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Outcompeting microbes: Understanding the future by looking at the past

March 1, 2021
Our knowledge of how oral microbes affect overall health increases as we learn more about the oral microbiome. Anne Nugent Guignon, MPH, RDH, CSP, investigates the development of strategies to control biofilm over the last 50 years.

My first year of clinical practice was really confusing. What I had been taught in dental school just wasn’t working out with my patients in Texas. Removing calculus every six months was supposed to be the ultimate goal, along with trying to convince patients that daily brushing and flossing were critical. It didn’t take long to realize that this plan did not produce the desired results for everyone I treated.

Textbook vs. reality

The textbook goal at that time defined a healthy mouth as having pink, firm, stippled gingivae, minimal deposits, and no bleeding. Yes, there were patients who fell into this category. Most who were classified as healthy performed the required daily brushing and flossing routine and had a hygiene visit like clockwork every six months. There were also plenty who defied explanation. Some patients had wall-to-wall plaque (the antiquated term we used in those days), yet there was no discernable disease. Other patients had no detectible deposits, but they had chronic, severe gingivitis or periodontitis with subsequent bone loss. And then there were dozens and dozens of Texas mavericks who never used string floss and only brushed once a day but maintained a consistent toothpick habit. These folks used picks all day long and had no evident disease. There were also a few outliers who loved using the new oral irrigation device called a Waterpik. Their soft tissue was impeccable.

A radical departure

At the end of my first year, I went out on a proverbial limb with two new ideas. One strategy involved exploring alternative ways patients could remove biofilm. The second part of the plan focused on tinkering with the microbial timetable.

I abandoned the “floss talk.” I wanted an activity that a patient could, and would, do. It was a partnership. My goal was to be a cheerleader. I looked at every device and new product on the market. Over time, I presented options, hoping that one day an idea or activity would resonate.

It was a great day when something worked. It didn’t matter what patients used as long as there were good results. If it was some kind of little brush or oral rinse and patients liked it, great! If they used an oral irrigator or toothpicks and were stable, I kept my mouth shut. It was a partnership. My role was to support success, not be a scorekeeper.

Intrinsically, I figured out microbes were part of the issue. The science at the time said the culprit was the physical presence of plaque or calculus. But things did not add up. What was going on when there were no detectible deposits, but the patient had ongoing disease?

In my mind, a patient’s success or failure appeared connected to overall health or lifestyle. This might seem naïve today, but back in the early 1970s inflammation and the role of the immune system in disease were not topics of discussion. My inner sense said something was going on. Women in menopause and those who were not sleeping well appeared to have a higher risk for periodontal disease and an impaired healing response. Those with autoimmune disorders or high stress levels were also at risk. The options available back then were not working. What I was taught simply did not improve patient outcomes.

An observational theory in the making

The lack of scientific support was not a deterrent. Out of sheer frustration, I concocted the following theory: “Obviously some people are highly allergic to their own plaque. I don’t know what else to suggest. Would you be willing to come in every three months?” Thankfully, my dentist employer did not object. He left me alone. Miraculously, patients agreed to quarterly visits. Patients’ active disease levels began to modulate. They were achieving new levels of success, and my schedule stayed full.

Inflammation and antimicrobial drug strategies

By the mid to late 1980s, discussions about microbes, inflammation, and the role of the immune system started to gain traction. Finally, there was a glimmer of substantiation for the successes I had observed for decades. History has a way of muddying the waters. When the focus shifted to inflammation, antimicrobial rinses and toothpaste products started popping up everywhere. Now the race was on to prescribe some sort of chemical miracle.

From the outset, my scientific mind rebelled against treating inflammation with drugs. If antimicrobial agents, such as chlorhexidine, were employed from day one, a significant amount of clinical data would be lost. Antimicrobials would mask the power of the immune system to initiate healing.

I resisted the intense pressure to include antimicrobial solutions during the first 12 months of patient therapy. It was critical to see if daily biofilm disruption and more frequent professional visits impacted the inflammatory process in a significant way. As patients stuck with their short recall intervals and customized home-care routines, it soon became evident that inflammation could be modified with targeted debridement strategies.

Microbial rumblings

Sig Socransky, DDS, a Boston-based periodontist, began his lifelong research into the microbiology of periodontal disease in the 1960s. By the late 1980s, his research, and that of many others, started to attract mainstream attention. Numerous studies pointed to the presence of specific microbes associated with periodontal disease. Socransky’s research group at the Forsyth Institute brought forward groundbreaking ideas about microbes. Specific pathogenic species were grouped into categories known as red, orange, and yellow complex microbes, indicating various levels of pathogenicity.1

Investigations about periodontal microbes emphasized gram-negative anaerobic species and spirochetes, but these microbes were difficult to grow. Early studies were limited to microbes that grew in a petri dish. Socransky firmly believed his initial research was hampered by the difficulty in culturing anaerobes and felt that at least 50% of the microbes were not being identified. Consequently, he adopted DNA-based technologies to expand his understanding of periodontal pathogens.2

Other noted scientists, such Max Listgarten, DDS, started questioning periodontal maintenance intervals. His research looked at the problem from a different point of view, one that would now go hand in hand with the emerging discussions about the role of the host’s immune system.3,4 Important and complex conversations were happening, and removing detectible hard and soft deposits from tooth structure was no longer the only goal.

The biofilm era is born

In the mid 1990s, microbiologist J. William Costerton, PhD, coined the term biofilm. Costerton’s explanation of how microbes behave in a biofilm community was groundbreaking.5 His work quicky gained attention. Scientists from around the world began viewing the microbial world differently. Based on Costerton’s biofilm studies, emerging research put a spotlight on the hows and whys of chronic infections.6 It became clear that chronic disease aberrations were dramatically different than conditions caused by a single organism, such as malaria or diphtheria.

In the initial biofilm years, the scientific community grew at Montana State University’s Center for Biofilm Research. Research collaborations demonstrated chronic disease-associated biofilms were complex communities of many species of bacteria, fungi, and viruses.7 Scientists determined biofilm microbes were encased in and protected by a self-generated, complex, slimy substance known as EPS, or extracellular polysaccharide.8 Dental plaque was one of the first biofilm communities Costerton and his colleagues studied.

During this formative decade, Bonnie Bassler, PhD, and her Princeton-based research team discovered quorum sensing, which is how microbes communicate with other organisms in a mixed-species community.9 Other studies reported how different microbial species cooperate and function in polymicrobial communities. Research also demonstrated there are distinct species-specific oxygen and pH requirements within the biofilm mass.

Ongoing research clearly revealed microbes work in harmony and support one another’s nutritional needs and environmental habitats when the community is balanced. This microbial expression ensures survival of the fittest.

Clinicians get caught up in the conversation

Dentistry preceded medicine in adopting biofilm-based disease concepts. Clinicians who were already treating periodontal patients every two to four months were being vindicated. Patients using oral irrigation and power brushes were also seeing astonishing results. Clinicians using microscopes in their treatment rooms saw diverse microbial populations and changes that were consistent with these interventions.

Salivary tests, such as OralDNA, gave clinicians more information. This specific test confirms the presence and levels of 11 different microbes, which are classified by the disease risk categories: high, medium, or low. But there was still much to learn.

Concurrently, microbiologist P. D. Marsh, PhD, referred to periodontal disease as an ecological catastrophe.10 Subsequently, Georges Hajishengallis, DDS, PhD, a clinician with an advanced degree in microbiology, started publishing research papers describing periodontal disease as a dysbiotic community of pathogens in ecological balance supported by a susceptible host.11 He further describes periodontal disease as inflammophilic, an environment where microbes require inflammatory by-products to support growth and sustain a balanced pathogenic community.12 He also coined the term keystone pathogen to describe microbes that are critical in creating the initial pathogenic community and pointed to the ability of a keystone pathogen to convert healthy microbes to pathobionts.13

One lone Texan looked at nonhealing wounds

In 2005, a wound-healing specialist from Lubbock, Texas, named Randy Wolcott, MD, became interested in biofilm. While most in the medical community were still treating complex infections with antibiotics and other traditional methodologies, Dr. Wolcott began treating nonhealing wounds differently.14 Rather than subjecting a patient to incessant rounds of antibiotics or, worse yet, a surgical amputation, Wolcott started manipulating wound sites in a manner reminiscent of how dental professionals were now treating gingivitis and periodontitis.15

Then, Wolcott met Costerton. The two developed a deep friendship, which morphed into profound, ongoing conversations. Costerton and Wolcott melded research with clinical observations. Their discussions about polymicrobial biofilm-based diseases are a delight and still available on YouTube.

Biofilm-based disease management

Like dental professionals, Wolcott was in the trenches treating patients. His medical treatment philosophy was based on regular and thorough debridement.16 Over the years, Wolcott’s treatment protocols also explored a wide range of options, including regular physical debridement, enzymes, xylitol, iodine, hyperbaric oxygen, irrigation, lactoferrin, ionic silver, and medicinal honey.17,18 He found antibiotics were the least successful tool in his arsenal, a conversation that is gaining a lot of traction in both the scientific and clinical communities.19-21

Wolcott regularly employed concurrent multiple strategies to attack the microbial pathogens. As he began using this approach, his patients’ nonhealing wounds started to resolve. Based on successful outcomes, he quit performing amputations.

Understanding the microbiology

Traditional medical labs did not culture for anaerobic organisms, so Wolcott created his own lab, Southwestern PCR, in 2008. He understood that anaerobic microbes were involved, and he wanted a more robust microbial perspective. His lab moved past petri dishes, embracing molecular genetics to explore the new frontier in wound healing.

Lab researchers incorporated polymerase chain reaction (PCR) technology and next generation sequencing (NGS). Soon, Wolcott’s lab and others across the country began reporting that complex mixes of anaerobes were key troublemakers in many types of chronic disease. In 2017, MicroGenDX acquired the lab and continues to provide valuable diagnostic data to medical and dental professionals across the country.22,23 After years of successful patient treatment, Wolcott retired from active medical practice, but his contributions are still reverberating throughout the health-care community.

Today’s periodontal microbial diagnostics

In 2020, MicroGenDX introduced PerioDX, an advanced diagnostic protocol that combines PCR with next-gen DNA sequencing from a saliva sample or a sample from a specific periodontal pocket site. PCR testing is rapid and capable of identifying between eight and 35 specific periodontal microbes, but there are limitations. PCR does not detect microbial mutations, and certain dominant species may not be detected. DNA sequencing fills the gap by detecting thousands of microbial species, including aerobes, anaerobes, facultative anaerobes, and fungi.

The sequencing report lists specific microbes but details the percentage of each species based on the DNA in the sample. The combined data results create a deeper picture about which microbes inhabit a specific periodontal pocket or the oral cavity in general.22 The most accurate and specific data for periodontal pathogens comes from actual pocket sampling as compared to a swish-based test that captures all microbes in the entire oral cavity and nasopharynx. 

2021 and beyond

Over the last 50 years, we have learned an enormous amount about microbes that inhabit the periodontal pocket. Our knowledge of how oral microbes affect overall health increases every day as we learn more and more about the oral microbiome. And our appreciation for the complexity of the human immune system and host response is growing as well. The information we have learned over the last half-century will continue to grow,24 and we will be challenged both intellectually and clinically by new findings as we move forward.

Somehow, decades ago, I stumbled upon a strategy that worked quite well for many patients. Today’s diagnostics and technologies are far more sophisticated. Overall, patient prognoses and outcomes are better today than they were 50 years ago. The next segment will examine the possibilities as we move into the future based on what we now know.

More from Anne Nugent Guignon, MPH, RDH, CSP:
Spit matters: Collecting critical data in the quest for oral homeostasis
Learning to adapt to pandemic challenges from each other


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  2. Teles RP, Teles FRF, Loesche WJ, et al. Rediscovering Sig Socransky, the genius and his legacy. J Dent Res. 2012;91(5):433-439. doi:10.1177/0022034512443689
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ANNE NUGENT GUIGNON, MPH, RDH, CSP, a visionary thinker, has received numerous accolades over four decades for mentoring, research, and guiding her profession. As an international speaker and prolific author, Anne focuses on the oral microbiome, erosion, hypersensitivity, salivary dysfunction, ergonomics, and employee law issues. She may be contacted at [email protected].
About the Author

Anne Nugent Guignon, MPH, RDH, CSP

ANNE NUGENT GUIGNON, MPH, RDH, CSP, has received numerous accolades over four decades for mentoring, research, and guiding her profession. As an international speaker and prolific author, Guignon focuses is on the oral microbiome, erosion, hypersensitivity, salivary dysfunction, ergonomics, and employee law issues. She may be contacted at [email protected].