Microbial Pathogenesis 106 (2017) 20e24

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Microbial Pathogenesis
journal homepage: www.elsevier.com/locate/micpath

Microbiome of dental implants and its clinical aspect

Reghunathan S. Preethanath a, Nadia W. AlNahas b, Sahar M. Bin Huraib c,
Hana O. Al-Balbeesi d, Naif Khalid Almalik e, M.H.N. Dalati f, Darshan Devang Divakar g, *
a
Department of Preventive Dental Sciences, Jazan University, P.O.BOX:114, Jazan, 82943, Saudi Arabia
b
Department of Periodontics and Community Dentistry, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
c
Dental Public Health, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
d
Department of Pediatric Dentistry and Orthodontics, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
e
Al-Nakeel Medical Center, Riyadh, Saudi Arabia
f
Springs Dental Care, New Road Side, Horsforth, Leeds, UK
g
Department Oral Medicine and Radiology, KVG Dental College and Hospital, Sullia, Karnataka, India

a r t i c l e i n f o a b s t r a c t

Article history: Although dental implants are most common prosthetic treatment used to replace missing tooth, it gained
Received 25 October 2016 considerable importance over a decade owing to the availability of advanced imagery techniques that can
Received in revised form help in achieving a greater success rate and much better osseointegration. However, the chances that the
24 January 2017
implanted tooth can be rejected due to inflammation caused by oral microflora still persist. This review
Accepted 6 February 2017
Available online 8 February 2017
gives the viewers an overall idea of the dental implants, role of advanced imaging in implantation and
instances of peri-implantitis that occur after implantation process. This review also entails the latest
research on the different treatment modalities against peri-implantitis documented in peer-review
Keywords:
Peri-implantitis
journals.
Dental microflora © 2017 Elsevier Ltd. All rights reserved.
Osseointegration
Colonisers

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
2. Importance of imaging in dental implantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
3. Microbial flora of dental implants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
4. Biofilm and tooth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
5. Biofilm and implant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
6. Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
7. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

1. Introduction itself with the bone is termed as osseointegration. With success

rates of more than 90%, implants are used by many dentists to
Dental implants are widely used by dentists as prosthesis to substitute missing teeth. As the prospects outweigh the conse-
replace damaged or lost tooth. Dental implants are titanium cyl- quences, coupled with the help of developing radiography, teeth
inders that form interfaces with the jaw establishing a bond with replacement has become much reliable. Despite high success rates
the bone [1]. This process where the implant locks and attaches of osseointegration, there exists more than 10% chances of implant
failure. This implant failure has been mainly attributed due to peri-
implantitis, where periodontal pathogens cause inflammation of
the hard and soft tissues (sub-acute and chronic inflammation [2]
* Corresponding author.
E-mail address: darshanddivakar@gmail.com (D.D. Divakar). surrounding the implants. Many Gram negative bacteria that

http://dx.doi.org/10.1016/j.micpath.2017.02.009
0882-4010/© 2017 Elsevier Ltd. All rights reserved.
 R.S. Preethanath et al. / Microbial Pathogenesis 106 (2017) 20e24
fester in the tissues surrounding the osseoimplants are solely
responsible for such implant rejection [1]. Several treatment mo-
dalities are helpful in reducing the inflammation around implants.
These treatment include surgical removal, use of antibiotics, and
laser therapy against the potential pathogens and facilitate re-
osseointegration thereby preventing the further spread of the
microorganisms.
This review article gives the consolidated view of the peri-
odontitis and the microbial flora associated with such complica-
tions. This article also features the diagnostic imaging tools that are
used by dentists in pre and post-operative follow-up procedures to
check the integration of implants on the jaw.
2. Importance of imaging in dental implantation
Imaging not only plays an important role prior to implantation
but also in the post-operative follow-up to check the efficiency of
the endosseus implants. Several advanced techniques have proven
to be useful in dentistry with a near 100% success rate of teeth
implantation. Such techniques have been implemented by dentists
to determine the sites where implants can be placed with ease and
to check the success rate of the implants to osseointegrate weeks
after prosthetic treatment.
Imaging techniques for diagnosis include high resolution
radiographic techniques such as periapical radiography, occlusal
radiography, lateral cephalometric radiographs, panoramic radi-
ography etc., and tomographical techniques. Interactive computed
tomography is being used as a conventional method to locate both
hard and soft tissues in the oral cavity and to help dentists perform
non-invasive operations [3e5]. Dentascan and Simplant are the CT
image reformatting software used for the three-dimensional
viewing of oral cavity. Although these software have a limited
range, they provide in-depth and accurate information and have
been a boon in disguise in the field of periodontology [6]. Pano-
ramic X-rays are being used to get detailed view of the tissues
around implants and to determine the stability of the implants.
These techniques help to keep osseointegration in check and to
know if the implant has any chances of inflammation due to peri-
odontal pathogens. Magnetic resonance imaging provides dentists
with wide applications through accurate tomography without any
distortion [7]. Magnetic resonance imaging (MRI) is used most
commonly in the valuation of the musculoskeletal system and
associated pathology. MRI has ability to measure the signals from
molecule like water and lipid protons enables it to be used in
quantitative measurements of bone porosity. MRI analysis has no
role to play in the preoperative bone volume or a post-operative
peri-implantitis. In fact, this examination is never prescribed in
the preoperative reports [8] However, its use in dentistry is limited
as it cannot characterize bone mineralization [3]. Post dental im-
plantation, these radiographic techniques are useful as they pro-
vide the dentists with long-term success rates by checking the
osseointegration of the implants [9]. Although, the benefits and
application range of these imaging techniques outweigh the asso-
ciated risks, several factors still contribute to implant rejection.
These factors include poor maintenance of the implants and the
growing microbial flora in the soft tissues in the vicinity of the
implants.
3. Microbial flora of dental implants
Normal microbiota of healthy implants include gram positive
rods and cocci [10]. Peri-implantitis is caused by pathogens
especially gram negative bacteria like Veillonella sp. and spiro-
chetes including Treponemadenticola [11]. Rams et al. (1990) re-
ported in a study that Staphylococci infections are prevalent in
21
periodontal diseases. Microorganisms harbouring in the soft tis-
sues near the dental implants include periodontal pathogens
namely Actinobacillus actinomycetemcomitans, Porphyromonas
gingivalis, Prevotella intermedia, Bacteroides forsythus and Trepo-
nemadenticola [12]. Periodontal pockets mainly harboured Fuso-
bacteriumnucleatum, Prevotella intermedia and Peptostreptococcus
micros [13].
Presence of spirochetes around ailing implants is in concor-
dance with study, which describes 42% of spirochetes and motile
rods around ailing implants due to infection [14]. Peptos-
treptococcus, Fusobacterium, enteric gram negative rods and yeasts
are among the predominant class of microbiota encountered in
cultures. On similar lines, organisms such as P.micros, Camphylo-
bacter rectus, Fusobacterium sp, Prevotella intermedia and Candida
albicans were recovered by Alcoforado et al., whereas Porphyr-
omonas gingivalis, P. intermedia, Fusobacterium, Actinobacillus
actinomycetmcomitans and spirochetes were identified in implants
by Mombelli et al. and Leonhardt et al. Recent studies corroborating
previous reports on the diverse microbiota associated with
implantitis are also available [14]. The possibility and extent of peri-
implant tissue destruction are insufficiently described in the
available studies, however the fact that tissue destruction may
progressively lead to aggressive periodontitis culminating into
chronic periodontitis cannot be overlooked. A cross sectional split
mouth study coupled with assessment of radiographic and clinical
parameters are inevitable towards an elaborate analysis of
implantitis (Table 1).
In terms of symptoms, implants in partial edentulous patients
were more symptomatic than the implants in complete edentulous
patients. The periodontal bacteria associated with the implantitis
symptoms, often found in greater numbers around the implants
include P. micros, Fusobacterium, and Eubacterium. Efficient anti-
microbial treatment may be helpful in suppressing the periodontal
implantitis. In one study, researchers have also found an uniden-
tified herpes virus causing implantitis [15]. Another study reported
the elevated levels of Campylobacter and P. micros in patients
receiving amoxicillin due to the production of beta lactamases [16].
4. Biofilm and tooth
Quorum sensing (QS) is used among bacteria for chemical
communication which are genetically governed in response to cell
density and influence several functions of the bacteria, e.g., viru-
lence, and the biofilm formation. The biofilm formation are directly
regulated by QS activity and more formation of biofilm would affect
the treatment via antibiotics as biofilm resist the external unfav-
ourable condition and bacteria persist inside biofilm for long term
[17]. Biofilm in the oral cavity is the result of a multistage process
that involves formation of a thin pellicle covering the tooth enamel.
This biofilm acts as a barrier for the microbes against host immu-
nity and antimicrobial drugs. Saliva is the major source of nutrients
for the bacteria in the oral cavity and invariably contains a sub-
stantial number of these microorganisms (approx. 107bacteria/ml).
Bacterial aggregation on the tooth surface is facilitated by the
protein and glycoprotein molecules on the tooth surface, implants
etc. In response, bacteria express special adhesion structures like
lectins and also produce extracellular polysaccharides, e.g., dex-
trans, levans, which aid in the formation of a thin multi-layered
biofilm polymers [18,19]. Streptococci such as S. viridens, S. mitis
and S. oralis are the initial colonisers to which the planktonic bac-
teria bind with the aid of the receptors. There are secondary colo-
nisers also which include Actinomyces species, S. mutans, and
S. sobrinus. Some bacteria like Fusobacterium nucleatum link the
early and secondary colonisers by multiplying and co-aggregating
with other species [20]. Major nutrients for these biofilms are
22 R.S. Preethanath et al. / Microbial Pathogenesis 106 (2017) 20e24

Table 1
Microbial findings at implants in human; a brief review of the literature.

Technique used Bacteria common in healthy Bacteria exclusive in peri-implantitis History of periodontal References
and peri-implantitis diseases in healthy control

Culture _ Fusobacterium, campylobacter, candida, Health control not involved Alcoforado et al. (1991) [45]
Culture _ Fusobacterium, Eikenella corrodens. Health control not involved Augthum et al. (1997) [46]
Culture Pg, Pi/Pn, Aa, Ss, enterococci, Pg, Pi, Tf, Aa, Td No Leonhardt et al., 1999 [47]
Candida spp
DNA Fss, Pi, Pn, Ec Aa, Pg No Hultin et al., 2002 [48]
Culture Fs, Pi/Pn, Ec, enterococci Aa, Tf, Td, enterococci, Pg, Pi/Pn No Botero et al., 2005 [49]
DNA Aa, Pg, Mm, Pn, Fs, Nm No Persson et al., 2006 [50]
DNA probe Aa, Pg, Pi, Tf, Tda _ Yes De Boever et al., 2006 [51]
DNA- DNA No differences in microbial complex. _ No Ager back et al. (2006) [52]
hydridization
DNA Tf, Pm, Lb, Cs, Pi, Sa _ No Salvi et al., 2008 [53]
DNA for 40 bacteria Cs, Fs, Fp, Lb, Nm Cs, Lb, Nm, Fs, Nm,Fp Yes Renvert et al., 2007 [54]
16 S rRNA Aa, Pga _ No Heuer et al., 2007 [55]
DNA for 36 bacteria Vp, Sg, Si, Fp Pg, Td, Tf, Fs, Pi, Pn, An, Si, Sm No Shibli et al., 2008 [56]
Culture Pg, Pi, Tf, Dp, Cr, Pm, Fs, Facultative _ Yes Emrani et al., 2009 [57]
enteric gramnegative cocci
DNA for 79 bacteria _ Fs, Sa, Hp, Aa, Tf Yes Persson et al., 2010 [58]
Culture _ Aa, Pg, Sm, Pm, Ps, Pa Tatsuro et al., 2010 [59]
Culture More complex flora in healthy than PI Gram anaerobic predominant in PI No Kumar et al., 2012 [60]

Aa Aggregatibacter actinomycetemcomitans, Pg Porphyromonas gingivalis, Tf Tannerella forsythia, Pi Prevotella intermedia, Td Treponema denticola, Dp Dialister pneu-
mosintes, Cr Campylobacter rectus, Pm Peptostreptococcus micros, Fs Fusobacterium species, Cs Capnocytophaga sputigena, Lb Leptotrichia buccalis, Nm Neisseria mucosa,
Mm Micromonas micros, Pn Prevotella nigrescens, Ss Staphylococcus spp, Sa Staphylococcus aureus, An Actinomyces naeslundii, Si Streptococcus intermedius, Sm Strepto-
coccus mitis, Vp Veillonella parvula, Sg Streptococcus gordonii, Fp Fusobacterium periodonticum, Kp Klebsiella pneumoniae, Ec Eikanella corrodens, Se Staphylococcus
epidermis, Hp Helicobacter pylori, Sm Solobacterium moorei., Pm- Parvimonas micra, Ps-Peptostreptococcus stomatis, Pa-Pseudoramibacter alactolyticus, C¼ Culture,
DNA ¼ Checkerboard DNA-DNA hybridization technique.
a
Only these bacteria were evaluated.

sourced from the saliva, gingival cervicular fluid, sugar rich me-
tabolites of bacteria and food debris. The plaques have their own
circulatory system and eventually start behaving like a complex
microorganism. The cell wall components of the oral microbiota
activate the host response. Within the plaque, cell-cell communi-
cation stimulates the gene expression, producing signals to sense
the local environment and receive communication from the adja-
cent bacteria. Genetic exchange, metabolic change and Quorum
sensing mediate the interspecies communication in biofilms.
Quorum sensing is a genetically controlled chemical communica-
tion produced due to increased cell density influencing virulence,
tolerance and biofilm formation in the bacteria. In the oral cavity,
gram positive bacteria produce two specific signalling molecules
namely competence stimulating Peptides (CST) and Autoinducer-2
(AI-2). AI-2 is a popular quorum sensing molecule produced by
both Gram positive and gram negative bacteria [20,21]. Initially, a
thin biofilm is formed that progresses in to the supra gingival
plaque leading to gingivitis. This is followed by the invasion of
anaerobic bacteria, which complicates the gingivitis by colonising
the sub gingival areas in a matured plaque thereby leading to a
well-defined form of periodontitis.
5. Biofilm and implant
Studies of plaque samples previously conducted demonstrate
the microbiological evidence of biofilm associated with implanti-
tis. It was found that almost 17 diseased implants showed less
number of cocci in deeper probing pockets compared to spiro-
chetes, which were more [22]. A similar pattern was observed in
yet another study wherein biofilms were demonstrated on dental
implants and teeth [23]. Usually, biofilms formation occurs as
early as 2e6 h, post species colonisation. In this process, the re-
sidual food particles contribute substantially in the attachment
and multiplication of the unattached microbiota that finally form
the biofilms further facilitating the attachment of secondary mi-
crobial colonisers [24]. On the implant surface the pellicle for-
mation starts within 30 min of exposure into the oral cavity,
however due to low albumin adsorption capacity of the pellicle,
plaque formation is reduced. As observed the initial colonisers are
generally gram positive cocci and actinomyces [25], whereas the
peri-implantitis and periodontitis pathogens colonising on the
Streptococci (P. gingivalis, P. intermedia, etc.) are the ones respon-
sible for peri-implantitis and periodontitis [1]. Biofilm formation is
directly related to the surface roughness and hence greater the
roughness, higher is the rate of biofilm formation around the
implants [26]. Wettability/hydrophobicity and surface free energy
(SFE) also influence the biofilm formation on implants. A previous
study that evaluated the biofilm accumulation on a smooth tita-
nium surface and sandblasted titanium surface showed that sur-
face roughening harbored lower percentage of cocci (64.2%)
compared to smooth abutments (81%) [27]. In another such study,
a similar phenomenon of supra-gingival plaque formation be-
tween the surface roughness within 96 h post implantation was
observed along with heightened plaque growth rate and patho-
genicity [28]. The initial weak binding of the bacteria is followed
by the final irreversible attachment, which is boosted by the rough
surface of the implant, thereby rendering an indirect protection to
the bacteria against mechanical shear. Though these studies in-
dicates binding of bacteria are affected by surface nature of
implant, there is inadequate indication that implants surfaces
nature are related to severity of infection (perimplantitis) Sys-
tematic review of Esposito et al., 2005 stated no evidence for any
particular type of dental implant with superior long-term success.
Further it is indicated that there is no significant difference be-
tween the two types of implant (rough and smooth) and it is
uncertain the role of roughness in the appearance of a peri-
implantitis [29].
6. Treatment
Peri-implantitis can be eliminated by many modalities after few
weeks of implants. These modalities include surgical removal of the
inflamed soft tissue with considerable bone mass followed by
antibiotic therapy to reduce the inflammation around the implants.
 R.S. Preethanath et al. / Microbial Pathogenesis 106 (2017) 20e24
Many such treatment procedures are being studied in animals like
monkeys, dogs etc. in order to evaluate the outcome and to study
the chances of re-osseointegration after peri-implantitis [15].
The gold standard for restoring bone defects even in dental
diseases, is still considered to be autologous bone grafting. Various
substitute materials are tested for use in bone defects when good
primary mechanical stability and contact with the host bone are
present. Additional clinical studies are required to govern the limits
and advantage of such a substitute following implantation.
Research is on-going for the expansion of alternative bone sub-
stitutes of both biological and synthetic origin [30,31].
Although use of antibiotics is aimed at reducing the pathogens
around dental implants and reducing the inflammation, successful
elimination and true re-osseointegration is not yet achieved [32].
Methods like surgical treatment, decontamination of affected
parts by using chemical agents and air abrasives (like sandblasting
on titanium implants) [16], use of lasers (ERL), etc. can be used to
control the spread and improve chances of implant re-osseo-
integration [33]. Diode soft laser in combination with toluidene
blue eliminated Porphyromonas gingivalis, Prevotella intermedia and
Actinobacillus actinomycetemcomitans [34]. The use of lasers in
implantation process has greatly replaced the use of other painful
treatment procedures over a decade. Antibiotics like amoxicillin,
metronidazole, doxycycline, and vancomycin can be used as non-
invasive therapy to reduce the inflammation [35,36]. However,
the use of non-invasive process like photodynamic therapy by us-
ing photosensitizer is unprecedented [37] (RRA Hayek et al., 2005).
General therapy includes treating dental implants with chlor-
hexidine and saline [38]. Additionally, local treatment with anti-
biotics, amoxicillin and metronidazole, have been used in a study
parallel to routine decontamination procedures. Plaque cleaning
also helps in significant reduction of peri-implantitis induced le-
sions. None of the methods like abrasives, lasers or chemical agents
has proven 100% success in counteracting peri-implantitis. How-
ever, means of achieving re-osseointegration of the implant and
disease resolution can be accomplished by debriding the affected
tissue aided by surface decontamination to prevent the spread of
infection [39]. Many antibiotics are aimed against periodontal
pathogens like A.actinomycetomitans, P.intermedia, P.gingivalis,
E.coli, E.cloace, S.aureus etc. [40]. Tetracycline was found to elimi-
nate many pathogens including Prevotella intermedia/nigrescens,
Fusobacterium sp., Bacteroidsforsythus, Campylobacter rectus, Acti-
nobacillus actinomycetemcomitans, Porphyromonas gingivalis and
Eikenella corrodens [32]. Effective removal of pathogens harbouring
around the implants and combination of different treatment mo-
dalities give the best result in resolution of peri-implantitis,
whereas incomplete decontamination procedures results in failed
integration of implants with the bone.
Various studies has stated that peri-implant disease infection
etiology is the result of the inability to maintain osseointegration.
Bacterial metabolites products from infection in periodontal seems
to stimulate the production of inflammatory markers which
destruct the peri-implant tissues. An upsurge in interleukin levels is
observed in patients with peri-implant disease, though there is
disagreement over its being use as a surogative markers in any of
such disease. A high concentration of IL-10, an anti-inflammatory
cytokine, produced by T-helper 2 cells and acts as a B cell stimu-
lator, plays important roles in the regulation of cellular and hu-
moral immune responses reported in patients with peri-
implantitis. In literature it is also indicated that the result of acti-
vation of the host immunoinflammatory response to bacterial
challenge could end with soft and hard tissue destruction associ-
ated with periodontal disease. An increased appearance of IL-1 and
IL-6 in periodontitis patients, may play an important role in peri-
odontal tissue destruction [41].
23
Good oral hygiene plays an important role in progression of
peri-implantitis and implant rejection. A study showed that
improper hygiene measures were correlated with the risk of peri-
implantitis and regular maintenance and good oral hygiene
reduced the development of peri-implantitis [42]. Bad habits
especially smoking pose a negative risk factor in eliminating peri-
implantitis. Apart from hygiene and smoking the risk of peri-
odontal disease is increased by many others noted factors which
include systemic diseases like diabetes, xerotomia as well as oste-
oporosis especially in women; medications such as steroids, anti-
epilepsy drugs, loose fillings. Additionally, raise of any such medi-
cal condition which triggers host immune response against anti-
bacterial mechanisms, such as human immunodeficiency virus
(HIV) infection, neutrophil disorders, will likely promote peri-
odontal disease [43].
7. Conclusion
The microbiota of peri-implant infections look like that of
periodontal infections, with some distinguished differences, how-
ever a deep sense of difference between two conditions would
enhance the treatment aspect. Knowledge and understanding of
peri-implant disease pathogenesis would be increasing with
application of metagenomics and metatrascriptomics analysis of
oral ecology [44].
Proper dental maintenance following implantation helps to
prevent peri-implantitis progression. Different types of radio-
graphic techniques and treatment methods have proven effective
in reducing the periodontal pathogen load without eliminating
them.
Newer antibiotics are required to treat periodontitis and peri-
implantitis. Although, dental implants have gained importance as
an excellent technique in situations demanding replacement of the
natural teeth, the likelihood of microbial infections surfacing dur-
ing and after this method impose serious concern on the outcome
of the implantation procedure. This problem needs thorough
evaluation with proper control measures at disposal in order to
prevent the failure of implants. Nevertheless, in future more studies
analysing the risk factors and the sources associated with peri-
implantitis are necessary reflecting the use of dental prosthetics
in subjects.
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