Contemporary perspective on plaque control

Abstract

The aim of this review article is to provide a scientific platform that will enable the dental team to develop a rational approach to plaque control based on the latest knowledge of the role of the oral microflora in health and disease. The resident oral microflora is natural and forms spatially-organised, interactive, multi-species biofilms on mucosal and dental surfaces in the mouth. These resident oral microbial communities play a key function in the normal development of the physiology of the host and are important in preventing colonisation by exogenous and often undesirable microbes. A dynamic balance exists between the resident microflora and the host in health, and disease results from a breakdown of this delicate relationship. Patients should be taught effective plaque control techniques that maintain dental biofilms at levels compatible with oral health so as to retain the beneficial properties of the resident microflora while reducing the risk of dental disease from excessive plaque accumulation. Antimicrobial and antiplaque agents in oral care products can augment mechanical plaque control by several direct and indirect mechanisms that not only involve reducing or removing dental biofilms but also include inhibiting bacterial metabolism when the agents are still present at sub-lethal concentrations.

Full text

Contemporary perspective
on plaque control
P. D. Marsh
1
VERIFIABLE CPD PAPER
requirements, how does the dental team
decide on a rational way forward? The aim
of this article is to briey review the cur-
rent knowledge in this area, give answers
to some common questions and provide
the evidence to support a contemporary
approach to plaque control.
WHAT IS THE RELATIONSHIP
BETWEEN HUMANS AND THEIR
NATURAL MICROFLORA?
It is a remarkable statistic that humans
are made up of about 10
14
cells
1
of which
only ten percent are mammalian. The
majority are the micro-organisms (the
natural resident microora) that inhabit
all environmentally-exposed surfaces of
the body, where they form biolms.
2
The
composition of these biolms varies at dis-
tinct sites around the body and is directly
inuenced by the biological and physical
conditions associated with the particu-
lar habitat. These biolms are formed of
symbiotic communities of different micro-
organisms that grow on, and interact
with, the surfaces they colonise. Biolms
develop in a structured way, are spatially-
and functionally-organised, and the con-
stituent species communicate and interact
with one another.
3
These polymicrobial
INTRODUCTION
Dental professionals are faced with a
number of apparent paradoxes when it
comes to advising patients on the most
appropriate strategy for plaque control.
During training, students are taught that
caries and periodontal diseases result from
the activity of bacteria in dental plaque
and that effective self-performed plaque
removal is an essential part of the preven-
tion and management of these diseases;
but now it is being reported that many of
the micro-organisms in the mouth make an
important contribution to our well-being!
Also, many plaque control products are
formulated with antimicrobial agents that
are described as being broad spectrum and
yet these products also have to meet the
regulatory guidelines that demand that
they do not disrupt the natural balance of
the normal oral microora. In the face of
these apparently contradictory views and
The aim of this review article is to provide a scientic platform that will enable the dental team to develop a rational ap-
proach to plaque control based on the latest knowledge of the role of the oral microora in health and disease. The resident
oral microora is natural and forms spatially-organised, interactive, multi-species biolms on mucosal and dental surfaces
in the mouth. These resident oral microbial communities play a key function in the normal development of the physiology
of the host and are important in preventing colonisation by exogenous and often undesirable microbes. A dynamic balance
exists between the resident microora and the host in health, and disease results from a breakdown of this delicate rela-
tionship. Patients should be taught effective plaque control techniques that maintain dental biolms at levels compatible
with oral health so as to retain the benecial properties of the resident microora while reducing the risk of dental disease
from excessive plaque accumulation. Antimicrobial and antiplaque agents in oral care products can augment mechanical
plaque control by several direct and indirect mechanisms that not only involve reducing or removing dental biolms but also
include inhibiting bacterial metabolism when the agents are still present at sub-lethal concentrations.
biofilms display novel properties; of
clinical relevance is that they are much
less susceptible to the host defences and
antimicrobial agents.
4
The reasons for this
are still the subject of much debate, but
are directly linked to the properties of the
biolm itself, since the organisms retain
their intrinsic sensitivity if the biolm is
dispersed. The most common explanations
for the reduced susceptibility of biolms
to antimicrobial agents include:
• Reduced penetration of the agent into
the biolm or quenching of the agent
at the surface of the biolm
• The novel properties expressed by
bacteria when growing on a surface
• Sub-optimal conditions for activity
• The slow growth rates of attached
bacteria within biolms.
The resident microora has evolved to
co-exist in harmony with the host and
carry out key functions that are essential
to our well-being. These functions include
the ability to prevent colonisation by
exogenous (and often pathogenic) micro-
organisms (a process termed colonisation
resistance), and in the normal development
of the physiology, nutrition and immune
system of the host.
2,5
1
Department of Oral Biology, Leeds Dental Institute,
University of Leeds, Clarendon Way, Leeds, LS2 9LU, UK
Correspondence to: Professor Philip Marsh
Email: p.d.marsh@leeds.ac.uk; Tel: +44 (0)1980 612 287
Refereed Paper
Accepted 4 April 2012
DOI: 10.1038/sj.bdj.2012.524
©
British Dental Journal 2012; 212: 601-606
• Explains current thinking on strategies to
control dental plaque biolms.
• Argues that it is necessary to restrict
biolm accumulation to levels compatible
with a healthy mouth in order to
maintain important benets provided by
some resident bacteria.
• Highlights that antimicrobial agents
delivered by effective oral care products
can augment mechanical plaque control
to improve oral health.
IN BRIEF
RESEARCH
BRITISH DENTAL JOURNAL VOLUME 212 NO. 12 JUN 23 2012 601
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RESEARCH
The mouth is similar to other sites in the
body in that it has a natural microora
with a characteristic composition that con-
fers benet (see later).
6
However, on occa-
sions, this benecial relationship can break
down and disease can occur (for example,
dental caries, periodontal diseases), while
halitosis can also be a consequence.
Therefore, it is essential to appreciate the
benets that are derived from a balanced
relationship between the oral microora
and the host and to understand the pro-
cesses that predispose a site to disease if
effective control and preventative meas-
ures are to be adopted. Of clinical rele-
vance is that these measures might vary
from person to person.
WHAT BENEFITS DO THE
RESIDENT ORAL MICROFLORA
PROVIDE TO THE HOST?
The mouth is well equipped with an array
of host defences provided by both the
innate and adaptive arms of the immune
system and yet all mucosal and dental sur-
faces are naturally colonised by a diverse
collection of micro-organisms. It is becom-
ing clear that the host is not indifferent to
the presence of these consortia of microbes
and has developed mechanisms that per-
mit a benecial relationship.
7
There is
evidence for active communication (‘cross-
talk’) between some of the resident bacte-
ria and mucosal cells that downregulates
potentially damaging pro-inammatory
host responses to the normal oral micro-
ora, while the host retains the ability to
respond to genuine microbial insults.
7,8
The
precise biological mechanisms involved in
this ‘cross-talk’ are still being determined,
but pathogenic and non-pathogenic bac-
teria may initiate different intracellular
signalling pathways and innate immune
responses in epithelial cells.
9
As at other body sites, the resident oral
microora displays ‘colonisation resist-
ance’ and prevents the establishment in
the mouth of the many exogenous micro-
organisms we come into contact with on
a daily basis. This is because the natural
oral microora is better adapted at attach-
ment to oral surfaces, is more efcient at
metabolising the available nutrients for
growth and can produce inhibitory fac-
tors and create hostile environments that
restrict colonisation by potential microbial
invaders. A consequence for patients on
long-term broad spectrum antibiotic treat-
ment is that the resident oral microora
can be suppressed resulting in overgrowth
by yeasts and environmental bacteria in
the mouth.
Recent ndings suggest that the resi-
dent oral bacteria contribute to the main-
tenance of healthy gastrointestinal and
cardiovascular systems via the metabolism
of dietary nitrate. Approximately 25% of
ingested nitrate is secreted in saliva where
some oral resident bacteria reduce nitrate
to nitrite. Nitrite can affect a number of
key physiological processes including
the regulation of blood ow, blood pres-
sure, gastric integrity and tissue protec-
tion against ischemic injury. Nitrite can
be further converted to nitric oxide in the
acidied stomach, and this has antimicro-
bial properties, and contributes to defence
against enteropathogens and in the regu-
lation of gastric mucosal blood ow and
mucus formation. The reduction of nitrate
to nitrite in saliva fell markedly in human
volunteers,
10–12
and laboratory animals,
11
when the resident salivary microora was
deliberately suppressed using antimicro-
bial agents. The suppression of endoge-
nous nitrate reduction in the animal model
resulted in a loss of the predicted biological
benets of nitrite, including reduced gas-
tric mucus thickness, while the expected
fall in blood pressure following a nitrate
supplement was prevented.
11
It is of clinical importance, therefore, that
oral antimicrobials are applied according to
the recommended instructions which aim
to maintain the microora of the mouth at
levels that are compatible with oral health,
but below those which are associated with
disease. This is in order to preserve the
benecial functions of these important
resident microbes which, it is becoming
clear, are essential for both the general and
oral health of that person. Thus, antibiotics
are not a recommendation for managing
chronic periodontal disease.
13
CAN WE DEFINE WHAT IS
‘NORMAL’ IN TERMS OF
OUR ORAL MICROFLORA?
It is surprisingly difcult to fully dene
what might be regarded as the normal,
resident oral microora. At present, only
about 50% of the oral microora can
be cultivated in the laboratory. This is
because of our ignorance of the growth
requirements of the more fastidious mem-
bers of the oral microora, but also due to
our naivety in attempting to grow bacteria
as pure cultures in the laboratory when
they have evolved to grow in oral bio-
lms as consortia and interact closely with
neighbouring species with complementary
properties.
14
The application of culture-
independent, molecular approaches has
identified about 1,200 different types
of microbe that can inhabit the human
mouth.
1
However, any particular mouth
may contain only up to about 80 species,
15
although the application of more power-
ful and sensitive molecular approaches
will increase this number, as species that
are present only in low numbers will be
detected. The Human Oral Microbiome
project is underway and aims to identify
and characterise all members of the resi-
dent oral microora;
1
the conclusion of
these studies will permit a more accurate
description of what is the ‘normal oral
microora’. Information is being placed in
a publically accessible web-based Human
Oral Microbiome Database (http://www.
homd.org), which also feeds information
into the larger Human Microbiome project.
The normal oral microora is diverse
and varies in composition between sites
due to differences in the prevailing bio-
logical conditions.
16
The load on mucosal
sites is low due to desquamation. In con-
trast, teeth (being non-shedding surfaces)
potentially permit the accumulation of
large masses of bacteria and their prod-
ucts, especially at stagnant or ‘difcult-to-
reach’ areas, unless effective oral hygiene
is practised. The microbial composition of
oral biolms varies depending on the site
or surface, because local environmental
conditions dictate which organisms are
able to colonise, grow and be either major
or minor components of the established
microbial community. For example, the
bacteria found in occlusal ssures are
mainly Gram positive (especially strep-
tococci), are facultatively anaerobic and
metabolise host and dietary sugars, and
the site is affected by the properties of
saliva. In contrast, the biolms from the
healthy gingival crevice contain many
Gram negative and obligately anaerobic
species, that have a proteolytic style of
metabolism, and the community is inu-
enced by gingival crevicular uid (GCF), a
serum-like exudate.
16
Certain bacteria are
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RESEARCH
commonly found in high proportions at
healthy sites and can be regarded as part
of the core resident oral microora. These
include members of the bacterial genera:
Streptococcus, Actinomyces, Neisseria,
Haemophilus, Veillonella, Prevotella and
Fusobacterium, but the individual species
and their proportions may vary between
sites and between people.
One of the challenges in dening what
is ‘normal’ in terms of the resident oral
microora is that, traditionally, compari-
sons have been made from different stud-
ies of ‘lists’ of bacterial names. In diverse
biolms, such as those in the oral cavity,
this may not be an appropriate approach.
Within any microbial community, bacteria
will have a particular role or function (for
example, the catabolism of complex host
glycoproteins to individual sugars and
peptides; proteolysis of host proteins and
peptides to simpler peptides and amino
acids respectively; consumption of oxygen
to create a more anaerobic environment
etc). Organisms with different ‘names’
could carry out equivalent roles or activi-
ties, so that the denition and description
of the resident oral microora should be
based around functional characteristics
rather than simply by bacterial name.
The composition of the oral microora
can remain stable over time (microbial
homeostasis).
17
This is not due to any bio-
logical indifference among the members
of the biolm community – the relation-
ship is not passive but highly dynamic.
Biofilm composition will respond to
changes in local environment (for exam-
ple, in saliva ow, status of host defences,
etc) and lifestyle (diet, smoking, etc). Such
changes can perturb biolm composition
and activity and predispose a site to dis-
ease. Oral diseases are generally associated
with shifts in the balance of the microora
at a site, so previously minor members
of the biolm become predominant, and
the overall metabolic activity of the bio-
lm changes.
18
Thus, in contrast to many
situations in medical microbiology, it is
too simplistic to talk of the presence of
‘good’ or ‘bad’ bacteria. Disease is a result
of undesirable changes to the microbial
balance, metabolism, and composition of
these dental biolms.
As we shall see, of clinical relevance
is the need to not only apply appropri-
ate plaque control strategies to reducing
dental disease, but to also try to identify
and remedy the factors that drive these
deleterious changes in the microbiologi-
cal composition and metabolism of these
biolms.
SO WHAT IS THE PURPOSE
OF PLAQUE CONTROL?
Patients need to maintain plaque at levels
compatible with health in order to prevent
the breakdown of microbial homeostasis
which would increase the risk of disease. It
is inappropriate and futile for patients and
dental professionals to attempt to eliminate
plaque biolms; rather, patients should
be using effective oral hygiene practices,
combined with an appropriate lifestyle, to
try to control plaque at levels compatible
with health so as to maintain the benecial
properties of the resident oral microora,
and reduce the risk of disease. In peri-
odontitis, plaque control ‘thresholds’ that
are compatible with a health-promoting
biomass vary from patient-to-patient, with
some requiring extremely good plaque
control, while others manage with less
stringent regimes.
WHICH MICRO-ORGANISMS
CAUSE DENTAL DISEASE?
Dental diseases are associated with an
imbalance in the composition of the resi-
dent oral microora.
18
Disease is linked to
the presence of higher proportions of cer-
tain species that are normally only minor
components in the biolm. In dental car-
ies, demineralisation is associated with
increased proportions of mutans strepto-
cocci, lactobacilli and bidobacteria. The
virulence traits are relatively nonspecic
and centred around sugar metabolism,
such as the ability of these bacteria to
rapidly transport sugars into the cell and
metabolise them to acid, and then to sur-
vive and grow under the conditions of
low pH generated within the biolm (acid
tolerance). The ability to synthesise intra-
cellular and extracellular polysaccharides
from sucrose also plays a role in devel-
oping a cariogenic biolm. In gingivitis,
there is an increase in plaque mass, which
provokes an inammatory response by the
host. If unresolved, by-stander damage to
the periodontium can occur from an inap-
propriate and exaggerated host response
to subgingival bacteria and their metabo-
lites. Many of the implicated bacteria are
currently unculturable; others are Gram
negative, obligately anaerobic and highly
proteolytic. Virulence traits of these bac-
teria include the production of proteases,
cytotoxins and inammatory mediators.
Biolms can form on mucosal surfaces,
and substantial numbers of bacteria can be
found on the tongue. In some subjects, this
can result in halitosis, which is also linked
to the metabolism of obligately anaero-
bic, proteolytic bacteria resulting in the
production of volatile sulphur and other
malodorous compounds.
19,20
Evidence linking oral and general health
is accumulating, particularly with respect
to diabetes mellitus and cardiovascular
and respiratory diseases. Some studies
also report a weak positive association
between periodontal disease and adverse
pregnancy outcomes.
21
The hypothesis
behind the link between oral and general
health is that many oral bacteria act as
opportunistic pathogens, especially if they
enter the blood stream and reach sites not
normally accessible to them (including
heart valves and atheromatous plaques);
or if the host defences are compromised
and subgingival biolms in periodontal
disease contain bacteria which (a) express
inammatory cell surface components (for
example, lipopolysaccharide) and (b) shed
metabolites which induce prostaglandins
and inammatory mediators. The vascu-
lar nature of the periodontium means that
these pro-inammatory mediators can
affect distant sites in the body. Oral micro-
organisms may also give rise to aspira-
tion pneumonia in susceptible patients
as anaerobic bacteria from periodontal
pockets have been isolated from infected
lungs.
22
This is another way in which effec-
tive oral hygiene can contribute to main-
taining the general health of an individual.
HOW CAN EFFECTIVE PLAQUE
CONTROL BE ACHIEVED?
As discussed earlier, dental plaque prefer-
entially accumulates at stagnant sites on
teeth that many individuals nd difcult to
clean- these sites are also the most disease
susceptible. Mechanical plaque control can
be effective, but needs to be meticulous
and patients have to be highly motivated
and with an appropriate lifestyle (that is,
an appropriate diet, avoid smoking, etc).
Consequently, oral care products have
been formulated that contain antiplaque or
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RESEARCH
antimicrobial agents to augment conven-
tional mechanical plaque control activi-
ties and interfere with biolm composition
and metabolism, especially at sites that
are difcult to clean and are commonly
missed during self-performed mechanical
plaque control.
Antiplaque agents function by remov-
ing or disrupting biolms, or by prevent-
ing the formation of new biolm, without
necessarily killing the component micro-
organisms. In contrast, antimicrobial
agents inhibit the growth of (bacteriostatic
action) or kill (bactericidal action) micro-
organisms in oral biolms and are dened
in terms of the minimum inhibitory con-
centration (MIC) or minimum bactericidal
concentration (MBC) respectively.
23
The
activity of these agents can be against a
limited (narrow spectrum) or wider (broad
spectrum) target group of micro-organ-
isms. The mode of action of antimicrobial
agents is inuenced by their concentration
and the length of time they are in con-
tact with the target organisms. Typically,
the MIC/MBC of an agent is determined
in the laboratory on liquid grown (plank-
tonic) cells in tests where the agent is in
contact with a pure culture of the organ-
ism for prolonged periods (24-48+hours).
However, as discussed above, bacteria
growing on a surface as a biolm show
reduced sensitivity to killing by antimi-
crobial agents, especially in older (more
mature) biolms. Moreover, the maximum
length of time recommended for people
to brush their teeth is in the order of two
minutes, followed by ossing and rinsing
with a mouthwash for 30-60seconds. A
major requirement of the antiplaque for-
mulation, therefore, is to deliver sufcient
concentration of the active ingredients to
have an effect on the biolm in that short
period of time. Alternatively, the formula-
tion should ensure the prolonged retention
of the active components on dental and
mucosal surfaces in the mouth so that they
can be released over time at levels that will
still deliver biological activity.
An example of the pharmacokinetic
prole of a representative antimicrobial
agent delivered to the mouth from an oral
care product is shown in Figure1. There
are only short periods where the agent is
present at a high concentration (that is,
at concentrations greater than the MIC or
MBC) followed by longer periods where
the agent is present at sub-lethal levels.
This prole has a signicant inuence
on the mode of action of these agents.
23
Organisms reported to have an apparent
similar sensitivity to an antimicrobial
agent (as determined in a standard MIC
assay format under laboratory conditions)
can vary markedly in their susceptibil-
ity when exposed to the agent for only
relatively short periods, as occurs during
routine oral use; and sometimes favourable
selective inhibitory effects can be obtained.
For example, although displaying similar
MIC values against Triclosan, Gram nega-
tive obligately anaerobic bacteria impli-
cated in gingivitis and periodontal diseases
are more susceptible than the Gram posi-
tive bacteria (streptococci and Actinomyces
species) found in health when exposed to
this agent for only short periods.
24
Many
Antimicrobial delivery
>MIC / MBC
sub-lethal
Time (hours)
bactericidal
action
inhibitory
action
Antimicrobial concentration
Fig. 1 Pharmacokinetics of antimicrobial agents delivered to the mouth.
23
A schematic
representation of the change in concentration over time following the delivery to the mouth on
two occasions of an antimicrobial agent from an oral care product. The agent may be present
above its MIC/MBC level for a relatively short period before it is lost from the mouth. The agent
may be present for longer at sub-lethal concentrations; agents may still exert benecial effects
by inhibiting traits associated with bacterial pathogenicity (see Table 1). The dynamics of the
curve will vary for each antimicrobial agent)
Table 1 Classes and examples of inhibitors used as antiplaque or antimicrobial agents
in mouthwashes and toothpastes, and their mode of action when present at sub-lethal
concentrations (see Fig. 1)
27,28
Class of inhibitor Example Antimicrobial action at sub-lethal concentrations*
Bisbiguanide Chlorhexidine**
Inhibits sugar transport and acid production
Inhibits amino acid uptake, polysaccharide synthesis
and bacterial membrane functions
Inhibits protease activity
Enzymes
Mutanase, dextranase,
amyloglucosidase-
glucose oxidase
Degrade bacterial polysaccharides that
make up plaque biolm matrix
Boosts salivary peroxidise system which
can inhibit bacterial glycolysis
Essential oil extracts
Menthol, thymol,
eucalyptol, methyl
salicylate **
Inhibit acid production and bacterial growth
Reduces lipopolysaccharide
Metal salts
Zinc, copper,
stannous ions
Inhibit sugar transport and acid production
Inhibit protease activity
Natural molecules
Plant extracts
(for example,
apigenin, tt-farnesol)
***
Inhibit acid production
Inhibit bacterial polysaccharide synthesis
Phenols Triclosan
Inhibit sugar transport and acid production
Inhibit protease activity
Quaternary ammonium
compounds
Cetylpyridinium
chloride**
Surfactants
Sodium lauryl
sulphate, delmopinol
Damage cell membranes
Inhibit bacterial enzymes
Key *Some of these inhibitory actions will also inhibit metabolic activities involved in halitosis; **Generally delivered by mouthrinse;
***
Some
compounds have yet to be incorporated into commercially-available oral care products
604 BRITISH DENTAL JOURNAL VOLUME 212 NO. 12 JUN 23 2012
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RESEARCH
active agents used in oral care products
are able to exert a clinically relevant effect
when present below the MIC/MBC by
inhibiting the expression of virulence traits
by oral bacteria, such as sugar transport
mechanisms, acid production, extracellu-
lar polysaccharide synthesis and protease
activity (Table1).
23
In this way, small but
regular (for example, twice daily) subtle
and minor inhibitory effects on the plaque
biolm can:
• Reduce damage to oral and dental
tissues by inhibiting the expression of
virulence traits
• Suppress the competitiveness of some
of the putative pathogens by both
restricting their growth and denying
them the environment they need to
ourish (for example, acidic conditions
or presence of novel host proteins).
It has been shown that plaque biolms
need to be established for two days or
longer before the pH gradients following
sucrose metabolism fall below the critical
pH for enamel demineralisation,
25
that is,
thinner biolms are less damaging to the
host than thicker and more mature bio-
lms. Thus, the action of oral care prod-
ucts can help to preserve an appropriate
biolm structure and promote the stabil-
ity of the benecial resident microora
(microbial homeostasis).
CAN WE TRANSLATE THIS KNOWL-
EDGE INTO CLINICAL PRACTICE?
It has been argued in this article that
the presence of biolms in the mouth is
both natural and is of benet to the host.
Therefore, there is a clear need to maintain
these benecial micro-organisms. Disease
is due to imbalances in the proportions
of this resident microora driven by del-
eterious changes in local environmental
conditions (the ecological plaque hypoth-
esis).
18,26
Briey, poor oral hygiene can
lead to an increase in plaque mass which,
when coupled with a substantial change
in environmental conditions in the mouth,
can affect the competitiveness of plaque
bacteria within the biolm, leading to
the enrichment of organisms most suited
to the altered environment and result in
a breakdown of microbial homeostasis
(Fig.2). In caries, an increased frequency
of sugar intake, or a reduction in saliva
ow, results in plaque biolms spend-
ing more time at low pH. This selects for
acid-producing and acid-tolerating spe-
cies (most commonly mutans streptococci,
but not exclusively so) at the expense of
health-associated bacteria that prefer pH
values around neutrality. Increases in
the acidogenic populations lead to even
more acid production and lower pH levels
within the biolm, which further disrupts
microbial homeostasis and promotes dem-
ineralisation.
18,26
In gingivitis, the inam-
matory response to plaque accumulation
results in an increased ow of GCF which,
in addition to introducing components of
the host defences, also delivers host mol-
ecules such as haemoglobin and transfer-
rin that act as essential nutrients for many
of the obligately anaerobic and proteolytic
bacteria detected in higher proportions in
periodontal disease. The metabolism of the
subgingival microora makes the site more
anaerobic and the local pH increases due to
proteolysis. These environmental changes
drive the selection of the diverse microbial
• Poor oral hygiene
• Lifestyle risk factors
Normal development
of host physiology
Colonisation
resistance
Cardiovascular and
gastrointestinal benets
Host
benets
Resident oral
microora
• Effective oral hygiene
• Effective and regular interventions
Increased plaque
accumulation
Thinner biolm
Maintain benecal microbes
Caries risk ↑
Suppression of
benecial bacteria
Inammation ↑
Gingivitis risk ↑
Halitosis risk ↑
Lower selective pressure
for oral ‘pathogens’
Less acid production,
reduced pH drop
from dietary sugars
Fewer obligate
anaerobes
Fig. 2 The relationship between the resident oral microora and the host in health and disease. The resident oral microora is important for the
normal development of many functions of the host in health, and contributes to the host defences (colonisation resistance). If plaque is allowed
to accumulate then the patient is at risk of caries, gingivitis or halitosis. Effective plaque control should maintain the oral microora at levels
that are compatible with health so as to retain the benecial properties of the resident oral microora, while minimising the risk of disease
BRITISH DENTAL JOURNAL VOLUME 212 NO. 12 JUN 23 2012 605
© 2012 Macmillan Publishers Limited. All rights reserved.

RESEARCH
consortia that are detected at inamed
sites.
18
A key principle of this hypothesis
is that disease can be treated not only by
(a) improving oral hygiene or (b) targeting
the putative pathogens directly, but also
by (c) interfering with the environmental
pressures that select for the pathogenic
microorganisms.
18
Antimicrobial agents in
oral care products can play an important
role in all of these stages,
27,28
for example,
by killing some of the key bacteria and
by reducing (at sub-lethal concentrations)
the deleterious consequences to the host
associated with acid production
29–31
and
proteolysis
29,32
that create the selection
pressures for the overgrowth of putative
pathogens in oral biolms.
23
The stratagem for using antimicrobial
agents in oral care products, therefore,
is quite distinct to that when prescribing
antibiotics in clinical medicine. In cases of
the latter, high doses of antibiotic (prefer-
ably with a bactericidal mode of action)
are given for a xed period with the inten-
tion of eliminating a recognised pathogen,
often from a site that should be relatively
sterile. In oral care, antimicrobial agents
are delivered in over-the-counter prod-
ucts and used unsupervised, on a regular
basis, at a site with a resident and bene-
cial microora. Thus, it can be appreciated
that agents that work subtly but effec-
tively over long time periods to suppress
or restrict the growth and metabolism of
certain sections of the biolm consortium
may be ideal for the long-term control of
oral biolms. These oral care products help
preserve the natural microbial composi-
tion and activity, as well as the important
benecial functions, of our resident oral
microora (Fig.2), and in so doing, help
reconcile the paradoxes described at the
start of this article.
The author has received a fee from Johnson &
Johnson for writing this review article and in the
past has acted as a consultant to, and received
research grants from, several oral care companies.
1. Dewhirst FE, Chen T, Izard J etal. The human oral
microbiome. J Bacteriol 2010; 192: 5002–5017.
2. Wilson M. Microbial inhabitants of humans. Their
ecology and role in health and disease. Cambridge:
Cambridge University Press, 2005.
3. Jakubovics NS. Talk of the town: interspecies
communication in oral biolms. Mol Oral Microbiol
2010; 25: 4–14.
4. Marsh PD. Dental plaque: biological signicance
of a biolm and community life-style. J Clin
Periodontol 2005; 32: 7–15.
5. Wilks M. Bacteria and early human development.
Early Hum Dev 2007; 83: 165–170.
6. Marsh PD. Role of the oral microora in health.
Microb Ecol Health D 2000; 12: 130–137.
7. Srinivasan N. Telling apart friend from foe: dis-
criminating between commensals and pathogens at
mucosal sites. Innate Immun 2010; 16: 391–404.
8. Cosseau C, Devine DA, Dullaghan E etal. The com-
mensal Streptococcus salivarius K12 downregulates
the innate immune responses of human epithelial
cells and promotes host-microbe homeostasis.
Infect Immun 2008; 76: 4,163–4,175.
9. Milward MR, Chapple IL, Wright HJ, Millard JL,
Matthews JB, Cooper PR. Differential activation of
NF-kappaB and gene expression in oral epithelial
cells by periodontal pathogens. Clin Exp Immunol
2007; 148: 307–324.
10. Govoni M, Jansson EA, Weitzberg E, Lundberg JO.
The increase in plasma nitrite after a dietary nitrate
load is markedly attenuated by an antibacterial
mouthwash. Nitric Oxide 2008; 19: 333–337.
11. Petersson J, Carlström M, Schreiber O etal.
Gastroprotective and blood pressure lowering
effects of dietary nitrate are abolished by an
antiseptic mouthwash. Free Radic Biol Med 2009;
46: 1068–1075.
12. Dougall HT, Smith L, Duncan C, Benjamin N. The
effect of amoxycillin on salivary nitrite concentra-
tions: an important mechanism of adverse reac-
tions? Br J Clin Pharmacol 1995; 39: 460–462.
13. Herrera D, Alonso B, León R, Roldán S, Sanz M.
Antimicrobial therapy in periodontitis: the use of
systemic antimicrobials against the subgingival
biolm. J Clin Periodontol 2008; 35: 45–66.
14. Wade WG. Has the use of molecular methods for
the characterization of the human oral microbiome
changed our understanding of the role of bacteria
in the pathogenesis of periodontal disease? J Clin
Periodontol 2011; 38: 7–16.
15. Aas JA, Paster BJ, Stokes LN, Olsen I, Dewhirst
FE. Dening the normal bacterial ora of the oral
cavity. J Clin Microbiol 2005; 43: 5721–5732.
16. Marsh PD, Martin MV. Oral Microbiology. 5th ed.
Edinburgh: Churchill Livingstone Elsevier, 2009.
17. Marsh PD. Host defenses and microbial homeosta-
sis: role of microbial interactions. J Dent Res 1989;
68: 1567–1575.
18. Marsh PD. Are dental diseases examples of ecologi-
cal catastrophes? Microbiology 2003; 149: 279–294.
19. Scully C, Greenman J. Halitosis (breath odour).
Periodontol 2000 2008; 48: 66–75.
20. Hughes FJ, McNab R. Oral malodour - a review.
Arch Oral Biol 2008; 53 (Suppl 1): S1–7.
21. Scannapieco FA, Dasanayake AP, Chhun N. Does
periodontal therapy reduce the risk for systemic
diseases? Dent Clin North Am 2010; 54: 163–181.
22. Paju S, Scannapieco FA. Oral biolms, periodontitis,
and pulmonary infections. Oral Dis 2007;
13: 508–512.
23. Marsh PD. Controlling the oral biolm with antimi-
crobials. J Dent 2010; 38 (Suppl 1): S11–15.
24. Bradshaw DJ, Marsh PD, Watson GK, Cummins D.
The effects of triclosan and zinc citrate, alone and
in combination, on a community of oral bacteria
grown invitro. J Dent Res 1993; 72: 25–30.
25. Imfeld TN, Lutz F. Intraplaque acid formation
assessed invivo in children and young adults.
Pediatr Dent 1980; 2: 87–93.
26. Takahashi N, Nyvad B. Caries ecology revisited:
microbial dynamics and the caries process. Caries
Res 2008; 42: 409–418.
27. Cummins D. Mechanisms of action of clinically
proven antiplaque agents. In Embery G, Rolla G
(eds). Clinical and biological aspects of dentifrices.
pp 205-228. Oxford: Oxford University Press, 1992.
28. Scheie AA, Petersen FC. Antimicrobials in caries
control. In Fejerskov O, Kidd EAM (eds). Dental car-
ies: the disease and its clinical management. 2nd ed.
pp 265-277. Oxford: Blackwell Munksgaard, 2008.
29. Rogers AH, Zilm PS, Gully NJ, Pfennig AL.
Chlorhexidine affects arginine metabolism as well
as glycolysis in a strain of Streptococcus sanguis.
Oral Microbiol Immunol 1987; 2: 172–182.
30. Wikén Albertsson K, Persson A, Lingström P, van
Dijken JW. Effects of mouthrinses containing
essential oils and alcohol-free chlorhexidine on
human plaque acidogenicity. Clin Oral Investig
2010; 14: 107–112.
31. Zhang JZ, Harper DS, Vogel GL, Schumacher G.
Effect of an essential oil mouthrinse, with and
without uoride, on plaque metabolic acid produc-
tion and pH after a sucrose challenge. Caries Res
2004; 38: 537–541.
32. Cummins D. Zinc citrate/Triclosan: a new anti-plaque
system for the control of plaque and the prevention
of gingivitis: short-term clinical and mode of action
studies. J Clin Periodontol 1991; 18: 455–461.
606 BRITISH DENTAL JOURNAL VOLUME 212 NO. 12 JUN 23 2012
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