A PODCAST FOR YOUR MOUTH!

Taste your way to oral health show notes

Can we taste our way to oral health?
Originally, us mouth obsessed ppl, thought of the taste receptors as a way to discern bitter from sweet to determine safe or dangerous goods.
But recently, over the last 10/15 yrs, taste receptor research is touching on other aspects of health like the microbiome, immunity, and psychology.
One piece of research really caught my eye a few years ago - out of Monell center in Philadelphia (and collab with Chinese university) - they have been studying smell and taste for over 50 years. The study involved mice that were deficient in specific taste receptor signaling molecules- they showed that gingival tissues that have SCCs (solitary chemosensory cells) utilize bitter receptors that respond to the oral microbiome. Mice deficient in the ability to signal with their taste receptors, had a significantly different oral microbiome that accelerated bone loss. In perio model, adding a bitter agent to the mouse gingiva unregulated anti microbial products and reduced bone loss. This was published in 2019.. and I’ve been obsessed ever since.
Intro on WTF we care about Taste receptors:
CZ story: I first became interested in taste receptors when I made the discovery that I cannot taste bitter foods. Someone had put arugula on a pizza and I was like what is the point of putting lettuce on pizza? Well, they alerted me to the fact that arugula happens to have a flavor…one that I could not perceive. Since then, i’ve learned so much more about taste and I’m super excited to share some of that with you. Of course taste receptors are important to help us engage with food and identify things that are bad for us- but taste receptor research has been uncovering SO MUCH MORE about taste and we are here to talk about it.
There are receptors for salt, sweet, sour, bitter, and umami (still investigating fat taste receptors) and within each taste category- many taste receptors comprise one group for example with the taste receptor family for bitter there are 25 different receptors! And they are expressed well beyond the tongue in places like: gut, respiratory, brain - tissues, as well as many immune cells.
*did you know that there is a supertaster test you can purchase on Amazon? It contains three different compounds (on paper strips) that effectively test your genetic variation for taste Receptor TAS2R38 (Thiourea, Sodium Benzoate, PTC: stands for phenylthiocarbamide and resembles toxic alkaloids found in some poisonous plants. Normal taster can’t distinguish between molecules. Standard supertaster if you can only taste PTC strips, Recessive if can taste PTC & Thiourea but not SB, dominant supertaster if can taste all three) Types of receptors- 5 (bitter sweet umami sour salt..fat?) 25 bitter (T2Rs) 1 sweet (T1R2/T1R3) 1 Umami (T1R1/T1R3) 1 sour receptor: potassium channel Salt receptor: epithelial-type Na+ channel on the apical membrane of some taste cells CD36 fat sensing gene?? move into SNPs related to pathos Locations: palate v tongue v gingival (body) Review Taste buds Old view (tongue had areas of taste), new view (each bud has all the receptors)- but back of throat has increased density of bitter taste receptors… initiate gag reflex Review Taste tissues mucosal/airways/GI- basically anywhere with a microbiome mouth and throat, but also in the intestines, brain, bladder and lower and upper respiratory tract, breast cancer cells, ovarian cancer cells and neuroblastoma, mediate the bronchodilatory effect in human airway smooth muscle (implication for asthma/COPD), TAS2R receptors negatively impact glucose homeostasis has produced a new area of diabetes research Early OTs (2006) found sweet taste receptors can detect natural sugars as well as nonnutritive sweeteners which can activate and regulate insulin and GLP-1, two important issues for people with diabetes-
Now Let’s Deep dive into the oral cavity! There are two functions for taste receptors in the oral cavity that have been identified thus far- the first is taste receptor involvement in gingival tissue turnover and the second is the taste receptor to taste and respond to the oral microbiome- so let’s jump into this- (CZ) Gingival tissues- recall: research around taste receptor involvement in tissue turnover that, if disrupted, can lead to periodontal disease AND 2010 paper Wendal investigated bitter tasters and cavities- the assumption was that bitter tasters/supertasters would have more caries due to poorer diet (higher sugar/lower greens) but they found the opposite: supertasters were somehow less likely to get cavities! Since then, others have tried to replicate- although often repeatable not all studies are consistent perhaps lending to societal differences: sp dietary/lifestyle diet/preferences/taste receptor genetics Korean study of 3500 ppl found that nontasters actually consumed more fruit and had higher BMI/Bodyweight than super tasters (exact opposite of their assumptions) -when you can only taste the sweetness of life, what stops you from eating it?! Gingival tissue and Taste Oral Microbes and Taste S mutans saves us from S aureus Bitter receptors and oral health Bitter Asthma Bitter Treatment Asthma Taste and Immunity P. aeruginosa and Taste Taste genes and gut microbes Sweet receptor discussion (JD) Sweet and umami receptors are G protein-coupled receptors (GPCRs) that belong to the the taste receptor family 1 (T1R) Can taste a variety of sweet compounds like natural sugars, NNS, sweet-tasting proteins, etc. Differences in taste perception typically associated w/ genetic variation People with Ile/Val genotypes consume less carbohydrates → lower risk of developing caries Children w/ low sensitivity to sweet → higher abundance of S. mutans (JD) Taste receptors in microbial sensing- discuss different mechanisms - The expression of bitter receptors on immune cells have been shown to assist in the recognition of microbial metabolites T2Rs in the airway can bind acyl homoserine lactones (AHLs) from pathogen P. aeruginosa → activated host immune response (Hariri et al, 2017; Freund et al, 2018) Bitter taste metabolites from bugs can activate T2Rs to induce NO production, which may upregulate phagocytosis of macrophages (Gopallawa et al, 2021) Inversely, sweet taste receptors may DOWNREGULATE innate immune response T1R2/3s activated by sugars or bacterial amino acids can inhibit T2R-dependent signaling → diminished immune response to microbial bitter products (Lee et al, 2017) (CZ) Bitter receptor discussion on antimicrobial peptide production University of Manitoba has a lot to say about taste in oral health: one study T2R14 can sense S. Mutans quorum sensing molecule - which decreased cell internalization for S aureus but not mutans - indicating that mutans may be somehow protective against an aureus infection. Conversely, S aureus induced HBD2 - a natural antimicrobial peptide from GECs - which is known to be broadly antimicrobial for G- and Candida. We use oral hygiene products that are anti microbial eg. CHX: recently it has been shown that some of these products can disrupt nitric oxide functions in the oral cavity (deplete oral bacteria necessary for nitrite breakdown) which can negatively affect blood pressure. Interestingly, CHX is bitter, causes disruption to taste, and blocks nitric oxide functions- nitric oxide is key to taste receptor function. Currently, there is a deficiency in taste receptor function research with regard to oral hygiene products- there are some researchers going after bitter compounds to understand potential benefits to oral health but so far no one has thought to evaluate current hygiene products for benefit/detriment to the taste receptor systems.
Can we taste our way to health? - Apparently it is a mind over matter discussion where the more we expose ourselves to a food, we become more accepting. I think about this in terms of taking on a raw food lifestyle (not suggesting this is good for anyone) - having grown up on the west coast, it’s easy to get swept up in food fads - but every time I opted for increasing greens/veggies/Whole Foods (and minimizing sugars/processed foods) there was a time period of grumpy discomfort but after a few days or every a couple weeks, I grew to enjoy the new array of options and felt happier/clearer thinking. It seems that research supports this phenomenon.
Can we modulate our receptors? One of my primary questions is that, yes we can change our diet.. but can this help us change our taste receptor expression pattern? Anyone who has been addicted to caffeine may be able to relate here: early in exposure to caffeine, you get a hit of adrenaline, heart rate increases but over time, it seems less effective such that you’re ingesting more to repeat results…so now you can have a cup of coffee at 4pm and still fall asleep as normal… which wouldn’t have been possible in the beginning. This is one example of caffeine tolerance. Taste Receptor research suggests this phenomenon is happening with Tastants as well! A mouse study that tested fasting, cholesterol lowering diet (rich in bitter compounds), as well as a high-fat diet to find that all interventions regulated a bitter receptor T2R138 (RNA expression) and signaling molecule in different locations of the intestines (upper/lower). In other words, changing diet can affect expression of the taste receptor system but it seems a bit more nuanced than an ‘off/on’ situation. Another study showed that mice exposed to long term exposure to salt and msg (umami) had decrease to chemical/sensory channels (NaCl channels and umami receptor (mRNA levels)- together, this suggests that we can regulate taste receptor activity- but long term exposure to same foods may induce tolerance leading to overeating -so, the take home would be to eat a wide variety of tastants.
Another level of modulation may come from our microbiome or environmental exposures: there is a lab at UPENN studying the crosstalk between taste receptors and TLRs (TLRs are another way our body ‘sees’ microbes) - both receptors can respond to bacteria/fungal/viral species differently and engage our immune system in a variety of ways. We are at a frontier here as not much data exists yet but preliminary research suggests there is crosstalk and that taste receptors may be another way to modulate our immune system.
We know that drugs can influence our taste - but we have not really evaluated how other non-food items are influencing our taste system. Like our exposure to oral hygiene products. CXH seems to disrupt the system… and due to the specific disruption to the nitric oxide system, other mouthwashes are being evaluated. There was a study showing that regular use of mouthwash (2x/day) over the course of several years increased the progression of prediabetic to diabetic. It was a very interesting study but it had some flaws. Still, their findings are compelling to suggest we will need to get a better understanding of all anti microbial interventions that we utilize in the mouth on a daily basis. We will have to wait to see how this all unfolds but I am truly on the edge of my seat waiting for more… Antiseptic mouthwash review
Insights and Fun Findings Covid and Taste: Nontasters look out! Self-reported observations suggest more regular hygiene habits increases bitter and sweet taste perception (Kaur Beckett 2021) Recent study showed an in vivo association between sugar intake and oral microbiota composition dominated by Actinomyces, Bifidobacterium, and Veillonella (Esberg et al 2020)

Love your Mouth Bugs! with Dr. Purnima Kumar SHOW NOTES

Background: The impetus for ‘Let’s get Oral’ is the realization that the people seem to underestimate the power of the mouth in all it’s function; from the aesthetics of the lips/teeth, systemic connections, allergy and immunology- the oversight reaches across academic research functions, therapeutic approaches, to the general acceptance of a person who has missing teeth.

Interview:

Intro: Why have we demonized the Oral Microbiome?
From dental cleaning, root scaling, microbiome guided therapy, chlorhexidine, Listerine, Stannous Fluoride. We are all trained to remove, deplete, and kill our mouth bacteria. How can we harness the oral microbiome for good? What should we be doing differently?

As dental professionals the oral microbiome is problematic and can create obvious problems from cavities to periodontal disease and tooth loss. As we uncover the mysteries of the oral microbiome, we have found that depleting some species with oral care products intended for therapy can cause a depletion in essential nitric oxide, which is essential for heart health; obviously our unique microbiome is nuanced and tricky and I cannot think of a single person more qualified to speak on this subject than Dr. Purnima Kumar, recently named Chair of Periodontics and Oral Medicine at University of Michigan.

Q: Can you share with us how you came into oral microbiome research?

C to P: You and I had been circling the oral health research community together but it wasn’t until several years ago that we were able to spend some time together after one of your lectures. My coworker and I were deeply moved by your research findings which primarily centered around healthy and never smokers which concluded with the increased diversity of the microbiome of smokers that predisposed them to periodontal pathology. Your work felt urgent for several reasons but if I were to name just one, it was that your work showed the increased diversity of the microbiome as a detriment rather than a benefit which was a departure from the notion that higher diversity meant healthier microbiome. *for those listening, richer/higher diversity in gut microbiome research has typically correlated with a healthier body, and this notion pervades research in other microbiomes niches like the oral cavity* I wanted to bring this up to get your perspective on two things:

Were the findings surprising to you?
How did these findings inform your next steps?

Q: The oral microbiome has been likened to a fingerprint, do you think we might better understand the microbial community by evaluating the microbial metabolome as an ecological parameter of health as opposed to the species level assessment? - how to simplify this question??

Q: There seems to be a growing awareness around the oral microbiome with microbiome guided therapy, microbiome testing, and probiotics. When looking broadly at the dental profession, where do you think we are headed with the oral microbiome in terms of chairside therapy?

Q: How do you see diagnostics and therapeutic approaches changing as we learn more?

Q: There have been some recent publications that suggest periodontal disease might predispose a patient to worse COVID outcomes. I would love your thoughts on those studies as well as your opinions around the potential capacity of the oral microbiome to shape immunity to other pathogens?

Q: I think we can all agree there is a systemic connection between the oral microbiome and the body, does this inform your research approach?

Q: One of my personal pet peeves in oral health research is that we know oral health care products can impact the state of oral pathology; either by contributing to inflammation with irritants like SLS or simply by removing bacterial species and shifting the inflammatory profile. In any other clinical investigation, the therapies utilized for daily control would be captured, but in oral health research this issue seems largely ignored. How do you feel about the idea of including this type of information in research studies?

End of Podcast wrap-up Questions:
Before we go- I wanted to ask a final question:
You use poetry to accentuate a particular learning in your study reports and review articles: can you tell the listeners about a poet or book of poetry you consider an essential for any collection?

Robert Hayden
Male Passage
Slave