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Figuring It OutFiguring It Out

 Michael Snyder is the chair of genetics and the director of the Center of Genomics and Personalized Medicine at Stanford University. He is widely regarded as a leading mind in functional genomics and proteomics, and his lab works on the forefront of detailed, longitudinal, integrative personal “omics” profiles to assess risk and monitor disease states in pursuit of a more personalized medicine. NBJ spoke with Snyder from his offices in Stanford. 

Marc Brush

October 1, 2014

7 Min Read
Figuring It Out

nbj: Tell us about your work at Stanford.

Michael Snyder: My research focuses on trying to understand health states from a very detailed genomic and biochemical perspective. That means we actually sequence people’s DNA to try and predict disease risk. We also do incredibly detailed profiles—we call them ‘omics profiles’—where we sample blood and look in detail at all the molecules. We look at all the RNA they make, all of the proteins, all of the metabolites we can measure. We also study epigenetics and DNA modifications, and we study immune responses. Lastly, we study the microbiome in incredible detail—gut, nasal, skin, tongue and urine microbiomes. We do these very detailed analyses, and then follow longitudinally over time to study the changes when people get diseases or respiratory viral infections. We’re actually studying pre-diabetics now to see how things change when they undergo stress responses.


nbj: It’s also personal, yes?

Snyder: This is a pilot study we started on me. We discovered from my DNA that I was at risk for type 2 diabetes and amazingly, during the course of this study, I actually got type 2 diabetes. My glucose elevated. Hemoglobin A1C, which measures glucose, went up to 6.7, and it was up for some time. It actually took me six months to get it down by exercise and changing my diet. Then several years later, it went up again to 7.0. It was up for quite a few months before I discovered it and started increasing my exercise to bring it back down.

We follow the metabolite and all of these other profiles where you could actually see my changes occur at a level no one’s ever seen before. Initially we were following about 40,000 molecules in my blood, but now we literally make billions of measurements to see these changes occur. We can discover the pathways that go up and down. I’ve been through six viral infections while we’ve been profiling me, so we see the changes.


nbj: How does this work connect to nutrition and supplementation?

Snyder: We’re just starting on that aspect of it. Before, we were sampling people and trying to follow them as they went along, but we were more in-tune with the viral infection work. Our health is really the product of our DNA and our environment, the things we are exposed to, including our food, so we are beginning the work to connect this better.

    Your microbiome is incredibly linked to your health state. There are a lot of studies out there now demonstrating this. In our hundred trillion cells, 10 trillion of those are our own human cells, but 90 trillion are bacteria and other things, mostly in our gut, but actually all over the place. One of the things that we’re doing now by studying the microbiome is trying to connect it directly to our metabolism. We know that our diet really influences this, but we don’t know enough about how. How supplements weigh into this—that’s exactly one of the things we’d like to study. Which supplements change the microbiome and then, in concert, change your metabolic profile?


nbj: The supplement industry seems to equate microbiome with probiotics, but that’s only the beginning. When did you add microbiomics to the mix?

Snyder: We started the microbiome work on me about two years ago, but there’s a larger study going now. We’re following 60 people, and we’re going to enlarge it to 70 people and maybe even add more. We will follow everything—their blood, their microbiome, everything, for three years. We’ll just see how it plays out. I’m coming into this incredibly unbiased. I want to see how your food, your activity, your blood, how do they correlate with your microbiome and health? I don’t have an opinion, one way or another, about which supplements correlate with what kind of outcome. Our mission is to try and see what we can learn. That’s ultimately the goal of what we—and hopefully many others—are trying to do here, and that is to be predictive. If you have a certain DNA and you eat this food and live a certain lifestyle, then this is what will happen to your health. It’s a complicated equation, but I do think it’s figure-out-able, if you will, to try and decipher health outcomes based on your DNA and the various exposures, including food, that you may encounter.

nbj: The complexity seems daunting at times. Can it really
be understood?

Snyder: I believe we can figure it out. We just need a lot of data. There are a lot of variables here—everything from sleep to stress response to food—but that just means we need to collect more data and control for these.

    We’re doing this longitudinally for a reason. We’ve built an incredibly huge profile on me for 4.5 years now, so you can start to correlate. For Mike Snyder, when I get a viral infection, these are the responses that I see. And we’re starting to build correlations for food intake as well. As I’m eating X, with X being certain kinds of food, this is my biochemical response. It means you do have to collect a lot of data, and it’s not simple, but because it’s the same person with controls for certain variables—that’s my DNA, my epigenome, my age—you learn something. Now, this is all correlative—if I eat X, I get a certain microbiome, and that doesn’t prove that X caused that, but it is certainly associative. From a health state, that may be mainly what you need anyway.

    This will be personalized. Because we’re all a bit different in our DNA, our metabolic profiles are different and it seems likely that our microbiome will be different and differ with the kinds of foods we eat. This is why personalizing is so important. We really want control over our ultimate metabolic and health state, and to get there, one area that you can actually manage is your food intake.


nbj: Any opinion of the modern American diet?

Snyder:  Yes, I’m concerned. It’s a very high-carb diet, with all of the sugar we eat. I’m a believer that this does influence our microbiome.  A lot of people think it restricts the diversity of our microbiome.  It’s the microbes, but it’s also the lack of diversity of microbes that might be contributing to why we’re not in good shape. We’ve got a great group of people in our cohorts who are participating in this to change their diet and see what happens to their metabolic profile when they do. It should be interesting.


nbj: Can you describe a key discovery from the work to date?

Snyder: The biggest insight that came out of my study was that, from my DNA, I could predict I was at risk for a disease which in fact I did get. That was a big deal, because it showed for the first time that you can use your DNA to predict disease risk and then catch a disease early. In my case, I caught my diabetes early when it came on and I was able, through exercise and changing my diet, to modulate it and get it under control. So, that’s lesson No. 1. Lesson No. 2 would be that my diabetes came on after a very nasty respiratory viral infection. It’s a common cold variant, but it’s not that common in adults and I’m an adult. I was out sick for several days, but my glucose shot through the roof and then it stayed up for a long time, so this is one of the first links between viral infections and type 2 diabetes. We’ll see how general these links prove out as we go through the study.


nbj: It’s like you identified the specific trigger for your disease.

Snyder: You’re absolutely right.  Again, your health is a product of your DNA and the various things you’re exposed to. In my case, the thing that triggered my glucose was this viral infection. So my DNA was predisposed and the virus triggered it. It’s probable that my diet contributed to it as well. Even though I had a bad diet before all of this, my glucose was running fine, but it’s clear that the viral infection had a significant impact on my glucose levels. It’s also clear that by exercising and changing my diet, I was able to bring my glucose under control, at least for a while, until it went up again when I stopped running. I’m getting it under control with more exercise now, but it’s quite probable that as I age it will come back again. I’m going to keep trying to modulate it by exercise and diet. In the worst case scenario, I’ll have to start taking some drugs and see if that works to get it under control. I know that’s not what the natural products industry likes to hear, but it may be what’s necessary for me and many others like me.

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