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Danny Grannick, CEO of Bristle Health, on the Microbiome Revolution – Our Longevity Futures, with Chris Curwen | Ep. 4

17 March 2021

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Over the last 150 years, our life expectancy has grown, from 40 years in 1850 to over 90 years today in some countries. This can be attributed to advances in medical science, improvements in public health, and equitable access to healthcare, especially for maternal and infant care.

What will the future hold for our world? Will we be overwhelmed by a ‘silver tsunami’ of retirees with poor health, or will we use the latest research findings to rejuvenate the elderly and extend their lifespan?

Our Longevity Futures is a show where I, Chris Curwen, speak to scientists, engineers, entrepreneurs, doctors, politicians, and community activists who are giving the world the hope that we can all live longer and better, and improve our health.

In this episode number 3 of ‘Our Longevity Futures’ we host 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 test to detect and analyse the oral microbiome. This will help to identify cavities and gum disease at their earliest stages – and then offer evidence-based recommendations and treatments for helping to prevent them.

Although oral health is often neglected, it has deep connections to the rest of the body and is a vital component of overall health. Diabetes, heart disease, and Alzheimer’s can all be linked to poor oral health. Oral diseases are often caused by the buildup of specific acid-releasing or disease-causing bacteria. Bristle Health’s technology will enable early detection of these pathogenic microbes, when the risk of transmission was low.

In this talk Danny provides an education on the oral microbiome. Explaining just how important it is in our personal health, its association with chronic disease such as Alzheimer’s, heart disease and diabetes, and how it is impacted by ageing.

Danny gives us a fascinating deep-dive into Bristle Heath. Providing insight into how the company came to be, why they chose to focus on the oral microbiome and what they hope for the future

Here are some of the highlights for my conversation with Danny:

Chris: Tell me about your journey to the creation of bristle health?

Danny: My whole team’s background has been in genomics and biotechnology for a long time. We’ve 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 start at a really exciting time. I think genomics was starting to make its transition from this kind of research environment into the clinic. And we started seeing improved patient outcomes in areas like oncology and rare genetic disease. And we’re still trying to figure out exactly when we landed on the idea for bristle, but yeah.

My co-founder Brian is your cliche person that has perfect oral hygiene and is almost religious about it. And inevitably has cavities every time he goes to the dentist. And I think it was just a. Seeing this very stark contrast and 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 diseases.

Chris: How did you go about building your team? How did you all know each other before bristle health?

Danny: Brian and I have known each other for years. We got our start at alumina together and had parallel career paths. And then Shiva and I had met a few years ago in San Francisco. His background is in investment banking. Has a really good foundation in the operations and finance areas. And 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 seems like a very natural fit. And David was a wild story. As the middle of a lockdown and. I knew that we needed a technical co-founder to really develop the asset. Even though we knew that the pieces were there, we really needed somebody to come in and put it together.

And 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. And David was one of the first people to respond. He was in the Bay area. And when I looked at his LinkedIn profile, I saw that kid not only had a PhD in microbiology and immunology, but he had actually taught microbiology to dental school students.

And the stars had just aligned. I think we got lunch the next week. And then two hours later, it was a done deal.

Chris: 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: When we think about the microbiome, which is really the broadly speaking, it’s a community of microbes and 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. And 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. But we have microbiome communities all around our bodies. There’s skin microbiomes and vaginal microbiome.

And in our case, we’re looking at the oral microbiome. So the makeup of. Those bacteria, fungi and 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. So we know that there are causally associated pathogenic bacteria with oral diseases like cavities and gum disease.

And what we’re 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.

It’s starting to show that changes in our oral health can reflect or can signal changes happening in other parts of our bodies.

Chris: Can you tell me about the oral microbiomes association with chronic disease. You mentioned a few of them there, such as Alzheimer’s and diabetes, heart disease. What’s the relationship here with them?

Danny: There’s a few different ways to look at it. We can look at the oral microbiome as a driver of disease. So for things like for something like periodontal disease, We know that periodontal disease is an infection. And when you have an overabundance of these pathogenic bacteria, it leads to the infection that we call gum disease.

Today, when we look at systemic health, we can look at changes in the oral microbiome as a manifestation of systemic disease. An early signal where. Changes in our bodies that we may not see, or that may not have shown symptoms in the rest of our bodies are actually starting to show themselves in the changes in our oral microbiome.

So the emergence of certain pathogenic bacteria or the depletion of others can signal biochemical changes going on in the rest of our bodies. And then there are other cases where. Oral disease can actually be a contributing risk factor for systemic disease. There’ve been some preclinical studies that have come out in the last couple of months that have shown a connection between some oral bacterial pathogens that lead to gum disease that are also thought to be contributors.

And the progression of things like Alzheimer’s and heart disease. So it’s like a two-way street, depending on the indication that you’re looking at.

Chris: When did you become interested in the oral microbiome specifically?

Danny: 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. And 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, and it opened up a lot of questions as to.

Why nobody was looking into it and what connections there were to the rest of to other indications and diseases. It just seemed like this very kind of 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, 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 seems 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: How does Bristol go about analyzing the oral microbiome?

Danny: So, broadly speaking, I think a lot of companies tend to analyze the oral microbiome. Using targeted assays is a really good example is a method called 16S. In 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 Bristol 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. So 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.

And 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 kind of communal driver of oral disease, as well as the relationship between oral and systemic health.

Chris: What are your methods to guarantee the accuracy of these results?

Danny: 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 and. That involves all of the kinds of regulatory steps that any other company in this space would go through, operating through your cap CLIA.

And then eventually we’d like to pursue FDA approval on the test and the equivalent for other areas in the world.

Chris: What level of evidence does Bristle rely on to support the recommendations that you make after having analysed an individual’s or a microbiome?

Danny: From a signature standpoint, as I said, there’ve 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 the way, but for the most part, the signatures that we’ve. That we’re using has been verified across numerous academic research studies.

So we’re very confident in the results of the test. From a recommendation standpoint, we’re actually relying on decades of clinical evidence. You can imagine that if you combined the recommendations across all of the dentists and all of the oral health care professionals were.

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 of it that they can take in their lives to improve their oral health and prevent oral disease.

It’s really one of the lowest hanging fruits in healthcare. When we talk about improving patient outcomes on a population scale.

Chris: Are you able to go into detail about these novel discoveries?

Danny: Broadly speaking, I mentioned that we intend to do a lot of research around the connection between oral and systemic health. And we’ve seen some promising research come out that has been able to derive oral microbiome signatures, and associated with things like increased risk or the diagnosis of systemic disease.

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

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

Danny: 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 exercising regularly can reduce your risk for heart disease. Maintaining good oral hygiene practices and being consistent. And the number of times you brush and floss, which is, the same advice that you get from a dentist, but those have very significant effects on our oral health status.

And then you get into the more nuanced areas personalized recommendations where our. The way that our body reacts to some of these pathogenic bacteria, you can differ from person to person. And that’s where we start to really drive value to our users intaking 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 underlying factors that could contribute to risk for oral disease.

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

Danny: Yeah, I think, it’s something that we’re 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, or 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 correlated with increased aging as well. And I think from a society standpoint, our population is living longer than ever before. And I think to the benefit of everybody, we’re also keeping our teeth for longer than ever before.

And 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. And 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.

We’ll have to see, it’s a balancing act, right? Like the. 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: Given the rapid downsizing costs of DNA sequencing we’ve witnessed over the past couple of years or, as well as the increased availability of individual medical records, how would you see personalized medicine evolving in the years to come, as someone who is the CEO of a biotech company?

Danny: Yeah, I think from a sequencing standpoint, the amount of innovation and discovery that has come as a result of the decreased cost and sequencing. It’s 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 and 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 kinds of production, scale, core labs. And then we have companies like Oxford Nanopore that are producing systems that are more decentralized.

That enables do it yourself kind of 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 then from the individual medical records Another kind of 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 the 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 because

of integrating various electronic health records from a. 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 like DNA and sequencing, right?

Like decentralized 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. Combining them on the back end, I think is 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: That brings up the really interesting topic of data protection. I was just wondering what your stance and Bristle Health stance is on keeping individual’s data and how that is handled within the business?

Danny: Yeah. So 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 and yeah. Fortunately, and unfortunately, I think we have learned from other companies in the past that they haven’t been as concerned when they went to market.

So we maintain a completely HIPAA compliant infrastructure. And part of, I think primarily the reason is because we value user privacy above everything else. And 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.

And building that infrastructure now just allows us to seamlessly grow the company and become more of that clinical provider.

Chris:  So could you just provide me with an explanation? What is HIPAA?

Danny: HIPAA is the compliance that has to do with personal health information, 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 oral microbiome profile. And 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.

And that’s exactly what we’re trying to protect by being HIPAA compliant or maintaining this kind of veil of privacy, between the results that we present and people that they’re connected to. Yeah. And there’ve been a lot of problems in the password. I think a lot of users tend to sign off on.

Companies that ended up using a lot of that information for commercial purposes. And that’s very much something that we don’t intend to do.

Chris: What stage is Bristle Health at, as a company?

Danny: So we’re a pretty young company. I think a little under a year old, but we’ve progressed really quickly. And 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. And 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 in lifestyle all the way through clinical recommendations for things like prescription products.

Chris: Where do you think Bristle Health will be in 5, 10, 25 years?

Danny: Something that I think about almost every day the easy answer is hopefully still around. The introduction of sequencing and molecular diagnoses and oral care is something that really hasn’t been done before. And 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. 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. And I’ve hoped that bristle is the company to, to shift the entire standard of care. And I also hope that we 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 at our data to create better therapeutics and better diagnostics, not only in oral health, but across the healthcare spectrum.

Chris: What does the future of health and wellness look like to you, zooming out from Bristol Health for a second, and looking at it from a wider angle?

Danny: The principles of bristle and really apply it to the rest of healthcare decentralized 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.

I think that we’re going to see this. Incredible shift where again we’re proactively managing our health instead of reactively treating disease. And we’re doing that anywhere, or meeting patients and where they are rather than having them come and seek treatment. I think we’ll already be seeing it in oncology and heart disease with companies like in VTA and Everly, in the United States at least.

And I know that there’s companies. Let’s get checked, 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.

At Gowing Life, we want to say a massive thank you to Danny for coming to talk to us. It is extremely exciting to see young biotech start-ups explore new areas of health and wellness, especially in the fascinating world of microbiomes, a field which has only recently begin to gather appropriate appreciation as to its importance. Bristle Health is not only pioneering research into the impact of the oral microbiome on health, but they are also focussing on how to use this expanding knowledge to improve the lives of everyone around them. We wish Danny and everyone at Bristle the best of luck, and are looking forward to keeping a track of them into the future.

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