The Oral Microbiome Revolution

Kamaldeep Singh -

Episode Transcript

Chris Curwen:

Hello, and welcome to this episode of Our Longevity Futures. I'm your host, Chris Curwen. And today, I have the pleasure of being joined by the CEO and co-founder of Bristle Health, Danny Grannick.

Bristle Health is a biotech company based in San Francisco, California, which is developing a home saliva kit to detect and analyze the oral microbiome.

Chris Curwen:

The oral microbiome is obviously important in gum disease and health, but it also has much deeper implications in just that, which is something we'll be getting into today. Welcome, Danny. And thank you so much for joining us.

Danny Grannick:

Yeah. Thanks for having me. Really exciting to be here.

Chris Curwen:

Yeah. No, it should be a great talk. Yeah. I just wanted to start out with asking about, just tell me about your journey to the creation of Bristle Health.

Danny Grannick:

Yeah. I think my whole team's background has been in genomics and biotechnology for a long time. We worked at companies like Illumina and Twist. I was most recently at Oxford Nanopore and they're doing some really exciting things in the sequencing space. We got our started at a really exciting time.

Danny Grannick:

I think genomics was starting to make its transition from this research environment into the clinic, and we started seeing improved patient outcomes in areas like oncology and rare genetic disease. We're still trying to figure out exactly when we landed on the idea for Bristle, but my co-founder, Brian, is your cliche person that has perfect oral hygiene, is almost religious about it, and inevitably has cavities every time he goes to the dentist.

Danny Grannick:

I think it was just us seeing this very stark contrast in the kinds of innovations that were hitting healthcare, and the lack of innovation in the oral care industry. We realized that it very much operates on this reactive standard of care. We use tools like X-rays and observational screenings that diagnose disease based on the severity of symptoms, when we knew that the technology existed to look at the real drivers of these disease.

Chris Curwen:

How did you go about building your team? Did you all know each other before Bristle Health?

Danny Grannick:

Brian and I have known each other for years. We got our start at Illumina together and had parallel career paths. And then Shivam and I had met a few years ago in San Francisco. His background is in investment banking, so he has a really good foundation in the operations and finance areas. I think we tended to have conversations in the corner about entrepreneurship before Bristle was ever an idea. So when we were putting the team together, it just seemed like a very natural fit.

Danny Grannick:

David was kind of a wild story. It's the middle of lockdown and I knew that we needed a technical co-founder to really develop the assay. Even though we knew that the pieces were there, we really needed somebody to come in and put it together. I ended up posting on Reddit of all places, looking for advice on how to meet technical co-founders because there were no scientific conferences, no networking events. David was one of the first people to respond.

Danny Grannick:

He was in the Bay area. When I looked at his LinkedIn profile, I saw that he had not only a PhD in microbiology and immunology, but he had actually taught microbiology to dental school students. The stars had just aligned. I think we got lunch the next week and then two hours later, it was a done deal.

Chris Curwen:

Wow. That sounds like a perfect way of meeting them. Bristle focuses on the oral microbiome. Can you just tell us a bit more about that and explain what the microbiome is to people that might not know? And why is the oral microbiome such an important aspect of our health?

Danny Grannick:

Yeah. I think when we think about the microbiome, which is really broadly speaking, it's a community of microbes; so bacteria, fungi, viruses that reside within our bodies. We tend to default to the gut microbiome. There's been a lot of companies and a lot of research in that area. The gut microbiome is that community that lives within your gut, and helps us digest food and has connections to various other aspects of our disease.

Danny Grannick:

But we have microbiome communities all around our bodies. There's skin microbiomes and vaginal microbiomes. In our case, we're looking at the oral microbiomes. So the makeup of those bacteria, fungi, viruses that reside in the oral cavity. And the very obvious connection to health is the connection between this microbiome community and our oral health. We know that there are causally associated pathogenic bacteria with oral diseases, like cavities and gum disease.

Danny Grannick:

And what we are discovering are deeper connections between our oral health status and our overall health. There's a saying, "The mouth is a mirror of our health," and we're finding that to be very true. Connections between cardiovascular disease, diabetes, and more recently, some really exciting research being done with Alzheimer's is starting to show that changes in our oral health can reflect or can signal changes happening in the other parts of our bodies.

Chris Curwen:

Yeah. Tell me about the oral microbiome's association with chronic disease. You mentioned a few of them there, such as Alzheimer's and diabetes, heart disease. What's the relationship here?

Danny Grannick:

I think that there's a few different ways to look at it. We can look at the oral and microbiome as a driver of disease. So for something like periodontal disease, we know that periodontal disease is an infection. When you have an overabundance of these pathogenic bacteria, it leads to the infection that we call gum disease today.

Danny Grannick:

When we look at systemic health, we can look at changes in the oral microbiome as a manifestation of systemic disease. So an early signal where changes in our bodies that we may not see, or that may not have shown symptoms, and the rest of our bodies are actually starting to show themselves in changes in our oral microbiome. The emergence of certain pathogenic bacteria or the depletion of others can signal biochemical changes going on in the rest of our bodies.

Danny Grannick:

Then there are other cases where oral disease can actually be a contributing risk factor for systemic disease. There have been some preclinical studies that have come out in the last couple months that have shown a connection between some oral bacterial pathogens that lead to gum disease that are also thought to be contributors in the progression of things like Alzheimer's and heart disease. It's like a two-way street, depending on the indication that you're looking at.

Chris Curwen:

When did you become interested in the oral microbiome specifically? I know you mentioned you were at Illumina and Oxford Nanopore. Obviously, well-known for their genomic sequencing, their DNA sequencing. So, what made you choose the oral microbiome?

Danny Grannick:

Yeah. I think we had done a lot of work across a lot of microbiome companies looking at these other areas. I mentioned the skin microbiome and the vaginal microbiome as a few examples. I think our initial interest really just came from the fact that given our pretty good understanding of what was going on in the industry, we had never seen a company really investigating the oral microbiome before.

Danny Grannick:

It opened up a lot of questions as to why nobody was looking into it and what connections there were to other indications and diseases. It just seemed like this very overlooked area, which I think is actually representative of oral health and care as an entire industry. And when we started looking into it further, we realized there have been decades of research into bacterial pathogens that contribute to oral disease.

Danny Grannick:

Just there was a chasm almost in introducing a lot of more advanced sequencing technologies into the research that had already been done. So it seemed like an amazing opportunity to make significant contributions to the space. And as we dug into the standard of oral care, we realized that we could also really drive improved patient outcomes by developing this test.

Chris Curwen:

Yeah. No, it seems like an absolutely fascinating area of study. How does Bristle go about analyzing the oral microbiome?

Danny Grannick:

Yeah. Broadly speaking, I think a lot of companies tend to analyze the oral microbiome using targeted assays. A really good example is a method called 16S. 16S is a targeted sequencing method that is able to identify bacteria and get their relative abundances. So you can imagine that you can derive some really interesting insights from that data. I would compare it to having a database of fingerprints and last names, and you're looking for maybe 10 people out of that entire database.

Danny Grannick:

Bristle is a bit different than other microbiome companies. We use a method called shotgun metagenomics, and that method performs whole genome sequencing across every organism in the sample. So we can detect things like bacteria, fungi, and viruses, and we're getting all of the contextual information around them. I guess going back to the example, you have fingerprints, you have the first name, the last name, maybe somebody's resume and a picture of them.

Danny Grannick:

This allows us to not only improve the sensitivity and specificity of our tests, but it gives us an amazing research platform to start investigating and uncovering some of these associations that are just starting to come to light between the communal driver of oral disease, as well as the relationship between oral and systemic health.

Chris Curwen:

Yeah. I love the idea of sort of a police report, but of bacteria rather than people. Brilliant. You mentioned the assay, the 16S I believe. What are your methods to guarantee the accuracy of these results?

Danny Grannick:

Yeah. We're going through quite a bit of validation internally for our initial signatures around oral disease. And while our test right now is operating in a wellness category where we're not reporting on diagnosis of oral disease, we intend to go through clinical validation of the assay. That involves all of the regulatory steps that any other company in the space would go through, operating through CAP/CLIA. Then eventually, we'd like to pursue FDA approval on the test and the equivalent for other areas in the world.

Chris Curwen:

What sort of level of evidence does Bristle rely on to support the recommendations that you make, after having analyzed an individual's oral microbiome?

Danny Grannick:

Yeah. So I think from a signature standpoint, as I said, there have been decades of research investigating some of these causal pathogens implicated in oral disease. And that provided us with a really good foundation that we could build our own signatures from. We've made a few novel discoveries along way, but for the most part, the signatures that we are using have been verified across numerous academic research studies, so we're very confident in the results of the test.

Danny Grannick:

From a recommendation standpoint, we're actually relying on similarly, decades of clinical evidence. You can imagine that if you combined the recommendations across all of the dentists and all of the oral healthcare professionals, we intend to make very novel discoveries into interventions that you can use to improve oral health, but we have an amazing chance to disperse existing knowledge to a lot of consumers that aren't aware of very simple steps that they can take in their lives to improve their oral health and prevent oral disease.

Danny Grannick:

It's really one of the, I think, lowest hanging fruits in healthcare when we talk about improving patient outcomes on a population scale.

Chris Curwen:

Are you able to go into detail about these novel discoveries yet? Or is this a sort of, if you tell me you have to kill me sort of situation?

Danny Grannick:

A bit of the latter. But no, I think broadly speaking, I mentioned that we intend to do a lot of research around the connection between oral and systemic health. We've seen some promising research come out that has been able to derive oral microbiome signatures and associate it with things like increased risk, or the diagnosis of systemic disease.

Danny Grannick:

From an intervention standpoint, there's a few areas. I think that we'll start to see more connection between our lifestyle factors, individual dietary preferences, various levels of hygiene from person to person that are going to have very significant effects on our oral health.

Danny Grannick:

Then from a therapeutic standpoint, there's a really good opportunity to shift the kind of oral care products that we use today, which are very broad spectrum. So they work for everybody, but don't really work for anybody. And start developing very targeted oral care products that selectively go after those pathogenic bacteria.

Chris Curwen:

After you've had your oral microbe analyzed and you get feedback, how do we actually go about maintaining a healthy oral microbiome? Is there any sort of tips and tricks, or is it very much tailored to the individual?

Danny Grannick:

I think it's a mixture of both. Like any other area of healthcare and maintaining any other area of health, there are always going to be really simple steps that anybody can take to improve their health. Just like exercising regularly can reduce your risk for heart disease, maintaining good oral hygiene practices and being consistent in the number of times you brush and floss, which is the same advice that you'd get from a dentist, but those have very significant effects on our oral health status.

Danny Grannick:

Then you get into the more nuanced areas, personalized recommendations where the way that our body reacts to some of these pathogenic bacteria can differ from person to person. And that's where we start to really drive value to our users in taking their personal dietary preferences and making recommendations to them on specific foods that they should avoid, specific oral care products that they should use, and then the underlying factors that could contribute to risk for oral disease.

Chris Curwen:

Here at Gowing Life, we look at a lot of things through the perspective of aging and longevity. So, how does aging affect the oral microbiome?

Danny Grannick:

Yeah. I think it's something that we are still investigating. I think the obvious answer is that we tend to see much higher prevalence of oral disease in the elderly population, and there's a few hypotheses around that. One is that obviously, your immune system gets weaker as you age, so you may not have that natural ability to fight off oral disease. I think excitingly, we'll see developments in this connection between Alzheimer's progression and oral disease, because those two are both kind of correlated with increased aging as well.

Danny Grannick:

And I think from a society standpoint, our population is living longer than ever before. I think to the benefit of everybody, we're also keeping our teeth for longer than ever before. While that's very good, it also presents the ability for pathogenic bacteria to grow in those crevices between the teeth that we see in the younger population. When you combine that with the idea that it's also hard for the elderly population to maintain good oral hygiene, I think that all of those factors play into this higher prevalence of oral disease in the aging population.

Danny Grannick:

We'll have to see. It's a balancing act. For us, it's tough because while we want everybody to live longer, it also introduces a higher risk of oral disease. So hopefully, we can help people. Hopefully we can be supportive of some of these longevity companies by helping people maintain good oral health as they start to live longer.

Chris Curwen:

It is almost making your job a little bit more challenging if we do make people live longer.

Danny Grannick:

A little more exciting.

Chris Curwen:

Given the rapidly downsizing costs of DNA sequencing that we've witnessed over the past couple of years, or past almost 15 years I believe, as well as the increased availability of individual medical records, how do you see personalized medicine evolving in the years to come, as someone who is the CEO of a biotech company?

Danny Grannick:

Yeah. I think from a sequencing standpoint, the amount of innovation and discovery that has come as a result of the decreased cost in sequencing, is incredible. And I think that we'll continue to see that. I'm really excited. I think that we can look at it from two perspectives. There's the decreased cost in what I would call centralized sequencing from companies like Illumina, that have systems that are very high throughput that you can access, but are generally being run through these production scale core labs.

Danny Grannick:

Then we have companies like Oxford Nanopore that are using systems that are more decentralized, that enable do-it-yourself genomics projects that I think are really exciting because it introduces this entirely new set of very diverse perspectives and research studies that can be done using next generation sequencing. So I think that we'll see a lot of developments coming from each of those kinds of innovation.

Danny Grannick:

Then from the individual medical records, another challenge in oral care is that it tends to be siloed from the rest of the medical healthcare system. There's no exchange of data, and I think that this causes a lot of gaps in what we would consider patient centered care. So a big goal for our company is to contribute to this idea of integrating dental and medical care as much as we can. And a component of that, I think is this idea of individual medical records.

Danny Grannick:

Because the challenge of integrating various electronic health records from an operation standpoint and from the perspective of healthcare providers themselves, is almost an insurmountable task. I think it's something that we've been working on for years. So the idea of being able to, much like DNA sequencing, decentralize access to that data and put it in the hands of the patient to where they can go see any provider in any kind of healthcare system and be able to present their medical records independent of the ability for us to combine them on the backend.

Danny Grannick:

I think it's really exciting. It's going to be able to give a lot of different care providers new perspectives into somebody's oral health. You'll be able to go see your primary care provider and present them with your dental information because you have all of that stored on your person.

Chris Curwen:

Yeah. I think that brings up a really interesting topic of data protection. I was just wondering what your stance and Bristle Health's stance is on keeping individuals' data and how that's handled within a business.

Danny Grannick:

Yeah. We're taking a very conservative approach when it comes to data privacy. I think that's one of our biggest concerns as an early stage company. Fortunately and unfortunately, I think we have learned from other companies in the past that haven't been as concerned when they went to market. We maintain a completely HIPAA compliant infrastructure.

Danny Grannick:

I think primarily, the reason is because we value user privacy above everything else. I think a good benefit of starting off with this HIPAA compliant infrastructure is that we do see ourselves moving towards becoming a covered entity, or at least working with covered entities in the future. Building that infrastructure now just allows us to seamlessly grow the company and become more of that clinical provider.

Chris Curwen:

Could you just provide me with just an explanation? What was that? Hippo? Hippo?

Danny Grannick:

HIPAA? Yeah. HIPAA compliance.

Chris Curwen:

What was that?

Danny Grannick:

Yeah. It has to do with personal health information, so PHI. And that is, broadly speaking, connecting various aspects of your health with your identity. So it's being able to say, here's an oral microbiome profile versus here is Danny Grannick's oral microbiome profile. What we want to prevent is third parties from getting access to healthcare information and being able to correlate or connect that information to an individual.

Danny Grannick:

That's exactly what we're trying to protect by being HIPAA compliant. We're maintaining this veil of privacy between the results that we present and the people that they're connected to. There have been a lot of problems in the past where I think a lot of users tend to sign off on companies that end up using a lot of that information for commercial purposes, and that's very much something that we don't intend to do.

Chris Curwen:

Well. Yeah. It was very refreshing and I think, a very progressive point of view that you take. That's great to hear. What stage is Bristle Health at as a company? Because I've learned that you have got some current funding. And how will that help to develop a product and the path to commercialization?

Danny Grannick:

Yeah. We're a pretty young company, I think a little under a year old, but we've progressed really quickly. A lot of that progress is due to the backing and the support of our early investors. Obviously, helping us kick off a number of research partnerships, and also releasing this early access test.

Danny Grannick:

While it's still in the wellness category, the funding will help us take our tests through clinical validation and build out this end-to-end solution for our users where we'll be able to present the oral microbiome results, as well as interventions that people can use. Again, both on the wellness side, so talking about it in lifestyle, all the way through clinical recommendations for things like prescription products.

Chris Curwen:

Yeah. I think it's an absolutely fascinating area. Where do you think Bristle Health will be in five, 10, 25 years?

Danny Grannick:

Yeah. It's something that I think about almost every day. The easy answer is hopefully, still around. I think realistically, as a company, the introduction of sequencing and molecular diagnoses in oral care is something that really hasn't been done before. I think to my earlier point, we have this incredible opportunity to not only change a component of healthcare, but actually upend the entire standard of care that we do today. It's a lot more than creating a better tool.

Danny Grannick:

We're talking about decentralizing access to oral care. Shifting that standard from the reactive treatment of disease to the proactive management of health, and addressing cavities and gum disease, the most prevalent conditions in the world that are almost entirely preventable if they can be caught early. So I think we have this amazing opportunity to drastically change our understanding and change the way that we address oral disease.

Danny Grannick:

I hope that bristle is the company to shift the entire standard of care. And I also hope that can be a leader and a collaborator in progressing our understanding of oral health and its role in systemic health. I think that there's amazing opportunities to leverage our products and our data to create better therapeutics and better diagnostics, not only in oral health, but across the healthcare spectrum.

Chris Curwen:

Yeah. Well, I think as you said, you've put into it some very good words of what your thoughts are about the future. But have you got anything else to add to what you might think the future of health and wellness might look like, zooming out from Bristle Health for a second and looking at it from a wider picture?

Danny Grannick:

Yeah. I think you can take a lot of the principles of Bristle and really apply it to the rest of healthcare. Decentralize testing and improve the technologies that we use to detect disease at the earliest stages when it's most addressable. Deliver interventions earlier when they're maximally effective to prevent disease, rather than reactively treat it.

Danny Grannick:

I think that we're going to see this incredible shift where again, we're proactively managing our health, instead of reactively treating disease. We're doing that anywhere. We're meeting patients where they are, rather than having them come and seek treatment. I think we're already seeing it in oncology and heart disease, with companies like Invitae and Everlywell in the United States at least.

Danny Grannick:

And I know that there's companies. LetsGetChecked comes to mind. I think it's based out of Europe, if I'm not mistaken. We'll continue to see the decentralization of testing technologies, and I think that we're going to see a whole new generation of therapeutics that are focused on addressing those causal drivers of disease at the earliest stages and eradicating them. Or at least that's what I hope.

Chris Curwen:

You and me both. Well, thank you so much. It's been absolutely fascinating talking to you, Danny. Yeah. I know you've got a busy schedule, so thank you so much for giving us the time of day to come and talk to us. Where can people find out a little bit more about you and keep up to date with everything that Bristle are doing?

Danny Grannick:

I would just recommend going to our website, bristlehealth.com. As I said, we're very early stage, so we're only shipping in the United States right now. But we're looking to expand.

Danny Grannick:

I think for people that want to stay up to date, we have a newsletter at the bottom of the homepage that you can sign up through. If there's interest in taking the test, please send us an email. The more requests we get, the faster we can accelerate expansion to the rest of the world.

Chris Curwen:

Amazing. Well, I wish you all the best of luck in that. And I hope to see it over in Europe sometime soon. That would be great. But yeah, so thank you so much for coming on. We really appreciate it.

Chris Curwen:

Guys, if you want to go and check out Gowing Life, go to our website, www.gowinglife.com, where you can find out all the updates and news from the world of longevity. So again, thank you so much for joining and we'll see you again next time. Thanks.

Danny Grannick:

Thanks.

 


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