Periodontal infections:understanding the complexity –Consensus of the SeventhEuropean Workshop onPeriodontologyAbstractIntroduction: Periodontal diseases are the pathological manifestation of the hostresponse against the bacterial challenge from the dental biofilm at the tooth/gingivalinterface. The remit of this working group was to update the existing knowledge on theinfectious nature of periodontal diseases.

Material and Methods: The literature was systematically searched and criticallyreviewed. Four manuscripts were produced in specific topics identified as key areas tounderstand the importance of the microorganisms in the etio-pathogenesis ofperiodontal diseases.

Results/Conclusions: The results and conclusions of the review process are presentedin the following papers, together with the group consensus statements aiming to answerthe following questions: (1) Has the use of molecular methods for the characterization ofthe human oral microbiome changed our understanding of the role of bacteria in thepathogenesis of periodontal disease process? (2) Are the periodontal microbial complexesassociated with specific cell and tissue responses? (3) How is the development of dentalbiofilms influenced by the host? (4) What can we learn about biofilm/host interactionsfrom the study of inflammatory bowel disease? This consensus report provides answers tothese questions with the most updated information on periodontal microbiology

Consensus Report

Periodontal diseases are the pathologicalmanifestation of the host response againstthe bacterial challenge from the dentalbiofilm at the tooth/gingival interface.

� Plaque-induced gingivitis is a chronicinflammatory response to the accu-mulation of supragingival biofilm.

� Periodontitis is a chronic inflamma-tory disease that results from a com-plex polymicrobial infection, leadingto tissue destruction as a consequenceof the perturbation of the homeostasisbetween the subgingival microbiotaand the host defenses in susceptibleindividuals. This bacterially driven

Mariano Sanz and Arie Jan vanWinkelhoff, on Behalf of WorkingGroup 1 of the Seventh EuropeanWorkshop on Periodontology

Facultad de Odontologia, Universidad

Complutense de Madrid, Madrid, Spain

Conflict of interest and source offunding statement

This workshop has been financially supportedby an unrestricted educational grant fromColgate. The sponsor had no impact on theprogram or on the deliberations of theEuropean Workshop. Group participantsdeclared that they had no conflict of interests.

Working Group 1: Philippe Bouchard (Paris,

France), Michael Curtis (London, UK), Gunnar

Dahlen (Goteborg, Sweden), Simone Fabrizi

(Madrid, Spain), Magda Feres (Sao Paulo, Bra-

zil), Elena Figuero (Madrid, Spain), Dorte Hau-

bek (Aarhus, Denmark), David Herrera

(Madrid, Spain), Amedeo Indriolo (Bergamo,

Italy), Moritz Kebschull (New York, USA), Phil

Marsh (Leeds, UK), Panos Papapanou (New

York, USA), Ulrich Schlagenhauf (Wuerzburg,

Germany), Ricardo Teles (Boston, USA),

WilliamWade (London, UK).

J Clin Periodontol 2011; 38 (Suppl. 11): 3–6 doi: 10.1111/j.1600-051X.2010.01681.x

3r 2011 John Wiley & Sons A/S

disease may be considered to differfrom an accepted definition of infec-tion (i.e. invasion by and multiplica-tion of pathogenic microorganisms ina body part or tissue which mayproduce subsequent tissue injury andprogress overt disease through a vari-ety of cellular or toxic mechanisms).

Research into the microbiota of otherbody mucosal surfaces has demonstratedimportant benefits to the host due toactivity of the resident bacteria. Evidenceis emerging that the resident oral micro-biota delivers similar benefits to the host.

The study of periodontal health-asso-ciated oral biofilms, as well as theirinteraction with the local tissues, willallow us to understand the potentialprotective mechanisms and define pre-ventive strategies.

Microbiological studies assessing acomprehensive description of the compo-sition and function of the oral microbiotamay allow us to identify bacterial signa-tures of relevance to microbial diagnosticapproaches and therapeutic targets.

The study of the complex interactionsbetween the subgingival microbiota andthe ulcerated epithelium at the tooth-gingival interface allows the study ofhost microbial interactions, which mayhelp the understanding of other complexmucosal infection.

The mouth is a reservoir of microor-ganism with the potential to cause diseasein other body sites. The in-depth knowl-edge of the characteristics and virulencefactors of these potential pathogens willhelp the understanding of the pathogen-esis and management of these infections.

Has the Use of Molecular Methods forthe Characterization of the HumanOral Microbiome (HOM) Changed ourUnderstanding of the Role ofBacteria in the Pathogenesis ofPeriodontal Disease Process?

Wade, W.G. (Wade 2011)

1. How has the introduction of molecu-lar microbiology changed our under-standing on the role of established(World Workshop on Periodontology,1996) periodontal pathogens as definedby the classic Socransky criteria?

The use of molecular techniques suchas DNA/DNA checkerboard analysis,cloning, etc. has further emphasizedthe association of the classic periodontalpathogens with periodontitis, introdu-cing the possible role as putative patho-gens of additional species such as

Eubacterium nodatum, Porphyromonasendodontalis, Prevotella tannerae, Fili-factor alocis or Treponema denticola.The introduction of molecular ecologytechniques has expanded our knowledgestressing the high species richness of thesubgingival microbiota and the possibleimportance of yet uncultivable bacteriathat being associated with diseased sitesdeserve further investigation in theirrole as periodontal pathogens.

2. How may the increased knowledgeon the composition of the subgingivalmicrobiota improve our understandingof the pathogenesis, diagnosis and treat-ment of periodontitis?

This increased awareness of a higherdiversity and complexity in the subgingi-val microbiota indicates the possibilityof identifying new pathogenic speciesor communities, however this new infor-mation has not yet impacted our currentdiagnosis and treatment. The currentmolecular technology provides us withnew resources to identify not only singlemicroorganisms, but communities withpotential pathogenic importance. More-over, the impact of genomic sequencinghas shown the extreme variability of thegenomes of strains within a given species,which stresses the importance of indivi-dual genes encoding virulence factors(function) rather than solely the presenceand levels of particular species.

3. What is the role of as yet unculturedbacteria identified by DNA sequencingalone?

The role of yet uncultured phylotypesin oral biofilms is unknown at presentdue to our inability to culture them, butit is possible to predict their likelyactivities and functions by comparisonwith related members of the subgingivalbiofilm, based on their phylogeneticposition. In addition, Fluorescence InSitu hybridization studies have con-firmed the presence and viability of yetuncultured phylotypes in oral biofilms.

4. What is the role of culture-basedmicrobiology versus molecular methodsin our current and future understandingof the importance of bacteria in perio-dontitis?

Culture-based microbiology is essen-tial to understand the properties of thesenew yet uncultured bacteria, in healthand disease. If we are able to grow them,we can study them both in vitro and invivo situations, and determine antimi-crobial susceptibility. There is a need tostudy these bacteria not only as singlespecies, but also as a consortium andinvestigate their interactions with

human cells and host tissues. There isa clear need to combine the culture-based and molecular techniques to gainfull understanding of the complexity ofthe subgingival microbiota.

5. How will the development of theHOM database change our views inperiodontal microbiology? How doesthis oral database relate to research inother chronic infections?

When the full genome sequences ofthe majority of oral bacteria are avail-able, it will be feasible to screen forgenes encoding virulence factors andother relevant functions. The HOM isthe best characterized of the micro-biomes associated with human bodysites and it is a useful resource to addto the expanding databases. It has thepotential to enhance future diagnosticand therapeutic applications.

Periodontal Microbial ComplexesAssociated with Specific Cell andTissue Responses

Moritz Kebschull and Panos N.

Papapanou (Kebschull & Papapanou2011)

1. What is the evidence to support aspecific host-tissue response to coloni-zation by specific microbiota?

The limited number of cross-sectionalstudies in humans to date has demon-strated that different microbial profilesare associated with distinct host tissueresponses (transcriptomic responses ingingival tissues and proteomic profiles ingingival crevicular fluid) even in tissueswith similar clinical presentation. Theseresults are in line with extensive in vitrostudies and a number of animal studiesthat demonstrated that different microor-ganisms elicit distinctive host-responses.

Hence, heterogeneous patho-physio-logical pathways may lead to similarclinical presentation. At present, thereis no single host response signature fordisease progression (consistent withextensive biomarker analysis).

2. Do different microbial species eli-cit specific host responses resulting intissue destruction?

Experimental animal studies haveshown that distinct microorganismsresult in different rates of bone loss.Furthermore, combinations of perio-dontal bacterial species have beenshown to have synergistic effects ontissue destruction.

In vitro studies also demonstratedadditive, synergistic, or antagonistic

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effects of combinations of different bac-teria when compared with correspond-ing mono-infections, resulting in alteredcellular responses with respect to cyto-kine production and apoptosis. Further-more, mono-infections with differentspecies have been shown to elicitcellular responses, which are consistentwith in vivo mechanisms of tissuedestruction.

3. What is the clinical relevance of thedifferences in host-parasite interactions?

Evidence from experimental andhuman studies has shown a direct influ-ence of different bacterial complexes ongene and protein expression in perio-dontal tissues and conceivably on clin-ical phenotypes.

This findings has not yet beenexplored in terms of clinical application,but the clinical relevance of understand-ing the microbial composition of theperiodontal pockets is supported by atleast three longitudinal studies (van derVelden et al. 2006, Fine et al. 2007,Haubek et al. 2008) in which coloniza-tion with specific subgingival bacteria(Aggregatibacter actinomycetemcomi-tans) and/or clonal types showed anincreased risk of onset and rate ofprogression of disease.

How is the Development of DentalBiofilms Influenced by the Host?

Philip D. Marsh and Deirdre A. Devine

(Marsh & Devine 2011)

1. What is the impact of the ecologicalfactors on the characteristics of thesupragingival and subgingival biofilms?

All microbial communities are shapedby both physical and biological factors.

For example, a change in the avail-ability of nutrients, pH and redox poten-tial of the site can alter the overallcomposition of the biofilm. In addition,lifestyle factors, such as diet, smoking,general health and oral hygiene practice,can act as modifiers of the characteris-tics of the biofilms.

2. What is the impact of other oralbiofilms on the microbiota of the tooth/gingival interface?

Biofilms on other oral surfaces harbormicroorganism associated with perio-dontal diseases and may act as a reser-voir for the tooth-gingival interface.

3. What is the role of person-to-person transmission in the compositionof the oral microbiota?

In young children, vertical trans-mission from the mother or primary

care giver is a major factor in thedevelopment of the oral microbiota,and this may include periodontal patho-gens. There is evidence that P. gingiva-lis and A. actinomycetemcomitans canbe transmitted from adult to adult.

4. Can we explain the geographicaldifferences in the composition of thesubgingival biofilm?

Geographical differences in thecomposition of the subgingival biofilmhave been reported. To date, thereis insufficient data to explain the basisof these differences. New studies areneeded to address this issue, includingthe application of new technologiesand the evaluation of the whole micro-biota.

5. Are the subgingival microbialchanges associated with periodontitis theresult of colonization by exogenousmicroorganisms and by the overgrowthof resident microbiota due to ecologicalchanges?

The resident oral microbiota is diverseand complex, and includes bacteriaassociated with periodontal health anddisease. However, certain periodontalpathogens can be detected in the subgin-gival environment in healthy subjects, butinfrequently and in low numbers. Theymay be acquired by vertical and horizon-tal transmission, but the chronology ofthe acquisition is currently unknown.Changes in the environment (bacterial-or host-induced) may alter the ecologicalcompetition between the potential patho-genic and beneficial bacterial species,altering the composition of the subgingi-val microbiota, and hence unbalancingthe health-associated host biofilm home-ostasis, triggering periodontitis.

6. Which strategies could be appliedto influence the composition of thetooth-associated biofilm, so that it iscompatible with periodontal health?

Effective oral hygiene practices, thatinvolve regular disruption of supragin-gival biofilm, are capable of maintaininga biofilm with a composition that iscompatible with periodontal health, inthe majority of subjects.

Adjunctive chemical agents thatreduce plaque formation and/or gingivalinflammation (thereby preventing envir-onmental changes that promote thegrowth of periodontal pathogens) maybe valid strategies.

Mechanical and chemical strategiescould target non-dental biofilms thatmay act as reservoirs of potentialperiodontal pathogens for tooth coloni-zation.

Potential strategies could be aimed ataltering the formation, ecology or struc-ture of the biofilm, such as reducingbacterial adherence, changing the extra-cellular matrix, altering quorum sensing,regulating the expression of virulencefactors, etc.

What Can We Learn about Biofilm/Host Interactions from the Study ofInflammatory Bowel Disease (IBD)?

Amedeo Indriolo, Salvatore Greco, PaoloRavelli, Stefano Fagiuoli (Indriolo et al.

2011)

1. What are the commonalities in thepathobiology between IBD and perio-dontitis?

a. Is the role of bacteria in IBDsimilar to that in periodontitis?

There are similarities in both chronicinflammatory diseases in regards to thelikely role of commensal bacteria ineliciting a host tissue inflammatoryresponse. The role of a specific groupof putative pathogens is probably differ-ent when comparing both diseases. InIBD, there is no evidence that a specificpathogen (e.g. Mycobacterium paratu-berculosis as it was initially hypothe-sized) has any etio-pathogenic role intriggering the disease events. In con-trast, in Periodontitis there is a groupof putative pathogens with a defined setof virulence factors that have been asso-ciated with disease.

Is the role of the host response in IBDsimilar to that in periodontitis? Thereare also similarities in both chronic inflam-matory diseases in regards to the hostresponse. Ulcerative colitis (UC) is char-acterized by a Th-2 response with a pre-valent overproduction of IL-13. Incontrast, Crohn’s disease (CD) is charac-terized by a Th-1 response with over-production of IFN-gamma. In periodontaldiseases, both responses have been sug-gested to play a role, with a Th-1 responsemore related to gingivitis and a Th-2 toperiodontitis. In IBD, an intrinsic dysregu-lation of the gut epithelial innate immuneresponses has been reported with differentexpression of Toll-like receptors. In perio-dontitis, this dysregulation has not beenreported, although there is evidence thatspecific periodontal pathogens may alterthe expression of these receptors.

b. Is the role of genetic and environ-mental factors in IBD similar to that ofperiodontitis?

Twin studies provide evidence ofgenetic predisposition for UC, although

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the specific responsible genes havenot been identified. In CD, however,an association with a CARD 15 genevariant has been demonstrated, withcarrier frequencies of one or more var-iant CARD 15 alleles (SNPs) between22% and 60% of the subjects. Thismutation of the NOD2/CARD15 (Cas-pase Recruitment Domain) gene impairsthe ability to recognize bacterial com-ponents of the commensal intestinalmicrobiota and triggers an inadequateimmune response. Twin studies alsoprovide evidence of genetic susceptibil-ity for periodontitis, and several SNPshave been associated with its prevalenceand severity, but the data is not consis-tent across different populations.

Smoking is a common risk factor forboth CD and periodontitis.

2. What is the epidemiological evi-dence for an association between IBDand periodontitis?

Oral conditions such as pyostomatisvegetans, gingival hyperplasia, papillo-matosis of the oral mucosa, vesiculareruptions, periodontitis and caries havebeen linked to IBD, specifically to CD.The evidence of a specific associationbetween IBD and periodontitis is scarce.There is a case control study reporting asignificant association between UC or CDand periodontitis (Brito et al. 2008) and a

recent cross-sectional study (Stein et al.2010) demonstrating a positive, althoughweak association between CD and perio-dontitis. Conversely, another case–controlstudy (Grossner-Schreiber et al. 2006) didnot find an association with periodontitis.

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Address:

Mariano Sanz

Facultad de Odontologin

Universidad Complutense de Madrid

Plaza Ramon Y Cajal

28040 Madrid

Spain

E-mail: marianosanz@odon.ucm.es

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