An interview with microbiologist Camille Zenobia, PhD, "oral health activist"

I started following @oralhealthactivist with no clue whom it was, but my good friend, a guru in biologic dentistry, liked their posts and I pulled the trigger. The feed was a mix of “super science” and engaging graphics with a splash of controversy. Perfect. There was a mention that the “activist” would be on one of the dental podcasts, and I dove in feet first. As I listened, I found her enchanting, provocative, and brilliant. Feeling that the entire dental community needed to hear more from her, I reached out asking for an interview that I hoped to have published. I also had serious questions of my own and was quickly becoming a fangirl. Graciously she agreed and I hope you find at the very least, some thought-provoking science.

Introducing Dr. Camille Zenobia

Rice: Your education is extensive. Will you share how you got where you are today?

Dr. Zenobia: Born and raised in Seattle, I entered the world of cosmetology just after high school, at age 17. I just wasn’t sure about spending a ton of money on a fine arts degree, which was my impulse, so I decided to wait it out as a hairdresser. I did some advanced training in London and worked at top tier salons in Seattle before opening my own salon in the early 2000s.

While I ran the salon, I put myself through a bachelor’s in science and majored in chemistry, and then moved to start my scientific career in an infectious disease laboratory at the University of Washington. Soon after, I entered graduate school for microbiology, where I fell in love with the immune landscape of the oral cavity while working with Porphyromonas gingivalis (Pg).

Since then, I moved east to work as a postdoctoral fellow with Dr. George Hajishengallis at the University of Pennsylvania, and then made the leap into the dental product manufacturing realm. I left the company at the beginning of the pandemic to work in medical affairs with an emphasis on education for health-care providers.

More by the author:

Salary diagnostics: The 411

Midlife transitions and oral health

Moving to a microbiome-community approach

Rice: You have been published 18 times. I want to talk about your recent research, “Does oral endotoxin contribute to systemic inflammation?”¹

Dr. Zenobia: My thesis work revolved around the unique characteristics of Pg endotoxin. This work continues to inform my thoughts as we move to a more all-encompassing microbiome-community approach to understanding and treating oral and systemic health.

My most recent paper, “Does oral endotoxin contribute to systemic inflammation?” discusses the role of oral bacteria and their endotoxins as potential primers for our immune surveillance system. Endotoxin is found on the surface of anaerobic bacteria, like Pg, and can signal to our immune cells. One fascinating discovery about Pg endotoxin is that during temperature or inflammatory fluctuations, the structure of the endotoxin can be altered to dampen or enhance immune response.

Interestingly, bacterial endotoxin can cause metabolic endotoxemia, which is linked to a host of inflammatory pathologies. It has recently been shown that periodontal disease and Pg can initiate gut dysbiosis and can cause metabolic endotoxemia. In my article, I compiled the disparate studies from periodontology, cardiovascular, rheumatology, and Alzheimer’s research that implicate endotoxin and oral pathology as key drivers of disease progression to derive a new hypothesis around how oral pathology with unique oral endotoxin phenotypes could induce gut dysbiosis and prime systemic responses together and cause the progression of different inflammatory pathologies that have long been correlated to periodontal disease.

Rice: Speaking of inflammation, you received an award from the American Academy of Periodontology for a study titled “Human variation in gingival inflammation.”² Tell us about that study.

Dr. Zenobia: The study that led to this publication was one of my projects when I worked at Colgate-Palmolive. It was driven by a postdoctoral fellow in my old thesis lab who really took the investigation to a new level by researching the dynamic changes to the oral microbiome and inflammatory cytokines that occurred during a split-face, experimental induced gingivitis model in otherwise healthy individuals.

What we found were three different response phenotypes. The majority was termed slow, while the others were low or high clinical responder groups. So, just as we see in the population, some people seem resistant to the development of gingivitis, while others appear susceptible or at higher risk. The clinical response groups had unique bacterial shifts and inflammatory profiles that helped to explain what was happening clinically.

I think the most surprising thing was that both the low and high response groups had similar rapid plaque accumulation and microbial succession profiles that differed significantly from the slow response group. Again, we know clinically there are some patients who are high plaque formers but not all will suffer from caries or gingivitis. So, this study has given us some very unique insights into the differences that we see clinically, which is why I think it was perfect for the Clinical Research Award, which is presented to the most outstanding published article with direct clinical relevance in periodontics.

Concerns about common product ingredients

Rice: When I listened to your original podcast, you were walking on controversial ground when talking about oral hygiene products. Recent conversations in the dental community about oral rinses and the potential detriment to good oral flora lead me to the next question. With your knowledge of infectious disease and microbiology, why are you not a fan of sodium lauryl sulfate (SLS) or stannous fluoride? I would also like your thoughts on chlorhexidine (CHX).

Dr. Zenobia: When we think of our oral hygiene products, we are generally looking at technology that was developed in the 1950s. We knew then that oral bacteria were a detriment to our teeth and gums and, therefore, the goal of the product was to remove bacteria.

Interestingly, when the FDA worked with industry to approve products for oral hygiene indications, there was a concern that the product might alter the microbial composition, and data was provided to show that these products did not significantly alter bacterial profiles. The tools that were utilized back then were crude and simple, as was our understanding of the microbiome overall.

We have only recently become aware that our microbiome is part of our metabolic health system. We have a lot of work to do in order to understand how our oral hygiene products may have impacted our microbial relationship over the last 70 years. That said, we also know that our oral bacteria can be a detriment to our teeth and gums. So, it is a perplexing subject with lots of considerations.

Fluoride was an obvious win back in the day, and I still believe it has its place. However, the use of fluoride is prevalent and natural sources also contribute to our overall exposure. There are regions that have so much natural fluoride that adding more can be detrimental. In addition, we have seen a rise in fluorosis such that the CDC has a cautionary webpage.

The unfortunate state of affairs in the United States is that fluoride is our only real oral hygiene product that is FDA approved for reducing cavities. Therefore, dentists are reluctant to suggest any other products despite knowing about the rise in fluorosis. The last thing I will say about fluoride specifically is that, while it has been shown to be a benefit, the improvement is subtle. I don’t think fluoride alone can stand against the arsenal of the Western food products that are overloaded with sugar. So, all of us in oral health need to do better about raising awareness about diet, health, and healthy habits (brush after that sneaky snack attack!).

Stannous fluoride addresses gingivitis as well as cavities. It is a very powerful tool. I can definitely get behind this product in some ways; however, stannous can be devastating for a very small segment of the consumer population and cause tissue sloughing. Most people who are affected by stannous understand the connection because it is so severe. Not everyone will have a severe reaction; some will have more subtle irritation.

What I don’t like about stannous is not the actual molecule but that most oral health professionals don’t really have an understanding about the many ingredients that might be causing problems in their patients. Instead of shaming patients for their assumed lack of hygiene or going straight for scaling and root planing, perhaps we could just take a moment and investigate a mild toothpaste to see if it helps reduce the inflammation before going for the “heavy artillery.”

The same issue could be said for SLS, a frothy tool to get your toothpaste nice and sudsy. It can cause mild to severe inflammation (less severe than stannous but more people can be affected). We now have so many other options that we can formulate toothpaste without SLS. Sensodyne recently removed SLS from some of its line of toothpastes, but some still contain it, so check ingredients before making recommendations.

In my opinion, we need many other options on the market so that people can experiment to find the right tool for them. Not everyone will experience the same irritation or benefit from every product. You can see from every clinical trial that the response rate is never 100%. Due to our lack of understanding around what oral hygiene products should look like to preserve a microbial relationship, we need to do some creative thinking and experimenting to find the right product for our patients.

Applying antimicrobial mouth rinses more strategically

Dr. Zenobia: I have lots to share about mouthwashes as they are a complex subject. For example, during the beginning of the COVID pandemic, we were looking for anything helpful to stop the spread of the virus. We knew quickly that the virus was spread from high viral load in the saliva and thus, the whole droplet/spray discussion (which may give some PTSD upon reflection).

I loved the idea that mouthrinses might help reduce viral spread and knew research was underway to evaluate mouthrinses for reduction of viral load in the mouth. The results were finally published, and they showed a nice viral load reduction. This finding might push anyone to start using mouthwash like we now use hand sanitizer. I thought it was a very nice finding, but I also knew that other research has implicated mouthwashes as detrimental to the oral microbiome.

First, and most shocking, was a study that found CHX mouthwash use in hospital settings to increase the mortality rate in patients.³ Second, antimicrobial/over-the-counter mouthwashes (including CHX) have been shown to reduce specific species of oral microbes that are essential for breaking down nitrogen-based nutrients in order to start the process of nitric oxide production for the body. Nitric oxide is essential for heart health, and the use of mouthwash has been linked to an increase in blood pressure. A lot has been written on the subject recently, and hospitals are working to reject CHX as the main oral care protocol for patients.^4-9 This seems counterproductive for a therapy such as CHX, which is utilized specifically for periodontal disease in patients already susceptible to cardiovascular issues.

So, while I do appreciate these tools for oral health, I think we need to seriously consider how to apply them strategically instead of empirically without pause. In other words, I would not choose to use mouthwash with these products every day, but rather, if I have periodontal disease and am going for scaling and root planing, I might use it before and after cleaning but not for months on end. Similarly, if trying to mitigate my COVID viral spread, I might choose to apply mouthwash when I am actively infected and need to engage with my in-house family.

In summary, I do not intend to demonize any tool that we can deploy as a lever for oral health, but we need to think very cautiously about how to utilize them to our benefit.

Oral health and immunity

Rice: That is a compelling discussion, and I am confident it will give us all something to ponder. The immune system is something I have great interest in and I want to become more familiar with oral immunology. Would you share a bit about it?

Dr. Zenobia: One of the things that drew me to the oral cavity is how very little we really understand about the immunology of the oral tissues. We are at a new frontier with mucosal immunology and are finding that our microbiome and innate immune system are uniquely designed to inform our adaptive immune system.

Why is this important? Well, we know that when we inject vaccines into our blood/muscle, we do not elicit mucosal protection and, interestingly, our mucosal tissues are typically where we encounter pathogens (e.g., COVID, influenza). Vaccines utilize adjuvants in order to stimulate our immune response to “take notice” of the piece of virus or bacteria we would like it to remember. I wrote a paper last year about how the oral microbiome might be acting as an adjuvant for infectious disease, which may help us understand how to “fine-tune” our mucosal immune response to a variety of pathogens.¹⁰

Rice: How did you become interested in the oral microbiome? I assume your work with Pg spawned the interest.

Dr. Zenobia: I have always wondered why one person, exposed to a pathogen, gets terribly sick while another person does not. Scientists have been working on infectious diseases for many years and still have very few explanations for why this can occur. I strongly suspect the oral microbiome may allow us to finally gain some insights on this tricky subject as we uncover the relationship between the innate and adaptive arms of mucosal immunology.

Rice: Your answer made me think that oral health providers may be on the brink of becoming one of the most important players in whole-body prevention. In 2011 you wrote a manuscript called “The relationship of the oral microbiota to periodontal health and disease.” I am eager to hear what gains we’ve made in 11 years. Additionally, what science do you think dental hygienists might be interested in?

Dr. Zenobia: We have made so many gains since that article, yet it still gets cited with regularity. I think that much of the current research fails to find a place in the dental practice. I would like to see more effort in continuing medical education courses to bring frontier science to practitioners but with an emphasis on how to employ the new understandings in practice.

I am currently meditating on how I could take this on. We need more awareness in general about how to really care for our mouths in a way that is nurturing. What I mean is that our approach has always been to strip, bleach, and nuke the microbiome out of our mouths. Our mouths are the most efficient self-healing machines of all our tissues. We only need to treat them with respect and feed them lots of healthy foods. We need a new approach that feels like skin care: gentle, nurturing, and supportive. An approach that allows us to feel like we care about our mouths instead of scrubbing them out like we would a toilet twice a day. Let’s show our mouths some love and respect. 

Editor's note: This article appeared in the March 2023 print edition of RDH magazine. Dental hygienists in North America are eligible for a complimentary print subscription. Sign up here.

References

1. Zenobia C, Darveau RP. Does oral endotoxin contribute to systemic inflammation? Front Oral Health. 2022;3:911420. doi:10.3389/froh.2022.911420
2. Bamashmous S, Kotsakis GA, Kerns KA, et al. Human variation in gingival inflammation. Proc Natl Acad Sci USA. 2021;118(27):e2012578118. doi:10.1073/pnas.2012578118
3. Deschepper M, Waegeman W, Eeckloo K, et al. Effects of chlorhexidine gluconate oral care on hospital mortality: a hospital-wide, observational cohort study. Intensive Care Med. 2018;44(7):1017-1026. doi:10.1007/s00134-018-5171-3
4. Brookes ZLS, Belfield LA, Ashworth A, et al. Effects of chlorhexidine mouthwash on the oral microbiome. J Dent. 2021;113:103768. doi:10.1016/j.jdent.2021.103768
5. Blot S. Antiseptic mouthwash, the nitrate-nitrite-nitric oxide pathway, and hospital mortality: a hypothesis generating review. Intensive Care Med. 2021;47(1):28-38. doi:10.1007/s00134-020-06276-z
6. Bryan NS, Tribble G, Angelov N. Oral microbiome and nitric oxide: the missing link in the management of blood pressure. Curr Hypertens Rep. 2017;19(4):33. doi:10.1007/s11906-017-0725-2
7. Joshipura KJ, Muñoz-Torres FJ, Morou-Bermudez E, Patel RP. Over-the-counter mouthwash use and risk of pre-diabetes/diabetes. Nitric Oxide. 2017;71:14-20. doi:10.1016/j.niox.2017.09.004
8. Sundqvist ML, Lundberg JO, Weitzberg E. Effects of antiseptic mouthwash on resting metabolic rate: a randomized, double-blind, crossover study. Nitric Oxide. 2016;61:38-44. doi:10.1016/j.niox.2016.10.003
9. Pignatelli P, Fabietti G, Ricci A, et al. How periodontal disease and presence of nitric oxide reducing oral bacteria can affect blood pressure. Int J Mol Sci. 2020;21(20):7538. doi:10.3390/ijms21207538
10. Zenobia C, Herpoldt KL, Freire M. Is the oral microbiome a source to enhance mucosal immunity against infectious diseases? NPJ Vaccines. 2021;6(1):80. doi:10.1038/s41541-021-00341-4