6 ms·

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 t

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.

margalabargala 3y 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 3y 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 https://www.futuremedicine.com/doi/10.2217/fmb-2018-0043
  - space_fountain 3y ago
    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
    - tadfisher 3y ago
      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.
      - yorwba 3y ago
        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.
  - Natsu 3y ago
    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.
space_fountain 3y 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 3y 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.
  - space_fountain 3y ago
    Oh interesting. I didn't realize. Are there theories on what causes that difference? Is it diet?
    - deleted 3y ago
      [deleted]
    - space_fountain 3y ago
      I read up on this a bit. It seems that it is diet. Captive primates eat a more grain rich diet while the wild ones get most of their sugar from fruit
smallnamespace 3y 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 3y 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 3y ago
    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.
mannyv 3y ago
FTA, the process is: blast mouth with oral antibiotics then swab the stuff on. It'll be interesting to see if it works.
bilsbie 3y ago
> Oral probiotics function primarily through bacteriocins What does this mean exactly?
tambourine_man 3y 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.
hedora 3y ago
Any thoughts on these folks? (They are your direct competitor.) https://probiorahealth.com/product/probiora/ 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=12369203 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?)
- mock-possum 3y 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.
- throwaway290 3y 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=()
MostlyStable 3y 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.
corethree 3y 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.
sonicanatidae 3y ago
I know nothing about oral bacteria, but I like the cut of your jib. I'm with this science guy!

margalabargala 3y 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 3y 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 https://www.futuremedicine.com/doi/10.2217/fmb-2018-0043
- space_fountain 3y ago
  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
  - tadfisher 3y ago
    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.
    - yorwba 3y ago
      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.
- Natsu 3y ago
  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.

space_fountain 3y 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 3y 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.
- space_fountain 3y ago
  Oh interesting. I didn't realize. Are there theories on what causes that difference? Is it diet?
  - deleted 3y ago
    [deleted]
  - space_fountain 3y ago
    I read up on this a bit. It seems that it is diet. Captive primates eat a more grain rich diet while the wild ones get most of their sugar from fruit

smallnamespace 3y 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 3y 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 3y ago
  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.

mannyv 3y ago

FTA, the process is: blast mouth with oral antibiotics then swab the stuff on. It'll be interesting to see if it works.

bilsbie 3y ago

> Oral probiotics function primarily through bacteriocins What does this mean exactly?

tambourine_man 3y 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.

hedora 3y ago

Any thoughts on these folks? (They are your direct competitor.) https://probiorahealth.com/product/probiora/ 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=12369203 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?)

mock-possum 3y 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.
throwaway290 3y 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=()

MostlyStable 3y 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.

corethree 3y 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.

sonicanatidae 3y ago

I know nothing about oral bacteria, but I like the cut of your jib. I'm with this science guy!