Host-microbiome interactions regarding peri-implantitis and dental implant loss
Journal of Translational Medicine volume 20, Article number: 425 (2022)
In the last decades, the ortho-aesthetic-functional rehabilitation had significant advances with the advent of implantology. Despite the success in implantology surgeries, there is a percentage of failures mainly due to in loco infections, through bacterial proliferation, presence of fungi and biofilm formation, originating peri-implantitis. In this sense, several studies have been conducted since then, seeking answers to numerous questions that remain unknown. Thus, the present work aims to discuss the interaction between host-oral microbiome and the development of peri-implantitis. Peri-implantitis was associated with a diversity of bacterial species, being Porphiromonas gingivalis, Treponema denticola and Tannerella forsythia described in higher proportion of peri-implantitis samples. In a parallel role, the injury of peri-implant tissue causes an inflammatory response mediated by activation of innate immune cells such as macrophages, dendritic cells, mast cells, and neutrophils. In summary, the host immune system activation may lead to imbalance of oral microbiota, and, in turn, the oral microbiota dysbiosis is reported leading to cytokines, chemokines, prostaglandins, and proteolytic enzymes production. These biological processes may be responsible for implant loss.
In the last decades, significative advances have been occurred through research about dental implants. Even though Branemark osteointegration system was not successful, it generated elevated amount of data that lead to improvements in implant techniques . It was at the turn of the millennium that a great revolution took place when the surgical and biomaterials areas brought greater clarity and the desired safety in the procedures performed. The rehabilitation of missing teeth is present in the history for a long time, but not long ago, intraosseous implants started to be installed in rough surfaces, causing no trauma to the adjacent bone and the prosthesis projected for longevity intentions . Due to the progress made, including the aesthetic-functional area of implants, there is an increase in the demand for these procedures in oral rehabilitation. According to Thoma et al. , the reasons for this success are studies in implant surface treatments, implant design, material, and techniques, occurring with the increased demand for treatments with dental implants. In addition, the improvement of oral microbiome knowledge has been looking for solutions to problems as biofilm formation and selection of pathogenic bacteria, to avoid infections episodes. This literature review aims to describe the factors involved in the implant survivor by microbiological perspective and immune host response.
The oral microbiome of peri-implantitis
The Human Oral Microbiome Database (www.homd.org) include, in the adult individual, approximately 772 prokaryotic species, where 70% is cultivable species, and 30% belong to the uncultivable class of microorganisms. Out of 70% culturable species, 57% have already been assigned to their names. Recently, the microbiome sequencing techniques has been used more frequently, allowing non-cultivable species to have been increasingly described.
Diversity of species colonization occurs into oral cavity, according to the region or even the conditions of this cavity, and the microorganisms are distributed according to their metabolic and biochemical characteristics. The salivary microbiome is essentially composed of a mixture of all microbial sites. Although there is an overlap of all species in all oral sites, species of Streptococcus spp., Gemella spp., Granulicatella spp., Neisseria spp., and Prevotella spp. are found more frequently in the saliva . On the other hand, it appears that bacteria that are located on the hard palate are not primarily the same as those present on the tongue. Rothia spp. and S. salivarius mainly colonizes the tongue or tooth surfaces, Simonsieur spp. colonizes only the hard palate, and Treponema spp. is typically restricted to the gingival and subgingival tissue . Oral healthy gingival tissue presents more commonly Streptococcus species, but, in the gingival disease’s tissue, Streptococcus spp. are replaced by Treponema spp. The Treponema spp. are described as one of the first pathogens in the gingival tissue (Fig. 1) .
Furthermore, bacteria are guided through adhesin binding receptors. Some receptors come from salivary proteins and through the affinity by bacteria initiating the biofilm accumulation. These receptors are derived from salivary components such as proteins rich in proline and serine, which are submitted to changes in conformation when adhered to surfaces such as the tooth where there is a specific interaction with a strong affinity. Issues such as adherence and functionality are some of the factors that help the bacterial complex to form the most convenient biofilm [7, 8].
It is quite usual the concern about the bacteria involved in the infection and biofilm formation, probably due to 16S sequencing methodology used by the most of studies. However, metagenomic studies have revealed that fungus has a large participation in biofilm establishment. Candida albicans, C. guilliermondii, C. glabrata, Rhodotorula spp. and Trichosporon spp. are identified in oral microbiota and the most yeasts identified had ability to form biofilms and presented resistance to the antifungal agents . In addition, diverse Trichosporum species are also able to form biofilms, such as T. asahii, T. asteroides, T. cutaneum and T. mucoides .
The investigation of the oral microbiota in pathogenic situations is necessary together with the advent of implantology to identify causes and seek for relevant solutions, so that patients do not lose the functionality, whether esthetic or bio-mechanical, of the installed implants caused by accumulation of biofilm and consequent loss of peri-implant bone support.
One of the main causes of implant loss is due to peri-implantitis incidence. Peri-implantitis is caused by the biofilm accumulation that occurs in the tissues around dental implant, causing inflammation in the peri-implant mucosa, followed by progressive loss of the supporting bone (Fig. 2) . Peri-implantitis is associated with a diversity of bacterial species, such as Tannerela forsythia, Porphiromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia and S. salivarius [12, 13]. P. gingivalis, Treponema denticola and Tannerella forsythia are described in higher proportion of peri-implantitis samples . Some studies also indicated the presence of pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa, acting in an opportunistic way in the infectious process; fungi and viruses are also part of this biofilm complex [14, 15].
In a temporal analysis is possible observe that Firmicutes phylum increase during the maturation of peri-implant plaque, and a decrease of Neisseria spp. and Porphyromonas spp. detection is observed after periimplantitis establishment . Initially the peri-mucositis appears and then the peri-implantitis can develop later. Peri-implant mucositis resembles gingivitis in natural teeth; it appears that there is an increase in both richness and diversity of the subgingival microbiome during gingivitis, and while richness remains high in periodontitis because no species are lost during the shift, it seems that some species become dominant (i.e., increase in proportion) in periodontitis associated communities, decreasing community evenness, and therefore reducing the overall diversity compared with gingivitis. Gingivitis and peri-mucositis microbiome are similar in etiology . Still, peri-implant mucositis is defined as an inflammation of the soft tissues (i.e., peri-implant mucosa) around the implant and presents clinically with bleeding upon simple probing . Through peri-implant mucositis, peri-implantitis can develop or not. There are etiological similarities between the biofilm found in periodontitis and peri-implantitis; however, in the second, differentiated bacteria were also identified. According to Klinge et al. , in terms of clinical appearance and pathogenesis, it is accepted that both have a common etiology: oral dysbiotic biofilm. However, the predominant bacteria in peri-implantitis comparing with healthy implants are Fusobacterium spp. and Treponema spp.; but, in peri-mucositis it was mostly colonized by Rothia spp. and Streptococcus spp . In summary, peri-mucositis is more associated with common periodontal pathogens, while peri-implantitis harbor differentially abundant communities . A study from Ghensi et al. suggest that Fusobacterium nucleatum appears to be the first specie that has increased abundance along the mucositis–peri-implantitis axis and result in more strongly peri-implantitis at later stages of the disease. In this way, the knowledge of the oral microbiome based on a phylogenetic database to be important to identify the pre- and post-surgical bacterial niche and develop studies for possible prevention or even prophylactic measures to reduce the loss of dental implants caused by peri-implantitis.
The dental implant composition and biofilm formation
Associated to microbiota influence, the material compounds the dental implant also develop important role in the osteointegration process and may act as originator to biofilm formation. On the other hand, their composition is also responsible for greater or lesser bacterial adhesion and consequent biofilm accumulation (Table 1). Bacterial infections are common cause of dental implant failure and due to challenging treatment, occasionally is necessary the tooth removal . Similar to the biofilm formation on natural teeth, bacterial colonization occurs within minutes after the implantation procedure and throughout the life cycle of an implant, therefore it is necessary an implant surface treatment. Surface roughness, which directly affects both osseointegration and biofilm formation, is the primary target for all kinds of surface modifications. However, it is difficult to determine because a surface roughness of at least 1–1.5 µm is needed to achieve a good bone fixation, while the bacterial retention threshold is 0.2 µm, above which an increase in bacterial accumulation occurs. Designing an optimal implant surface, there must be a fine balance between antimicrobial activity and the desired osteoconductive properties. The balance is difficult to achieve as greater surface roughness promotes firmer bone fixation but is directly proportional to bacterial retention, which may promote biofilm formation in the long run .
Titanium has been used for dental implants since the 1960s and is one of the most biocompatible materials, biologically inert and highly resistant to corrosion due to spontaneous formation of a titanium oxide (TiO2) film on its surface, which separates the metal from its environment, providing bio security against local infections . A layer of apatite hydroxide is applied to the implant surface to obtain better osteoconductive, helping in the osteointegration process . So, titanium is still the most widely used dental implant material. However, insufficient soft tissue integration and vulnerability to biofilm accumulation are described for this implant composition . An in vitro study from Souza et al. , revealed that titanium products, especially ions, have potential to change the microbiological composition of biofilms formed on its surfaces. The authors affirm that the presence of titanium products around dental implants may contribute to oral microbiota dysbiosis and, in consequence, to peri-implantitis development.
The zirconium dioxide (zirconia) has earned its place to substitute titanium in implant manufacturing due to its excellent biocompatibility, tissue integration inducing low degree of bone resorption, and low affinity to bacterial biofilm, besides its biomechanical properties [29,30,31]. However, according to Sanon et al. , the main concern about this material due to technical failures occurred like fracture of the material, that is the reason of titanium remains the best material; so, the association of both titanium and zirconium dioxide material is one option to avoid this effect. According to Tang et al. , modifying the surface of zirconia with a TiO2 coating might be favorable for osteogenic effects. In addition, Jo et al.  showed that, when the surface of titanium implants coated with zirconia via atomic layer deposition, the level of S. mutans and P. gingivalis adhesion is reduced regardless of the presence of zirconia crystal phases deposited on the surface.
Ceramic-based alternatives are promising to avoid metal surfaces use; however, according to Matter et al.  the processing and shaping them is demanding, and thus accessible design options are limited. These authors develop nanostructured implant coatings based on such multi-metal oxide nanohybrid building blocks tailored to both hard and soft tissue healing. Ceria has proven anti-inflammatory and antimicrobial properties and their association with bioglass demonstrate a reduction of methicillin-resistant S. aureus (MRSA) growth .
Currently, nanostructures have been suggested as solution for better osteointegration e success of implants. Nanostructured implants have an increased surface area, allowing for better adsorption of proteins and improved attachment of cells to the implant. To improve the implant surface porosity, roughness, and wettability, and to incorporate bioactive components, a wide spectrum of nanocoating techniques has been utilized on dental implants . Associated to increased osteoblast proliferation, the titanium nanoparticles surface appears demonstrate low bacterial adhesion and low biofim maturation of pathogenic species Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia, after 30 days of exposition, compared with other surfaces composition . Another study from Bright et al.  showed a decrease in pathogenic species Sthapylococcus aureus and Pseudomonas aeruginosa viability in the 2 μm layer furthest from the nanostructured surface from titanium nanostructured Ti6Al4V.
Regarding chemical modifications, nano-level modifications are achieved to increase the surface’s hydrophilicity and thus promote osseointegration while reducing hydrophobic bacterial adhesion. Moreover, more robust, and direct stimulation of osseointegration and mitigation of biofilm formation can be accomplished by specific biological modifications. For example, growth factor-coating is known to enhance osseointegration, while antibacterial agent-coating directly combats bacteria and enhances implant properties .
According to the Heo et al. , gold nanoparticles have been successfully tested immobilizing titanium implant surfaces as osteo inductive agent for fast osseointegration. The effectiveness in vitro and in vivo were investigated and, in both experiences, they ensure that gold nanoparticles can be useful as osteo-integration, inducing dental implants to form osteo interface also helping the maintenance of a new bone formation as well. Baumer et al.  affirms on her studies that miR-335-5p/Lipidoid nanoparticles coated on titanium surfaces has shown a transfection efficiency, cell adhesion, proliferation, and osteogenic activity of the bone-implant interface, therefore it might be used as a new methodology to improve the osteogenic capacity of biomedical vcom D'Ercole et al.  demonstrate that wettability and nano-roughness of PEEK can significantly affect the concentration of bacteria Colonies Formation Units (CFUs) and biofilm biomass from Streptococcus oralis, demonstrating bactericidal and/or anti-adhesive effect. In addition, a carbon fiber-reinforced PEEK (CFR-PEEK) has been evaluated to replace titanium in manufacture of implants. According to Tamarakar et al.  the amount of stress generated within the bone in the case of the CFR PEEK implants with different restorative crowns was smaller in comparison with the titanium implants in oblique loading. This could help reduce lateral stress on implants as well as crestal bone loss. No microbiological studies were performed for this structure until now, to verify the biofilm formation.
Recent studies bring new probable future solutions to rehabilitate missing teeth. According to Galler et al. , stem cells have been studied for teeth regeneration. Many successful engineering initiatives related not only to the whole tooth regeneration but also for enamel, the dentin-pulp complex and periodontal ligament have been developed. This task might enable regenerative development for the dentistry in the future.
Regardless of the composition of the implant, manufacturing failures are generally responsible for less osseointegration and increased bacterial colonization, leading to an increase in peri-implantitis rates. According to Belibasakis et al. , biocorrosion of the implant, abutment loosening, prosthetic screen loosening, milled abutment, or prosthetic screw, decemented crown may affect microbial colonization and disease progression.
In addition, there is a straight co-relation between the peri-implantitis development and implant structural manufacturing characteristics as well as prosthetic manufacturing errors which causes surfaces exposure and collaborates for biofilm formation. Peri-implantitis and peri-mucositis are generally identified in patients with non-closed crown edges, loose crown-retained screws, loose abutment screws and broken abutment screws, considered risky reasons associated with the implantation time, and implant position . In addition, prosthesis not well positioned causing difficulties for the appropriate hygiene leading to biofilm formation and a future peri-implantitis .
Additional influencing factors for implant loss is the implant type, wider implant diameter, and number of implants per patient . In a study from Zahng et al. , peri-implantitis and peri-mucositis occurred at lower rates in the Straumann system, while the Osstem system had higher occurrences, and significant higher incidence was observed in the anterior maxilla area. In addition, Jansson et al.  described difference in peri-implantitis and peri-mucositis incidence in the implant surface. The implant regions with highest incidence of moderate/severe peri-implantitis, and consequent bone loss, were mandibular incisor/canine and maxillary incisor/canine; while the occurrence of peri-mucositis was in the regions of maxillary molar, maxillary incisor/canine, and mandibular premolar.
Host immune system and microbiota interactions in peri-implantitis
Peri-implantitis is a multifactorial condition affecting soft tissue and bone around the implant and is resulting from an imbalanced interaction between the pathogen and the host immune response. This process is characterized by inflammation in the peri-implant mucosa and subsequent progressive loss of supporting bone [46,47,48]. The host immune system activation may lead to imbalance of oral microbiota. In turn, the oral microbiota dysbiosis is reported leading to cytokines, chemokines, prostaglandins, and proteolytic enzymes production . Microorganisms from oral microbiota are spread in the oral cavity forming communities interacting synergistically. One microorganism act providing a substratum for the attachment and colonization of another. In addition, physical interactions between the microorganisms can modulate gene expression, including survivor advantage or virulence genes. The availability of nutrients and oxygen are some of factors determining for this distribution .
The injury of peri-implant tissue causes an inflammatory response mediated by activation of innate immune cells such as macrophages, dendritic cells, mast cells, and neutrophils. The neutrophils promote the release of pro-inflammatory citokines IL-1 and TNF-α, which in turn activate the osteolytic and inflammatory tissue damage observed in peri-implantitis . According to Hashim et al. , defects in the number or efficacy of neutrophils predispose individuals to development of periodontal disease. Paradoxically, neutrophil activity, as part of a deregulated inflammatory response, appears to be an important element in the destructive disease process. The absence of CXCR-2 neutrophil receptor in gingival tissue significant was associated with changes in the local microbiome, resulting in an increase of periodontal disease. This effect demonstrates the important role of neutrophils in balancing the oral microbiota. Furthermore, the presence of active CXCR-2 neutrophil receptors was able to reestablish the gingival tissue microbiota .
Meanwhile, macrophages might have a binary role in directing the implant failure or success, depending on their phenotype . M2 macrophages could lead to osseointegration and effective wound healing, while the M1 macrophages could exacerbate the inflammatory process and accelerate osteolysis leading to dental implant failure. Macrophage polarization has been observed in peri-implantitis lesions. Increased populations of M1 macrophages on peri-implantitis samples were observed when compared to periodontal disease samples. Advanced peri-implantitis cases expressed a significantly higher M1 profile when compared with M2 expression (Fig. 3) [52, 53]. Contrasting these observations, a machine learning-assisted immune profile was designed by Wang et al. , where patients at low risk of developing peri-implantitis exhibited elevated M1/M2-like macrophage ratios, higher frequencies of regulatory T cells and lower B-cell infiltration. The association of increased M1 population and low risk of peri-implantitis could be explained by the promotion of Th1 responses which are more effective at controlling pathogens that may contribute to disease progression. However, more studies by using this technology are necessary to confirm this founds.
Furthermore, the low-risk immune profile is also characterized by enhanced complement signaling and higher levels of Th1 and Th17 cytokines. An increased expression of complement components correlated with improved outcomes. In addition, F. nucleatum and Prevotella intermedia were significantly enriched in high-risk individuals, compared with the low-risk group. F. nucleatum is also reported inducing human beta defensins that act as antimicrobial and chemotactic agents, due to a lipo-protein FAD-I (Fusobacterium Associated Defensin Inducer) associated with their outer membrane . The combination of complement activation and increased cytokine production could contribute to limit the microbial burden on the oral cavity of the patients, resulting in reduced risk of peri-implantitis in this group.
Saremi et al.  evaluated the influence of immune gene polymorphisms on the development of peri-implantitis and revealed that allele and genotype frequencies of IL-10 ─ 819 C/T, IL-10 ─ 592 C/A, and IL-1ß + 3954 C/T, significantly differed between diseased and healthy patients, indicating that these specific gene polymorphisms may play a role in the pathogenesis of peri-implantitis. In addition, several studies evaluating gene expression showed several pathways regulating in the inflammatory response in the peri-implantitis. Treg and TH17 cells influence the inflammatory process in periodontal diseases and appears to play an essential role in the destruction of the peri-implant tissues . P. gengivalis is one of major pathogen-causing peri-implantitis and studies demonstrate that this pathogen may active several pathways for immune system response, including LOX-1 and TLR4 receptors, that induces the production of osteopontin, involved in differentiation of odontoblast-like cells, and Wnt5a, a ligand of Wnt signaling pathways involved in leukocyte infiltration and cytokine/chemokine production. In addition, IL-1β, MMP2 and MMP9 production in response to P. gingivalis in THP-1 macrophages was also dependent on LOX-1 [46, 56, 57].
Another factor that has been linked to inflammation and tissue damage is the excess of cement on the prosthetic crown, that is associated with bacterial accumulation . It also promotes tissue inflammation since it is recognized as a foreign body by the host immune system. The immune activation and increased bacterial rates are associated with histological changes in the tooth and lead to lower survival of local osteoblasts.
Li et al.  demonstrates that a fine tuning of osteoclast-osteoblast balance is required for a perfect synchronization of bone resorption and formation, to maintain efficient bone remodeling and bone homeostasis. By contrast, activation of the inflammasome during bacterial infection may leads to bacterial spreading or even an uncontrolled bone destruction, which is very common in periodontitis, periapical periodontitis, peri-implantitis and other related conditions. This uncontrolled inflammasome activity may cause alveolar osteolysis by activated macrophages, monocytes, neutrophils, and adaptive immune cells like T helper 17 cells. This whole immune response causes an increase in osteoclasts and concomitant decrease of osteoblasts. In addition, osteocytes play an important role in alveolar bone loss, since they respond to inflammatory changes by secreting molecules that affect bone resorption and formation, causing bone loss .
Potential preventions or therapies for microbiological-driven peri-implantitis
The current antibiotic resistance rates associated with microbiota dysbiosis caused by antibiotic and antiseptic usage, probiotics have been suggested as option for peri-implantitis treatment. Probiotics are defined as living and viable microorganisms which, when administered in adequate quantities, confer benefits to the organism . Probiotics are considered a safe and useful tool, since reduces the immunogenicity of microbiotas by improve the balance of the host microorganisms, inhibiting pathogens. In addition, the host balance result in immune homeostasis, and consequent decreasing of proinflammatory cytokines (Table 2) .
Lactobacillus species have been used for years to balance gut and vaginal microbiotas, and currently is suggested also to oral microbiota. In a study from Kõll-Klais et al.  the most prevalent Lactobacillus species in oral microbiota from healthy individual were L. gasseri and L. fermentum, while in chronic periodontitis patients, L. plantarum was more frequent. In in vitro tests, Lactobacillus spp. was able to inhibit the pathogenic bacteria S. mutans, A. actinomycetemcomitans, P. gingivalis and P. intermedia. Strongest antimicrobial activity was associated with L. paracasei, L. plantarum, L. rhamnosus and L. salivarius.
L. reuteri-based probiotics are used for gut microbiota balance and was suggested for oral microbiota to peri-implantitis treatment. Two studies showed low decreasing of peri-implantitis rate; however, there was a reduction in the number of periodontal and peri-implant causing species, as P. gingivalis [61, 63]. On the other hand, after treatment with the probiotic L. reuteri in patients with implants presenting mucositis, the clinical parameters improved, and the cytokine levels decreased, suggesting a preventing role of L. reuteri-based probiotics . Though not always achieving significance, studies show difference in the depth of the probing in the treatment of peri-implantitis, when using L. reuteri probiotic, which can be clinically effective in terms of pocket depth reduction in this treatment [65, 66]. Until now, studies demonstrated that the L. reuteri-based probiotics appears to be not so effective solution for peri-implantitis diseases; however, more studies evaluating other probiotics composition need to be performed to make available an associated therapy and reduction of antiseptic and antibiotic usage.
A novel proposal to S. salivarius-based probiotic in reduction of biofilm formation in implant was demonstrated by Vacca et al. . The authors demonstrated an interaction between bacteriocin produced by S. salivarius inhibiting the quorum-sensing signals and reducing the S. intermedius biofilm production in titanium implant surface; so, this probiotic could be considered in non-surgical therapy to prevent biofilm-related implant diseases. On the other hand, a study from Martorano-Fernandes et al.  suggests that the use of S. salivarius as a probiotic would be ineffective in peri‐implant disease treatment, when caused by C. albicans pathogen.
There is a lack of diversity about probiotic composition for peri-implantitis therapy, so, more studies are necessary to invested in an adjuvant and non-medicated solution, to avoid as much as possible as the imbalance of the oral microbiota.
Obtaining knowledge about the specificity of the oral microbiome shows the complexity and difficult task against oral infections. The host-microbiome interactions may contribute for the periimplantitis development. According to this review, we have observed the oral microbiome dysbiosis may be the starting point for an unbalanced concentration of different bacteria species, therefore it collaborates for a strong biofilm formation due to its bacteria diversity. This process associated with some implant structural manufacturing and prosthetic mistakes may facilitate and become easier the biofilm formation. The host immune system has an important role in the oral dysbiosis, leading to citokines, chemokines, prostaglandins, and proteolytic enzymes production in the oral microbiota, which may induce unusual bacteria interactions causing bone loss derivate from peri-implantitis development, and possible implant loss. Probiotics are considered a safe and useful tool, since reduces the immunogenicity of microbiotas by improving the balance of the host microorganisms, inhibiting pathogens. The identification of the microbiome, as well as its quantification, are fundamental data necessary for future behavioral analysis of these colonization and their conveniences in the creation of biofilms and their interactions relating to peri-implantitis development.
Availability of data and materials
Albrektsson T, Wennerberg A. The impact of oral implants - past and future, 1966–2042. J Can Dent Assoc. 2005;71(5):327.
Block MS. Dental implants: the last 100 years. J Oral Maxillofac Surg. 2018;76(1):11–26. https://doi.org/10.1016/j.joms.2017.08.045.
Thoma DS, Sailer I, Ioannidis A, Zwahlen M, Makarov N, Pjetursson BE. A systematic review of the survival and complication rates of resin-bonded fixed dental prostheses after a mean observation period of at least 5 years. Clin Oral Implants Res. 2017;28(11):1421–32. https://doi.org/10.1111/clr.13007.
Mager DL, Ximenez-Fyvie LA, Haffajee AD, Socransky SS. Distribution of selected bacterial species on intraoral surfaces. J Clin Periodontol. 2003;30(7):644–54. https://doi.org/10.1034/j.1600-051x.2003.00376.x.
Segata N, Haake SK, Mannon P, Lemon KP, Waldron L, Gevers D, Huttenhower C, Izard J. Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples. Genome Biol. 2012;13(6):R42. https://doi.org/10.1186/gb-2012-13-6-r42.
Bao K, Li X, Poveda L, Qi W, Selevsek N, Gumus P, Emingil G, Grossmann J, Diaz PI, Hajishengallis G, Bostanci N, Belibasakis GN. Proteome and Microbiome Mapping of Human Gingival Tissue in Health and Disease. Front Cell Infect Microbiol. 2020;2(10): 588155. https://doi.org/10.3389/fcimb.2020.588155.
Kolenbrander PE. Oral microbial communities: biofilms, interactions, and genetic systems. Annu Rev Microbiol. 2000;54:413–37. https://doi.org/10.1146/annurev.micro.54.1.413.
Valm AM, Mark Welch JL, Rieken CW, Hasegawa Y, Sogin ML, Oldenbourg R, Dewhirst FE, Borisy GG. Systems-level analysis of microbial community organization through combinatorial labeling and spectral imaging. Proc Natl Acad Sci U S A. 2011;108(10):4152–7. https://doi.org/10.1073/pnas.1101134108.
Mazari W, Boucherit-Otmani Z, El-Haci IA, Ilahi A, Boucherit K. Risk assessment for the spread of Candida sp. in dental chair unit waterlines using molecular techniques. Int Dent J. 2018;68(6):386–92. https://doi.org/10.1111/idj.12401.
Premamalini T, Anitha S, Mohanapriya K, Kindo AJ. Evaluation of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide method for assessing biofilm formation in vitro by Trichosporon spp. J Lab Physicians. 2018;10(4):380–6. https://doi.org/10.4103/JLP.JLP_37_18.
Berglundh T, Armitage G, Araujo MG, Avila-Ortiz G, Blanco J, Camargo PM, Chen S, Cochran D, Derks J, Figuero E, Hämmerle CHF, Heitz-Mayfield LJA, Huynh-Ba G, Iacono V, Koo KT, Lambert F, McCauley L, Quirynen M, Renvert S, Salvi GE, Schwarz F, Tarnow D, Tomasi C, Wang HL, Zitzmann N. Peri-implant diseases and conditions: Consensus report of workgroup 4 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Clin Periodontol. 2018;45(Suppl 20):S286–91. https://doi.org/10.1111/jcpe.12957 (PMID: 29926491).
Persson GR, Renvert S. Cluster of bacteria associated with peri-implantitis. Clin Implant Dent Relat Res. 2014;16(6):783–93. https://doi.org/10.1111/cid.12052.
Mulla M, Mulla M, Hegde S, Koshy AV. In vitro assessment of the effect of probiotic lactobacillus reuteri on peri-implantitis microflora. BMC Oral Health. 2021;21(1):408. https://doi.org/10.1186/s12903-021-01762-2.
Mombelli A, Décaillet F. The characteristics of biofilms in peri-implant disease. J Clin Periodontol. 2011;38(Suppl 11):203–13. https://doi.org/10.1111/j.1600-051X.2010.01666.x.
Schwarz F, Derks J, Monje A, Wang HL. Peri-implantitis. J Periodontol. 2018;89(Suppl 1):S267–90. https://doi.org/10.1002/JPER.16-0350.
Jiang Q, Yu Y, Xu R, Zhang Z, Liang C, Sun H, Deng F, Yu X. The temporal shift of peri-implant microbiota during the biofilm formation and maturation in a canine model. Microb Pathog. 2021;158: 105100. https://doi.org/10.1016/j.micpath.2021.105100.
Abusleme L, Hoare A, Hong BY, Diaz PI. Microbial signatures of health, gingivitis, and periodontitis. Periodontol. 2000;86(1):57–78. https://doi.org/10.1111/prd.12362.
Lang NP, Berglundh T. Working Group 4 of Seventh European Workshop on Periodontology. Periimplant diseases: where are we now?–Consensus of the Seventh European Workshop on Periodontology. J Clin Periodontol. 2011;38(Suppl 11):178–81. https://doi.org/10.1111/j.1600-051X.2010.01674.x.
Klinge B, Klinge A, Bertl K, Stavropoulos A. Peri-implant diseases. Eur J Oral Sci. 2018;126(Suppl 1):88–94. https://doi.org/10.1111/eos.12529.
Polymeri A, van der Horst J, Buijs MJ, Zaura E, Wismeijer D, Crielaard W, Loos BG, Laine ML, Brandt BW. Submucosal microbiome of peri-implant sites: A cross-sectional study. J Clin Periodontol. 2021;48(9):1228–39. https://doi.org/10.1111/jcpe.13502.
Belibasakis GN, Manoil D. Microbial Community-Driven Etiopathogenesis of Peri-Implantitis. J Dent Res. 2021;100(1):21–8. https://doi.org/10.1177/0022034520949851.
Ghensi P, Manghi P, Zolfo M, Armanini F, Pasolli E, Bolzan M, Bertelle A, Dell’Acqua F, Dellasega E, Waldner R, Tessarolo F, Tomasi C, Segata N. Strong oral plaque microbiome signatures for dental implant diseases identified by strain-resolution metagenomics. NPJ Biofilms Microbiomes. 2020;6(1):47. https://doi.org/10.1038/s41522-020-00155-7.
Matter MT, Maliqi L, Keevend K, Guimond S, Ng J, Armagan E, Rottmar M, Herrmann IK. One-step synthesis of versatile antimicrobial nano-architected implant coatings for hard and soft tissue healing. ACS Appl Mater Interfaces. 2021;13(28):33300–10. https://doi.org/10.1021/acsami.1c10121.
Kligman S, Ren Z, Chung CH, Perillo MA, Chang YC, Koo H, Zheng Z, Li C. The Impact of Dental Implant Surface Modifications on Osseointegration and Biofilm Formation. J Clin Med. 2021;10(8):1641. https://doi.org/10.3390/jcm10081641.PMID:33921531;PMCID:PMC8070594.
Zhu X, Chen J, Scheideler L, Reichl R, Geis-Gerstorfer J. Effects of topography and composition of titanium surface oxides on osteoblast responses. Biomaterials. 2004;25(18):4087–103. https://doi.org/10.1016/j.biomaterials.2003.11.01.
Ogle OE. Implant surface material, design, and osseointegration. Dent Clin North Am. 2015;59(2):505–20. https://doi.org/10.1016/j.cden.2014.12.003.
Craig RG, LeGeros RZ. Early events associated with periodontal connective tissue attachment formation on titanium and hydroxyapatite surfaces. J Biomed Mater Res. 1999;47(4):585–94. https://doi.org/10.1002/(sici)1097-4636(19991215)47:4%3c585::aid-jbm16%3e3.0.co;2-o.
Souza JGS, Costa Oliveira BE, Bertolini M, Lima CV, Retamal-Valdes B, de Faveri M, Feres M, Barão VAR. Titanium particles and ions favor dysbiosis in oral biofilms. J Periodontal Res. 2020;55(2):258–66. https://doi.org/10.1111/jre.12711.
Covacci V, Bruzzese N, Maccauro G, Andreassi C, Ricci GA, Piconi C, Marmo E, Burger W, Cittadini A. In vitro evaluation of the mutagenic and carcinogenic power of high purity zirconia ceramic. Biomaterials. 1999;20(4):371–6. https://doi.org/10.1016/s0142-9612(98)00182-3.
Sennerby L, Dasmah A, Larsson B, Iverhed M. Bone tissue responses to surface-modified zirconia implants: a histomorphometric and removal torque study in the rabbit. Clin Implant Dent Relat Res. 2005;7(Suppl 1):S13-20. https://doi.org/10.1111/j.1708-8208.2005.tb00070.x.
Al-Radha AS, Dymock D, Younes C, O’Sullivan D. Surface properties of titanium and zirconia dental implant materials and their effect on bacterial adhesion. J Dent. 2012;40(2):146–53. https://doi.org/10.1016/j.jdent.2011.12.006.
Sanon C, Chevalier J, Douillard T, Cattani-Lorente M, Scherrer SS, Gremillard L. A new testing protocol for zirconia dental implants. Dent Mater. 2015;31(1):15–25. https://doi.org/10.1016/j.dental.2014.09.002.
Tang S, Zhang J, Ding N, Zhang Z. Biological activity of titania coating prepared with zirconium oxychloride and titania on zirconia surface. J Mech Behav Biomed Mater. 2021;123: 104780. https://doi.org/10.1016/j.jmbbm.2021.104780.
Jo Y, Kim YT, Cho H, Ji MK, Heo J, Lim HP. Atomic layer deposition of ZrO2 on titanium inhibits bacterial adhesion and enhances osteoblast viability. Int J Nanomedicine. 2021;24(16):1509–23. https://doi.org/10.2147/IJN.S298449.
Camargo SEA, Xia X, Fares C, Ren F, Hsu SM, Budei D, Aravindraja C, Kesavalu L, Esquivel-Upshaw JF. Nanostructured Surfaces to Promote Osteoblast Proliferation and Minimize Bacterial Adhesion on Titanium. Materials (Basel). 2021;14(16):4357. https://doi.org/10.3390/ma14164357.
Bright R, Hayles A, Fernandes D, Visalakshan RM, Ninan N, Palms D, Burzava A, Barker D, Brown T, Vasilev K. In vitro bactericidal efficacy of nanostructured Ti6Al4V surfaces is bacterial load dependent. ACS Appl Mater Interfaces. 2021;13(32):38007–17. https://doi.org/10.1021/acsami.1c06919.
Heo DN, Ko WK, Lee HR, Lee SJ, Lee D, Um SH, Lee JH, Woo YH, Zhang LG, Lee DW, Kwon IK. Titanium dental implants surface-immobilized with gold nanoparticles as osteoinductive agents for rapid osseointegration. J Colloid Interface Sci. 2016;1(469):129–37. https://doi.org/10.1016/j.jcis.2016.02.022.
Bäumer A, Toekan S, Saure D, Körner G. Survival and success of implants in a private periodontal practice: a 10 year retrospective study. BMC Oral Health. 2020;20(1):92. https://doi.org/10.1186/s12903-020-01064-z.
Kim WT, Park DC, Yang WH, Cho CH, Choi WY. Effects of Electrospinning Parameters on the Microstructure of PVP/TiO2 Nanofibers. Nanomaterials (Basel). 2021;11(6):1616. https://doi.org/10.3390/nano11061616.
Najeeb S, Zafar MS, Khurshid Z, Siddiqui F. Applications of polyetheretherketone (PEEK) in oral implantology and prosthodontics. J Prosthodont Res. 2016;60(1):12–9. https://doi.org/10.1016/j.jpor.2015.10.001.
D’Ercole S, Cellini L, Pilato S, Di Lodovico S, Iezzi G, Piattelli A, Petrini M. Material characterization and Streptococcus oralis adhesion on Polyetheretherketone (PEEK) and titanium surfaces used in implantology. J Mater Sci Mater Med. 2020;31(10):84. https://doi.org/10.1007/s10856-020-06408-3.
Tamrakar SK, Mishra SK, Chowdhary R, Rao S. Comparative analysis of stress distribution around CFR-PEEK implants and titanium implants with different prosthetic crowns: A finite element analysis. Dent Med Probl. 2021;58(3):359–67. https://doi.org/10.17219/dmp/133234.
Galler KM, D’Souza RN. Tissue engineering approaches for regenerative dentistry. Regen Med. 2011;6(1):111–24. https://doi.org/10.2217/rme.10.86.
Zahng TT, Hu XJ, Lin L. Prevalence of peri-implantitis and peri-implant mucositis within 15 years of implant placement. Shanghai Kou Qiang Yi Xue. 2021;30(3):292–6.
Jansson L, Guan T, Modin C, Buhlin K. Radiographic peri-implant bone loss after a function time up to 15 years. Acta Odontol Scand. 2021;30:1–7. https://doi.org/10.1080/00016357.2021.1958003.
Zhang Q, Liu J, Ma L, Bai N, Xu H. Wnt5a is involved in LOX-1 and TLR4 induced host inflammatory response in peri-implantitis. J Periodontal Res. 2020;55(2):199–208. https://doi.org/10.1111/jre.12702.
Saremi L, Shafizadeh M, Esmaeilzadeh E, Ghaffari ME, Mahdavi MH, Amid R, Kadkhodazadeh M. Assessment of IL-10, IL-1ß and TNF-α gene polymorphisms in patients with peri-implantitis and healthy controls. Mol Biol Rep. 2021;48(3):2285–90. https://doi.org/10.1007/s11033-021-06253-9.
Giro G, Tebar A, Franco L, Racy D, Bastos MF, Shibli JA. Treg and TH17 link to immune response in individuals with peri-implantitis: a preliminary report. Clin Oral Investig. 2021;25(3):1291–7. https://doi.org/10.1007/s00784-020-03435-w.
Lamont RJ, Koo H, Hajishengallis G. The oral microbiota: dynamic communities and host interactions. Nat Rev Microbiol. 2018;16(12):745–59. https://doi.org/10.1038/s41579-018-0089-x.PMID:30301974;PMCID:PMC6278837.
Baseri M, Radmand F, Hamedi R, Yousefi M, Kafil HS. Immunological Aspects of Dental Implant Rejection. Biomed Res Int. 2020;9(2020):7279509. https://doi.org/10.1155/2020/7279509.
Hashim A, Alsam A, Payne MA, Aduse-Opoku J, Curtis MA, Joseph S. Loss of neutrophil homing to the periodontal tissues modulates the composition and disease potential of the oral microbiota. Infect Immun. 2021. https://doi.org/10.1128/IAI.00309-21.
Fretwurst T, Garaicoa-Pazmino C, Nelson K, Giannobile WV, Squarize CH, Larsson L, Castilho RM. Characterization of macrophages infiltrating peri-implantitis lesions. Clin Oral Implants Res. 2020;31(3):274–81. https://doi.org/10.1111/clr.13568.
Galarraga-Vinueza ME, Obreja K, Ramanauskaite A, Magini R, Begic A, Sader R, Schwarz F. Macrophage polarization in peri-implantitis lesions. Clin Oral Investig. 2021;25(4):2335–44. https://doi.org/10.1007/s00784-020-03556-2.
Wang CW, Hao Y, Di Gianfilippo R, Sugai J, Li J, Gong W, Kornman KS, Wang HL, Kamada N, Xie Y, Giannobile WV, Lei YL. Machine learning-assisted immune profiling stratifies peri-implantitis patients with unique microbial colonization and clinical outcomes. Theranostics. 2021;11(14):6703–16. https://doi.org/10.7150/thno.57775.
Ghosh SK, Feng Z, Fujioka H, Lux R, McCormick TS, Weinberg A. Conceptual perspectives: bacterial antimicrobial peptide induction as a novel strategy for symbiosis with the human host. Front Microbiol. 2018;26(9):302. https://doi.org/10.3389/fmicb.2018.00302.
Che C, Liu J, Yang J, Ma L, Bai N, Zhang Q. Osteopontin is essential for IL-1β production and apoptosis in peri-implantitis. Clin Implant Dent Relat Res. 2018;20(3):384–92. https://doi.org/10.1111/cid.12592.
Che C, Liu J, Ma L, Xu H, Bai N, Zhang Q. LOX-1 is involved in IL-1β production and extracellular matrix breakdown in dental peri-implantitis. Int Immunopharmacol. 2017;52:127–35. https://doi.org/10.1016/j.intimp.2017.09.003.
Tatullo M, Marrelli M, Mastrangelo F, Gherlone E. Bone Inflammation, bone infection and dental implants failure: histological and cytological aspects related to cement excess. J Bone Jt Infect. 2017;2(2):84–9. https://doi.org/10.7150/jbji.17507.
Li Y, Ling J, Jiang Q. Inflammasomes in Alveolar Bone Loss. Front Immunol. 2021;9(12): 691013. https://doi.org/10.3389/fimmu.2021.691013.
Huang X, Xie M, Xie Y, Mei F, Lu X, Li X, Chen L. The roles of osteocytes in alveolar bone destruction in periodontitis. J Transl Med. 2020;18(1):479. https://doi.org/10.1186/s12967-020-02664-7.
Lauritano D, Carinci F, Palmieri A, Cura F, Caruso S, Candotto V. Reuterinos® as adjuvant for peri-implant treatment: A pilot study. Int J Immunopathol Pharmacol. 2019. https://doi.org/10.1177/205873841982774.
Kõll-Klais P, Mändar R, Leibur E, Marcotte H, Hammarström L, Mikelsaar M. Oral lactobacilli in chronic periodontitis and periodontal health: species composition and antimicrobial activity. Oral Microbiol Immunol. 2005;20(6):354–61. https://doi.org/10.1111/j.1399-302X.2005.00239.x.
Galofré M, Palao D, Vicario M, Nart J, Violant D. Clinical and microbiological evaluation of the effect of Lactobacillus reuteri in the treatment of mucositis and peri-implantitis: A triple-blind randomized clinical trial. J Periodontal Res. 2018;53(3):378–90. https://doi.org/10.1111/jre.12523.
Flichy-Fernández AJ, Ata-Ali J, Alegre-Domingo T, Candel-Martí E, Ata-Ali F, Palacio JR, Peñarrocha-Diago M. The effect of orally administered probiotic Lactobacillus reuteri-containing tablets in peri-implant mucositis: a double-blind randomized controlled trial. J Periodontal Res. 2015;50(6):775–85. https://doi.org/10.1111/jre.12264.
Arbildo-Vega HI, Panda S, Bal A, Mohanty R, Rendón-Alvarado A, Das AC, Cruzado-Oliva FH, Infantes-Ruíz ED, Manfredi B, Vásquez-Rodrigo H, Mortellaro C, Giacomello MS, Parrini M, Greco Lucchina A, Del Fabbro M. Clinical effectiveness of Lactobacillus reuteri in the treatment of peri-implant diseases: a systematic review and meta-analysis. J Biol Regul Homeost Agents. 2021;35(1):79–88. https://doi.org/10.23812/21-2supp1-7.
Peña M, Barallat L, Vilarrasa J, Vicario M, Violant D, Nart J. Evaluation of the effect of probiotics in the treatment of peri-implant mucositis: a triple-blind randomized clinical trial. Clin Oral Investig. 2019;23(4):1673–83. https://doi.org/10.1007/s00784-018-2578-8.
Vacca C, Contu MP, Rossi C, Ferrando ML, Blus C, Szmukler-Moncler S, Scano A, Orrù G. In vitro Interactions between Streptococcus intermedius and Streptococcus salivarius K12 on a Titanium Cylindrical Surface. Pathogens. 2020;9(12):1069. https://doi.org/10.3390/pathogens9121069.
Martorano-Fernandes L, Rodrigues NC, de SouzaBorges MH, Cavalcanti YW, de Almeida LFD. Interkingdom interaction between C. albicans and S. salivarius on titanium surfaces. BMC Oral Health. 2020;20(1):349. https://doi.org/10.1186/s12903-020-01334-w.
We would like to thank Universidade São Francisco; National Council for Scientific and Technological Development (CNPq), Ministry of Science and Technology, Brazil; and The São Paulo State Research Foundation (FAPESP); for supporting in our researchers.
This study was supported by Universidade São Francisco.
Ethics approval and consent to participate
Consent for publication
The authors declare no conflicts of interest.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Alves, C.H., Russi, K.L., Rocha, N.C. et al. Host-microbiome interactions regarding peri-implantitis and dental implant loss. J Transl Med 20, 425 (2022). https://doi.org/10.1186/s12967-022-03636-9
- Oral microbiome
- Dental implants
- Oral diseases