david_l_lin

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

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.

Indeed we do! We have an oral microbiome test you can find here: https://www.bristlehealth.com/pages/products

and our first probiotic here: https://www.bristlehealth.com/pages/probiotic

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.

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.

Majority were not on medication.

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?

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.

well, for the most part in healthcare we treat symptoms not causes.

cavities caused by acid producing bacteria? drill and fill

gum disease caused by oral dysbiosis? bone and gum grafts

diabetes from autoimmunity? insulin

high cholesterol from… anything? statins

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!

https://www.nature.com/articles/s41398-022-01922-0 https://www.nature.com/articles/s41598-021-94498-6

All you need to do is visit the dentistry reddit sub and look at threads like this: https://www.reddit.com/r/Dentistry/comments/vnv25a/how_is_he.... They all operate on "production" because billing is top priority.

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.

I wonder if the same is happening to mouth microbes, which could explain the epidemic of oral disease in developed countries.

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.

Honestly, neither. Biology is complex and messy, and often not at all intuitive.

Just watched John Q (2002) last night, and can't believe that despite all the attention it gets, nothing has changed at all. Can't say I'm surprised though.

A lot of studies have shown that literally taking up genomic space is a function. So by definition, all genes have a function. Non-genes have functions. The topological organization of genomes is a function.

Even an exogenously expressed non-human protein still has a "function". even if you force it to be expressed. We may not understand its effects, but it is certainly doing something. Even just taking up a space is a biological function, which an exogenously expressed protein is doing. The same applies to genes that do not get translated to protein, by definition of "doing something" they have a function.

Your viral integration example is actually a perfect example of one where all genes indeed do a have a function, but they are not readily apparent to us. Genes that control latency may not expressed until specific conditions, and that is their function, to control expression. Some genes control integration.

I spent 5 years of my life doing my PhD studying viral replication, and the "unknown function of viral genes" was a constant topic of discussion, but we all agreed, they have a function.

"this outcome fails when this byte of data is missing"

The outcomes here are not failures, they are measurable phenotypic differences, which they use to group genes into phenotypic outcomes. The typical "knockout -> failure to perform a function" is not what's being measured here.

All genes have a function. This paper helps us understand genes of unknown function (which is a LOT of them).

Some of these functions are not intuitive: maybe they regulate the function of another protein, maybe they only function in the context of a particular stressor, etc. You can think of nearly unlimited scenarios to apply and you start to understand the complexity of understanding how a gene functions.

Not really?

It says that some genes result in the same outcome when knocked out as other genes, and identifies novel genes that putatively participate in the same pathways as others. This helps get at the potential function of genes without known functions.

Bristle cofounder here. In short, we found that people using an electric toothbrush have increased commensal species in their oral microbiome compared to those using a manual brush. We looked at potential confounders, and found that this effect was negated if you only brush once per day.

We also found that bacterial species that cause bad breath (halitosis) were higher in people using a manual brush, but only people under 30 had reduced scores when using an electric brush. Surprisingly, people with existing gum disease did not benefit as much from an electric toothbrush.

Our data suggest that an electric toothbrush is better at removing biofilm than a manual one. Additionally, accumulation of biofilm seeds an environment for slow-growing anaerobic species. Frequent efficient removal of this biofilm is important for growth of commensal species, and reduction in pathogenic anaerobes that can cause disease.

TLDR: Brush 2x per day, and use an electric toothbrush, especially if you're under 30 and don't have existing gum disease.

you will get paid SIGNIFICANTLY less than you would doing almost anything else

Definitely true.

have zero autonomy

Might be true? But in the right research group, this is definitely not true. I actually find that I had far more autonomy in academia than in industry. There are far fewer deadlines, less time pressure, and more curiosity-driven projects that are entirely owned by you.

and get no respect

Might be true, but I find a lot of people in industry feel they get no respect as well. As an academic, I actually found that I respected academics more than I did people in industry. Though this is entirely anecdotal.

I was an academic until my 30s before going to industry, and actually find that the autonomy is the number one reason people like academia. YOU drive the projects because only YOU know the research that deeply. YOU get to be at the forefront, and YOU know things nobody else might ever know, until you get to share them through publications and presentations. Academic projects have essentially no deadline (projects are on multi-year long timescales rather than quarters or months in industry).

Healthcare is notoriously slow with adoption of new technology. IMO this is because healthcare is fee-for-service, which is basically incompatible with prevention. A movement to value-based care would vastly improve adoption of preventive and personalized healthcare.

Findings of this study suggest that the US expenditure on cancer care may not be commensurate with improved cancer outcomes.

Well yeah, the cost of healthcare in the US is astronomical. https://www.healthsystemtracker.org/chart-collection/health-...

This would be the same across diseases, not just cancer.

Not really, we don't do tests if it won't impact treatment, and in this case there is no change in treatment (yet) based on inflammatory cytokines.

Why isn’t this fact used clinically, at least for diagnosis, then?

1. Primarily because IL6 and IFNg are inflammatory cytokines that when increased can indicate any number of things, most commonly caused by infection tissue damage, or other chronic inflammatory diseases like IBD. These cytokines are not unique to depression.

2. Clinical definitions of depression are not related to or dependent on inflammation. AFAIK diagnostic measures of depression are only related to mood.

3. Medicine is notoriously slow at leveraging scientific findings. We’ve known for decades about the power of early cancer detection by cfDNA sequencing yet we still rely on symptoms to catch cancer, when it’s often too late. My jaded opinion is that fee for service is not compatible with disease prevention.

Cofounder at Bristle here. In short, we found that analyzing the oral microbiome from a simple at-home saliva-based test is 88.32% accurate at diagnosing gum disease (even when we ignore severity of disease). We're working on improving the accuracy through improvements in our bioinformatics and data pipelines. With ~47% of Americans over 30 having some form of gum disease, we're hoping this data helps to improve methods of preventing gum disease beyond the failing dogma of "brush and floss more"

The rise of zoonotic infections should not be surprising at all given the rate of deforestation and general disregard for nature.

I find that many of the PhD students who struggle are not prepared for the mostly self-driven nature of the pursuit, and have not had enough work experience to know how to choose a supervisor.

The statistics support this: a majority of the PhD dropouts are students straight from undergrad who performed well academically, but have never had work experience.

Finishing a PhD is as much about selecting a good PI as it is love of the science. Anecdotally I've seen many great students struggle because of lack of support from their PI, and many "worse" students do extremely well because they chose a terrific PI who builds a support system around their students so they almost cannot fail.

Hi! That's a great question that we've heard more than once. We're compiling the data, and so far we simply don't have enough data around water flossing vs string to draw any conclusions. In general, it definitely appears that any flossing is better than none with a caveat:

There are flossing "responders" and "non-responders" that we are looking into and hopefully we'll have another post to share soon. It appears that the oral microbiome may be able to predict whether flossing (or perhaps water flossing) actually improves your health because for some it does not have as much of an effect as others.