An interview with Larry Weiss, MD

Larry Weiss, MD is a physician, scientist, and entrepreneur specializing in microbiome research and biotechnology. The founder of Symbiome and Weiss Bioscience, a microbiome research and development company, Larry was also the founding Chief Medical Officer at AOBiome and the founder of CleanWell. Larry has an MD from Stanford and a BS from Cornell in Biochemistry. Here, Dara interviews him about his work with the microbiome and what it all means for modern-day skin.

Dara: You’re a pioneer in the area of microbiome-focused skincare. What got you so interested in studying the microbiome, and when did that happen?

LARRY:

For some time, any physician paying attention began to notice a growing burden of inflammatory disease: it’s tripled in the past 30 years. The stress we’re exposing ourselves to has serious health consequences, and our bodies have lost their resilience—their ability to respond to stress without becoming inflamed.

Then, right around 2000, early data around the microbiome changed our entire perspective and made us realize that the relationship between us and our microbiome is deeply involved in this increased burden of inflammation; the microbiome was the original immunomodulator.

The microbiome, as we’ve learned, is as much a part of a person as their heart or lungs; this is a microbial planet, where bacteria have been around for at least 4 billion years. We evolved out of this microbiome, and it’s part of us. (We’re not the pinnacle of evolution, as it turns out — we’re the spoiled and arrogant newcomers benefiting from a 4 billion year old biologic trust fund from which we emerged.)

We all realize now that industrialized modern humans have lost a good amount of our microbiome, and with the loss of these bacteria, we lost their function: where the skin is concerned, their function is to protect it and to provide it with essential nutritional support.

So, all of this percolated as new data came out, which in 2014 resulted in the release of a product I helped create called Mother Dirt. (I started with skincare products, by the way, because skin gets people’s attention. And if your skin is inflamed, you’re systemically inflamed.) Mother Dirt was really the first skin microbiome product that anyone was aware of, a suspension of live bacteria — truly a probiotic. And what we found with this product was that when you put back into the skin microbiome one of the things that it’s lost over the years, instead of adverse side effects, you see beneficial side effects.

But it turns out that we'd lost more than one type of bacteria.

So I did some work with a semi-nomadic tribe in the Amazon over the course of seven years to find out more about the bacteria we’ve lost. Guess how much of it is gone? 80%. We’re missing about 80% of the bacteria that used to live on our skin. But there’s something that’s even more important than what those bacteria are: it’s all the things those bacteria were doing for us. It’s their output. These bacteria are responsible for the resilience that underpins our health.

Dara: We obviously need to talk about your work with the semi-nomadic tribe, but first, let’s talk about what these bacteria are doing for us — or what they used to do for us.

LARRY: Here’s the way you can think about it.

We live in an oxygen-rich environment. We’re bathed in ultraviolet, oxygen, and water, and this creates a high-energy free radical, basically a high-energy electron, called superoxide. 2.7 billion years ago when oxygen showed up in our environment, bacteria solved this problem. So one major group of things they make, one major piece of their output, are antioxidants—or oxidation reduction.

The other major group of things they make, or their output, are what we call secondary metabolites that provide nourishment. This includes fatty acids and fat-soluble vitamins, peptides, and amino acids. And the important thing is that they’re biologically intact. We think of these things as individual molecules, but they’re never individual molecules; they’re classes of molecules with a certain kind of activity.

For example, we evolved with yeast on our skin—part of our microbiome—that made retinoids. But not just the ones we think of in our skincare (retinol, retinaldehyde, and retinoic acid); a broad variety of them, a whole universe of retinoids. And that universe of retinoids was responsive to environmental inputs; it created a chemical environment that was resilient and self-regulating.

In contrast, when we as modern-day humans separate out the most potent one, retinoic acid, and we put a single entity of a potent molecule in a formula, it doesn’t have the responsiveness or resilience of that self-regulating universe of retinoids. And when we apply a product with retinoic acid on our skin, we’ll get the benefits…but we’ll also get the side effects.

None of us have that yeast on our skin anymore; that’s just one small example of what we’ve lost over time. And now, what’s left of our microbiome is stressed: it doesn’t have the protection it used to, so we have chronic levels of oxidation and inflammation, which is the manifestation of that oxidation. And we don’t have the nourishment provided by all of these fatty acids, vitamins, peptides, and amino acids that are essential for healthy skin. (Our skin needs them, but our bodies don’t make them because we never had to; they existed in our environment until relatively recently.)

Dara: So, to summarize —

The bacteria that we’ve lost from our microbiome over time, due to our modern-day lifestyle, are critical for our skin because they provide

a) antioxidant protection (we all know how important that is) and

b) essential nutrients to keep it healthy and resilient (which includes maintaining its barrier health, another thing that we all know about).

And they do that in a way that is more “naturally intelligent” (broader-reaching, more self-regulating) than adding back a single one of these nutrients or antioxidants could be.

This brings us back to the semi-nomadic tribe, whose members do get more of this protection and nourishment due to their more robust microbiome. How did your work with them come about?

LARRY: 

My work at AO Biome, where I developed Mother Dirt, was based on the hypothesis that we’d lost a specific bacteria that’s found throughout nature. I knew that if I wanted to prove that proposition, I’d need to find an intact community of foragers and sequence their microbiome…which is easy to say, but very difficult to do.

Dara: Why would you need to find a community of foragers?

LARRY: Because they’d have a rich, diverse, robust microbiome; they’re harmonized with the microbial environment in which they live. That’s what we had when all humans were foragers, but now we’re harmonized with the built environment, which is highly diminished.

Well, one day in 2015 or thereabouts, I was listening to Snap Judgment on NPR, and a young man was telling the story of his father, an American anthropologist in the 1970s and 80s, who went to study an Amazonian tribe called the Yanomami and found this uncontacted village. What began as this anthropologist’s nine-month-long graduate program ballooned to a twelve-year odyssey, during which the head man of the village betrothed his sister to him, and he married her. (You can imagine the chaos that this particular event created.) They had three children; David, this young man, was the eldest child.

When David was five years old, his mother had decided to stay with her family in the Amazon. David, who stayed in the States with his father, eventually got a degree in biology, raised a little money, and mounted an expedition to find his mother. He did, which is astonishing, because the Yanomami tribe is semi-nomadic. He hadn’t seen her for twenty years.

I got in touch with David to find out if there was a way for us to work together to see if this particular bacteria in Mother Dirt, ammonia oxidizing bacteria, could be found in a remote place like his mother’s environment. For a lot of reasons, that didn’t work out. But then he called me a year later and said, “How would you like to study the microbiome of my family?” A question to which there is only one correct answer.

So we ran a total of three expeditions, sampled every aspect of that community’s microbiome—skin, gut, mouth, nose, pharynx, the environment—and built the most comprehensive survey of what a biologically intact microbiome looks like in a foraging community, in a population that lives a disease-free life the way our species spent most of its time on this planet. 

And what makes the Yanomami interesting is that they have no inflammatory disease at all. Acne, eczema, rosacea, psoriasis: they don’t exist anywhere in these populations. They don’t have heart disease; their coronary arteries in their 70s and 80s are cleaner than ours in our teens. They don’t sunburn, and they don’t get skin cancer as far as we know. 

We sequenced everything, built a survey, and published it in Nature this past summer, and that represents our true North, our reference point. It’s true that a group of foragers in a different ecosystem will have a different population of bacteria. But I believe what we’d find, if we looked at the output of that ecosystem or that of any other foragers, is that it would look very much the same as the output of this one: we’d see the resilience that comes from that antioxidant protection and essential nourishment. 

Knowing all of this changed everything, because rather than the old approach to skin health and overall health, which was to fix broken stuff about which we knew very little, we now had the option to restore health, because we now knew what it looked like.

We can’t just put the bacteria back, though. Even if I wanted to, it would be a bad idea because our immune systems haven’t seen most of these types of bacteria before.

But you can focus on the output. You can sustainably harvest plants from essentially the same environment because the bacteria on the skin of the people living around there — we call this ecosystem of bacteria the biofilm — is significantly similar to the biofilm on the plants. And if you do a precision fermentation with those plants, because everything in the Amazon is constantly fermenting, this will create those missing metabolites, the output of those bacteria.

So at Symbiome, we built precision ferments from Amazonian botanicals — the same types of plants that people like the Yanomami have been safely using in their folklore and in their food for over 10,000 years — to activate those same missing metabolic pathways that we’ve lost and create those fatty acids, triglycerides, vitamins, and antioxidants in a way that is biologically intact. And out of those, we’ve built skincare products.

But as I see it, I’m not in the skincare business; I’m in the health business. It’s a much broader process: this is about changing our whole relationship to the decisions we make and the products we buy.

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Check out our Symbiome Brand Spotlight, where Larry tells us more about Symbiome’s products; the difference between prebiotics, probiotics, and postbiotics, and why that matters for skincare; and what you’ll notice when you use what he calls “skin food.”

And shop the Symbiome products on Ayla's shelves here.