LYNNE SLIM, RDH, BSDH, MSDH
Two giants in the dental research community died recently, and I would like to dedicate this column to them. One was Dr. Sigmund Socransky, a periodontal researcher at the Forsyth Institute. Dr. Socransky is best known to me - a controversial periodontal nerd - for his microbial clusters that defined different states of periodontal disease and the application of checkerboard DNA-DNA hybridization method of analyzing oral microbes in health and disease. Another great loss was that of Dr. J. William Costerton, teacher, researcher, and worldwide speaker on his discovery of "biofilms." In microbiology, he is commonly referred to as the Father of Biofilms.
Due in part to the lifetime work of Socransky and Costerton, our understanding of the etiology and treatment of inflammatory periodontal disease has changed. I'd like to review the ongoing uncertainties about the relationship between biofilm inhabitants and periodontal disease.
In reviewing the historical phases and the relationship between the oral microbiota and the initiation or progression of periodontal disease, let's reflect briefly on some of the important sequences of discovery (See Table 1). Back in the 17th century, van Leeuwenhoek collected samples of plaque from his teeth, mixed the plaque with water and saw "living animalcules" that he could kill when drinking hot coffee. Koch, in the late 19th century, expressed the opinion that a specific microorganism could be regarded as the causal factor for a specific disease if certain conditions - now termed "Koch's postulates" - were met. The microorganism should be identified in all cases of the disease, and examined and not found when this disease does not occur. The microorganism should be prepared and grown in pure culture. It should be able to produce the disease in culture even after many generations. The microorganism should be retrievable from an experimentally diseased animal and able to be recultured.
The hypothesis of nonspecific plaque dates back to the 19th century and, specifically, to the search for bacterial species associated with dental caries. At this period, it was reasoned that caries was nonspecific and that all plaque bacteria were able to produce acids, resulting in the development of caries.1 Loesche, another giant in periodontal research, feverishly studied bacterial anaerobes and their role in periodontal disease, and hypothesized that clinical symptoms are almost always significantly associated with the overgrowth of a finite number of anaerobic species, such as Porphyromonas gingivalis, Bacteroides forsythus, and Treponema denticola in the subgingival plaque. He strongly recommended the judicious short-term use of antimicrobial agents targeted against specific anaerobes.1,2 He indicated that this approach, which was supported by several double-masked clinical studies, was contrary to centuries of dental teaching which stated that periodontal disease resulted from the overgrowth of plaque on tooth surfaces; i.e., a "dirty mouth."1
In addition, he postulated that the antimicrobial treatment of periodontal infections might impact cardiovascular health, including stroke. He mentioned that an antimicrobial approach to the treatment of periodontal diseases might be as effective as a surgical approach in the restoration and maintenance of a periodontally healthy dentition.1
In the 19th century, laboratory techniques were limited to traditional capturing/culturing techniques using agar gelatin petri dishes, microphotography of bacteria, and bacterial staining. Since then, modern techniques for the identification and quantitation of microorganisms from their DNA came along, followed by molecular techniques that can map a bacterial population in situ (on site) in infected tissue. We can also now view biofilm architecture in its natural state using confocal laser microscopy. Confocal laser scanning microscopy is a method to acquire serial optical images of high resolution from specific depths (optical sectioning of an object) and subsequently three-dimensional computer reconstructions of an object.
In 2005-2006, Haffajee and Socransky edited two outstanding issues in a periodontal journal I read on a regular basis, and I devoured them for a number of reasons.3,4 I had never before read (in so much detail) about the multiplicity of factors that impact the oral microbiota in periodontal health/disease, especially host factors, and it was the first time I began to understand the complexity of biofilm development.3-8 Haffajee and Socransky employed checkerboard DNA-DNA hybridization in addition to culturing techniques in providing data for their chapters. They included very colorful figures, including many that showed the contrast between subgingival bacterial species count in health and disease. Since then, research employing newer molecular techniques has been moving at a feverish pace.
Costerton's contributions to our understanding of periodontal diseases go hand in hand with the etiology of biofilm diseases and the direct observation of biofilm architecture in their natural ecosystem. He believed in using powerful new tools of DNA-based population analysis directly to the inflamed site, and he taught us that bacteria growing in biofilms adopt a phenotype unlike that of planktonic counterparts. For example, bacteria in biofilms don't respond well to conventional systemic antibiotics; therefore, saliva testing and prescribing systemic antibiotics isn't part of the standard of care. In the medical community, mainstream researchers have repeatedly tried to kill biofilms by giving patients high doses of antibiotics. When given in high doses, the antibiotic may temporarily weaken the biofilm, but it is incapable of destroying it because certain cells inevitably persist and allow the biofilm to regenerate.8-11 In addition, when the infection reappears, it is usually in an antibiotic-resistant form.3-11 Therefore, don't be duped by those speakers and writers who promote the use of systemic antibiotics in all patients with chronic periodontitis. Instead, read the science concerning biofilm inhibition and talk to biofilm researchers in the medical community for unbiased information.
Hajishengallis et al. now may have thrown a monkey wrench into the hypotheses in Table 1 by explaining the results of a mouse NIH-supported study in which P. gingivalis (P.g) triggered periodontitis while residing in low numbers.12P.g hijacks front-line immune cells that are waiting like sentinel soldiers on guard for enemies in the subgingival crevice and reprograms them to their advantage. As a result of this surprise immune cell-napping or abduction, more benign bacterial residents (including many gram-positive microorganisms) opportunistically swarm and infect the periodontium. As the battle wages between the new warriors and the immune system, P.g sits back and "feasts on the inflammatory spoils," according to Dr. Hajishengallis. P.g appears to behave as a "keystone pathogen" - a concept that refers to a low-abundance species that exerts a disproportionate effect on its environment while enjoying a parasitic lifestyle. In other words, the homeostasis of the host is disrupted by P.g, and periodontitis is the direct result.
P. gingivalis appears to be one of the brainiest culprits in the initiation of disease even though it's a low-abundance bacterial species. It has mastered the art of disrupting homeostasis, or equilibrium, among the bacterial inhabitants of the subgingival crevice and innate immunity cells. Also in mouse studies, P.g has learned how to exploit signaling cross talk, which is a way for innate immune cells to process incoming information about intruders.
What's the call to action for hygienists based on a reflection of these historical changes? I strongly recommend that hygienists make clinical decisions based on good science - not old, incomplete, or biased information.
1. Follow the research concerning biofilm inhibitors and host modulation agents. Conventional periodontal treatment is sometimes insufficient to control inflammation in patients with recurrent disease.
2. Be wary of profit-centered approaches to the treatment of periodontal disease in general dental practices, including salivary testing for periodontal pathogens. Conventional systemic antibiotics should be reserved for acute presentations such as periodontal abscesses. In medicine, patients who are put on high-dose antibiotics for biofilm infections will find that the infection will reappear in an antibiotic-resistant form.
3. Refer to a periodontist for diagnosis and treatment of moderate to severe periodontitis. Work with a local periodontist to develop guidelines for referral.
REFERENCES
1. Loesche WJ, Grossman NJ. Periodontal disease as a specific, albeit chronic infection: diagnosis and treatment. Oral Microbiol Rev. 2001; 14(4):727-752.
2. Banas JA. Walter Loesche - a maverick in transitional research in dentistry. J Dent Res. 2009; 88(12):1092-1095.
3. Haffajee AD, Socransky SS. (Ed.) Microbiology of periodontal diseases: pathogens, virulence and ecology. Perio 2000. 2005; 38(6).
4. Haffajee AD, Socransky SS. (Ed.) Microbiology of periodontal diseases: genetics, polymicrobial communities, selected pathogens and treatment. Perio 2000. 2006; 42(1).
5. Socransky SS, Haffajee AD, Dzink JL. Relationship of subgingival microbial complexes to clinical features at the sampled sites. J Clin Periodontol. Aug. 1988; 15(7):440-444.
6. Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent RL Jr. Microbial complexes in subgingival plaque. J Clin Periodontol. Feb. 1998; 25(2):134-144.
7. Dibart S, Skobe Z, Snapp KR, Socransky SS, Smith CM, Kent R. Identification of bacterial species on or in crevicular epithelial cells from healthy and periodontally diseased patients using DNA-DNA hybridization. Oral Microbiol Immunol. Feb. 1998; 13(1):30-35.
8. Preshaw PM. Systemic antibiotics in the management of chronic periodontitis. Eur J Prosthodont Restor Dent. June 2004; 12(2):63-69.
9. Lewis K. Persister cells and the riddle of biofilm survival. Biochemistry (Mosc). Feb. 2005; 70(2):267-274.
10. Smith AW. Biofilms and antibiotic therapy: is there a role for combating bacterial resistance by the use of novel drug delivery systems? Adv Drug Deliv Rev. Jul. 2005; 57(10):1539-1550.
11. Havard DB, Ray JM. How can we as dentists minimize our contribution to the problem of antibiotic resistance? Oral Maxillofac Surg Clin North Am. Nov. 2011; 23(4):551-555.
12. Hajishengallis G et al. Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Cell Host & Microbe 2011; 10:497-550.
Historical Phases: Relationship between Specific Microorganisms and Periodontal Disease | ||
Date | Hypothesis | Defined |
19th century | Koch's Postulates | Microorganisms are typically found in abundance in all organisms suffering from disease, can be isolated and cultured and the cultured microorganism should cause disease when introduced into a healthy organism. |
19th Century - 1976 | Non-Specific Plaque Hypothesis | Disease is due to the collective action of all of the microorganisms in dental plaque. |
1976 | Specific Plaque Hypothesis (Loesche) | Disease results from the action of one or more several specific pathogenic species and is often associated with a relative increase in the numbers of these organisms found in dental plaque. |
1992 | Socransky & Haffajee Periodontal Pathogen Association Hypotheses | Periodontal pathogens are found more frequently and in higher numbers in disease states than in healthy individuals. Host response to a specific pathogen contributes to tissue damage and virulence factors (properties of a putative pathogen) may function to damage host tissues. Ability of a putative pathogen to function in producing disease should be demonstrated in animal models. Two periodontal pathogens that fulfilled Socransky's criteria are Actinobacillus actinomycetemcomitans in the form of localized juvenile periodontitis and Porphyromonas gingivalis in the form of periodontal disease known as chronic periodontitis. Checkerboard DNA-DNA hybridization of plaque/biofilm samples revealed unique colonization patterns and positive cooperaton among "clustered" groups of bacteria. Clusters are created based on similarities and differences in nutritional and atmospheric environments and they influence each other. |
2011 | Hajishengallis et al. Keystone Pathogen Hypothesis | Periodontal inflammatory disease can be caused through dysregulation of host-polymicrobial interactions instigated by a single species that appears to act as a keystone pathogen. |
LYNNE SLIM, RDH, BSDH, MSDH, is an award-winning writer who has published extensively in dental/dental hygiene journals. Lynne is the CEO of Perio C Dent, a dental practice management company that specializes in the incorporation of conservative periodontal therapy into the hygiene department of dental practices. Lynne is also the owner and moderator of the periotherapist yahoo group: www.yahoogroups.com/group/periotherapist. Lynne speaks on the topic of conservative periodontal therapy and other dental hygiene-related topics. She can be reached at [email protected] or www.periocdent.com. She was a 2012 Philips Oral Healthcare/RDH Mentor of Distinction.
