david_l_lin

This is an excellent anecdote for exactly why we are building Bristle. We're finding more and more that oral health is not a one-size fits all. I'm glad you've been able to find something that works for you.

If you look closely at the data from the blog, there are flossing "responders" and "non-responders". I'll have some follow-up data published about this soon, but we've been able to define oral microbiome archetypes that we're using to predict which oral health regimens may actually work for you. There are some people who never floss and still never get gum disease or caries, and unfortunately some who do everything they can with no improvement.

cofounder at Bristle here. Unfortunately there is a lack of data around the efficacy of behavioral, lifestyle, and product interventions on oral health despite decades of dentists telling their patients to "brush and floss more". We decided we would share some of our findings with the community in an effort to shed some light on the importance of the oral microbiome in oral health.

I’m glad you brought up the history of halitosis and marketing. In fact, the oft recommended twice-per-year visit to the dentist began as a pepsodent ad! It turns out that in low risk individuals, the frequency of dental cleaning and checkups did not improve oral health outcomes.

https://evidence.nihr.ac.uk/alert/dental-check-ups-every-six...

Now onto halitosis. Intra-oral halitosis is caused by volatile sulfur compounds and volatile organic compounds that are generated by microbes in the mouth: aka the oral microbiome. A number of studies have shown that halitosis is associated with specific bacterial species that have been shown to create these compounds both in vivo and in vitro. A good review on the subject is here:

https://pubmed.ncbi.nlm.nih.gov/32748883/

A number of clinical trials aimed at the efficacy of mouthwashes, probiotics, probiotics, lozenges have even been published. The general consensus is that mouthwashes offer temporary relief (through broadly decreasing microbial burden), and some probiotics are effective long term, but there is still much to uncover in this space as community dynamics of the microbiome are complex.

https://pubmed.ncbi.nlm.nih.gov/30834725/ https://pubmed.ncbi.nlm.nih.gov/27508274/ https://pubmed.ncbi.nlm.nih.gov/31799694/

Regular oral hygiene is a decent predictor of oral health. However this does not explain why the incidence of caries and irreversible gum disease are so high. Almost half of all Americans have some form of gum disease, which we can predict using the oral microbiome, which are the same people that regularly see a dentist and have “normal” hygiene habits.

Let’s stop normalizing reactive medicine and start thinking about personalized preventive approaches to health. There is no one size fits all approach to your systemic health, and the same applies to oral health.

Depending on your oral microbiome, there are more specific mouthwashes that primarily target anaerobic species that are implicated in diseases like gum disease and halitosis. Fluoride is highly effective at reducing caries incidence, but some newer ingredients also exist (such as nanohydroxyapatite) with high clinical efficacy if you worry about fluoride overexposure.

Additionally, depending on your oral microbiome, and your risk for oral disease, we recommend other products that can reduce your risk of disease and prevent the outgrowth of species implicated in oral disease.

Unfortunately we don’t ship to Australia yet! Someday soon I hope!

This is because of negative impacts that broad antimicrobials have on your oral microbiome. These mouthwashes essentially burn away your microbiome and allow for new species to repopulate the niche. Many times this means that anaerobic species that cause halitosis can come fill in the space.

Not directly related, but Listerine and other broad antimicrobial mouthwashes have been shown to have a negative impact on the oral microbiome similar to how antibiotics cause dysbiosis in the gut.

At Bristle Health, we advocate for products that foster an environment that supports your oral microbiome rather than destroy it, as it’s crucial to both your oral and systemic health. You can find more about our research here:

www.bristlehealth.com

Might be related, but mouthwash use is correlated with a drop in systemic nitric oxide levels due to the negative impact on the oral microbiome. You can find a review here:

https://pubmed.ncbi.nlm.nih.gov/35081826/

At Bristle (oral microbiome testing) we advocate against broad antimicrobial mouthrinses as they can negatively impact your oral health similar to how antibiotics cause dysbiosis in the gut.

The associations between gut microbes and disease may be valid, but simply not actionable. The gut has incredible size, and is thousands of niches rather than a bag of marbles.

The oral microbiome, however, is an entirely different story. Decades of research show causal links between oral bacteria and disease. And it’s readily accessible so it can be easily tested and modulated.

Let’s stop using “microbiome” to describe the gut only. The gut microbiome may be full of overhyped studies, but the oral microbiome or the skin microbiome are entirely different stories.

Bristle (YC W21) | Software Engineer | San Francisco Bay Area, San Diego, US | REMOTE | Full Time | https://www.bristlehealth.com/

Bristle is a consumer wellness biotechnology company that leverages genomics and the oral microbiome to detect oral disease before the onset of irreversible symptoms that require expensive procedures like root canals and gum grafts. Our mission is to shift the standard of oral health care to personalized preventative solutions rather than reactive treatments. From a simple at-home saliva test, we provide users a convenient way to check their oral health status, discover the microbes in your mouth, and receive personalized recommendations and products to improve their oral health.

We’re hiring for a front-end or full-stack software engineer to help us iterate on our product!

Our stack is built primarily on TypeScript, React, Go, Postgres, Docker, AWS, and Python. If you're a jack of all trades and are looking for diverse projects that will have a significant impact, then we'd love for you to apply! Reach out to david at bristlehealth.com, I look forward to connecting!

Bristle (YC W21) | Multiple Positions | San Francisco Bay Area, San Diego, US | Remote possible | Full Time | https://www.bristlehealth.com/

Bristle is a consumer wellness biotechnology company that leverages genomics and the oral microbiome to detect oral disease before the onset of irreversible symptoms that require expensive procedures like root canals and gum grafts. Our mission is to shift the standard of oral health care to personalized preventative solutions rather than reactive treatments. From a simple at-home saliva test, we provide users a convenient way to check their oral health status and receive personalized recommendations and products to improve their oral health.

We’re hiring for the following positions:

- DevOps Engineer: https://bristle.notion.site/DevOps-Engineer-Bristle-9988c2fe...

- Backend Developer: https://bristle.notion.site/Fullstack-Back-end-Engineer-Bris...

- Bioinformatics Scientist: https://bristle.notion.site/Bioinformatics-Scientist-Bristle...

Our stack is built primarily on Go, Postgres, Docker, AWS, TypeScript, React, and Python. If you're a jack of all trades and are looking for diverse projects that will have a significant impact, then we'd love for you to apply! Reach out to david @bristlehealth.com, I look forward to connecting!

Caveat: I did not read the paper but can weigh in on this:

1. The eye has immune privilege, similar to that of the brain, meaning it can tolerate antigens that would normally trigger an immune response elsewhere, like your arm.

2. Fragments of proteins expressed internally are normally presented on the surface of cells through a process called antigen-presentation. This allows immune cells to "see" when cells are infected and expressing proteins in the cytosol they normally would not.

Together this means that exogenous expression of proteins in the eye do not trigger inflammation because the eye is immune privileged, but if those proteins were expressed in the arm, there would be an immune response even if proteins are only cytosolic.

Halitosis is absolutely a wellness indication that we eventually plan to report on as we gain more insight to the pathways involved. A number of studies have suggested that sulfate reducing bacteria may be a culprit for bad breath, and we eventually may be able to target those specific microbes and limit halitosis in the near future.

We do not sell personal microbiome, genetic, or survey-related data and don't have plans to do so. We will make every effort to keep your personal data yours. We de-identify all your data so that it can only be analyzed as an aggregate, so while your microbiome data and health survey data contribute to new scientific discoveries, they also remain completely personal. It will be nearly impossible for interested parties (such as insurance companies) to get a hold of your personal information on the Bristle platform and use it as leverage for their pricing. Hopefully this helps relieve some of your concerns, as we have similar concerns around health-related privacy, too!

There have been some intriguing studies associating the oral microbiome with systemic diseases such as cardiovascular indications, diabetes, oral cancers, and neurological diseases such as Parkinson's and Alzheimer's. Some studies even suggest causal links between pathogens that reside in the mouth and arterial plaque and even neurodegeneration.

With the Bristle platform, we will have the resolution to dive deeper into these associations, and potentially improve patient outcomes through targeting the oral microbiome.

One major feature of gram-negative bacteria is their production of LPS, which is inherently inflammatory and can contribute to disease. That said, many gram-positive bacteria can also be pathogenic. The relationship between bacterial pathogenicity is more nuanced than just their cell wall composition. We believe that Bristle can serve as a platform to reveal some of the host-pathogen interactions in the oral cavity.

A majority of the products marketed today non-specifically ablate the microbiome. While they are effective at reducing the microbial titer as a whole, they are ineffective at specifically targeting pathogenic microbes associated with disease.

Definitely! There's still a lot of unknowns in the microbiome space, and it's something we hope to look into as we gather more data. Some studies have suggested that adolescent oral microbiome profiles can serve as indicators of future health outcomes. Review here: https://pubmed.ncbi.nlm.nih.gov/32350240/

Well said! Incumbents in the space have a lot to gain from the status quo of "drill, fill, and bill". This has limited the adoption of new diagnostic technology and advances in preventive health. We hope to eventually replace observational screenings that detect the onset of irreversible symptoms with early detection and interventions that prevent disease altogether.

Forgoing the details, from the user perspective, the product is almost entirely direct to consumer, and the Bristle platform provides users the opportunity to both request a test and further consult with a dentist. Prescriptions and interventions will be physician-mediated upon interpretation of test results.

Regarding the oral focus: Our core technology is based around the oral microbiome for a number of key reasons.

1. decades of research have shown causal relationships between the oral microbiome and preventable gum disease. 2. the oral microbiome is much lower in diversity than the fecal microbiome, granting the opportunity for the development of relatively low-cost diagnostics that leverage the microbiome. 3. new and exciting studies have shown correlations between the oral microbiome and a number of systemic health indications, which we hope to continue to uncover with our platform.

Great question! We recommend a cadence similar to that of a dental checkup (at least every 6 months) depending on your oral health status. We will eventually provide insight into whether applied interventions are effective at improving your oral health, and can prescribe personalized recommendations based around your oral microbiome. A single test can provide unique insight and objective data to users about their oral health status, and in the near future we hope to be able to provide a complete end-to-end solution (from test to diagnosis to treatment) even after just your first test.

We do not sell your DNA and do not have future plans to do so, in fact we don't currently store your personal genome information, and would inform you if this were to change. We will ask for consent before doing any analysis on your personal DNA, if we were to expand studies to include human genomic markers.

Each microbiome is unique, and preventive measures against bacteria that cause gum disease may not be effective against bacteria that contribute to cavities and vice versa. The solutions (such as prescription-strength fluoridated toothpastes, antimicrobial mouthwashes, or personalized probiotics) that we plan to recommend may require a prescription that we anticipate we will be able to fulfill only after a diagnostic evaluation. This provider-mediated solution is critical to avoiding unnecessary and potentially harmful prescriptions, while also preventing disease.

We're working on building a knowledge base, as there are several pseudoscience wellness recommendations that have no clinical validity, and will share these on our blog that you can find on our website. A Bristle mission is to also develop more effective personalized therapeutics and oral care products that effectively treat microbiome dysbiosis to prevent disease prior to the onset of symptoms and irreversible disease.

Great questions! We implement a host-depletion step in both the wet lab, to increase sequencing depth of the microbiome, and dry lab. You may be concerned about potential bias introduced, and we've done some extensive research with our depletion and sequencing methods to reduce the cost of the test while also maintaining integrity of the microbiome profiles.

Regarding pipelines: we use a custom pipeline that is similar in principle to available pipelines you mentioned (part of our secret sauce). We are actively working on functional analysis, as we hope to eventually develop targeted therapeutics that exploit microbial pathways to prevent disease.

That's a great suggestion, we'll work on getting this added to our list of FAQs.

Short of giving away some of our secret sauce and analysis pipeline, what we do is sequence the nucleic acids in your saliva in a de-identified fashion such that only Bristle scientists can match your sequence data with any potential identifiers. As data comes off the sequencer, we use a bioinformatic pipeline to remove 98%+ of human genetic data prior to any analysis such that its impossible to derive meaningful genetic information from the sample. The end result is that we effectively store only microbiome sequence data and not your personal genetic data. We store all of your data in accordance with HIPAA guidelines.

Your de-identfiied data (metadata and microbiome data) may be used in aggregate analysis to mine for novel biomarkers of disease, and to develop novel therapeutics targeting the oral microbiome for the treatment of disease.

Our early access test is recreational. However, we anticipate to provide clinical decisions for oral health in the near future. By signing up for the educational test today, you are also contributing to scientific discoveries and helping to develop future products that can prevent disease.

Thank you for your input, that's completely understandable. We're describing in our website the product that is undergoing clinical validation, but want to provide consumers an opportunity to gain insight into their oral microbiome, as there are no equivalent comprehensive oral microbiome tests. The "early access" test is a limited offering that provides novel data to users.

We are making it clear to users during on-boarding and in the microbiome report that our test is currently for educational and research purposes only. You are right, there are health implications behind results of the test, and we hope that the data we provide empower users to make impactful positive decisions around their oral health.

We are on-boarding early access users off the wait-list in small batches in the hopes of discussing the product 1:1 with each of them. Our assay is currently undergoing regulatory approval and we anticipate to have a diagnostic offering by the end of 2021.

Our goal is to make sure users up front know what they are receiving with the early access test, so if you have other suggestions or concerns we'd love to chat with you - feel free to email us at info@bristlehealth.com

Thanks for catching that! We'll get it fixed right away!