A few resources:

The Economist, “Microbial ecosystems in the mouth and gut are linked to many ills”: https://www.economist.com/science-and-technology/2021/02/10/...

Personal health care expenditures, by source of funds and type of expenditure: United States, 2007–2017: https://www.cdc.gov/nchs/data/hus/2018/fig18.pdf US Dental care expenditures 2017: https://www.ada.org/~/media/ADA/Science%20and%20Research/HPI...

Healthcare expenditure trends in the US: https://www.cdc.gov/nchs/data/hus/2018/044.pdf

US Surgeon General Report on Oral Health (2000): https://www.nidcr.nih.gov/sites/default/files/2017-10/hck1oc...

The human oral microbiome in health and disease: from sequences to ecosystems: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074908/

Oral microbiota of periodontal health and disease and their changes after nonsurgical periodontal therapy: https://www.nature.com/articles/s41396-017-0037-1

ADA Periodontitis stats: https://www.ada.org/en/publications/ada-news/2018-archive/ju...

The “Gum–Gut” Axis in Inflammatory Bowel Diseases: A Hypothesis-Driven Review of Associations and Advances: https://www.frontiersin.org/articles/10.3389/fimmu.2021.6201...

I'm reminded of a medical maxim: Never run a test if it the results won't affect treatment decisions.

I'm that vein: Is this really a medical test, or is it just recreational?

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.

In highschool, I had an acquaintance whose father was a dentist, and had developed a ‘bad breath detector’ test.

You seemed to stop mid-thought... was there a point you were making here?

> detect the earliest signs of cavities and gum disease - then provide evidence-based recommendations and treatments to help prevent them.

What preventative treatment is this? If it isn't just "brush & floss", then what is it? If it's so great, why not just tell everyone about it now - why do you need a microbiome test?

There's Cavibloc, which is supposed to reduce cavity-inducing bacteria. It was developed at UCLA. There's also CloSYS, which is basically a highly diluted bleach that clears your mouth of bacteria. It is ADA approved. There's also Xylitol, which is also supposed to help reduce bad bacteria. I've been using all of these for the past year, and my most recent dental cleaning had almost no tartar buildup, which is really unusual for me. I have poor flossing habits. You can look into the book "Kiss your dentist goodbye" by Dr. Ellie Phillips for more info. FYI she's not a quack, but some of her claims have been controversial among other dentists.

> but some of her claims have been controversial among other dentists.

I have a lot of dentist family and friends. Anything that isn't "drill and fill" is controversial to them. :)

Dental school these days seems to really stress that everything must be treated with intervention by a dentist that happens to bring money to their practice.

They are also super frightened of new technology. There was a technology that was like a new kind of mouthpiece with microbrushes that could brush your entire mouth in a few seconds. The dentists I know would barely even look at the picture before dismissing it.

I don't know why this is, but I'm pretty sure it has to do with the way their schooling works.

We became exposed to this mentality and reluctance to adapt when exploring solutions to our son’s cavities. There is an amazingly effective treatment called SDF that arrests cavities with no need for drilling by painting it on in a procedure that takes about 1 minute. It’s proven to work, is non invasive, and much easier to use to treat a squirming small child. It’s been used for decades in Japan. Only recently did it become allowed in the US. Yet a couple of years ago it was still shockingly difficult to find dentists who knew about or approved of its use. I was also surprised to find very little literature linking particular bacteria to tooth decay. I think Bristle is on to something here, and I am glad that they are pushing this research forward. Tooth decay seems to have many of the hallmarks of an infection, yet its primary treatment is still to remove damaged portions of teeth with a drill. It feels remarkably primitive.

Since Silver Diamine Fluoride is a little newer, it helps to look at Silver Nitrate, which has the same mechanism save for the, you know, fluoride (which is a boon).

Medical management of caries is anathema to assuming seven figures in debt to hang up a license and turn on the lights, and I’m not implying ill will. The first world countries with national healthcare sans dental could use this without coming close to the dental standard of care - a cavity arrested with silver nitrate is actually better to drill and fill since the infection is halted.

Did you see any of the permanent staining that is mentioned in a sister comment's aappublications link (https://www.aappublications.org/news/2016/08/05/SilverDiamin...)?

If anyone is looking for more information on SDF (silver diamine fluoride), there is some information here:

https://www.aappublications.org/news/2016/08/05/SilverDiamin...

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.

Are you guys familiar with Dr. Ellie Phillips? I'm definitely not a dental health expert, but she seems to be objective about how tooth decay occurs, see: https://drellie.com/2020/10/19/what-happens-to-teeth-when-yo...

I wonder if she'd have useful input on your product. Of course, she's trying to promote her own stuff (she sells Xylitol mints) but she also advocates for OTS treatments like Listerine.

I'm not familiar with her, but I agree she does seem objective and could have some useful input. We'll reach out.

Thanks for sending!

But should you simply kill all bacteria in your mouth? Perhaps some are actually useful?

There are many that are not only useful, but essential to oral health.

You can supplement with probiotics, which have been proven in quality studies to improve mouth/nose/throat health, and, to a lesser extent, even prevent caries. The bacteria cultures are known by their shorthand K12 and M18, respectively. In New Zealand this is part of official health guidelines.

On phone so can't look for references but look it up, it is well supported.

I think I read here recently that mouthwash can cause cancer – even the non-alcoholic one, presumably because of the altered microbiome.

I’ll get hammered for my statement because it’s beyond antidotal. I’m also a bit superstitious, and feel I should just dummy up right now.

I’ve noticed some people just have good teeth, and others are not so lucky.

I’ve been down on my luck for years now. Close to being homeless. I haven’t been to a dentist in over two decades. I still have my all my teeth, except wisdom which I had pulled proactively when I had insurance.

Why do I still have my teeth, and my gums don’t bleed, or are recessed?

1. I feel it’s because I developed a neurotic compulsion to pick my teeth with those disgusting disposable tooth picks, with the floss. (I say disgusting because I see them discarded everywhere, and I worked for the inventor of the product. (Actually his wealthy father invented them, and fully funded his sailboating brat of a son a son to peddle them. He is now a 1 percenter, and yes—I’m jealous.

2. I’ve tried to use an ultrasonic toothbrush once a day.

3. I don’t eat much sugar, but I eat a lot of carbs?

4. Buy a few dental cleaning picks/tools, and learn how to scale your teeth yourself. If you’re gentile, and use common sense, you can get most of the gunk off. Below the gum line is another story though?

Take what I said with a grain of salt. A dentist told me 20 years ago, “you have great teeth, but let’s wait for the X-ray, and look at the bone. He said I got lucky.

I hope my next exam goes the same way?

There's definitely luck with teeth! My dad and grandpa are both dentists so my family had access to every kind of tooth care on a regular basis.

I don't know anyone who gets more cavities than me and my mom. Seriously every time we go to the dentist we're either getting a new filling or replacing an old one.

I even spent 3 years (for non-dental reasons) eating no sweets and not much changed. We just have "weak teeth". I could maybe take better care of mine but my mom is an obsessive brusher/flosser and it hasn't helped her much.

Can definitely confirm this. My brother and I grew up on the same diet, followed the same routine of brushing twice daily, flossing, using mouth wash and going to the dentist at the same time but for some reason he has only had like 2 fillings in the last 25 years while I've had to get some work done on almost every tooth and have had like 6 root canals done.

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.

Since you mention prescriptions and providers, does this mean you intend to distribute the product through dentists?

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.

> What do you do with my data?

> Your privacy is a top priority for us. Our test will pick up some of your DNA - it’s impossible to completely avoid - but we only look at the microbes from your saliva and we take steps in our workflow to throw out human data during analysis.

Can you do better than this? What exactly do you do with the data? What do you store? How do you store it? What do you throw away? When do you throw it away?

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.

Why not put all this info on the site?

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

Is the data really de-identified?

Would our microbiome data be a sort of fingerprint?

I'm a Bristle paying customer, and love the entire conceptual area of microbiomes and self-directed assays. IMHO microbiome science provides a new kind of quantification of health and wellness, and suggests new vectors for treatments and feedback, and can even help enable discoveries of experimental confounders and colliders.

For a good introduction I suggest the paper "Oral microbiome: Unveiling the fundamentals" at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503789/

Thanks so much for your support! You’ve said it beautifully, and we are driven by the potential of the microbiome to better guide health and treatment decisions, and ultimately improve lives.

I love where we're going as an industry in using the tools we have in genetics (and other assays) to better target care and understand the causes of medical issues.

For the range of bacteria you can identify, what are some common treatments / behavioral that finding them might indicate? Or is it more information at this point?

For our early access product, we will be providing you your comprehensive microbiome profile, how you compare to other users, and relative oral health scores. We also provide a summary of current literature around a number of key microbes in the oral microbiome, and their related health associations.

At the moment, we cannot make any health recommendations, but in the next few months we plan to expand our product to include recommendations and fulfillment of prescription toothpastes, mouthwashes, and other preventive tools that we know are effective in improving oral health.

Additionally, we learn more from each user that takes our test, and can expand guidance around other indications where the oral microbiome is implicated to play a role, such as diabetes, cardiovascular disease, and possibly even neurodegenerative disorders. Eventually, the data we gather will also be used to develop personalized therapeutics tailored to treat specific microbial profiles in the oral microbiome.

Are you guys depleting host or enriching microbial? Are you analyzing the data as a composition via log contrasts? Are you using available pipelines (kraken, metaphlan, etc) or something custom? Any plans on doing a functional pathway analysis (ie. humann pipeline) on top of the microbial analysis?

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.

Thanks for the response. I think protocol-bias is something that will be hard to control for. The collection kit, extraction method, library prep method can influence the results significantly from my experience. For example, we've seen significant differences in results between tagmentation-based lib prep vs ligation-based.

Stopped going to the dentist several years ago because I've never gotten a cavity in my life. Would be interested to try this just to check and make sure my luck isn't running out.

A huge reason we started Bristle was to answer this exact question!

Is one test sufficient to really be valuable to a customer? The oral biome seems pretty wild and varying, even just with changes in diet. It seems one test may be useful, but it seems that many tests at some interval are more useful (assessing change, intervention outcomes, etc.). It seems like you would want your initial customers to be people with chronic issues or genetic history predisposing them. Wouldn’t a single test result be more of personal trivia to the average person?

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.

It seems really weird to me that you're selling a "non-diagnostic" early access test but also claiming on your website that "Bristle analyzes your oral microbiome to detect oral diseases." I've seen early access in video games, but never before in a medical device. I'm sure you have lawyers who told you this was okay, but I feel like the whole reason that you have to do clinical trials before selling a product (the spirit of the law, so to speak) is that many consumers will believe that the test you're giving them is producing valid results, even if you have a fine print disclaimer saying that it is for "medical purposes." If someone took this test and wrongly assumed that the results meant they were safe from oral diseases, that could have a really negative impact for them.

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

Looks neat! My wife is a dentist so I hear a lot about developments in this area.

The first question I have is about the business model — people already sadly often cut the dentist when cutting costs, so it seems like it would be hard to get a lot of people paying you $50-100 for a test whose outcome is either “you are ok” or “more costs incoming”. How do you see it working?

We couldn’t agree with you more about people avoiding the dentist when cutting costs, which is always sad to see given the long-term importance of oral health. Our test is initially designed for the population of Americans who already don’t see the dentist, value the convenience of at-home care, and are interested in incorporating preventive health into their daily lives.

There is a large population of Americans (60 – 80MM) who regularly avoid seeing the dentist out of fear/anxiety or inconvenience, many of whom are millennials in major cities. Our goal is to provide these individuals an opportunity to understand their oral health in a non-invasive and convenient way, and then pair that with treatments delivered directly to their doorstep. Many of these treatments such as prescription toothpastes or mouthwashes are underutilized, largely because they are only effective if diseases like gum disease are caught early enough. Analyzing the oral microbiome enables us to do exactly that, and then we can remotely monitor patients to ensure that disease risk subsides. A major focus area for us is educating consumers about the impact of maintaining good oral health and preventing early signs of disease from progressing in order to avoid expensive procedures like cavity fillings and root canals in the future.

Focusing on oral seems like a strange strategy.

Ubiome offered 5 kinds of tests including oral. The vast majority of test purchases were poop related.

What size of a market do you envision? Are you trying to grow to ubiome's level or stay niche?

Oral diseases like cavities and gum disease are some of the most prevalent in the world and are largely preventable if detected early enough. Current tools like x-rays and observational screenings only detect symptoms once they have manifested. We can use genomics and the oral microbiome to realize earlier detection and ultimately, reduce disease progression.

There is a large portion of the population that actively avoids dental visits out of inconvenience or fear/anxiety (60-80MM). We provide a non-invasive, low-cost way for these individuals to understand the status of their oral health from the convenience of their home.

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.

Is there a "best time" for someone to provide saliva? Is this dependent on schedule and/or age? And is this different if you are doing intermittent fasting?

This is a great question! We are actively looking into circadian oscillations of the oral microbiome, but don't currently have any recommendations around specific times for sample collection. The same goes for intermittent fasting! We only recommend that users don't eat or drink for at least 30 minutes prior to sample collection.

Can you drop some non legal plain language on what you do with data?

Frankly speaking, I 100% would assume you're going to sell my DNA and information to huge body of people.

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.

yeah but do you give access to information that comes from users engaging with your service?

is your revenue generated from anything other than products and dtc services?

ive just become skeptical of any company suggesting they can be profitable/have a future without a data pipeline that allows others to buy their data, run analysis on data, build models on data.

and i believe in the near future we run a real risk of insurance prices being based on dna and models of health built on user data.

anyways, blah blah blah, seems like a great idea!

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!

> 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

How is it nearly impossible?

From what I understand, this oral "profile" is stored and then provided to the user on demand.

Isn't the general premise that overall health is causally linked to this profile? If the data was monetized differently in the future, couldn't the association between user and this oral profile possibly give insurance companies something to base pricing decisions on?

How could the report itself be anonymized? Send the user a link to a stored report devoid of any and all personally identifiable data and then destroy any and all personally identifiable data associated with the link?

How can anyone trust someone to actually do what they "promise" with their data without extremely punitive regulation?

Some people suffer from bad breath due to their oral microbiome. Could your test diagnose that too and suggest solutions?

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.

Look into K12 and M18 probiotics, I commented elsewhere in this thread about it.

I really want to do this (sounds really cool!) but the signup page here really rubs me the wrong way, I don't feel comfortable giving out my card info to be charged at some undetermined time in the future.

Is there an email list I can get on to notify me? If not, please post again when you're ready to accept orders.

Completely understand! We are accepting groups off the waitlist in batches so we can ensure a timely return of results to users. To give you a sense of timing, we have been accepting individuals off the waitlist, processing payment, and shipping kits within 2 - 4 weeks of sign up.

Given we are offering this test for a limited time, we cannot make any promises on how much longer it will be available to the public. If you would like to stay updated on future product releases, you can sign up for the email newsletter at the bottom of our website. Hope that helps!

How does your IRB feel about having people pay to be part of a study?

Do you look for specific non-dental disease factors, such as microbes that can lead to damage to the heart valves? What about signs of oral cancers (would those be strained out in the process of rejecting the human cells?)

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.

What about the part about charging people to participate in a study? That seems backwards and morally questionable. Usually the entity doing the study reimburses the participants for their expenses and inconvenience. Is this not an IRB-approved study?

Will the early access users get access to the treatment recommendations when the ability to give recommendations for treatment becomes available or will they have to do another round to get that? If I can do the test now and get the updates later I’d be a lot more comfortable signing up.

We'll be continually updating your early access report with new discoveries we uncover along the way, but we may not be able to provide treatment recommendations from the early access test once we flip to clinical. Things like lifestyle, diet, hygiene can be provided. Regardless, I'd recommend retaking the test when we launch the clinical product since your oral microbiome may have changed since the time you took the early access test, so the recommendations between now and then might be different!

So do we actually have useful data for this? Are oral microbiomes regular enough that you can tell me "hey you're missing species X, go make out with someone with good teeth to reintroduce it to your mouth"?

Great question. We have a good idea of which species drive oral diseases, so we can tell if you have an overgrowth of these species. Our hope is through Bristle we can better characterize what constitutes a healthy microbiome so we can develop better oral care products and guide treatments (though we haven't studied the effects of making out yet)

Related (oral related to gut that is)?

Over 140k virus species in the human gut, half of which are new to science

https://news.ycombinator.com/item?id=26389397

Thanks for sending this! One aspect of our test we're excited for is the ability to profile viruses, fungi, and bacteriophages since we use Shotgun Whole Genome Sequencing on the microbes (vs. a technology like 16s that only profiles a single bacterial gene).

Interesting work!

Are there any treatments that kill the pathogenic but leave the beneficial microbes?

Does mouthwash kill them equally? What about h2o2 or xylitol?

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.

I'd just add that we're hoping to develop products that specifically reduce/eliminate oral pathogens while encouraging growth of probiotic species

That sounds great. Does xylitol do that to an extent?

It seems that more research is needed to confirm, but there are some studies and use cases where Xylitol seems to prevent tooth decay. This study has a great review[1] under "Xylitol and other polyols": https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830181/

FYI - If I click to accept cookies in the middle of filling out the form, it wipes the form of any information.

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

Interesting that there are no commercial 'probiotics' for children onward to adulthood.

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/

Have you considered complementing DNA testing with selling specalty augar (to detect Streptococcus mutans for example) and instruction manuals with an online forum?

There is, look into K12 and M18, species of streptococcus salivarius with proven oral health benefits. They are available as supplements, and in New Zealand they officially use these to treat children with recurring nose/throat diseases. Studies back this up.

Do most pathogenic microbes tend to be gram negative? If so why is that?

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.

Do you find long term partners tend to have the same oral microbiome?

Great question! We haven't looked into this ourselves yet, but a 2014 study found "that average partners have a more similar oral microbiota composition compared to unrelated individuals, with by far most pronounced similarity for communities associated with the tongue surface" and is "most pronounced in couples with relatively high intimate kiss frequencies".

https://microbiomejournal.biomedcentral.com/articles/10.1186...