=biology =medicine
You may have heard that tooth decay is caused by bacteria producing lactic acid. Let's consider that a little more deeply.
criteria for decay
To effectively cause cavities, bacteria must meet 4 criteria:
- Anchoring (with special proteins) to either the tooth surface or something
connected to it.
- Biofilm production to trap nutrients and protect the
bacteria.
- Metabolism that produces acid, especially lactic acid.
-
Growth in acidic conditions.
Some of those can be done by different bacteria, but cavities are made most effectively when a single species can do all of them.
many species of bacteria exist
Converting glucose to lactic acid is one of the (biologically) easiest
ways to get energy (ATP) from it. As such, lactic acid bacteria are one of
the most common types, and as you may know, there are a lot of bacteria
species, maybe around a
million.
Human mouths have over 700 known bacterial species, and probably more
unknown ones.
That being the case, you should expect that multiple
types of bacteria are responsible for dental caries, aka cavities.
Streptococcus mutans
If you've looked into tooth decay, perhaps you've heard of S mutans,
which notably meets all of the above criteria.
Here's an introductory
paper on it.
If you
have a sugary drink, then notice your teeth became more sticky, that's not
the sugar just naturally sticking to your teeth. S mutans makes an enzyme
(dextransucrase) that makes a sticky polymer (dextran) from sucrose
specifically; using sucrose is more thermodynamically favorable than using
glucose or fructose. But of course, there are other
bacteria
that make exopolysaccharides.
S mutans also:
- Produces lactic acid.
- Can tolerate relatively low pH.
- Uses
sortase
enzymes
to anchor cell wall proteins to teeth.
looking under the lamppost
I've heard people say that "S mutans is the bacteria responsible for
tooth decay", and I was immediately suspicious. Sure, it's been found on
teeth, and it can degrade enamel, but outside of a lab, there are always
multiple bacteria.
S mutans grows better in lab cultures than most
bacteria, which is part of why it's been focused on. Why is that?
S
mutans makes mutacins, which are a type of antibiotic. (The ones produced are
strain-specific.) Because of that, at high densities and without something to
wash away extracellular chemicals, S mutans tends to outcompete other
bacteria present in mouths. As a result, when people tried to culture
bacteria from dental plaque, it would often dominate.
If you
do PCR on samples of plaque and saliva, you'll find S mutans in the
majority of them, but not all of them.
That said,
while there are other cavity-causing bacteria, anything meeting the above 4
criteria and generally adapted to life in mouths will tend to have most of
the properties that all S mutans strains do. So, using it as a reference
target isn't wrong.
some other bacteria
First off, there are many strains of S mutans, and the difference
between strains and species is a bit loose when there's asexual
reproduction. S sobrinus is closely related to S mutans, meets those 4
criteria, and is associated with cavities, but it's considered a different
species.
Lactobacillus bacteria produce lactic acid and have good
acid tolerance. They don't adhere to teeth as well as S mutans, but can
stick to other bacteria that stick to teeth. And Lactobacillus reuteri
produces exopolysaccharides.
Actinomyces bacteria seem to be
important in cavities, especially on the roots of teeth.
let them fight
Mitis streptococci (eg S sanguinis and S gordonii) release millimolar
concentrations of H2O2, which inhibits S. mutans. As mentioned above, S
mutans produces mutacins, and some of those target mitis streptococci. Also,
S mutans can tolerate lower pH (greater acidity) than mitis bacteria.
Yes, S gordonii
can cause cavities, but as it stops growing at higher pH, it does that less
than S mutans.
S oligofermentans is also common in humans, and also seems to inhibit
growth of S mutans (and other acid-tolerant bacteria) largely via H2O2
production. It's even been proposed as a probiotic.
treatments
What might be good ways to prevent tooth decay?
chemicals
hydrogen peroxide
As I mentioned above, there's a
tradeoff between acid tolerance and H2O2 tolerance, and different bacteria
optimize for different conditions.
Perhaps by adding some H2O2
occasionally, the balance of bacteria could be persistently shifted away
from more acid-tolerant species? I'm not sure, but it seems possible, and
swishing with 0.1% H2O2 solution seems unlikely to cause much harm. I'm not
the FDA, so that's good enough for me!
chlorhexidine
Lots of mouthwash formulations have
chlorhexidine as an
antimicrobial. I don't use those myself, so I hadn't really looked into it,
but let's see...oh, no, I don't like the look of that molecule.
And
in practice, it...thaaaat's not a good sign.
Why would you even use
chloroaniline...wait, it's just a mediocre cationic surfactant? Just use a
choline fatty acid ester then! What's wrong with these people?
anti-biofilm drugs
Biofilm production from sugars
and anchoring to the tooth surface both involve a small number of enzymes
that are outside bacteria. That makes them easier to target with drugs than
usual.
There are some people working on fancy anti-biofilm
drugs. That seems
fine, but also probably expensive. Well, I suppose rich people like having
nice teeth?
enzymes
If dextran
can be made by enzymes, perhaps people have found enzymes that can unmake
it? Indeed, many
dextranases have
been found.
In that case, perhaps people have considered using those
to prevent tooth decay? Well, not only has it been considered, but they're
used in some products for pets! For example, Zymox makes a multi-enzyme
product for dogs & cats with: dextranase + mutanase + lactoperoxidase +
lysozyme + lactoferrin. You can even buy it on
Amazon!
(I also have a page just for stuff on
amazon, if you need to reach their free shipping threshold.)
(To be
precise, lactoferrin isn't an enzyme; it's a multipurpose protein that,
here, I think mainly acts by chelating iron, which all cells need.)
In theory, the same approach could be used for people, but I would of course
never advocate using veterinary products on humans, even if they're
theoretically the same chemicals with the same quality control. Yes, I know
the lower costs of veterinary treatment can make US healthcare seem
expensive, but don't worry: private equity groups are working
on
establishing vet monopolies.
dentin substitutes
Teeth are normally close to an equilibrium where the rate of deposition on
them is similar to the rate of dissolution and wear. When deposition is too
slow, sometimes people just need more calcium, but when that's not enough,
how about adding some kind of protein that's similar to dentin and is
compatible with normal tooth structure?
That's right, I'm talking
about oligopeptide
P11-4. IIRC, it was
approved in Europe in 2012 and then one of the Curodont products got FDA
approval in 2019. Maybe dentists should use that type of thing more...?
probiotics
There's
a startup called Lantern Bioworks working on a probiotic they call Lumina.
That's a modified strain of S mutans that:
- produces ethanol instead of lactic acid
- produces an
antibiotic
- has resistance
to that antibiotic
- lacks a mechanism for horizontal gene transfer
So, first off, that antibiotic is already produced by some S mutans strains,
and it hasn't led to their dominance. It seems relatively easy for bacteria
to develop resistance to, so they would. Or rather, some already have, since
it exists in nature.
And I think horizontal gene transfer would still
happen despite the attempt at preventing it. Also it...already happened.
Also, if you change S mutans to not produce lactic acid, that strain
will get outcompeted by bacteria that can't tolerate pH as low but produce,
say, some H2O2. As mentioned above.
Also, if you have some GM strain
of S mutans that anchors to teeth and kills off other strains but doesn't
produce lactic acid, then Lactobacillus will stick to your GM bacteria and
proceed to produce lactic acid.
So there are some problems. But is it
possible to produce a GM bacteria that would displace S
mutans and related species like S sobrinus? It's a tricky problem, and my
biochemistry skills are meager compared to my teachers, but I'm inclined to
say "yes".
How might you do that? I'd probably start with one of
those naturally competitive bacteria that are less acid-tolerant and make
some H2O2. Actually, maybe I'd start by looking at bacteria in the mouths of
people with no cavities, like
this. See also eg
L paracasei
28.4.
Folks like Lantern Bioworks should remember to bow to the master before they begin.
brush your teeth
Many people around the world use brushes to clean their teeth. You may even
have done that yourself. Often, a paste is added to the brush used to clean
teeth - "toothpaste" and a "toothbrush", if you will.
That brushing
can break up biofilms, and remove bacteria and food from teeth. In theory,
it could be done many times a day, but there are a few problems with that:
- It takes some time.
- Most people don't carry a toothbrush & toothpaste
with them, and using it in eg a restaurant bathroom tends to be
inconvenient.
- Toothpaste is kind of abrasive, and using it several
times a day can be worse than having some more bacteria.
There's actually a partial solution to those problems: additional tooth brushing without using toothpaste. Most people think you have to use toothpaste every time you brush your teeth, but that's a big lie told by Big Toothpaste.
eat less sucrose?
I
suppose that's an option, but if the replacement is high-fructose corn
syrup, is that an improvement? From a shallow perspective they seem
metabolically equivalent, but there actually are some
differences
in the effects. Longer-term, fructose is more reactive, so high blood levels
of fructose instead of sucrose seems somewhat worse.
From my
perspective, trading some of the problems of high blood sugar for
more-easily-mitigated dental issues seems like a sweet deal.