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david_l_lin · 2 years ago
This story has been around for far too long and evidence is unbelievably weak, and the claims border on fraudulent.

1. The claim that this strain outcompetes the same S mutans from occupying the same niche cannot be true unless this strain is also capable of creating and tolerating environments with low pH. By definition if it creates acid to the same degree it will also cause cavities.

2. Single applications are insufficient to cause any persistent colonization. Even multiple daily applications of oral probiotics don’t lead to colonization. Oral probiotics function primarily through bacteriocins, not through colonization (except in very rare cases). This is because the existing microbiome is incredibly difficult to outcompete. The community in your mouth has evolved for as long as you have lived, and in some ways was shaped for generations before as it’s technically inherited from your ancestors.

3. S mutans is not the only species that causes cavities. S sobrinus, S wiggsiae, B dentium, about a dozen other acidogenic species also cause cavities.

Source: I’m a cofounder at Bristle Health, the oral microbiome company.

smallnamespace · 2 years ago
From the article, the claim is that this strain of S mutans variant produces mutacin-1140 which allows it to outcompete other strains of S mutans and other Gram-positive bacteria.

I have no particular opinion about whether this claim is plausible or true, but you don't address this at all in your comment even though it's directly relevant.

For example, if this strain's production of mutacin-1140 allows it to kill other bacteria locally then it could maintain a niche despite higher pH. One way to view this is bacteriocin production substituting for lactic acid production as a weapon against competing bacteria.

Also, the percentage of the novel S mutans strain colonization is being measured in the first chart and shows initial 90%+ followed by a later drop and stabilization. It would be helpful to more directly address the evidence as presented.

EDIT: Also, this S mutans strain doesn't need to outcompete the entire existing oral microbiome. Even if mutacin-1140 is less effective than lactic acid at creating a niche, it suffices to just maintain a toehold in the microbiome while outcompeting existing acid-producing S mutans strains.

justinclift · 2 years ago
> if this strain's production of mutacin-1140 allows it to kill other bacteria ...

Wonder if it could in a different direction, giving rise to other oral bacteria also unaffected by mutacin-1140?

MostlyStable · 2 years ago
The article includes evidence that shows persistent colonization for a year after a single application. And it appears to be a steady prevalence for the last 6 months of that.

Now, to be fair, what I would have _liked_ to see is actually percent prevalense of the various cavity causing bacteria for that year, since that's the thing we really care about (in case this bacteria _isn't_ succesfully killing those strains).

But it certainly appears that they have succesfully engineered a strain that can persist in your mouth after a single application (although they admittedly claim that this application needs to follow a special cleaning procedure to remove most of the existing bacteria)

Your comment seems to really not address any of the specific information provided in the article and seems to be a generic response to the idea.

I love hearing from experts who disagree with an article, it's important to hear those views. But this would have been a much more valuable comment if it could have responded more specifically to the claims and information in the article rather than the general idea.

margalabargala · 2 years ago
Your first point seems wrong.

> cannot be true unless this strain is also capable of creating and tolerating environments with low pH

Whether it can tolerate low pH environments is not particularly related to whether it creates low pH environments. If it's agnostic to pH levels around that range, then it can inhabit that niche whether or not there is acid being secreted.

david_l_lin · 2 years ago
I should clarify: there’s some more details to why S mutans actually requires low pH. The correct term wouldn’t be “tolerate low pH” but rather “requires low pH” for its stable colonization.

S mutans creates incipient lesions by making acid, incipient lesions are micro environments where the low pH that causes enamel decay is determined by the biofilm on its surface. S mutans cannot thrive in environments with neutral or high pH. the existing community (including other Streptococcus species) create local alkaline environment via multiple metabolic pathways, including the most well studied and prevalent arginine deiminase system. A “normal” healthy community antagonizes S mutans by maintaining a normal pH in saliva and the tooth surface, preventing stable colonization by S mutans.

Without acid production, S mutans cannot stably colonize. and is readily outcompeted by the existing community. Any novel strains of S mutans to “compete for the same niche” will suffer the same weakness unless they create acid. but if this “probiotic” also creates acid, then by definition it also causes cavities.

edit: adding citation https://www.futuremedicine.com/doi/10.2217/fmb-2018-0043

hedora · 2 years ago
Any thoughts on these folks? (They are your direct competitor.)

https://probiorahealth.com/product/probiora/

A decade or so ago, their founder started with genetically modified bacteria that supposedly outcompete wildtype strains. The regulators responded in the only sane way possible, and it didn't go to human trials, from what I can tell.

List of publications from their founder:

https://pubmed.ncbi.nlm.nih.gov/?term=Hillman+JD&cauthor_id=...

Later, they just cultured a large number of wild strains, looking for ones with the desired properties, and now sell a mixture of three of them.

(Edit: I just realized the company in the article is selling the old work from Hillman's lab, but he is not a member of the team. I'm guessing you don't have a high opinion of this follow on work either then?)

throwaway290 · 2 years ago
Your first link redirects to Google.

     curl -v https://probiorahealth.com/product/probiora/

    > GET /product/probiora/ HTTP/1.1
    > Host: probiorahealth.com
    > User-Agent: curl/8.1.2
    > Accept: */*
    > 
    < HTTP/1.1 302 Moved Temporarily
    < Server: nginx/1.14.0 (Ubuntu)
    < Date: ...
    < Content-Type: text/html
    < Content-Length: 170
    < Connection: keep-alive
    < Location: https://www.google.com
    < Strict-Transport-Security: max-age=63072000; includeSubDomains; preload
    < X-Frame-Options: SAMEORIGIN
    < X-Content-Type-Options: nosniff
    < X-XSS-Protection: 1; mode=block
    < Referrer-Policy: strict-origin
    < Permissions-Policy: geolocation=(),midi=(),sync-xhr=(),microphone=(),camera=(),magnetometer=(),gyroscope=(),fullscreen=(self),payment=()

mock-possum · 2 years ago
Absolutely anecdotal - for a couple months Ive been taking a probioria tab every night before bed, and my mouth seems to be less gross pasty sticky in the morning.

I’m curious to see whether my dental hygienist notices any improvement next visit.

space_fountain · 2 years ago
A part of the story that has always made the claim more plausible to me is the claim that apes tend not to get cavities at the same rate we do. Since they have teeth that are as susceptible to acid as ours the story goes their diet tends to lead to other populations of bacteria in their mouthes out competing the cavity causing ones. Then people will go on to say that this ecosystem of mouth bacteria have co-evolved. The reason we have so much trouble is that we've changed our diets drastically relatively recently aka a few hundred thousand years. It sounds like you would argue that some part of that story is wrong. Maybe the bit where eventually a less damaging microbiome would evolve?
mplewis · 2 years ago
The idea that primates get cavities less frequently than modern humans is a bit outdated and not terribly supported by recent studies. The main difference is in the location of the cavities, not frequency – apes tend to get cavities in their front teeth, humans tend to get cavities in the molars.
corethree · 2 years ago
I'll take your remark into account but you are a competitor and also biased. Doesn't mean what you say isn't true, but it's definitely misaligned incentives. Thank you for your input.
tambourine_man · 2 years ago
Yes, I remember reading about something like this a very long time ago. You’d wake up with a fresh breath (alcohol) instead of spoiled milk (lactic acid). And less cavities. Just like revolutionary batteries, I’ll believe it when we reach the millions of users.
bilsbie · 2 years ago
> Oral probiotics function primarily through bacteriocins

What does this mean exactly?

mannyv · 2 years ago
FTA, the process is: blast mouth with oral antibiotics then swab the stuff on.

It'll be interesting to see if it works.

sonicanatidae · 2 years ago
I know nothing about oral bacteria, but I like the cut of your jib.

I'm with this science guy!

phero_cnstrcts · 2 years ago
> The FDA demanded a study of 100 subjects, all of whom had to be “age 18-30, with removable dentures, living alone and far from school zones”. Hillman wasn’t sure there even were 100 young people with dentures, but the FDA wouldn’t budge from requiring this impossible trial. Hillman gave up and switched to other projects

Interesting that the FDA can request such things. Would be a good way to block disruptive products that larger companies wouldn’t like.

jseliger · 2 years ago
The FDA is often bad: https://jakeseliger.com/2023/07/22/i-am-dying-of-squamous-ce....

It is good at "protecting" people from things that might help them. Like many others, I'm being protected from treatments that might harm me, so the cancer I've got can kill me instead.

autoexec · 2 years ago
Any luck with that federal Right To Try angle?
inglor_cz · 2 years ago
Hello Jake, I just wanted to tell you that I admire your fighting spirit. Best of luck to you and your wife.
hypercube33 · 2 years ago
It's wild we aren't digging into bacteria phages and instead roll down the antibiotics road while it's ok to use them for sandwich meats. Yes they are living and adapt but so does bacteria.
elcritch · 2 years ago
Somehow I keep loosing confidence in the FDA. That basically sounds like a special interest group giving unreasonable requirements to prevent it succeeding.

What’s the chance that some of the FDA personnel were linked to companies in dental or dental care products? Perhaps some national association of dentists?

Symmetry · 2 years ago
It's actually a lot better than it used to be. You wouldn't see a situation where beta blockers were available in Europe a decade ahead of the US nowadays.

Dead Comment

erellsworth · 2 years ago
I worked for a place that recruited people to test stuff like toothpaste, mouthwash, and other personal care products way back in mid 00s. We worked with a lot of big-name companies, and one of them was trying to get approval for a very similar product. The criteria were very similar to what's described here, where the person had to be perfectly healthy and also wear dentures. I think it took us about a year to recruit like 3 people before they just gave up and dropped the whole thing.
Symmetry · 2 years ago
In 2020 the FDA wanted people developing tests for Covid-19 to get some SARS to make sure their test didn't accidentally show a false positive when SARS was present. But of course there was no way the CDC was going to hand out SARS to random research labs.

I'm pretty sure this is just someone at the FDA trying to be diligent in their own way. Mostly this is downstream of powerful companies being able to sue the FDA for allowing things if the FDA doesn't follow procedure, which the FDA wants to avoid.

gumby · 2 years ago
> They offered my wife and me free samples (based on her work, not as compensation for writing this post); she accepted, and I’m still debating.

Given that it's an oral colonist it seems likely that the author has tried the free sample as well, even if they were to live in a no-kissing houshold.

The title is a lovely garden path sentence: "A genetically modified bacterium that outcompetes bacteria causing tooth decay" -- a straightforward parse leads you to the plausible assumption that the genetically modified bacterium causes tooth decay. The insertion of a "the" before "bacteria" would remove the ambiguity.

ghodith · 2 years ago
> Given that it's an oral colonist it seems likely that the author has tried the free sample as well, even if they were to live in a no-kissing houshold.

The author addresses this under the header "2.1: As users kiss their loved ones, who kiss others in turn, will this spread exponentially and take over the world?"

Nthringas · 2 years ago
funny how one "the" flips the meaning of the sentence

I thought I was being paranoid until I started reading the article

I choose to believe this is a freudian slip, which means they're trying to cause tooth decay while pretending to do the opposite.

If I were dentistry as a business, I wouldn't like this permanent (final) solution to tooth decay because of my unreasonably suspicions that the odontological treatment I received as a child was unconsciously intended to make me continue to need 'dental care' instead of fixing anything. Last time I was at a (very expensive private) dental clinic the treatment they pushed on to me was killing my tooth so I would buy one. I'm pretty sure some hugely powerful branch of dentistry is betting on people in my demographic (who get their teeth killed off) buying a full set of teeth from them in the future.

But I would only accept Thompson teeth, the only teeth capable of chewing other teeth

isoprophlex · 2 years ago
Rise up sheeple, and rinse out your mouth with bleach twice daily to remove any gentech germs! Big Teeth and their engineered bacteria are keeping us down!
rubidium · 2 years ago
Anecdote time: My great grandmother lived to be 102 and never had a cavity. Kept all her teeth to the end.

One time, an orderly who thought she was just being senile tried to reach into her mouth to take out her teeth (thinking she had dentures). My great grandmother bit that person; hope they learned not all old people are senile!

I’m 40% of the way there. No cavities and rave reviews from my dentist. I brush—-best case —-once a day.

I’d not be surprised if it’s a genetic lottery of tooth enamel, tooth size (small) and mouth biome.

_ah · 2 years ago
I'm very similar. I have excellent oral health... brush 2x/day, don't floss. Two interesting datapoints:

1. I changed jobs a few times, and for various reasons I neglected to see a dentist for 10 years. When I finally went back, had perfect oral health and no cavities. My hygienist still remembers me because this event was so far outside her experience + expectations.

2. My wife had "normal" tooth decay problems throughout her life, until we started dating, at which point she's had no further cavities. ;)

To answer the normal questions: I don't do anything particularly special with my diet except a general avoidance of sweetened drinks - no soda pop, no sweeteners in my coffee.

If anyone wants to swab my mouth and pay me a small licensing royalty for commercialization please get in touch. Heh.

bzykubd · 2 years ago
You should start a company providing kissing therapies
zo1 · 2 years ago
One suggestion/theory I'd like to posit about this. There may be a third factor, and that is our "awareness" of what's in our mouth. After I eat food, I can't stand for any food that is lingering or stuck anywhere on my teeth. It gets picked out with my tongue, water, or something else. It could be that a lot of people that have bad oral "health" are unaware of the amount of food they're letting float around in their mouth because they never became aware or able to "sense" the insides of their mouth.
renewiltord · 2 years ago
It would be cool if you would submit your DNA to a public database. It could be useful at some future time.
fastball · 2 years ago
How's your breath? Frequently you either have a mouth microbiome that ends up acidic and prone to cavities, or you end up with a high pH mouth which lends itself to tartar buildup and halitosis.

Of course if your teeth are decaying due to cavities and this is left untreated, halitosis is also a common result.

depressedpanda · 2 years ago
Not OP but this is how it is for me.

Also, anecdotally, from people I've spoken to, it seems they get either caries or tartar. It's a decent sample size, more than a dozen.

Yet the last time I went to a dentist, 2010 or so, she claimed to have never heard of this, and I couldn't find any good studies either. Do you know of any?

rubidium · 2 years ago
I don’t get negative reviews to my knowledge :)

Maybe it’s the balance of regular coffee intake for lowering pH but a naturally higher pH?

shmde · 2 years ago
What is your diet ? I am assuminf there is no processed sugar or refined wheat/gluten ?
mikk14 · 2 years ago
Not OP, but in a similar situation. I'm 39, the last time a dentist looked in my mouth I was probably 16 or so* and I brush only once a day (after breakfast, which is the least effective over doing it before going to sleep). Never had a cavity. I don't think I have halitosis, at least the people I have kissed over the years never complained to me.

Being Italian, I eat pasta literally every day, and my daily breakfast is chocolate chip cookies.

My impression is that mouth health is 100% genetics and biome lottery.

* I have extreme mistrust in their profession, due to bad experiences. When I was a kid, I injured a milk tooth which turned black. The dentist shrugged and said that it would fall normally. It didn't and it fucked up all permanent teeth that sprouted in random directions in the area. Every single dentist surveyed to fix the problem requested gigantic payments (to the tune of tens thousands of dollars, this was in the 90s in Italy, so adjust for inflation and cost of living to know how crazy this was) without providing any result guarantees, so I kept my crooked teeth. It doesn't help dentistry in Italy is that profession where you mainly do tax evasion, and occasionally look into people mouths to pass the time.

lm28469 · 2 years ago
Diet doesn't do much if you have bad genetics, I eat and brush the same as my gf, we don't smoke/drink, exercise the same, we basically have the same exact lifestyle. She has teeth issues multiple times a year, I never had a single problem
rubidium · 2 years ago
Nothing that severe. I have beer, toast, sandwiches and burgers. I don't do a ton of sweets / soda but I do some (and if I do my teeth definitely get a fuzz that motivates brushing!).

My great grandma loved jello “salad”s (eg jello with fruit in it). It’s just genetics.

Beijinger · 2 years ago
I just rinse my mouth every night with sugar, in addition to brushing. Have not had problems since. Effect of three-year consumption of erythritol, xylitol and sorbitol candies on various plaque and salivary caries-related variables https://pubmed.ncbi.nlm.nih.gov/24095985/

Xylitol and erythritol inhibit real-time biofilm formation of Streptococcus mutans https://pubmed.ncbi.nlm.nih.gov/32600259/

And, what I always expected, it is better to rinse with two sugars:

Exploration of singular and synergistic effect of xylitol and erythritol on causative agents of dental caries https://pubmed.ncbi.nlm.nih.gov/32286378/

two tablespoons and 50 ml of handwarm water (the stuff does not really dissolve good), a few drops of this: https://www.apodiscounter.de/myrrhentinktur-hetterich-30ml-p...

This tincture might not be available in the US due to alcohol content. I saw only oil based versions in the US.

bigDinosaur · 2 years ago
Sugar alcohols*. You certainly should not rinse your mouse with sucrose as your first sentence implies would be fine.
sgt · 2 years ago
I rinse my mouth regularly with coffee and chocolate containing sugar. I always thought it was a bad thing. Bring on the donuts!
Beijinger · 2 years ago
I eliminated regular sugar to a bare minimum in my diet.

https://en.wikipedia.org/wiki/Pure,_White_and_Deadly

unaindz · 2 years ago
You last link returned no results.

But I think this is the same in a 50ml bottle. https://www-apodiscounter-de.translate.goog/myrrhentinktur-h...

danielsousame · 2 years ago
Two tablespoons of which? One of each? Two of each?

What's the purpose of the myrrh? It seems to appear a bit out of nowhere in the recipe

rrgok · 2 years ago
Ah, I've been doing the same but only with xylitol. Maybe I should by both, erythritol and xylitol, and make cavity killing cocktail.
pkaye · 2 years ago
Is there a way to determine if FDA actually set this requirement for the study? Is it on public record? Or do we just have to rely on what they claim.

Also why not try getting it approved elsewhere first like in the EU if FDA is making it harder to approve?

at_a_remove · 2 years ago
I can only add that I wrote Dr. Hillman over a decade ago and he wasn't specific about it, only that the FDA's requirements were not reasonable.
ChrisArchitect · 2 years ago
Related:

Story out of Japan that has been getting attention in the last year around here

Japan pharma startup to begin human trials of tooth regrowth drug in 2024

https://news.ycombinator.com/item?id=37638956

tempestn · 2 years ago
This specific product aside, it seems to me there could be huge future potential in therapies involving genetically engineered bacteria. We can modify bacteria far more easily than we can our own genomes. And we're just beginning to develop an understanding of the gut microbiome. As that understanding improves, surely there will be opportunities to make beneficial changes.