Skip to main content
NCBI home page
NPJ Biofilms and Microbiomes logoLink to NPJ Biofilms and Microbiomes
. 2024 Jul 13;10:56. doi: 10.1038/s41522-024-00529-1

Recent advances in the pathogenesis and prevention strategies of dental calculus

Yu Wei 1,#, Gao-peng Dang 1,#, Zhao-yang Ren 1,#, Mei-chen Wan 1, Chen-yu Wang 1, Hong-bo Li 2, Tong Zhang 2, Franklin R Tay 3, Li-na Niu 1,✉
PMCID: PMC11246453  PMID: 39003275

Abstract

Dental calculus severely affects the oral health of humans and animal pets. Calculus deposition affects the gingival appearance and causes inflammation. Failure to remove dental calculus from the dentition results in oral diseases such as periodontitis. Apart from adversely affecting oral health, some systemic diseases are closely related to dental calculus deposition. Hence, identifying the mechanisms of dental calculus formation helps protect oral and systemic health. A plethora of biological and physicochemical factors contribute to the physiological equilibrium in the oral cavity. Bacteria are an important part of the equation. Calculus formation commences when the bacterial equilibrium is broken. Bacteria accumulate locally and form biofilms on the tooth surface. The bacteria promote increases in local calcium and phosphorus concentrations, which triggers biomineralization and the development of dental calculus. Current treatments only help to relieve the symptoms caused by calculus deposition. These symptoms are prone to relapse if calculus removal is not under control. There is a need for a treatment regime that combines short-term and long-term goals in addressing calculus formation. The present review introduces the mechanisms of dental calculus formation, influencing factors, and the relationship between dental calculus and several systemic diseases. This is followed by the presentation of a conceptual solution for improving existing treatment strategies and minimizing recurrence.

Subject terms: Bacteria, Biofilms

Introduction

Dental calculusis a common health problem in the human body. It has a high rate of occurrence (~90%) among the general population1,2. Recent studies reported that dental calculus is also associated with digestive, neurological, and cardiovascular diseases (Table 1). The quality of life of the involved subjects is seriously threatened if the secondary harm caused by dental calculus is not appropriately addressed.

Table 1.

Secondary diseases and their pathogenic factors due to dental calculus

Body Part Disease Pathogenic Factor Refs.
Oral cavity Gingivitis Bacterial biofilm 75,76
Periodontitis Bacterial biofilm; the NLRP3 inflammasome 77
Oral submucous fibrosis Copper in dental calculus 78
Oral squamous cell carcinoma Cadmium in dental calculus 79
Digestive system Colorectal cancer P. gingivalis; the NLRP3 inflammasome 80
Esophageal cancer P. gingivalis; Tannerella forsythia 81,82
Inflammatory bowel disease Ectopic colonization of oral pathogens; the recruitment of macrophages and T cells 83,84
Nervous system Blood-brain barrier damage P. gingivalis 85
Alzheimer’s disease Gingipains 86
Cerebral abscesses Bacterial infection 87
Stroke P. gingivalis 88,89
Cardiovascular system Combined hypertension Dysbiosis of oral microbiota; damage to vascular epithelium; immune responses 90,91
Angina pectoris - 92
Heart infarction Bacteremia; endotoxemia 93
Atherosclerosis P.gingivalis 94
Open in a new tab

Dental calculus is difficult to remove. Its rough surface provides good conditions for bacteria adhesion and growth. As a cradle for bacterial colonization and reproduction, dental calculus is most likely to accumulate along the gingival margins. Bacteria present in dental calculus continuously irritate periodontal tissue. Bone resorption, periodontal pocket formation, periodontal pus overflow, root exposure, and tooth loss inevitably occur during the advanced stages of periodontitis3.

The present review first introduces the mechanisms of dental calculus formation. Multiple factors contribute to the formation of the calculus. These factors may be divided into bacterial factors, immune factors, and host factors. These three factors interact with each other to promote calculus formation (Fig. 1). Novel strategies for the prevention of dental calculus have also been developed over the past few years. These strategies include laser technology, nanotechnology, and the application of biological agents. These preventive and treatment strategies will be discussed, from principles to application, to provide insight for future research.

Fig. 1. Pathogenesis of dental calculus involves bacteria and matrix mineralization.

Fig. 1

Open in a new tab

Bacteria induce destruction of biological macromolecules, tissue abnormalities, and inflammatory responses. Mineralized matrix releases heavy metal ions and causes inflammatory responses. (ROS reactive oxygen species, M1 classically activated macrophages, M2 alternatively activated macrophages, Th cells T helper cells, TNF-a tumor necrosis factor-a) (The figure does not contain any third-party material, the figure and each of the elements in the figure were created by the authors).

Mechanisms of dental calculus formation

Dental calculus consists of inorganic components and an organic matrix derived from saliva, gingival crevicular fluid, and bacterial products4. Bacteria are critical for the formation of dental calculus. They form biofilms on the surface of natural teeth and dentures. The biofilms undergo mineralization and become dental calculus5. This section introduces the mechanisms of dental calculus formation by focusing on the changes in bacteria.

Bacterial factors

Dental calculus forms through the mineralization of dental plaque, and can persist on ancient skeletal remains for thousands of years. These remains are capable of preserving ancient biomolecules, including intact DNA and proteins6. Consequently, researchers have utilized ancient dental calculus to examine the composition and function of oral microbial communities. Key oral pathogens have been identified from ancient dental calculus7. Furthermore, analyses of ancient dental calculus suggest that changes in bacterial diversity correlate with dietary shifts and variations in social environments8.

Formation and functions of bacterial biofilm and matrix

Bacterial biofilm consists of bacteria that are surrounded by a polymeric matrix produced by the bacteria9. The process of bacterial biofilm formation has been well investigated. Bacteria first attach reversibly to teeth through van der Waals forces and hydrophobic interactions. They use their pili to irreversibly attach to tooth surfaces, and form colonies to stabilize their attachment10. During the process, a self-produced matrix of extracellular polymeric substance (EPS) acts as a hard shell to protect the bacteria from external pressure11. The EPS has additional functions such as mediation of bacteria migration and provision of signaling targets. Accumulation of small bacterial clusters and bacterial layers subsequently results in the formation of plaque biofilm12. Channels and pores within the biofilm help the circulation of nutrition between the internal biofilm milieu and the exterior environment13. Bacteria present in dental plaque are divided into early colonizers and late colonizers. Early colonizers are typically facultative anaerobes and saccharolytic species that thrive on salivary mucins and other glycoproteins3. Late colonizers are usually proteolytic obligate anaerobes. The “bridge organism” between early and late colonizers is Fusobacterium nucleatum. This bacterium is capable of co-aggregating with other bacteria species14. Mature biofilms provide a platform for mineralization15. Among the plethora of bacteria present in plaque biofilms, Streptococcus sanguinis is the primary colonizer. Streptococcus mutans and Streptococcus gordonii co-aggregate over the primary colonizer via molecular interactions. The variety of bacterial species and interaction between distinct layers results in the formation of stable plaque biofilms16 (Fig. 2). Changes within the bacteria also play an important role in mature biofilms. As a second messenger, intracellular cyclic di-guanosine monophosphate promotes surface attachment of biofilms. Reduction in intracellular cyclic di-guanosine monophosphate causes biofilm dispersion17.

Fig. 2. Formation and development of plaque biofilms.

Fig. 2

Open in a new tab

a On natural tooth surfaces, initial colonization takes place over 0–18 h and, at this point, the biofilm is dominated by pioneer colonizers that are adapted to adhere to saliva pellicle constituents and to tolerate the presence of oxygen. If left unperturbed, the biofilm gradually matures without dramatic shifts in the microbial composition between 18 h and 4 days. From 4 to 7 days, obligate anaerobes increase at the gum margins. b Interactions between microorganisms that may drive the community assembly of oral biofilms71. a and b are reproduced with permission from the publisher.

The composition of the extracellular matrix also affects the status of plaque biofilms18. Compared with healthy teeth samples, teeth with dental calculus have more bacterial virulence proteins, which worsen the periodontal microenvironments. Glucosyltransferases produced by bacteria are released to the dental calculus matrix by exocytosis19. These enzymes catalyze the production of exopolysaccharides and promote bacteria adhesion to the surface of early biofilms20. Matrix macromolecules such as extracellular DNA (exDNA) are characteristic of mature biofilm in periodontitis. Extracellular DNA exists in the matrix in two forms: free DNA and extracellular DNA traps(ETs) (Fig. 3). Irrespective of the origin of exDNA, these molecules play a crucial role in initiating biofilm formation and sustaining the biofilm’s three-dimensional structure21,22. The adhesion of S. mutans to hydrophobic surfaces and the viscoelasticity of biofilms are enhanced by exDNA. Under nutrient-limiting conditions, bacteria release exDNA enzymes that utilize exDNA as a surrogate source of nutrition23. Besides, Quorum sensing among biofilm bacteria, cyclic diguanylate, and small non-coding RNAs within the matrix regulatory network is involved in the regulation of biofilm formation24.

Fig. 3. The origin of exDNA.

Fig. 3

Open in a new tab

a Free DNA is derived from multiple sources. These molecules are produced mainly by endogenous pathways, including active secretion, erythrocyte nucleation, necrosis, and degradation of ETs from neutrophils. b Three types of extracellular vesicles carry exDNA22. Figure reproduced with permission from the publisher.

Biofilm formation on dental implants and teeth follows a similar pattern. However, there are a few differences due to the implant materials used. These materials have a lower capacity for albumin absorption compared with natural teeth. This property results in reduced biofilm formation around implants. The process of biofilm formation begins on the implant surface ~30 min after exposure to the oral environment. In contrast, biofilms around natural teeth form within minutes25. Initially, implants are primarily colonized by gram-positive cocci, rods, and actinomyces species, which attach to salivary agglutinins and proline-rich proteins. These early colonizers pave the way for subsequent attachment by late colonizers such as Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Fusobacterium nucleatum. The stepwise colonization by bacteria facilitates the development of biofilm and escalates its pathogenicity over time26. In addition, microgaps ranging from 2.5–60 μm in the implant-abutment interface impair the seal, allowing bacteria to infiltrate and form biofilms within the implant’s inner threads27. Biofilms contribute to the formation of dental calculus, which in turn deteriorates the surface of the implant and increases its roughness. This roughness fosters further bacterial re-colonization, hindering the reattachment and proliferation of host cells28.

Mechanism of dental calculus biofilm mineralization

Mature plaque biofilms formed on the surfaces of teeth and dentures provide platforms for mineralization. Plaque bacteria are engaged in different metabolic processes that interact with inorganic minerals to produce mineral precipitates in dental calculus. The most common minerals deposited by bacteria are calcium carbonate and calcium phosphate29. The most frequent calcium phosphate crystalline phases found in dental calculus are hydroxyapatite, octacalcium phosphate, and whitlockite30. However, the local concentrations of calcium and phosphate ions are not high enough to cause spontaneous precipitation31. Therefore, bacteria play an important role in mineral deposition. It is necessary to understand the mineralization mechanism of the interaction between bacteria and minerals.

Bacteria release different enzymes during the mineralization process. Recently, the release of alkaline phosphatase (ALP) was reported to be associated with periodontal inflammatory responses32. ALP has also been identified as a hallmark enzyme in periodontitis. Microorganisms in the dental biofilm induce the death of epithelial cells. Destruction of the epithelial barrier induces infected epithelial cells and immune cells to produce pro-inflammatory cytokines and chemokines, such as IL-1β, IL-6, and IL-833. The pro-inflammatory cytokines recruit inflammatory cells and initiate the subsequent inflammatory response. The ALP is released by bacteria34. Bacterial ALPs are found extracellularly, bonding on the surface of the bacteria. Alkaline phosphatase has the ability to dephosphorylate teichoic acid, a molecule that plays a key role in bacterial colonization on teeth. With the release of phosphate ions, calcium ions may become supersaturated35. It is also reported that ALP regulated biofilm formation by promoting aerobic pathways35. This shows the importance of ALP in the mineralization of biofilm.

In addition, positively-charged polycationic compounds also induce dental calculus mineralization36. For instance, streptococcal bacterial protein is rich in positively-charged amino acids. It acts as a substrate for the nucleation and growth of inorganic mineral particles37. Environmental changes also affect dental calculus mineralization. Bacteria produce enzymes that influence the environment and regulate calcium and phosphorus content38. Ureolytic bacteria hydrolyze salivary and dietary urea via the enzyme urease to produce ammonia and carbon dioxide, increasing the pH value. Thus, calcium phosphate saturation increases in plaque fluid and accelerates the formation of dental calculus17.

Effects of physicochemical factors on bacteria

The relationship between the oral microbiota and the oral physicochemical environment changes dynamically. This relationship may evolve from a healthy symbiotic relationship to pathological dysbiosis39. Studying the influence of oral physicochemical factors on bacterial status can help elucidate the mechanisms of calculus formation. In addition, changes in physical and chemical factors may also cause changes in supragingival or subgingival plaque microflora (Fig. 4).

Fig. 4. Physical and chemical factors present in supragingival or subgingival plaque.

Fig. 4

Open in a new tab

The types of bacteria located in the supragingival and subgingival plaques are different. The physicochemical factors affecting the bacteria in the two sites are also different72. This schematic is reproduced with permission from the publisher.

Immune factors

Periodontal crevices and pockets are filled with gingival crevicular fluid. The latter is rich in immune cells. Under the stimulus of a biofilm, neutrophils40, and macrophages41 are recruited to the pocket site and activated. Neutrophil extracellular traps (NETs), secreted by neutrophils, play a dual role in both protecting the host from infections and facilitating the mineralization of dental calculus. These NETs are capable of capturing pathogens, thereby limiting infection42. There is substantial evidence suggesting that NETs are instrumental in the formation of gallstones, salivary stones, and monosodium urate crystals43–45. A recent study revealed that NETs-DNA acts as nucleation sites for pathological mineralization of dental calculus. The study demonstrated that bacteria within the mature biofilms secrete histone-like proteins that alter the chiral structure of NETs-DNA from the B-form to the Z-form. This transformation reduces the susceptibility of NETs to degradation by deoxyribonuclease I, thereby enhancing their ability to induce mineralization46 (Fig. 5). Bacteria and mineralized crystallites further recruit and polarize macrophages into classically-activated subtypes47. The activated macrophages release exosome-like calcifying extracellular vesicles. These vesicles are rich in calcium ions and are capable of mineralization. During the formation of calculus, neutrophils act more promptly than macrophages48. Hence, it is important to reduce the contribution of neutrophils to mineralization. Targeted inhibition of extracellular nuclease released by bacteria may enhance the efficiency of neutrophils and delay the mineralization of bacterial biofilms.

Fig. 5. Formation of dental calculus in the presence of NETs.

Fig. 5

Open in a new tab

a Bacterial biofilms trigger the transformation of NET-DNA into DNase-I-resistant NET-Z-DNA. b NET-DNA plays a role in regulating ectopic mineralization in vitro. c The mineralization mechanism of dental calculus involving NETs46. a, b, and c are reproduced with permission from the publisher.

Host factors

Lifestyles have significant effects on calcium phosphate saturation and bacterial colonization. Tobacco smoking induces higher salivary calcium contents which increase the formation of calculus49–51. A carbohydrate-dominated diet may induce dental calculus by promoting bacterial colonization on the plaque53. Sucrose is the most widely consumed dietary carbohydrate. This sugar modifies the local microenvironment, and is closely associated with increased dysbiosis in oral biofilms52. Replacing refined carbohydrates with foods high in fat and vitamin D could lessen bacterial adhesion to teeth53. However, it is necessary to ascertain whether individuals aiming to mitigate dental calculus find such dietary substitutions acceptable.

Novel prevention and treatment strategies for dental calculus

Conventional methods of dental calculus prevention and treatment are brushing, scaling, and root planning (SRP). Improving oral hygiene by brushing or using chlorhexidine mouth rinses is the most economical and convenient way to prevent the development of calculus54. The use of SRP polishes the tooth surface to prevent the re-deposition of biofilms and dental calculi55. Given the main pathogenic factors of periodontitis are dental calculus and plaque that are attached to the root surface, this oral disease may be treated by subgingival scaling. This treatment reduces the depth of periodontal pockets and renders the root surface smooth. The condition that is favorable to facilitate the reattachment of the gingiva to the root surface is created56. These changes reduce the chance for bacteria to attach. Apart from physical removal techniques, chemical agents such as pyrophosphates play a crucial role in dental calculus management. Pyrophosphates disrupt bacterial growth by hindering the biosynthesis of the bacterial cell wall, which obstructs lipid transport essential for cell wall integrity55. These compounds also lower calcium and phosphorus concentrations in the periodontal microenvironment. Consequently, pyrophosphates contribute to reducing the essential components required for bacterial mineralization57. This helps to prevent dental calculus formation.

Innovative treatment modalities for dental calculus have emerged in recent years. These include laser technology, new kinds of toothpaste, and natural plant-derived compounds58,59. In addition, vaccines and nanotechnology offer unique perspectives for the control of dental calculus.

Physical intervention is a common approach to preventing and treating dental calculus. Ultrasound relies on cavitation and acoustic microstreaming to achieve cleaning60. Shockwaves generated by lasers alter biofilm permeability to enable easier elimination of pathogenic bacteria61. Calculus removal with lasers leaves no residual calculi, which is better when compared with conventional manual instruments62. However, the use of erbium-doped yttrium/aluminum/garnet laser and erbium-chromium-doped yttrium/scandium/gallium/garnet laser results in rougher root surfaces56. A combination of SRP and erbium laser is the solution to solve the problem. It removes residual debris from the root surface with little or no adverse thermal damage on the root surface63. Thermal damage, especially increased temperature within the periodontium, is considered a potential hazard to the dental pulp and periodontal tissues64. Thus, the advantage of laser technology for calculus removal is relatively limited due to the risk of thermal damage59. The effectiveness of the erbium laser and SRP in non-surgical periodontal treatment needs further evaluation.

Damage to patients’ enamel surfaces with manual and ultrasonic scalers has been a problem that plagued clinicians. To address this issue, scientists developed a novel actuator-driven pulsed water jet (ADPJ) system65. The system is capable of selectively removing materials based on their hardness. Because of the different hardness of teeth and dental calculus, the ADPJ system removes dental calculus with appropriate jet pressure without damaging the enamel surface of the tooth66. The ADPJ system was shown to significantly reduce the amount of dental calculus, and the removal rate was dependent on the applied voltage. No enamel damage was observed on the tooth surface after using the ADPJ system when compared to conventional scalers.

Aragonite (a calcium carbonate mineral phase) can be extracted from animals such as cuttlefish. It is an abrasive with a hardness that facilitates the removal of dental calculus67. Scientists tested the effectiveness of aragonite toothpaste derived from squid to remove dental calculus53. The aragonite toothpaste had a good effect in removing calculus, preventing calculus formation, and improving gingival health. The aragonite toothpaste dud bit causes any enamel damage53.

Vaccines have been anticipated to improve the prevention and treatment of periodontal disease. However, the immunopathological complexity of periodontal disease complicates the development of periodontal vaccines57. Studies suggest that successful periodontal vaccines may require mucosal delivery and polyvalent approaches. This strategy requires clinical trials for validation of the treatment outcomes57.

Other scientists utilized nanoparticles and biological agents to prevent the formation of bacterial biofilms. Metal and metal oxide nanoparticles have broad application prospects due to their small size, large specific surface area, and antibacterial properties68. The incorporation of silver and gold nanoparticles in toothbrushes enhances the mechanical control of dental plaque69. Platinum nanoparticles have many outstanding features. They provide powerful mechanical control and have the potential to degrade proteins and periodontal disease-associated inflammatory factors, such as lipopolysaccharides70. The specific mechanism of nanoparticles on bacteria is shown in Fig. 6.

Fig. 6. Mechanisms of nanoparticle-mediated antimicrobial and anti-biofilm activities against oral bacteria.

Fig. 6

Open in a new tab

a The inhibition of glucosyl transferase by nanoparticles results in reduced exopolysaccharide production and biofilm formation. b Nanoparticle-mediated biochemical changes occur at the cellular level. c The changes take place in the membranes of individual cells72. a, b, and c are reproduced with permission from the publisher.

Factors such as the size of the nanoparticles can also affect the efficacy of calculus removal. Other novel methods for preventing calculus formation are in their infancy of development (Fig. 7).

Fig. 7. Nanoparticle-mediated antimicrobial and anti-biofilm activities against oral bacteria.

Fig. 7

Open in a new tab

a Size and shape, surface, and interior properties of nanoparticles are important for their use in biofilm-infection control73. b Effect of antibiotics on biofilms. Other strategies employed for the treatment of biofilms include the use of antimicrobial peptides (AMP), bio-surfactants (rhamnolipid), phage particles, cheat cells, and different EPS-disrupting enzymes74. a and b are reproduced with permission from the publisher.

Active patient participation and maintenance of good oral hygiene are essential to prevent plaque and biofilm formation. The development of mouthwash or toothpaste may be a promising avenue to facilitate the prevention of calculus formation. These products exhibit low toxicity, high biosafety, and exceptional efficacy. By continuously exploring novel treatment modalities, the incidence of dental calculus will be greatly reduced. This also reduces the potential harm of dental calculus on systemic diseases.

Outlook

Periodontal diseases caused by dental calculus affect both oral and systemic health. The present review systematically describes the mechanisms of calculus formation in the human oral environment. Considerations need to be given to both bacterial and environmental factors that cause calculus deposition on tooth surfaces. The mechanisms of plaque biofilm formation as well as the alteration of bacterial types during the formation of biofilm and calculus are also highlighted. In addition, the influence of the inflammatory state of the body and the physicochemical state of the saliva on the formation of dental calculus has also been demonstrated. To alleviate clinical problems, new treatment methods for calculus removal have emerged in recent years. However, the interconnection between dental calculus formation and other systemic diseases is not completely understood.

In the future, healthcare workers need to objectively address multiple factors such as age, gender, race, and religious belief. Systematic classification of patients as well as the condition of diseases will be used to design individualized treatment. At the same time, doctors need to raise awareness of the importance of oral hygiene and the early diagnosis of gingival and periodontal problems. To achieve this goal, preventive and curative oral health policies adapted to patients’ diverse living environments need to be planned and implemented, with resources, goals, and priorities identified.

Acknowledgements

This study was funded by the National Clinical Research Center for Oral Diseases (Grant no. LCA202004), the National Natural Science Foundation of China (82325012) and the Shaanxi Key Scientific and Technological Innovation Team (2020TD-033).

Author contributions

Y.W. contributed to the conception, design, drafted, and critically revised the manuscript. G.D. contributed to the conception, design, drafted, and critically revised the manuscript. Z.R. contributed to the conception, design, drafted, and critically revised the manuscript. M.W. contributed to the conception and critically revised the manuscript. C.W. contributed to the conception and critically revised the manuscript. H.L. critically revised the manuscript. T.Z. critically revised the manuscript. F.R.T. critically revised the manuscript. L.N. critically revised the manuscript. All authors read and approved the final manuscript.

Data availability

Data sharing does not apply to this article as no datasets were generated or analyzed during the current study.

Competing interests

The authors declare no competing interests.

Footnotes

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

These authors contributed equally: Yu Wei, Gao-peng Dang, Zhao-yang Ren.

References

  • 1.Fons-Badal C, et al. Analysis of predisposing factors for rapid dental calculus formation. J. Clin. Med. 2020;9:858. doi: 10.3390/jcm9030858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Ramseier CA, et al. Natural history of periodontitis: disease progression and tooth loss over 40 years. J. Clin. Periodontol. 2017;44:1182–1191. doi: 10.1111/jcpe.12782. [DOI] [PubMed] [Google Scholar]
  • 3.Velsko IM, et al. Microbial differences between dental plaque and historic dental calculus are related to oral biofilm maturation stage. Microbiome. 2019;7:156–162. doi: 10.1186/s40168-019-0717-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Envelope L, et al. Effect of salivary urea, pH and ureolytic microflora on dental calculus formation and its correlation with periodontal status. J. Oral. Biol. Craniofacial Res. 2023;13:8–12. doi: 10.1016/j.jobcr.2022.10.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Saraiya K, et al. Dental calculus—an evergrowing heap of periodontal pathogens. J. Integr. Health Sci. 2019;7:73. doi: 10.4103/JIHS.JIHS_21_19. [DOI] [Google Scholar]
  • 6.Hardy K, Buckley S, Copeland L. Pleistocene dental calculus: recovering information on paleolithic food items, medicines, paleoenvironment and microbes. Evol. Anthropol. 2018;27:234–246. doi: 10.1002/evan.21718. [DOI] [PubMed] [Google Scholar]
  • 7.Bravo-Lopez M, et al. Paleogenomic insights into the red complex bacteria Tannerella forsythia in pre-Hispanic and colonial individuals from Mexico. Philos. Trans. R. Soc. Lond. B Biol. 2020;375:20190580. doi: 10.1098/rstb.2019.0580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Lokmer A, et al. Response of the human gut and saliva microbiome to urbanization in Cameroon. Sci. Rep. 2020;10:2856. doi: 10.1038/s41598-020-59849-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Bîrluţiu RM, Bîrluţiu V, Cismasiu RS, Mihalache P, Mihalache M. Bacterial biofilm: a mini-review of an emerging life form of bacteria. Acta Med. Transilv. 2017;22:68–71. [Google Scholar]
  • 10.Barnier JP, et al. The minor pilin PilV provides a conserved adhesion site throughout the antigenically variable meningococcal type IV pilus. Proc. Natl Acad. Sci. USA. 2021;118:e2109364118. doi: 10.1073/pnas.2109364118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Vandana, Das S. Genetic regulation, biosynthesis and applications of extracellular polysaccharides of the biofilm matrix of bacteria. Carbohydr. Polym. 2022;291:119536. doi: 10.1016/j.carbpol.2022.119536. [DOI] [PubMed] [Google Scholar]
  • 12.Zeineldin M, Esmael A, Al-Hindi RR, Alharbi MG. Beyond the risk of biofilms: an up-and-coming battleground of bacterial life and potential antibiofilm agents. Life. 2023;13:503. doi: 10.3390/life13020503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Dragoš A, Kovács ÁT. The peculiar functions of the bacterial extracellular matrix. Trends Microbiol. 2017;25:257–266. doi: 10.1016/j.tim.2016.12.010. [DOI] [PubMed] [Google Scholar]
  • 14.Kolenbrander PE, Palmer RJJ, Periasamy S, Jakubovics NS. Oral multispecies biofilm development and the key role of cell-cell distance. Nat. Rev. Microbiol. 2010;8:471–480. doi: 10.1038/nrmicro2381. [DOI] [PubMed] [Google Scholar]
  • 15.Balaji VR, Niazi TM, Dhanasekaran M. An unusual presentation of dental calculus. J. Indian Soc. Periodontol. 2019;23:484–486. doi: 10.4103/jisp.jisp_680_18. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Bartold PM, Van Dyke TE. An appraisal of the role of specific bacteria in the initial pathogenesis of periodontitis. J. Clin. Periodontol. 2019;46:6–11. doi: 10.1111/jcpe.13046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Huang H, et al. Towards the biofilm characterization and regulation in biological wastewater treatment. Appl. Microbiol. Biotechnol. 2019;103:1115–1129. doi: 10.1007/s00253-018-9511-6. [DOI] [PubMed] [Google Scholar]
  • 18.Jakubovics NS, Goodman SD, Mashburn-Warren L, Stafford GP, Cieplik F. The dental plaque biofilm matrix. Periodontology 2000. 2021;86:32–56. doi: 10.1111/prd.12361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Chen X, Daliri EB, Tyagi A, Oh DH. Cariogenic biofilm: pathology-related phenotypes and targeted therapy. Microorganisms. 2021;9:1311. doi: 10.3390/microorganisms9061311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Wang R, Wang YG, Lei ZX, Hao LY, Jiang L. Glucosyltransferase-modulated Streptococcus mutans adhesion to different surfaces involved in biofilm formation by atomic force microscopy. Microbiol. Immunol. 2021;69:493–500. doi: 10.1111/1348-0421.13025. [DOI] [PubMed] [Google Scholar]
  • 21.Pakkulnan R, et al. Extracellular DNA facilitates bacterial adhesion during Burkholderia pseudomallei biofilm formation. PLoS One. 2019;14:e0213288. doi: 10.1371/journal.pone.0213288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Niu L. Z. et al. Extracellular DNA as potential contributors to pathological calcification. Interdiscip. Med. e20230061 (2024).
  • 23.Serrage HJ, Jepson MA, Rostami N. Understanding the matrix: the role of extracellular DNA in oral biofilms. Front. Oral. Health. 2021;2:640129. doi: 10.3389/froh.2021.640129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Condinho M, et al. The role of RNA regulators, quorum sensing and c-di-GMP in bacterial biofilm formation. FEBS Open Biol. 2023;13:975–991. doi: 10.1002/2211-5463.13389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Dhir Sangeeta. Biofilm and dental implant: the microbial link. J. Indian Soc. Periodontol. 2013;17:5–11. doi: 10.4103/0972-124X.107466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Belibasakis GN, Manoil D. Microbial community-driven etiopathogenesis of peri-implantitis. J. Dent. Res. 2021;1:21–28. doi: 10.1177/0022034520949851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Costa RC, et al. Extracellular biofilm matrix leads to microbial dysbiosis and reduces biofilm susceptibility to antimicrobials on titanium biomaterial: an in vitro and in situ study. Clin. Oral. Implants Res. 2020;12:1173–1186. doi: 10.1111/clr.13663. [DOI] [PubMed] [Google Scholar]
  • 28.Ramesh D, et al. Detoxification of titanium implant surfaces: evaluation of surface morphology and bone-forming cell compatibility. J. Bio Tribo Corros. 2017;3:50. doi: 10.1007/s40735-017-0111-2. [DOI] [Google Scholar]
  • 29.Oppenheimer-Shaanan Y, et al. Assembly of functional mineral scaffolds within microbial biofilm. npj Biofilms Microbiomes. 2016;2:15031. doi: 10.1038/npjbiofilms.2015.31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Akcalı A, Lang NP. Dental calculus: the calcified biofilm and its role in disease development. Periodontology 2000. 2018;76:109–115. doi: 10.1111/prd.12151. [DOI] [PubMed] [Google Scholar]
  • 31.Khongkhunthian S, et al. Comparisons between two biochemical markers in evaluating periodontal disease severity: a cross-sectional study. BMC Oral. Health. 2014;14:107. doi: 10.1186/1472-6831-14-107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Koppolu P, Sirisha S, Mishra A, Deshpande K. Alkaline phosphatase and acid phosphatase levels in saliva and serum of patients with healthy periodontium, gingivitis, and periodontitis before and after scaling with root planing: a clinico-biochemical study. Saudi J. Biol. Sci. 2021;28:380–385. doi: 10.1016/j.sjbs.2020.10.016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Groeger S, Meyle J. Oral mucosal epithelial cells. Front. Immunol. 2018;10:208. doi: 10.3389/fimmu.2019.00208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Sun H, Li P, Kong Q, Deng F, Yu X. Zoledronic acid affects the process of Porphyromonas gingivalis infecting oral mucosal epithelial barrier: an in-vivo and in-vitro study. Biosearch Technol. 2023;13:1104826. doi: 10.3389/fcimb.2023.1104826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Prasad UV, et al. Phosphorylation controls the functioning of Staphylococcus aureus isocitrate dehydrogenase–favours biofilm formation. J. Enzym. Inhib. Med. Chem. 2015;30:655–661. doi: 10.3109/14756366.2014.959945. [DOI] [PubMed] [Google Scholar]
  • 36.Tianming Du, et al. Apatite minerals derived from collagen phosphorylation modification induce the hierarchical intrafibrillar mineralization of collagen fibers. J. Biomed. Mater. Res. 2019;107:2403–2413. doi: 10.1002/jbm.a.36747. [DOI] [PubMed] [Google Scholar]
  • 37.Tasha M, et al. Commensal and pathogenic members of the dental calculus microbiome of Badia pozzeveri individuals from the 11th to 19th centuries. Genes. 2019;10:299. doi: 10.3390/genes10040299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Deeksha J, et al. Influence of salivary PH and urea level on calculus formation—a clinico—biochemical study. RGUHS J. Dent. Sci. 2021;13:2–6. doi: 10.26715/rjds.13_1_2. [DOI] [Google Scholar]
  • 39.Cornejo Ulloa P, van der Veen MH, Krom BP. Review: modulation of the oral microbiome by the host to promote ecological balance. Odontology. 2019;107:437–448. doi: 10.1007/s10266-019-00413-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Uriarte SM, Edmisson JS, Jimenez-Flores E. Human neutrophils and oral microbiota: a constant tug-of-war between a harmonious and a discordant coexistence. Immunol. Rev. 2016;273:282–298. doi: 10.1111/imr.12451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J. Clin. Investig. 2012;122:787–795. doi: 10.1172/JCI59643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Branzk N, et al. Neutrophils sense microbe size and selectively release neutrophil extracellular traps in response to large pathogens. Nat. Immunol. 2014;15:1017–1025. doi: 10.1038/ni.2987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Muñoz LE, et al. Neutrophil extracellular traps initiate gallstone formation. Immunity. 2019;51:443–450.e4. doi: 10.1016/j.immuni.2019.07.002. [DOI] [PubMed] [Google Scholar]
  • 44.Schapher M, et al. Neutrophil extracellular traps promote the development and growth of human salivary stones. Cells. 2020;9:2139. doi: 10.3390/cells9092139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Schauer C, et al. Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines. Nat. Med. 2014;20:511–517. doi: 10.1038/nm.3547. [DOI] [PubMed] [Google Scholar]
  • 46.Wan, M. C. et al. Bacteria-mediated resistance of neutrophil extracellular traps to enzymatic degradation drives the formation of dental calculi. Nat. Biomed. Eng. 1–14 (2024). [DOI] [PubMed]
  • 47.Thiriot JD, Martinez-Martinez YB, Endsley JJ, Torres AG. Hacking the host: exploitation of macrophage polarization by intracellular bacterial pathogens. Pathog. Dis. 2020;78:ftaa009. doi: 10.1093/femspd/ftaa009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Kang M, et al. Bone regeneration is mediated by macrophage extracellular vesicles. Bone. 2020;141:115627. doi: 10.1016/j.bone.2020.115627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Kambalyal P, Kambalyal P, Hungund S. Comparison of salivary calcium level in smokers and non-smokers with chronic periodontitis, aggressive periodontitis, and healthy controls. J. Int. Soc. Prev. Community Dent. 2015;5:68–73. doi: 10.4103/2231-0762.171595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Bergström J. Tobacco smoking and subgingival dental calculus. J. Clin. Periodontol. 2005;32:81–88. doi: 10.1111/j.1600-051X.2004.00638.x. [DOI] [PubMed] [Google Scholar]
  • 51.Lee H, et al. Dental Calculi of Siberian natives, Russian settlers, and Korean people of Joseon Dynasty period in the 16th to 19th century Eurasia continent. Biomed. Res. Int. 2022;2022:5765604. doi: 10.1155/2022/5765604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52.Souza JGS, et al. Effect of sucrose on biofilm formed in situ on titanium material. J. Periodontol. 2019;90:141–148. doi: 10.1002/JPER.18-0219. [DOI] [PubMed] [Google Scholar]
  • 53.Orriss IR, Arnett TR, Russell RG. Pyrophosphate: a key inhibitor of mineralisation. Curr. Opin. Pharmacol. 2019;28:57–68. doi: 10.1016/j.coph.2016.03.003. [DOI] [PubMed] [Google Scholar]
  • 54.James P, et al. Chlorhexidine mouthrinse as an adjunctive treatment for gingival health. Cochrane Database Syst. Rev. 2017;3:CD008676. doi: 10.1002/14651858.CD008676.pub2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55.Hancock S, Schofield G, Zinn C. Healthy food, healthy teeth: a formative study to assess knowledge of foods for oral health in children and adults. Nutrients. 2022;14:2984. doi: 10.3390/nu14142984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Cobb CM. Clinical significance of non-surgical periodontal therapy: an evidence-based perspective of scaling and root planing. J. Clin. Periodontol. 2002;29:6–16. doi: 10.1034/j.1600-051X.29.s2.4.x. [DOI] [PubMed] [Google Scholar]
  • 57.Nie X, et al. Caging pyrophosphate structure blocks the cell wall synthesis to kill bacteria without detectable resistance. Chem. Eng. J. 2022;450:138373. doi: 10.1016/j.cej.2022.138373. [DOI] [Google Scholar]
  • 58.Allende MK, Samplonius A. Dental anthropological report: exploring plant-based treatments through the analysis of dental calculus and sediment of dental caries in a woman from the Late Preceramic period Peru. Ann. Anat. 2021;240:151849. doi: 10.1016/j.aanat.2021.151849. [DOI] [PubMed] [Google Scholar]
  • 59.Schoenly JE, Seka W, Rechmann P. Pulsed laser ablation of dental calculus in the near ultraviolet. J. Biomed. Opt. 2014;19:028003. doi: 10.1117/1.JBO.19.2.028003. [DOI] [PubMed] [Google Scholar]
  • 60.Qi Y, et al. Effects of physical stimulation in the field of oral health. Scanning. 2021;2021:5517567. doi: 10.1155/2021/5517567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61.Burcu OO, et al. A comparison of Er:YAG laser with photon-initiated photoacoustic streaming, Nd:YAG laser, and conventional irrigation on the eradication of root dentinal tubule infection by Enterococcus faecalis biofilms: a scanning electron microscopy study. Scanning. 2017;2017:6215482. doi: 10.1155/2017/6215482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 62.Yaghini J, Naghsh N, Attaei E, Birang R, Birang E. Root surface roughness after scaling and root planing with Er:YAG laser compared to hand and ultrasonic instruments by profilometry. J. Dent. 2015;12:899–905. [PMC free article] [PubMed] [Google Scholar]
  • 63.Kim SY, Kang MK, Kang SM, Kim HE. Effects of ultrasonic instrumentation on enamel surfaces with various defects. Int. J. Dent. Hyg. 2018;16:219–224. doi: 10.1111/idh.12339. [DOI] [PubMed] [Google Scholar]
  • 64.Kwon SJ, et al. Thermal irritation of teeth during dental treatment procedures. Restor. Dent. Endod. 2013;38:105–112. doi: 10.5395/rde.2013.38.3.105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 65.Sato Y, et al. The effectiveness of an actuator-driven pulsed water jet for the removal of artificial dental calculus: a preliminary study. BMC Oral. Health. 2020;20:205. doi: 10.1186/s12903-020-01190-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 66.Leszczyńska A, Buczko P, Buczko W, Pietruska M. Periodontal pharmacotherapy-an updated review. Adv. Med. Sci. 2011;56:123–131. doi: 10.2478/v10039-011-0044-9. [DOI] [PubMed] [Google Scholar]
  • 67.Čadež V, et al. Formation and morphogenesis of a cuttlebone’s aragonite biomineral structures for the common cuttlefish (Sepia officinalis) on the nanoscale: revisited. J. Colloid Interface Sci. 2017;508:95–104. doi: 10.1016/j.jcis.2017.08.028. [DOI] [PubMed] [Google Scholar]
  • 68.Pushpalatha C, et al. Zinc oxide nanoparticles: a review on its applications in dentistry. Front. Bioeng. Biotechnol. 2022;10:917990. doi: 10.3389/fbioe.2022.917990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 69.Qian YZ, et al. Triple PLGA/PCL scaffold modification including silver impregnation, collagen coating, and electrospinning significantly improve biocompatibility, antimicrobial, and osteogenic properties for orofacial tissue regeneration. ACS Appl. Mater. Interfaces. 2019;11:37381–37396. doi: 10.1021/acsami.9b07053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 70.Hiroo, et al. Organic resolution function and effects of platinum nanoparticles on bacteria and organic matter. PloS One. 2019;14:e0222634. doi: 10.1371/journal.pone.0222634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 71.Jakubovics NS. Intermicrobial interactions as a driver for community composition and stratification of oral biofilms. J. Mol. Biol. 2015;427:3662–3675. doi: 10.1016/j.jmb.2015.09.022. [DOI] [PubMed] [Google Scholar]
  • 72.Khan ST, Al-Khedhairy AA, Musarrat J. ZnO and TiO2 nanoparticles as novel antimicrobial agents for oral hygiene: a review. J. Nanopart. Res. 2015;256:276. doi: 10.1007/s11051-015-3074-6. [DOI] [Google Scholar]
  • 73.Liu Y, et al. Nanotechnology-based antimicrobials and delivery systems for biofilm-infection control. Chem. Soc. Rev. 2019;48:428–446. doi: 10.1039/C7CS00807D. [DOI] [PubMed] [Google Scholar]
  • 74.Saxena P, et al. Biofilms: architecture, resistance, quorum sensing and control mechanisms. Indian J. Microbiol. 2019;59:3–12. doi: 10.1007/s12088-018-0757-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 75.Fan W, et al. Epidemiology and associated factors of gingivitis in adolescents in Guangdong Province, Southern China: a cross-sectional study. BMC Oral. Health. 2021;21:311. doi: 10.1186/s12903-021-01666-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 76.Liu X, et al. The prevalence of gingivitis and related risk factors in schoolchildren aged 6-12 years old. BMC Oral. Health. 2022;22:623. doi: 10.1186/s12903-022-02670-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 77.Mae M, et al. The role of cytokines produced via the NLRP3 inflammasome in mouse macrophages stimulated with dental calculus in osteoclastogenesis. Int. J. Mol. Sci. 2021;22:12434. doi: 10.3390/ijms222212434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 78.He XF, et al. Evaluation of copper levels in dental calculus of OSF patients with chewing dried areca-nut quids in Hunan Province of mainland China. Biol. Trace Elem. Res. 2023;201:677–682. doi: 10.1007/s12011-022-03210-w. [DOI] [PubMed] [Google Scholar]
  • 79.Zhang B, et al. Evaluation of cadmium levels in dental calculus of male oral SCC patients with Betel-Quid Chewing in Hunan Province of China. Biol. Trace Elem. Res. 2019;191:348–353. doi: 10.1007/s12011-019-1639-4. [DOI] [PubMed] [Google Scholar]
  • 80.Wang X, et al. Porphyromonas gingivalis promotes colorectal carcinoma by activating the hematopoietic NLRP3 inflammasome. Cancer Res. 2021;81:2745–2759. doi: 10.1158/0008-5472.CAN-20-3827. [DOI] [PubMed] [Google Scholar]
  • 81.Jia X, Liu J, He Y, Huang X. Porphyromonas gingivalis secretion leads to dysplasia of normal esophageal epithelial cells via the Sonic hedgehog pathway. Front. Cell Infect. Microbiol. 2022;12:982636. doi: 10.3389/fcimb.2022.982636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 82.Kawasaki M, et al. Oral infectious bacteria in dental plaque and saliva as risk factors in patients with esophageal cancer. Cancer. 2021;127:512–519. doi: 10.1002/cncr.33316. [DOI] [PubMed] [Google Scholar]
  • 83.Kobayashi R, Ogawa Y, Hashizume-Takizawa T, Kurita-Ochiai T. Oral bacteria affect the gut microbiome and intestinal immunity. Pathog. Dis. 2020;78:ftaa024. doi: 10.1093/femspd/ftaa024. [DOI] [PubMed] [Google Scholar]
  • 84.Atarashi K, et al. Ectopic colonization of oral bacteria in the intestine drives T(H)1 cell induction and inflammation. Science. 2017;358:359–365. doi: 10.1126/science.aan4526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 85.Lei S, et al. Porphyromonas gingivalis bacteremia increases the permeability of the blood-brain barrier via the Mfsd2a/Caveolin-1 mediated transcytosis pathway. Int. J. Oral. Sci. 2023;15:3. doi: 10.1038/s41368-022-00215-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 86.Dominy SS, et al. Porphyromonas gingivalis in Alzheimer’s disease brains: evidence for disease causation and treatment with small-molecule inhibitors. Sci. Adv. 2019;5:eaau3333. doi: 10.1126/sciadv.aau3333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 87.Roy H, et al. Oral microbes and the formation of cerebral abscesses: a single-centre retrospective study. J. Dent. 2023;128:104366. doi: 10.1016/j.jdent.2022.104366. [DOI] [PubMed] [Google Scholar]
  • 88.Söder B, Meurman JH, Södre PÖ. Gingival inflammation associates with stroke—a role for oral health personnel in prevention: a database study. PLoS One. 2015;10:e0137142. doi: 10.1371/journal.pone.0137142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 89.Pussinen PJ, Alfthan G, Jousilahti P, Paju S, Tuomilehto J. Systemic exposure to Porphyromonas gingivalis predicts incident stroke. Atherosclerosis. 2007;193:222–228. doi: 10.1016/j.atherosclerosis.2006.06.027. [DOI] [PubMed] [Google Scholar]
  • 90.Tsai KZ, et al. Association between dental calculus and hypertension phenotypes in highly fit adults: CHIEF oral health study. Am. J. Hypertens. 2023;36:102–108. doi: 10.1093/ajh/hpac119. [DOI] [PubMed] [Google Scholar]
  • 91.Surma S, et al. Periodontitis, blood pressure, and the risk and control of arterial hypertension: epidemiological, clinical, and pathophysiological aspects-review of the literature and clinical trials. Curr. Hypertens. Rep. 2021;23:27. doi: 10.1007/s11906-021-01140-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 92.Söder B, Meurman JH, Söder P. Dental calculus links statistically to Angina pectoris: 26-year observational study. PLoS One. 2016;11:e0157797. doi: 10.1371/journal.pone.0157797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 93.Söder B, Meurman JH, Söder P. Dental calculus is associated with death from heart infarction. Biomed. Res. Int. 2014;2014:569675. doi: 10.1155/2014/569675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 94.Xie M, et al. BMAL1-downregulation aggravates Porphyromonas gingivalis-induced atherosclerosis by encouraging oxidative stress. Circ. Res. 2020;126:e15–e29. doi: 10.1161/CIRCRESAHA.119.315502. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

Data sharing does not apply to this article as no datasets were generated or analyzed during the current study.

Articles from NPJ Biofilms and Microbiomes are provided here courtesy of Nature Publishing Group

RESOURCES