The Leading Voices in Food
E209: Microbiome Research and a Vision of Precision Medicine
The microbiome is fascinating and how diet affects it is something we all want to know. The work of today’s guest, Dr. Abigail Johnson, tells us a lot. She’s on the faculty and the School of Public Health at the University of Minnesota and is an expert on diet and the microbiome and their impact on health and disease.
Abigail Johnson is an assistant professor in the Division of Epidemiology & Community Health at the University of Minnesota School of Public Health. She is the Associate Director of the Nutrition Coordinating Center there. Her research explores the relationships between diet and the human gut microbiome in health and disease using novel computational methods for dietary data. She focuses on 1) analysis of diet and microbiome after dietary interventions, 2) methods development for dietary data analysis and visualization, and 3) understanding the interactions between foods, microbes, and fungi during different stages of development. She is interested in exploring how diet and the microbiome interact to influence chronic diseases including prediabetes, diabetes, and cancer.
So there’s an awful lot of interest in your work but let’s start with kind of a broad question. So there’s much talk in the news and obviously in the scientific world about the microbiome and one fundamental question is this, how much should we pay attention? How important is this all? Is it important enough for dietary recommendations to be modified? For policies to be affected? Give us the big picture from your perspective.
I think it’s really important. I wouldn’t be studying it if I didn’t think it was important. I think that there’s so much that we don’t know about what all of the microbes that are in and on our bodies are doing that impacts our health. There’s just so much that we don’t know at the moment that I think it’s very important that we continue to study it. From a nutrition perspective which is where I spend my time, I think that there is a lot of potential that we could eventually understand how we can use food to change the microbiome. From that perspective, we might get to the point that we can make recommendations that affect national nutritional guidance like the Dietary Guidelines for Americans, for example. I don’t know that we are there yet, but I do think that we are learning more and more with every passing year that gets us closer to being able to say some things definitively.
That’s consistent with the way I’ve been seeing it and it’s nice to hear it affirmed by an expert. So, your research on diet and health uses, and now I’m quoting from your website, “novel computational methods,” can you explain what the methods might involve and how they improve the assessment of what people eat?
I did my postdoc with Dr. Dan Knights here at the University of Minnesota. I joined his lab as a nutrition scientist with very minimal background in statistics but an interest in computer science. I told him when I joined his lab that I wanted to learn to code. I immersed myself in this world of people doing bioinformatics and using computer science and bioinformatics to answer questions about the microbiome. What I noticed while I was in my postdoc was that a lot of the questions, statistical problems, and computational problems that exist in the microbiome space where people are coming up with unique ways to solve those problems mathematically are really analogous to issues that the field of nutrition has also been grappling with – sort of since its existence. When I say novel computational methods, I’m often referring to really stealing methods from the microbiome space and applying them to nutritional data. Like microbiome data, nutritional data have these sort of strange qualities that make them interesting from a mathematical standpoint. To be more specific, I’ve developed an approach that uses trees. In microbiome space we use phylogenetic trees to share information in statistical approaches to understand how communities are different. For example if we both haves E. coli species and they’re actually different species, we can still use the fact that they’re both E. Coli to understand the similarities between our different microbiome compositions. In the nutrition world, we think about foods as they fit under umbrellas of food groups. I’ve basically stolen the method of using trees in the microbiome and applied that to nutrition. That’s kind of the novel computational approach that I take when trying to understand diet and dietary patterns.
That sounds like a real advance. What are some of the highlights of your work on microbiome in the diet?
In my work, I’ve been able to find signatures. We can pick up the signature of what you ate in your microbiome and the way your microbiome changes. We can link that back to your diet on a daily timescale. So if we have information about what you ate in the three days prior to providing a microbiome sample, then we can make some prediction about how your microbiome is going to change the next time we sample you. So not really good at predicting how it’s going to change yet, but at least if we have the data, we can link you up with your diet and understand that the changes that happen in your diet show up in your gut microbiome. Also, being able to identify to some level of specificity, how much of the variation in microbiome, be it across populations or within an individual, can be connected back to differences in dietary intake.
You know that work that you’re doing on using the microbiome as a measure of what people eat is a real advance, isn’t it? For so many years the nutrition field has relied on people’s reports of what they eat to make judgements about the relationship between diet and health and even individual dietary recommendations. But it’s hard for people to be accurate about that. Having something like this could be a real breakthrough, couldn’t it?
Yes, I’m really hopeful. We’re not there yet, but in my dream we would be able to take a fecal sample and know something about what you ate and that could help us avoid having to do dietary recalls, for example. We can get past this fact that people can’t remember what they ate. That’s sort of the dream where I see methods development going in the future.
One of the titles of one of your papers really fascinated me and the title is this “US Immigration Westernizes the Human Gut Microbiome.” That’s really fascinating. Can you tell us more about that study?
Yes, so this was a study that took place in Dan Knights Lab at the University of Minnesota. It was led by Pajau Vangay, and she’s an incredible computational scientist and food scientist. She is also a second generation Hmong immigrant to the United States. So I was lucky enough to support her work. She was the one who led this study and basically the study to evaluate microbiome samples from groups of Hmong and Quran immigrants (there happens to be a large Hmong and Quran immigrant population in the Twin Cities in Minnesota). They asked could we collect microbiome samples from these groups of people? Many of them came to the US during the Vietnam War. So there is a time course to look at. We’ve got first generation and second generation immigrants. They collected samples from first generation, second generation immigrants. Pajau went and visited a refugee camp and was able to get samples from people who were still living in Thailand. And, a small group of people who actually moved to Minnesota during the time that she was collecting data. She got this rich data set as well as information about diet from all of these people who participated in this study. We were able to see a trend toward the microbiome changing from the Thai sort of looking microbiome to a more US looking microbiome when we compared across this continuum to people who were born in the United States. It was really cool. The first question that everybody who sees this data asks is well, it must just because of dietary acculturation, right? You move to the US and you start eating Big Macs and burgers and that’s what changes your microbiome. What we actually found, which is very interesting, was that the dietary shifts didn’t really account for that much of the changes. We were able to attribute about 16% of the change in variation that happened in the microbiome to changes in diet – so dietary acculturation – but it wasn’t as much of the variation change that we expected we would find. It leaves a lot of questions out there about what is causing changes in the gut microbiome when you move to a new location. Is it because of the food? We know that some of that can be explained by food, but there’s also this unexplained variation that we’re still interested in figuring out what’s driving it.
Boy, you’re right. That’s a very cool result. I was going to ask about the acculturation issue because I know when people move from one country to another, their food habits are some of the things that will live the longest in the new culture. The fact that you’re not finding diet to be 100% responsible for that finding is really interesting. Is there speculation about what it might be?
Yes, we have some theories. We speculate a little bit about could it be environment that you live in. You know, are there microbes that you’re coming into contact within your environment, microbes that you’re coming into contact with by interacting with new people living in new spaces, going to work in new environments. Could it be that there was something that we didn’t measure? Like were you given a lot of antibiotics or antifungals at the time of immigration that we didn’t capture properly? We did capture information about antibiotic exposures but maybe not enough information or is there something about the water that you drink when you moved to the US that’s different? Those are sort of some of the theories that we had around what might be explaining some of the variation.
Do you think it’s within the realm of possibility that greater exposure to the forever chemicals that are coming in things like plastics and food wrapping and water bottles and spinoff from tires and things like that could be contributing?
I don’t know. It’s a good question. How would we study it?
I don’t know. I’ll have to rely on you for that but I can imagine it shows how complex the issue is because when people move from one place to another, there are thousands of things that are changing and isolating any one of them is not easy. Thank you for the description of that study. It’s really interesting. Now I’d like to ask you about precision medicine and precision nutrition. These terms are coming up more and more. What is precision nutrition and how does the microbiome fit into the picture?
Great question. Precision nutrition is a really interesting and exciting concept. In clinical dietetics, if you asked a clinical dietician, they would tell you that what they do is already precision nutrition. They work with patients who are trying to control their cholesterol or manage their diabetes and their blood glucose, and they provide personalized dietary recommendations based on what that person usually eats and what they want to see change in their biomarkers, for example. If you talk to a clinical dietician, they will tell you that they already do precision nutrition. But what I think we are starting to move towards and what the excitement is around is that precision nutrition could be using big data to do that type of individualized nutrition advice for big groups, almost population level nutritional recommendations. Where the microbiome fits in is that there was a pivotal study by Zeevi et al that linked changes in blood glucose response to foods to individualized signatures that were in part informed by the gut microbiome. There’s a lot of excitement that understanding the gut microbiome might help us to better provide precision or precise nutrition recommendations to people with big data. That’s how I conceptualize precision nutrition right now.
For the people listening who may want to do everything they can to have a healthy microbiome, what are the dietary things they might consider?
I don’t think that we have a clear single answer for this but when I’m asked this question, I come back to three dietary features that seem like, at least in cross-sectional observational studies show up again and again. The first is dietary fiber and getting enough dietary fiber. There’s some pretty good evidence that the amount of dietary fiber that we currently recommend, around 28 grams a day, give or take a gram or two, depending on your specific needs, that amount of fiber is probably good for your gut microbiome. There’s some evidence that may be going up to say 35 grams of fiber per day might be beneficial. The piece that goes on top of that from a microbiome perspective is potentially having a diverse variety of fiber types. We often talk fiber about as this monolith but really fiber is a whole bunch of different biochemical components, non-digestible parts of plants primarily that feed our gut bacteria. Getting diverse variety of fibers is probably important. To do that, it looks like getting a variety of plant foods into the diet is what might be most important to support a quote unquote “healthy” microbiome. Although a caveat that we don’t really know what a healthy microbiome looks like yet. When people talk about healthy microbiome, they’re often mostly talking about having a higher diversity of gut microbes. The third piece of the puzzle, at least from what we understand at the moment, is that possibly adding fermented foods and maybe specifically fermented vegetables or fermented plant foods may be beneficial for the gut microbiome. So those three things – diversity of plants, and diversity of fiber that kind of goes along with that, and then some sort of fermented food – those look like the three things that might be beneficial from my perspective.
Let me just ask about the fermented foods for a second. So I hear people talk about yogurt, kefir, things like sauerkraut and kimchi. Are these sort of things all kind of interchangeable with one another as people think about adding fermented foods to their diet? Or are there some that would be preferable to others?
I don’t know if we know yet. We have a lot of good data going back many, many many years looking at fermented dairy. Most of our research in the nutritional literature looks at fermented dairy – so yogurts. More recently we are starting to get data to look at things like kefir, but there’s not very much literature available looking at fermented vegetables like lacto-fermented vegetables. Like your sauerkrauts and your kimchis. I think it’s an active area of research. We need to do a lot more work in that space before we can make more specific recommendations. Right now, I would lump them all together but from my perspective, I suspect that a fermented vegetable might have different impacts on the gut microbiome when compared with a fermented dairy product.
Okay, thanks. It’s a fascinating question and it sounds like as the research marches ahead that we’ll have some answers to that. Let me ask kind of a big question to end. It strikes me that there’s real cause to be optimistic here, that there’s a kind of a whole new level of understanding about diet and health and how the microbiome is playing a big role in that. We might be headed toward the point where there are some policy priorities that would be in place or some dietary recommendations. Do you think it’s too early to be thinking about those or are there some things we could say now?
I think it might be a little bit too early. I think what we really need to do as a field is to make sure that we are thinking about everyone when we’re doing this research. By that I mean that we’re enrolling diverse groups of people into our research studies so that we’re not only learning about precision nutrition and the microbiome from this white American centric approach. Then, I think once we have a diverse data pool to look at, including different eating traditions that are not just western eating traditions, then we might be able to make some of these steps towards enacting policies or making recommendations at the population level that incorporate some of these precision nutrition or microbiome targeting approaches. I think the first step is just making sure we’re doing really solid research that doesn’t leave anyone out and that we’re not just doing precision nutrition for people who have a lot of resources.