Oral Diseases (1999) 5, 278–285
 1999 Stockton Press All rights reserved. 1354-523X/99 $15.00
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REVIEW
Oral Microbiology
Oral colonization by anaerobic bacteria during childhood:
role in health and disease
E Könönen1,2
1
Anaerobe Reference Laboratory, National Public Health Institute, Helsinki, Finland; and 2Department of Medical Microbiology and
Immunology, University of Aarhus, Denmark
Anaerobes constitute a significant part of bacterial com-
munities in human mouths. Their ability to colonize and
survive in the environment, where remarkable changes
occur during early childhood, is fundamental for oral
homeostasis. However, relatively little is known of the
time of colonization and succession of anaerobic species
in the oral cavity. This article presents an up-to-date
review on the development of the oral anaerobic
microflora in respect to age, and in addition, considers
some aspects of the role of oral anaerobes in health
and disease.
Keywords: anaerobes; children; oral cavity; review
Introduction
The surfaces of the human oral cavity are colonized by
various bacteria that form the indigenous oral microflora.
Anaerobic species constitute a significant part of this bac-
terial community. The anaerobic microflora is an integral
component of the function of this body site, but the oral
cavity also serves as a colonization site for anaerobic
bacterial species and clones that are involved in infectious
processes, both in oral and non-oral sites.
Anaerobes are the bacteria most often posing problems
in identification and recognition due to the need of sophisti-
cated methods. Improvement in anaerobic methodology
during the last two decades led to intensive research interest
in oral microbiology. However, most of that interest has
been focused on the investigation of the subgingival
microflora in periodontal diseases. Although the onset and
species involved in the primary colonization of infants are
of great importance by forming the basis for further colon-
ization, the development of the oral anaerobic microflora
with age is still inadequately understood. The purpose of
this review is, by taking into account the current bacterial
Correspondence: Dr Eija Könönen, Anaerobe Reference Laboratory,
National Public Health Institute, Mannerheimintie 166, FIN-00300 Hel-
sinki, Finland. Fax: 00 358 9 4744 8238, E-mail: Eija.Kononen얀ktl.fi
Received 7 January 1999; revised and accepted 4 May 1999
taxonomy, to present up-to-date information on the devel-
opment of the oral anaerobic microflora in respect to age
and succession of colonizing anaerobes as well as to con-
sider some aspects of oral anaerobes in health and disease
during early childhood.
Oral cavity as a habitat for anaerobes
Microorganisms attach to different surfaces in a selective
manner (Gibbons and van Houte, 1971; Gibbons, 1984). At
an infant’s birth the oral mucosal surfaces, such as the dor-
sum of the tongue and the buccal and palatal mucosae, are
available for various microorganisms to be colonized.
Tooth eruption significantly increases the number of poten-
tial niches and attachment sites when hard tooth surfaces
as well as gingival crevices allow further microbial coloniz-
ation. During the early years of life the oral environment
changes continuously; the primary, mixed and permanent
dentitions develop. Saliva (and in some extent the gingival
crevicular fluid) constantly bathes the oral surfaces offering
nutrients for bacterial growth (de Jong and van der Hoeven,
1987). On the other hand, saliva contains various enzymes,
antibodies and other immunologically active components
capable of inhibiting the microbial adhesion and growth
(Tenovuo et al, 1987).
Bacteria adhere not only to available surfaces but also to
each other by specific cell-to-cell interactions, thus forming
multigeneric coaggregations that are regulated by partner
specificity and binding stability (Kolenbrander and Ander-
sen, 1986). In addition, nutritional interactions, stimulatory
or inhibitory, between different bacterial species influence
the composition and stability of the oral flora (Distler and
Kröncke, 1981; Grenier and Mayrand, 1986; Marsh, 1989).
Oxygen tension is an important environmental determi-
nant for microorganisms. For a long time obligate ana-
erobes in infants’ edentulous mouths were considered
occasional findings because of the firm belief that anaerobic
species are dependent on the gaseous atmosphere only
present in the environment of gingival crevices (Socransky
and Manganiello, 1971; Evaldson et al, 1982; Hentges,
1993). Therefore, the establishment of oral anaerobes was
associated with emergence of teeth. According to Costerton

et al (1994), microbes tend to form biofilms on available
surfaces where various microenvironments with different
pH, oxygen concentrations and electric potentials are then
developed for biofilm bacteria. This recent concept presents
a conceivable explanation for fastidious anaerobic growth
even in infants’ edentulous mouths.
Primary colonization
Birth separates the sterile intrauterine life from the extra-
uterine existence of an individual who is then exposed to
continuous contacts with microbes via other individuals,
animals, and the local environment. The development of
the indigenous microflora begins. Adhesion of bacteria to
mucosal surfaces is the initial event in the colonization
(Gibbons, 1984). Many of the bacterial species available
are just passing the oral cavity as transient invaders, while
some species find a suitable surface for their attachment and
growth. Infants may be particularly amenable to microbial
colonization, since specific antibodies capable of inhibiting
bacterial adherence on oral mucosal surfaces, such as
secretory immunoglobulin A (S-IgA), are present only at
low levels in early infancy (Fitzsimmons et al, 1994). The
colonization of the oral cavity begins with streptococci
(Carlsson et al, 1970; Rotimi and Duerden, 1981; Pearce
et al, 1995). Interestingly, some early colonizing viridans
streptococci can produce enzymes that specifically cleave
antibodies of the IgA1 subclass, which predominates in sal-
iva (see review by Kilian et al, 1996). This capability may
aid them to evade the host immune response and, probably,
also aids other early species that lack this capability to be
colonized. However, no data exist on the mutual association
between the frequency and proportion of IgA1 protease-
producing viridans streptococci and the composition of the
oral microflora.
Mechanisms of bacterial coaggregations in dental plaque
have been intensively studied by Kolenbrander and his
coworkers. Streptococci, and in less amount actinomycetes,
that have a unique capability of intrageneric coaggregations
initially colonize pellicle-coated tooth surfaces (Nyvad and
Kilian, 1987; Kolenbrander et al, 1990). This initial colon-
ization by streptococci and actinomycetes then allows
further colonization by other bacterial species that is
determined by species-specific adhesin and receptor mol-
ecules (Kolenbrander and Andersen, 1986). All early
colonizing species on tooth surfaces are primarily capable
of coaggregating with streptococci and/or actinomycetes,
whereas the presence of Fusobacterium nucleatum may be
a prerequisite as an intermediary species for establishment
of certain late colonizing species, such as selenomonads
and eubacteria (Kolenbrander et al, 1989). Recently, Brad-
shaw et al (1998) demonstrated that the presence of F.
nucleatum in mixed cultures can be essential for other
anaerobic species to survive under aerated conditions.
Thus, the key species in intergeneric bacterial coaggre-
gation and biofilm formation seems to be F. nucleatum.
Cascade colonization on mucosal surfaces could be regu-
lated by fairly similar partnership mechanisms as on tooth
surfaces. Indeed, results of our on-going longitudinal study
on the development of the oral microflora in infancy
(Könönen et al, 1999c) indicate that anaerobic bacterial
Oral colonization by anaerobic bacteria during childhood
E Könönen
279
species have a different susceptible time for their colonization,
probably due to interrelationships in bacterial succession.
Age-related colonization of oral anaerobes
Table 1 summarizes the main anaerobic groups that estab-
lish in the oral cavity during infancy and early childhood.
When discussing the onset and succession of colonizing
species, it is important to recognize that a longitudinal
study approach is required to determine whether a bacterial
species really has established or has only been a transient
finding.
Infants
The first longitudinal data available on the oral flora during
early infancy originate from the sixties, when McCarthy et
al (1965) examined the occurrence of oral bacteria in
infants from the age of 1 day to 1 year. Anaerobic growth,
mainly consisting of facultative streptococci, dominated
over aerobic growth. Obligately anaerobic cocci, Veil-
lonella spp., were detected in 75% of the infants by the
fourth month of age, but gram-negative anaerobic rods only
sporadically. Obviously, the latter finding was influenced
by shortcomings in anaerobic methods at that time. Later
studies, although cross-sectional in design but using current
anaerobic techniques, demonstrated that several gram-
negative anaerobic rods inhabit the oral cavity before 6
months of age (Frisken et al, 1990; Könönen et al, 1992a).
Our recent study (Könönen et al, 1999c), where saliva
was used as an overview of the bacteria in infants’ mouths,
presents up-to-date information on the establishment of the
oral anaerobic microflora during the first year of life. The
longitudinal study design revealed a periodical tendency in
the establishment of oral anaerobes; anaerobic bacterial
groups could be divided into two main categories in regard
to their frequent or occasional presence in the oral cavity
during the first half year of life. Obligately anaerobic Veil-
lonella spp. and the Prevotella melaninogenica group
organisms as well as facultatively anaerobic Actinomyces
spp. were common salivary findings already in 2-month-
old infants, and in addition, the frequency of F. nucleatum,
Porphyromonas catoniae, non-pigmented Prevotella spp.,
and Leptotrichia spp. remarkably increased between 2 and
6 months of age. Their frequencies increased similarly both
in predentate and dentate infants with one exception; P.
catoniae was more frequent in infants with the early emerg-
ence of the first tooth. Among the ‘late colonizers’, corrod-
ing rods, Capnocytophaga spp., and other fusobacteria than
F. nucleatum reached the prevalence of 10% in infants up
to 1 year of age. Once established, the species tended to
persist in the mouth. These recent longitudinal data on the
first year of life (Könönen et al, 1999c) clearly demon-
strated that the presence of obligate anaerobes in infants’
mouths, even edentulous, is not just an occasional event.
In addition, the oral colonization proved to be a rather
selective process in terms of the age in which infants are
susceptible to colonization by different anaerobic species.
Children with deciduous dentition
After the first year of life, remarkable increases in the fre-
quency of several oral anaerobic groups occur; early
 Oral colonization by anaerobic bacteria during childhood
E Könönen
280
Table 1 Establishment of oral anaerobes in early childhood
Age: 0–2 months 2–6 months
Gramⴚ: Veillonella spp.
P. melaninogenica
group
F. nucleatum
P. catoniae
non-pigm. Prevotella spp.
Leptotrichia spp.
corroding rods*
Capnocytophaga spp.*
other fusobacteria
Gramⴙ: Actinomyces spp.*
(Data adapted from Alaluusua and Asikainen, 1988; Könönen et al, 1992a, 1994a, 1999c)
*Facultative/microaerophilic
colonizing species can be isolated nearly from every mouth
and also ‘late colonizers’, such as other fusobacteria than
F. nucleatum, Capnocytophaga spp., corroding rods,
Selenomonas spp., and the Prevotella intermedia group
organisms, are frequently present in the oral cavity before
4 years of age (Könönen et al, 1994a, 1996). Among the
P. intermedia group, Prevotella nigrescens and Prevotella
pallens are common colonizers during childhood, unlike P.
intermedia (Mättö et al, 1996; Könönen et al, 1998b). The
increasing frequencies may be explained by erupted teeth
but also by more matured biofilms on oral surfaces that
offer favourable microenvironments for anaerobes due to
metabolically cooperative species (Costerton et al, 1994;
Bradshaw et al, 1996). Interestingly, the most frequent
anaerobic species in infants’ mouths at 1 year of age proved
to be F. nucleatum (Könönen et al, 1999c), and further,
was ubiquitously present after the second year of life
(Könönen et al, 1994a). The findings perfectly fit with the
concept of the crucial role of F. nucleatum in intergeneric
coaggregation and biofilm formation (Kolenbrander et al,
1989; Bradshaw et al, 1998). Indeed, children with decidu-
ous dentition already harbour a multiform oral anaerobic
microflora (Moore et al, 1984; Frisken et al, 1987;
Könönen et al, 1994a). However, the transition to mature
oral microflora corresponding to that of adults probably
does not take place until puberty (Moore et al, 1993).
Colonization of periodontal pathogens
Obligately or facultatively anaerobic, mainly gram-negative
bacteria are recovered in high proportions from subgingival
samples of periodontitis patients (see reviews by Moore and
Moore, 1994; Haffajee and Socransky, 1994). Among these
species, Actinobacillus actinomycetemcomitans, Porphyro-
monas gingivalis, and Bacteroides forsythus were identified
as main periodontal pathogens in the Consensus report on
periodontal diseases (1996). During the first 3 years of life,
none of these main pathogens have been found by culture
techniques (Frisken et al, 1990; Könönen et al, 1992a,
6–12 months 1–4 years 4–7 years
Selenomonas spp.
P. nigrescens
P. pallens
A. actinomycetemcomitans*
Clostridium spp.
Peptostreptococcus spp.
1994a, 1999c)—they are absent or present but under the
detection limit. By using a polymerase chain reaction
(PCR)-based assay, the detection rates of P. gingivalis from
children in all year cohorts in the USA have been approxi-
mately 40% (McClellan et al, 1996) but in Finnish children
between 5 and 10 years of age only 5% (Mättö et al, 1998).
From periodontally healthy children between 4 and 7 years
of age, a 13% detection rate of A. actinomycetemcomitans
has been reported in Finland (Alaluusua and Asikainen,
1988), in contrast to a German study (Conrads et al, 1996),
where neither A. actinomycetemcomitans nor P. gingivalis
was recovered from subgingival samples of healthy chil-
dren at 3 to 5 years of age by using PCR and dot-blot
hybridization.
Also P. intermedia and P. nigrescens are often men-
tioned as suspected periodontopathogens in the pertinent
literature (Moore and Moore, 1994; Haffajee and Socran-
sky, 1994; Consensus Report, 1996). Occasional findings
of P. intermedia have been reported already in infants
(Frisken et al, 1990; Könönen et al, 1992a), however, no
separation between these phenotypically similar species
was then performed. More recent studies have confirmed
P. nigrescens as a true colonizer in childhood unlike P.
intermedia that seems to be absent in young children
(Fukushima et al, 1992; Mättö et al, 1996; van Steenbergen
et al, 1997). A new member of the P. intermedia group,
P. pallens (Könönen et al, 1998a), is also frequently found
in young children and their periodontally healthy mothers
(Könönen et al, 1998b). Taken together, most evidence of
the periodontopathic potential among the P. intermedia
group organisms has concentrated in P. intermedia (Dahlén
et al, 1990; Mättö et al, 1996). Very limited data exist on
the distribution of different species or subspecies within
other heterogeneous anaerobic groups, eg, Selenomonas
spp., Capnocytophaga spp. and F. nucleatum, in relation to
age or oral health status.
The colonization very likely depends on the supply of
suitable bacteria from infant’s surroundings. Individual dif-

ferences observed in the colonization pattern (Moore et al,
1984, 1993; Könönen et al, 1999c) may be explained by
variable bacterial load in saliva of attendants and other
close contacts. Indeed, the likelihood to be colonized by
periodontopathogens increases in children who have per-
iodontally diseased family members (Watson et al, 1994;
Asikainen et al, 1996). However, the colonization of main
periodontal pathogens rarely takes place in early childhood
(Frisken et al, 1987, 1990; Könönen et al, 1992a, 1994a;
Conrads et al, 1996). When preventive measures are
planned, the source and route of transmission but also the
favourable time for stable establishment of periodontal
pathogens are of concern.
Acquisition of oral anaerobic bacteria
Genotyping methods are needed to trace bacteria to the
clonal level when examining the origin and transmission of
bacterial strains between individuals. In this respect, restric-
tion endonuclease analysis, ribotyping, and arbitrarily
primed-PCR (AP-PCR) typing are among the methods that
have been applied for oral anaerobic bacteria.
Clonal heterogeneity
The clonal heterogeneity among pioneer commensals, such
as Streptococcus mitis biovar 1, seems to be very high
(Hohwy and Kilian, 1995; Fitzsimmons et al, 1996). In line
with that, among an early colonizing anaerobic commensal
species, P. melaninogenica (Könönen et al, 1992a, 1999c),
101 different ribotypes were found in 11 mother–child pairs
and up to seven simultaneous clones could be recovered
from an individual (Könönen et al, 1994b). In contrast to
this early colonizing anaerobic species, a more limited
intraindividual heterogeneity (1–2 clones/individual) has
been detected among the Prevotella intermedia group
organisms, ie, P. intermedia, P. nigrescens, and P. pallens
(Mättö et al, 1996; van Steenbergen et al, 1997; Könönen
et al, 1998b), also isolated from young children.
Generally, the clonal heterogeneity among putative per-
iodontal pathogens is limited. In Caucasian children, 1–2
different clones of A. actinomycetemcomitans per child
have been found (Alaluusua et al, 1993; Petit et al, 1994;
Asikainen et al, 1996). However, a possibly higher degree
of intraindividual variation of A. actinomycetemcomitans
may exist in children of Asian origin (Saarela et al, 1996).
Recent studies by Haubek et al (1995, 1997) revealed a
striking finding among A. actinomycetemcomitans popu-
lations from different ethnic groups: a highly virulent clone
of this periodontal pathogen was exclusively limited to juv-
enile periodontitis patients of African origin.
Bacterial transmission
Children obviously acquire oral bacteria via saliva of their
frequent close contacts, the mother being the most
important source (Li and Caufield, 1995). In our previous
study (Könönen et al, 1992b), we observed that the infants’
colonization frequency of F. nucleatum and P. melanino-
genica was doubled, when the maternal salivary level of
these anaerobic bacteria reached 104 CFU ml⫺1. Because
no genotyping methods were used in that study, it was not
possible to show whether transmission between a mother
Oral colonization by anaerobic bacteria during childhood
E Könönen
281
and her child had really occurred. Thus, in a subsequent
study (Könönen et al, 1994b) ribotyping was chosen as the
method and P. melaninogenica as the model to assess the
possible clonal identity of these anaerobic strains from
mothers and their children. Recently, we examined the
transmission of the P. intermedia group organisms isolated
from mother–child pairs by using AP-PCR typing
(unpublished data). In part the ribotypes of P. melanino-
genica and the AP-PCR types of P. nigrescens and P.
pallens were common in mother–child pairs indicating that
transmission between a mother and her child had occurred,
however, the origin of many genotypes in children
remained unknown. Concerning common bacteria, such as
P. melaninogenica, that may be explained by other sources
than the mother but also by intensive strain turnover among
early bacterial populations.
In several studies (Alaluusua et al, 1993; Petit et al,
1994; Asikainen et al, 1996; Saarela et al, 1996; van Steen-
bergen et al, 1997) similar clones of periodontal pathogens,
especially A. actinomycetemcomitans, have been found in
children over 5 years of age and their parent(s). As deterio-
rated periodontal status reflects the presence of periodonto-
pathogens in moderate to high numbers in saliva (von Troil-
Lindén et al, 1995), periodontally diseased family members
may recurrently expose a child to potential pathogens via
salivary contacts during everyday activities. The factors
that then determine whether the colonization occurs and
which bacterial strains persist in the child’s mouth are not
precisely known. However, bacterial strains vary in regard
to their adhesion properties as seen for A. actinomycetemco-
mitans (Mintz and Fives-Taylor, 1994). Since adhesion is
the decisive step for bacteria to be colonized to host cells
(Gibbons, 1984), favourable adhesion properties may
account for successful colonization of infecting strains.
Stability of colonization
By using molecular techniques and a longitudinal study
design the stability of a bacterial strain can be demon-
strated. Among nine children we were able to find one child
with the same ribotype of P. melaninogenica both in the
infant and child period (Könönen et al, 1994a). Our study
showed that already in the mouth of an edentulous infant
a stable colonization of an obligatory anaerobic strain is
possible, though not common.
Especially in the developing oral ecosystem bacterial
clones may easily ‘come and go’. A frequent turnover of
strains has been shown among S. mitis biovar 1 populations
during infancy (Hohwy, 1997). A similar phenomenon was
seen in anaerobic P. melaninogenica populations; in young
children new P. melaninogenica strains partly displaced the
original strains whereas in their mothers the colonization
of P. melaninogenica strains showed greater stability
(Könönen et al, 1994b). It is plausible that extensive anti-
genic variation among these pioneer commensals at least
partly explain their successful early establishment in the
oral cavity.
Whether there is a certain period when bacterial strains
will be established as a member in microbial communities
of the mouth and what the implications of a stable coloniz-
ation are, are discussed as follows.
 Oral colonization by anaerobic bacteria during childhood
E Könönen
282
Significance of oral anaerobes in childhood
Normal microflora
A number of commensal bacteria are regarded to be of
benefit to the health of the host. For example, anaerobic
bacteria seem to be important in resisting the intestinal
colonization by potentially pathogenic microorganisms (see
review by Vollaard and Clasener, 1994). In early infancy,
the mode of the delivery (vaginal delivery vs cesarean
section) and feeding (breast milk vs infant formula) as well
as the exposure to antibiotics are the main factors that deter-
mine the gastrointestinal colonization (Long and Swenson,
1977; Balmer and Wharton, 1989; Nord and Edlund, 1991).
It is conceivable to assume that similar factors influence
the composition of the microflora in a developing oral eco-
system.
The oral cavity is one of the main entries for several
invading pathogens; the oral indigenous microflora, includ-
ing several anaerobic species, acts as the major defence
against the colonization of non-oral commensals or patho-
gens, eg, Escherichia coli (Marsh, 1989). Despite the ben-
eficial role, however, anaerobic members of the indigenous
oral microflora can participate in infectious processes both
in the mouth and in other sites of the body.
Periodontal infections
Complex interactions between the host and the existing
ecological microenvironment will determine the outcome
of periodontal infections. Microbiologically, there will be
a marked shift in the subgingival microflora from the initial
dominance of gram-positive facultative species to the domi-
nance of gram-negative anaerobic species, when proceed-
ing from healthy periodontium to periodontitis (Slots, 1979;
van Palenstein Helderman, 1981).
Localized or generalized periodontal destruction can
already affect the primary dentition, even though periodon-
tal diseases are rare in early childhood. Various forms of
periodontitis in young children are mainly connected with
certain syndromes or abnormalities in leukocyte functions
(see review by Watanabe, 1990). Microbial findings in pre-
pubertal periodontitis include especially A. actinomycetem-
comitans but also other common species in periodontal
pockets, such as P. gingivalis, P. intermedia, Eikenella cor-
rodens, and Capnocytophaga sputigena (Watanabe, 1990).
The tendency of periodontitis to aggregate in families
has partly been explained by genetic factors and partly by
environmental factors (Boughman et al, 1990; Michalowicz
et al, 1991; Moore et al, 1993; van der Velden et al, 1993).
Van der Velden et al (1993) investigated the effect of sib-
ling relationship on the periodontal status in a Javan popu-
lation deprived from regular dental care with a high preva-
lence of periodontal diseases and observed a significant
sibship effect for several clinical and microbiological para-
meters. Moore et al (1993) used a twin model to estimate
genetic and environmental influences on the composition
of the subgingival flora of an individual. They concluded
that the colonization pattern of several bacterial species
among the microflora was genetically determined, whereas
for some other species the environment was the decisive
factor.
Family members are exposed to similar clones of per-
iodontal pathogens (Alaluusua et al, 1993; Petit et al, 1994;
Asikainen et al, 1996; Saarela et al, 1996; van Steenbergen
et al, 1997), most probably via salivary transmission. It is
notable that different clones of periodontal pathogens may
have different pathogenic potential (Haubek et al, 1997).
Early colonization by a pathogenic strain may increase and
a delayed colonization may reduce the risk of periodontal
diseases. However, whether the early colonization and sub-
sequent establishment of a periodontopathogen, in many
cases A. actinomycetemcomitans, associate with the onset
of periodontitis later in life, is not yet shown. Some retro-
spective evidence by radiographs indicates that periodontal
disease in adolescence can be traced to childhood (Sjödin
et al, 1993).
Non-oral infections
The oral microflora is an important reservoir of bacterial
strains that can cause opportunistic infections outside its
natural environment. Anaerobic bacteria are mainly present
in mixed infections where they offer synergistic advantage
to facultative microorganisms (Styrt and Gorbach, 1989).
It is plausible that anaerobes isolated from infectious
lesions in the upper part of the body originate from the
oral cavity.
Pediatric infections in the upper respiratory tract and in
the head and neck with potential involvement of oral anaer-
obic bacteria are listed in Table 2. Common anaerobic fin-
dings in infections outside the oral cavity are F. nucleatum,
pigmented and non-pigmented Prevotella spp., and Veil-
lonella spp. (Brook, 1994, 1995, 1996). As a part of our
on-going longitudinal study on the development of the
nasopharyngeal microflora, we observed that various anaer-
obic species, F. nucleatum and the P. melaninogenica
group as the most frequent ones, in combination with
aerobes commonly belonged to infants’ nasopharyngeal
microflora during episodes of acute otitis media (Könönen
et al, 1999a). Nasopharyngeal colonization of traditional
respiratory pathogens precedes the bouts of acute otitis
(Faden et al, 1997), however, the question whether ana-
erobes play a significant role in the pathogenesis of acute
otitis media or whether they are present in the nasopharynx
just because of the favourable environment due to infection,
has remained open.
Antibiotic resistance
Treatment of pediatric bacterial infections is often based on
the use of the beta-lactam group antibiotics. High fre-
quencies of penicillin resistance (both ␤-lactamase-
mediated and non-␤-lactamase-mediated) among common
oral anaerobic bacteria, such as pigmented Prevotella spp.,
F. nucleatum and Veillonella spp., in young children
(Könönen et al, 1995, 1997, 1999b; Nyfors et al, 1999a,b)
infer the increased risk of involvement of resistent strains
in pediatric infections of oral origin.
Penicillin resistance is mainly caused by bacteria that can
produce ␤-lactamase, an enzyme which is capable of
destroying ␤-lactam antibiotics. According to our experi-
ence, the frequency of ␤-lactamase production by oral
gram-negative anaerobes is surprisingly high already in
early childhood (Könönen et al, 1995, 1997, 1999b; Nyfors
et al, 1999b) (Table 3). The reasons for the reported
increasing frequency of ␤-lactamase-producing strains
 Oral colonization by anaerobic bacteria during childhood
E Könönen

283
Table 2 Pediatric infections in the upper respiratory tract and in head and neck with (potential) involvement of oral anaerobes

Infection Main anaerobic findings

Prepubertal periodontitis A. actinomycetemcomitans, P. gingivalis, P. intermedia

Endodontic infections P. propionicum, P. micros, F. nucleatum, E. alactolyticum
Peritonsillar abscesses P. melaninogenica, Peptostreptococcus spp., F. nucleatum, E. lentum
Other abscesses F. nucleatum, P. melaninogenica, P. asaccharolytica, P. intermedia
Chronic otitis P. melaninogenica, P. asaccharolytica, P. intermedia, P. oralis
Chronic sinusitis F. nucleatum, Veillonella spp., P. melaninogenica, P. intermedia
Aspiration pneumonia F. nucleatum, P. intermedia, P. melaninogenica, P. oris/buccae

(Data adapted from Watanabe, 1990; Sato et al, 1993; Brook, 1981, 1994, 1995, 1996)

Table 3 Proportions of children carrying indicated ␤-lactamase-
producing anaerobic species in the oral cavity
Anaerobic species Frequency (%)
P. melaninogenica 100
P. loescheii 75
P. denticola 69
P. nigrescens 13
P. pallens 78
F. nucleatum 50
(Data adapted from Könönen et al, 1997, 1999b)
among the normal oral microflora are somewhat unclear.
As both ␤-lactamase-producing and non-producing variants
simultaneously can be present in the mouth (Könönen et
al, 1995, 1999b; Nyfors et al, 1999b), several isolates per
sample should be tested to demonstrate the true rate of ␤-
lactamase production within a bacterial species; the testing
of multiple isolates in our studies conceivably may explain,
at least in part, the observed high frequency of ␤-lactamase
production by several oral anaerobes. Another reason could
be the proliferation of antibiotic-resistant strains due to the
administration of antibiotics that may cause the enzyme
induction or the selection of constitutive ␤-lactamase-
producing subpopulations (Barza et al, 1987). Indeed,
infants’ exposure to antibiotics, either own or via mother,
seems to remarkably increase the frequency of ␤-lactamase-
producing gram-negative anaerobic rods in infants’ saliva
(Nyfors et al, 1999b).
The significance of ␤-lactamase-producing species in the
normal microflora is suggested to be based on their indirect
pathogenicity by secreting free ␤-lactamase in their
environment which may lead to therapeutic failures when
low-dosage of penicillin is used to eradicate otherwise peni-
cillin susceptible pathogens (Brook and Yocum, 1983;
Brook and Gober, 1995). To precisely prove this concept,
one should demonstrate if an adequate concentration of free
␤-lactamase by these ␤-lactamase-producing species is
secreted in surrounding tissues. Another important aspect
is that the normal microflora represents a reservoir of genes
that are responsible for resistance to different antibiotics by
several resistance mechanisms and that these genes can be
transferred from antibiotic-resistant indigenous bacteria to
human pathogens (Levy et al, 1988). In oral pigmented
Prevotella spp., resistance genes seem to be located in
conjugal elements and transferred via these elements
between different bacterial species (Guiney and Bouic,
1990; Walker and Bueno, 1997). Besides these indirect
consequences of the antibiotic resistance, the high fre-
quencies of resistant anaerobic strains among the oral
microflora may have a significant impact on the treatment
outcome and practices of pediatric infections of oral origin.
Concluding remarks
The oral cavity is colonized by anaerobic bacteria already
in early infancy. Individual species of oral anaerobes seem
to rely on different periods amenable for their establish-
ment. However, intensive strain turnover within some com-
mensal species occurs. The widely accepted concept of the
stabilized microflora in adults, where a new bacterial strain
is difficult to implant, does not seem to apply to infants.
The acquisition of oral commensals and potential patho-
gens, their interrelationships, and in addition, the age period
for a stable colonization of bacterial clones are fundamental
factors in planning prophylaxis and treatment for oral dis-
eases.
Even outside the oral cavity, the understanding of the
rules that regulate the composition of the human oral
microflora is of concern. The oral anaerobic microflora rep-
resents a significant reservoir of antibiotic-resistant strains.
Via transferable elements resistance genes can be trans-
mitted between different bacterial strains and species. Con-
ceivably, the frequencies of antibiotic resistance may still
increase. Antimicrobial susceptibility and resistance pat-
terns of oral anaerobes should be taken into account in the
treatment of pediatric anaerobic infections of oral origin.
Acknowledgement
The author wishes to thank Professor Mogens Kilian for his help-
ful comments during the writing of this review.
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