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.
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.
The mutation that allows it to produce this (and to survive it) is a naturally occurring one. This strain, with that mutation, was found in the wild, which was what gave rise to the idea to use it in this way in the first place. One of the modifications they _did_ do was to break this bacteria's lateral gene transfer machinery so that it can't spread these genes to other strains.
However it is likely that, since this one strain managed to evolve this trait, that others have as well.
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.
> 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.
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.
The article gives this as the explanation of how it is supposed to work:
BCS3-LI has four main genetic modifications:
It produces a weak antibiotic, mutacin-1140, which kills competing oral bacteria.
It’s immune to mutacin-1140, so it doesn’t kill itself.
It metabolizes sugar through a different chemical pathway that ends in alcohol instead of lactic acid.
It lacks a peptide that its species usually uses to arrange gene transfers with other bacteria.
The antibiotic helps it win the Darwinian competition in your mouth to become King Of The Oral Bacteria. The alcohol metabolism means it won’t produce lactic acid (and so won’t cause tooth decay). The peptide knockout prevents it from transferring genes back and forth with other bacteria that might either inactivate it or leak its advantage.
> It metabolizes sugar through a different chemical pathway that ends in alcohol instead of lactic acid.
It'd be quite funny to live in a future where cavities don't exist, but breathalysers are useless. (without rinsing your mouth out first, I guess) Hopefully it doesn't dry out gums and cause gum disease.
The article extensively talks about the amount produced. While it has not been tested against breathalyzers, it is producing so little alcohol that it seems unlikely to be a problem. The claim in the article is that, across 24 hours, you might consume a few miligrams of alcohol, as compared to "if you swallowed 1/10th of your mouthwash, that would be ~200 milligrams of alcohol". So across the entire day, you are producing a couple orders of magnitude less alcohol than is in 1/10th of a mouthwash treatment (or 1/5th I guess if you use it twice a day).
So to be specific what you're skeptical of here is that S. mutans can outcompete other bacteria without its ability to generate acid If this engineered version can stay in the mouth it should be able to live in the exact same lesions the non mutated version can right? It should still have all the adaptations to live in a low pH environment. I guess this is an extraordinary claim so it's right to be more cautious than the internet usually is, but that also seems to be an easy thing to test for. You can swab someone's mouth who's taken this and see if they still have the mutated bacteria or if it's been out competed
Also keep in mind that this strain was discovered about 50 years ago in a human host (the "grad student" reference). The tech is in mutating it further to prevent adaptation, but the beneficial mutation (secretion of mutacin-1140) appears to be the product of natural evolution.
The beneficial mutation is not secretion of mutacin-1140, but absence of lactic acid production. Transplanting only the original mutacin-1140-producing strain wouldn't help anyone, since it still produces lactic acid that would destroy your teeth all the same.
david_l_lin upthread is stressing that lactic acid is ordinary Streptococcus mutans' primary defense against other bacteria and it wouldn't be able to survive without it.
The significance of mutacin-1140 is that it provides an alternative means of defense against other bacteria (or maybe offense would be a better word) which potentially makes lactic acid redundant.
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.
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?)
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.
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?
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.
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.
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.
Except that we can! The oral microbiome can be modulated to get exactly what you’re asking: remove pathogens that are good at creating acid and replacing them with ones that are good at remineralizing.
Shameless plug for my company (Bristle Health) that is trying to do exactly that via oral microbiome testing and personalized recommendations and products to improve.
Interesting, can you tell more? I’ve tried oral probiotics without much effect.
Did notice a difference for a couple of days after taking antibiotics for a week for something else, but it quickly subsided (my regular micro biome probably quickly recolonised the mouth).
All the species in the probiotic have been clinically studied with evidence that supports improvement in the oral microbiome and reduction of oral disease. Although, for transparency, the mechanism of action of some of the probiotics is still unclear, and we're working on figuring that out to improve oral probiotics and products in the future.
>Eighty-five FES patients and 35 CHR subjects were psychotropic medication naïve and all participants were free of substance abuse, suicidal ideation, and unstable medical illness.
Super interesting study! Other studies also associated the oral microbiome with cognitive health, like depression and Alzheimer's, but this is an interesting finding.
>H2S-producing bacteria exhibited disease-stage-specific enrichment and could be potential diagnostic biomarkers
This would suggest that people with bad breath may have higher risk of schizophrenia? Or maybe the reverse? I also wonder if this was controlled for oral hygiene routines and oral health in general? I would assume people with uncontrolled schizophrenia have worse oral health, which may be a factor?
Makes me wonder what parts of your mental and emotional health are mediated by your own breath?
Since the brain attenuates everything outside of the status quo what portion of what it is spending energy attenuating is your own malodorous exhalations?
How does the static labor of keeping your autonomous body on cruise control affect your mental and emotional health? If we could identify and control some of those things, how would their presence or absence alter your mood and worldview?
This is anecdotal but, I used to know somebody with schizophrenia. This person regularly took care of their teeth but had pretty bad dental problems. Lots of cavities and gum disease and such. Apparently they were even told by a dentist at one point they just had 'bad bacteria' in their mouth and would likely have tooth problems for the rest of their life.
In the last 5 years or so, research has shown tight associations between specific pathogens in the mouth and inflammation throughout the body.
Fusobacterium nucleatum and colorectal tumors, Porphyromonas gingivalis and tangles in the brain, Prevotella intermedia and rheumatoid arthritis, the list goes on.
It might be no surprise that you are what you eat, and you eat 100 billion bacteria every day via swallowing your saliva. The gut microbiome gets a lot of traction on HN for its associations with... well anything, but the oral microbiome is relatively ignored.
At Bristle, I'm hoping we can shed some light on the importance of the oral microbiome, and people will eventually stop collecting their poop, and just collect their spit.
It's interesting that we've become so obsessed with the gut microbiome even though stool only captures a tiny fraction of the composition of the gut.
Similarly, the salivary oral microbiome has also been correlated with mental disorders, cognitive health, is modulated by diet, and plays a major role in systemic health. And saliva is objectively easier to collect. Instead of jumping straight into collecting poop, we should be collecting our spit instead!
I have a chicken and egg issue with microbiome stuff. Does your microbiome look different because you are suffering from an issue, or does your microbiome looking different cause the issue.
Kind of like when an auto-immune disorder is causing inflammation. You can treat the inflammation, but you aren't treating the real problem.
I recently had mouth surgery where they had to open up the lower part to access the jaw bones. From what I understand, they sterilize your mouth pretty well beforehand. I had to rinse my mouth out with a foul tasting mouthwash and woke up with strange tastes and dark products around my lips. Since then, I've felt like crap. At first I thought it was the surgery itself. Then a long effect of the anesthesia. Except that it did not go away.
Anyway, I recently read a lot about probiotics and decided to try L. reuteri orally.
The result is so instantaneous that I was scared it might be psychosomatic from a placebo. But if it is indeed a placebo, it is the strongest I have experienced, so I doubt it.
My mouth went from always dry and smelly to well hydrated in one day. After 5 days, my mood completely changed, including the quality of my sleep.
I don't know if I was depressed per se, I had not consulted anyone. However, I had a heavy weight on my shoulders that is now gone.
Since that experience, I have added L. reuteri pills made for gut health to my diet. I am now considering making my own probiotic yogurts and as a family we have started to experiment with fermented sauces and pickled vegetables.
There is something very important about probiotics that is almost overlooked. I think we should all pay much more attention to it.
I don’t doubt that money is their highest priority, as that is the case for most people when it comes to their job. But the implication that they are sabotaging our teeth or giving bad advice in order to be able to bill us for bigger procedures down the line is a much bigger claim.
> Year after year, Lund had performed certain procedures at extraordinarily high rates. Whereas a typical dentist might perform root canals on previously crowned teeth in only 3 to 7 percent of cases, Lund was performing them in 90 percent of cases. As Zeidler later alleged in court documents, Lund had performed invasive, costly, and seemingly unnecessary procedures on dozens and dozens of patients, some of whom he had been seeing for decades. Terry Mitchell and Joyce Cordi were far from alone. In fact, they had not even endured the worst of it.
They don't have to sabotage people, all they have to do is nothing - in terms of researching new better ways to prevent issues - and they're already set.
I think it's because incumbents in the space have played a huge role in preventing adoption of new technologies that actually prevent disease. Dentists make money not from preventing disease, but from performing procedures when disease has already progressed to the point of no return.
Cavities and gum disease are bacterial infections that are completely preventable. I feel the need to plug what we've been building at https://www.bristlehealth.com/. We've built an at-home test that leverages the microbes in the mouth to detect disease, and provide actionable and personalized recommendations that can reduce your risk of gum disease, cavities and persistent bad breath.
Nobody wants to go to the dentist until it’s too late, because it’s so expensive nor covered by health insurance.
Even if it’s not intentional, dentists aren’t R&D specialists. They’re a service, at a premium price, whose livelihood depends on people going for treatments.
They don’t have one. There is no lever. This is conspiracy theory nonsense, but even if there was a lever they wouldn’t need to pull it.
I move in social circles with a lot of people from the dental care industry and I can tell you that no one is worried about running out of treatment opportunities.
I’ve met hundreds of dentists over the last 18 years and they all spend their days asking patients to brush and floss. It’s a simple thing, it's pretty cheap, and prevents almost all oral diseases regardless of diet or genetics. It's easier than changing your diet. It's a LOT easier than changing your mouth biome. It's practically a miracle cure when done regularly with decent technique.
And… the vast majority of people simply don’t brush and floss like they should. I'd guess that the group that does is about the same size as those who actually get enough exercise, which is about 23.2% in America[1]. People consume mind-boggling amounts of refined sugars and generally don’t take care of their teeth.
There is no sinister cabal keeping people in cavities and gum disease because, it’s simply not needed.
The lever is the lack of funding and motivation brought about by the previous factors. It’s not an individual choice, rather a medical industry wide systemic issue.
Fee for service in health care is not compatible with prevention. The vast majority of oral issues are preventable because they stem from bacterial infections. Dentists take full advantage of information asymmetry: patients assume the dentist knows best. They are incentivized to maintain the status quo that has patients pay enormous costs out of pocket for procedures that could have been prevented early on.
At Bristle, we’ve created an at-home oral health test that also pairs you with ingredient recommendations to prevent the progression of oral disease. The goal is to give data around oral health without the misaligned incentives of a practitioner who benefits from your demise.
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.