18:56] So I've labeled these, the four Fs of food. One of them is a little bit of a cheat because it's phytonutrients. It's a phonetic F. So maybe it's better to call them the phonetic Fs of food.

[19:08] And that's fibers, phytonutrients, bioactive fats, and ferments.

So, fibers, we've heard so much about fibers. and that we need to increase our fiber. What we hear less about is there's an incredible diversity of fibers. And so just increasing one fiber is likely not sufficient, but increasing the diversity of fibers is really important.

You see pictures of the allium family, onions and shallots, where fructans type of fiber are particularly high. And then another grouping underneath where resistant starch is high. It's things like green bananas and oats.

Phytonutrients, that's a broader term for polyphenols. These are the components in food that give them their color. You'll see pretty bright colored foods on the left here, turmeric and grapes. And these are just small molecules. They are used by the plant to deal with adversity and stress, whether that comes from drought or from the sun. But within us, really important for informing how to process the nutrients that are coming in, informing our microbiome and our mitochondria, the powerhouses of the cell.

[20:32] Bioactive fats would be things like omega-3s and then ferments. So it's not just the bacteria that are present in ferments, but the things that those bacteria are making that are incredibly important. And so, you know, yogurt and kefir and sauerkraut and kimchi.

What's super interesting is if you look across the blue zones, and you can see I've kind of grouped them into Japan and Nicoya Peninsula, Loma Linda, and then the Mediterranean countries, there are common denominators across each of these four Fs, the fibers, polyphenols, fats, and ferments, that are found in all these diets.

For fiber, you'd see beans and potatoes and whole grains. Phenols, you'd see teas and coffee, cacao, turmeric, herbs, spices, fruits and vegetables. For the fats, you see olives and avocados, nuts, seeds, fish, free-range meats. And for ferments, you see vinegars and drinks, fermented vegetables, beans and dairy. So, the common denominator is there.

The cuisines are different, but these key elements of the food are similar. And the key elements can actually be grouped together in terms of their four Fs.

[21:57] All right. Some have called this the dark matter of nutrition and begs the question, well, how did we miss these things? I trace my time back to the foundation and working in low and middle income countries where things like scurvy and kwashiorkor and pellagra, were still present. These are vitamin D deficiency, protein deficiency, and B3 deficiency.

Back at the turn of the century, we were very good at finding individual nutrients that correlated with individual diseases. You take that nutrient away, you get the disease, you add the nutrient back, and you cure the disease. It was that simple. That is the beauty of the reductionist approach to medicine, to nutrition.

[22:47] Similarly, in infectious disease, there's so-called Koch's postulates, where it's a single bacteria that causes a single disease. You take that bacteria, you give it to somebody who causes disease, you can isolate it from that person that has the disease, and then you can give it to another person. That is the reductionist approach to medicine. That is what modern medicine has been very good at.

What it's been less good at is identifying systems and interacting parts. And the microbiome and these instructions, the fibers and polyphenols work differently.

It's not a one-to-one ratio. You can't say this particular fiber is linked to this disease, but there's a bunch of fibers and there's a bunch of different bacteria that are translating those fibers into key molecules that are important for disease. So this is one of the reasons, maybe not the only one, we've missed these key signals, But now we're keen to understand them.

[23:50] Coming back to this inflection point, it's not just the things that we've added, as I've said, simple carbohydrates, additives, fats, sodium, but it's these things that are missing truly. And it's the relationship between these or the ratios between these that might be particularly important to health.

This is what I call the microbiome mitochondria axis. And it basically breaks down in a snapshot how all this works.

So let me walk you through this. So, on the left here is food. Food has its nutrients, but it also has these bioactive factors, the 4Fs. Those 4Fs are very important to the microbiome, both to support a healthy microbiome, that community of trillions of organisms that lives within our gut.

[24:45] The microbiome is also transforming those factors into other bioactive molecules that are more readily absorbed into the body. And those impact then the powerhouses in our cells, the mitochondria, the brethren of the little microbes within our guts, the evolutionary related structures that power our cells.

When this breaks down when you have unhealthy food that's missing these factors it depletes the microbiome you lead to dysfunctional mitochondria and that dysfunctional mitochondria leads to disease now this is a very simple way of looking at disease but I think it's a powerful lens certainly not the only approach but it's a very important element to how food is linked to disease and you can see underneath here I've listed just about every disease.

For each of these diseases within the literature, there's very deep research that's making these connections between food, microbiome, mitochondria, and metabolic disease, immune disease, frailty, neurological disease, and cardiovascular disease and cancer.

[25:53] So, I've talked about how these bioactives, these four Fs of food are transformed by the microbiome into bioactive signals that then get absorbed into our body.

Let's trace some of these as examples. So, fiber. Fiber is transformed by a microbiome into many different things, but one of those things is butyrate.

Butyrate is called a short-chain fatty acid. It's basically like a fat, but super tiny. And this is a busy slide, but it's just to say this transformation happens. There's more than just butyrate, there's acetate, there's propionate, and other things too. All of these are contributing to the health of our different cells in our body, which you can see across the bottom.

[26:46] Now, what's interesting, butyrate also helps stimulate GLP-1. That's a completely different story but this is how GLP-1 which is the analog for the actual ingredient in Wegovy and Ozempic which are these breakthrough weight loss drugs there's an analogous system that happens within our gut but that asides butyrate itself directly is impacting all these different organs and cells okay that's all fine and good but what does this mean for health 

So, this is one study an interesting study in a pediatric population that basically took 54 patients that were obese broke them into two different groups one group that got butyrate and then another group that got placebo, so just a sugar pill. And over the course of six months, there is a pretty dramatic difference in the weight loss between these two groups.

[27:51] Now, both groups were also counseled around traditional weight loss methods. And the only difference between the groups was really just whether one got the butyrate supplement or not.

So yeah, really intriguing, interesting signal here around butyrate and pediatric obesity. Just one clinical intervention trial that showed some positive results with one of these bioactives produced by the microbiome from fiber.

[28:24] But, what about the other Fs? In this case, a phonetic F, phenols. These are the compounds that give plants their color, largely. So there's one polyphenol called ellagic acid.

Again, this is a busy slide, but I'll break it down for you.

[28:43] Ellagic acid is a polyphenol present in berries and pomegranates and walnuts and some other nuts too. And when it makes its way down into the colon, it's converted into Urolithin A. Again, Urolithin A is one of these molecules that has dramatic effects across the body. It's impacting the health of mitochondria and how rapidly they're turned over within the cells and how healthy the mitochondria are.

[29:10] All right, so let's look at a study that investigates this bioactive Urolithin A. Now, this is an adult population, and it was 16 men, 50 women, 60 participants total that were given the placebo, and then the other half were given Urolithin A. This was done for four months. And then they were asked to essentially walk six miles and it measured how far they went in six miles.

The primary outcome study was not sensitive for it. There was not a significant difference, but was interesting. And it looks like this slide is missing this part. So, my apologies, but what they did find is the strength of muscl. One of the muscles in the hands and one of the muscles in the legs, a tibialis anterior, were quite remarkably stronger in the group that received the Urolithin A versus the placebo. So, a negative study, but still intriguing results around muscle strength, if not ability to walk six miles.

[30:28] All right, and then so now the last example, looking at the third phonetic F, and that's fats.

Fat, linoleic acid is one type of fat, and it is converted to something called conjugated linoleic acid, CLA, by the microbiome, and this again has pleiotropic effects on the body.

This compound has been studied much longer, and these are forest plots for weight, body, and fat. A forest plot is basically just a way of looking at many studies at once. So, each of these horizontal lines represents a study. And whether that line crosses that center line, that determines whether it's significant.

[31:14] So you put all these studies together, and then you get the diamond at the bottom. If that diamond crosses that center line, then it's not significant, but if it does not cross the center line, then there is basically a positive signal there. Therefore, body fat and insulin resistance, there's both positive signals.

[31:41] Here we are now back at the microbiome mitochondria axis, and you have healthy foods, you create a diverse microbiome, you have functional mitochondria, and metabolic health. So, the flip side of disease, if we have the full complement of these Fs.

And back to this model of changes in disease in our population, the question is, what do we do at this point now in the green arrow?

And if we look to the advice of one of the fathers of modern medicine, Hippocrates, he said, let food be thy medicine, might add to that, and its 4Fs, which would be fibers, phenols, fats, bioactives, and ferments.

[32:36] We talked about essentially how we missed this already, and, you know, you have the deficiency model, the reductionist model on the left here, what modern medicine is good at. On the right, these systems, complexity, diversity, redundancy, and this is where nutrition science is moving and studying.

[32:59] So the question is, can we add these things back? Yes, we should eat all foods. But can we take some of these things that have been removed in processing and turn them into useful products?

This is a model for how that might be done. On the left, you have whole foods, the healthy lifestyle slog. On the right, you have this sort of magic bullet dream. Single pill is going to fix everything. Some might say that's GLP-1s, although there's side effects associated with those, and it's not a perfect solution for sure.

In the middle here, there's this idea of functional nutrition, where you're adding some of these things back to processed foods. You're making processed foods incrementally better, things like the fibers and the phytonutrients, the healthy fats.

[33:55] Kind of a pragmatic approach recognizing that eating whole foods for everyone is not possible in our busy lifestyles and truth be told it can be quite expensive to eat fresh whole foods as well. This is the heart of my research; I'm working on a way of measuring the quality or the balance of foods, not just the concentrated bad things, but the missing good things, and coming up with an algorithm for doing that. So, you can take the really complicated nutrition facts panels and effortlessly transform that into a zero to 100 score.

There's subscores to this as well for protein and carbohydrates, but there's an overall score that the algorithm will produce. And this helps you look at the relative health of, for example, different raisin brands or different snack bars to choose the one that is going to be a higher quality or better balanced food.

[35:01] There's other algorithms that have done this. You can see NutriScore, even NOVA classification, which was the original definition of Whole Foods, and HealthStar and Food Compass. This is just how Nutrient Consume Score, which is a score I've been working on, measures compared to those in terms of p-values and significance.

NCS on the left and the other systems on the right, NCS having a pretty big jump in significance and how it associates with the healthiest foods and the least healthy foods correlating with percent obesity in the NHANES cohort.

This is theory of change, where in the future, I see continued emphasis on whole foods, but introducing these functional foods, which are incrementally better, how certain mobile technologies can help us determine which of those foods might be healthier. So, it's not just purely based on marketing.

[36:05] There will always be early adopters. There will be these early better-for-you foods, and much like power locks in cars of the 1970s and 80s, they will become the standard, is the hope, as there's public adoption and greater use of these foods; prices will come down. This ideally can lead to a transformation in health.

So, this is the overall model here where we've had these inflection points of imbalanced foods leading to an increase in disease. And our future, ideally, will be recognizing, gosh. We need to add these things back, recreate balance in our food, not just focus on avoiding carbs and fats and now increasing protein, but actually it's the full package. How do we measure the balance of that full package?

[37:06] So hope for the future. And back to where we started, nutrition is as simple as I used to tell my daughters. The food goes in and the poop comes out.