Periodontitis: Advances in Experimental Research (Advances in Experimental Medicine and Biology, 1373)

Periodontitis is a disease that affects more than half the adult population in the world. Treatment is often based on ancient recommendations consisting in mechanically removing material from damaged zones. However, novel therapeutic management strategies exist, from prevention to efficient treatment, and regeneration. The need of integrative approaches to circumvent this worldwide pledge can be achieved through: A better understanding of this complex disease by promoting scientific research and a comprehensive multidisciplinary approach, including epidemiology, microbiology, immunology, physiology, therapeutics, psychology, etc. A better outreach by promoting vulgarization and recommendations for health professionals. A better information of the empowered patients, leading them to consider prevention and to take part in their therapeutic course. The book “Periodontitis: Advances in Experimental Research” includes atimely collection of chapters covering all the fields of research about periodontitis, consisting in concise reviews by the best specialists themselves and with clinical perspectives for periodontitis. Recent technological advances have allowed to explore shadowed areas of periodontology. The book “Periodontitis: Advances in Experimental Research” is a unique occasion to set a milestone for a more integrated field of periodontitis, with a broad scientific, medical, and public audience thanks to dedicated sections in each chapter: Abstract and main body (scientific audience and expert clinicians) Highlights (scientific audience and clinicians) Impact for Practice (clinicians and economical/political decision makers) Summary for Patients (patients and economical/political decision makers) Preface List of Reviewers Contents 1: Advances in Experimental Research About Periodontitis: Lessons from the Past, Ideas for the Future 1.1 Past Achievements in Periodontal Research 1.1.1 New Concepts to Understand Periodontitis Pathophysiology 1.1.1.1 Periodontitis: A Microbial Disease 1.1.1.2 Bacterial Candidates: Isolation and Axenization 1.1.1.3 Periodontitis: A Biofilm-Based Disease 1.1.1.4 Periodontitis: A Microbiota Disease 1.1.1.5 Periodontitis: An Inflammatory Disease 1.1.2 New Technologies to Reach New Fields of Research 1.1.2.1 New Technical Possibilities Generate New Scientific Questions 1.1.2.2 New Methods Generate New Readouts 1.1.2.3 New Analyses Generate New Concepts 1.1.3 New Tools for Therapeutic Management 1.1.3.1 Biofilm Control 1.1.3.2 Modulation of Host Responses 1.1.3.3 Tissue Engineering 1.2 Considerations for the Future 1.2.1 Variability: More Than Just a Statistical Matter 1.2.1.1 Genetic Diversity in Patients 1.2.1.2 Diversity in Clinical Manifestations and in Micro-niches 1.2.1.3 Diversity in Research 1.2.1.4 Only One Periodontitis? 1.2.1.5 Perspectives for Clinical Management 1.2.2 Emerging and Expanding Fields 1.2.2.1 Peri-Implantitis and Peri-Implant Mucositis 1.2.2.2 The Immune System: More Than a Passive Sentinel 1.2.2.3 Molecular Biology Beyond Genomics and Taxonomics 1.2.2.4 New Models 1.2.3 Considering the Patient Beyond Their Mouth 1.2.3.1 Considering the Patient as a Whole 1.2.3.2 Considering the Patient’s Environment 1.2.3.3 Considering the Patient’s Mind 1.3 Concluding Remarks References Part I: Periodontal Microbiota 2: Microbiota in Periodontitis: Advances in the Omic Era 2.1 Introduction 2.1.1 Exploring Microbial Dysbiosis in Periodontal Infections Using Metagenomics and Metataxonomics 2.1.2 Microbial Classification for Prediction in Periodontal Dysbiosis 2.1.3 Understanding Microbial Dysbiosis and Host Responses Through Metatranscriptomics 2.2 Conclusion and Perspectives References 3: Aggregatibacter actinomycetemcomitans: From Basic to Advanced Research 3.1 Introduction 3.2 From Sero-Epidemiology to Microbial Susceptibility: Advances and Challenges 3.2.1 Taxonomy, Dissemination, and Organization 3.2.1.1 Taxonomy 3.2.1.2 Serotypes and Dissemination 3.2.1.3 Genotyping and Dissemination 3.2.1.4 A. actinomycetemcomitans: Commensal or Pathogen? 3.2.1.5 Oral Habitats, Organization and Interaction 3.2.2 Isolation and Identification 3.2.2.1 Samples Collection, Transport and Storage 3.2.2.2 Isolation 3.2.2.3 Identification 3.2.3 Virulence 3.2.3.1 Exotoxins 3.2.3.2 Cytolethal Distending Toxin 3.2.3.3 Endotoxins 3.2.3.4 Cytokine-Binding Molecules and Outer Membrane Vesicles 3.2.3.5 Impact of A. actinomycetemcomitans Infection on the Onset and Progression of Periodontal Disease 3.2.4 Issues in Antimicrobial Susceptibility 3.3 Advances in Therapy and Prevention 3.3.1 Microbiological Diagnostic: Is It Useful for Patients? 3.3.2 Therapeutic Targeting and Prevention Strategies 3.4 Conclusions References 4: Meta-analyses on the Periodontal Archaeome 4.1 Introduction 4.2 Results 4.2.1 Narrative Synthesis and the Quality Assessment of Individual Studies 4.2.2 The Taxonomy of the Archaea domain in Periodontal Sites 4.2.3 The Prevalence of Archaea in Periodontal Sites and Its Association with Periodontitis 4.2.4 Periodontal Treatment 4.2.5 Certainty of Evidence 4.3 Discussion 4.3.1 Archaea Detection in Periodontitis and Healthy Subgingival Sites 4.3.2 The Methanogens in Subgingival Biofilms 4.3.3 Putative Roles of Other Archaeal Groups in Periodontitis 4.3.3.1 Thermoplasmatales 4.3.3.2 Ammonia-Oxidizing Archaea 4.3.3.3 Halophilic Archaea 4.4 Conclusion and Perspectives 4.5 Methods 4.5.1 Studies Eligibility and Search Strategy 4.5.2 Quality Assessment of Individual Studies 4.5.3 Data Extraction and Qualitative Analysis 4.5.4 Meta-analyses and Certainty of Evidence References 5: Parasites in Periodontal Health and Disease: A Systematic Review and Meta-analysis 5.1 Introduction 5.2 Materials and Methods 5.2.1 Systematic Review 5.2.1.1 Pubmed Search Strategies and Retrieval 5.2.1.2 LILACS Search Strategies 5.2.1.3 Google Scholar 5.2.1.4 Selection of Publications 5.2.2 Meta-analysis 5.3 Results 5.3.1 Entamoeba gingivalis 5.3.2 Trichomonas tenax 5.4 Discussion 5.5 Author Contribution References 6: Fungi—A Component of the Oral Microbiome Involved in Periodontal Diseases 6.1 Fungal Species as a Part of the Microbiome of the Human Oral Cavity 6.2 Factors Predisposing to Fungal Infections in the Periodontium 6.3 Virulence Factors Involved in the Fungal Invasion of Periodontal Tissue 6.3.1 Adhesion and Biofilm Formation 6.3.2 Fungal Hydrolytic Enzymes and Toxins 6.3.3 Fungal—Host Interactions 6.4 The Mixed-Species Biofilm Formation in the Periodontitis: Mechanism of Mutual Interactions Between Fungi and Bacteria 6.4.1 Synergistic Interactions 6.4.2 Antagonistic Interactions 6.4.3 The Periodontal Cells in the Face of Mixed Infections 6.5 New Trends in Prevention and Treatment of Periodontitis 6.6 Conclusion and Perspectives References 7: Herpesviruses in Periodontitis: An Umbrella Review 7.1 Introduction 7.2 Materials and Methods 7.2.1 Review Questions 7.2.2 Outcome Measures 7.2.3 Selection Criteria 7.2.4 Literature Search 7.2.5 Data Extraction 7.2.6 Quality Assessment of Included Reviews Using the AMSTAR 2 Tool 7.3 Results 7.3.1 Literature Search Process 7.3.2 Characteristics of Included Studies 7.3.3 Summary of Meta-analysis 7.3.4 Methodological Quality 7.3.5 Principal Findings 7.3.5.1 The Detection of Herpesviruses in Marginal Periodontitis 7.3.5.2 The Detection of Herpesviruses in Apical Periodontitis of Endodontic Origin 7.4 Discussion 7.5 Conclusion and Perspectives References Part II: Periodontitis Pathophysiology 8: Recent Updates on Microbial Biofilms in Periodontitis: An Analysis of In Vitro Biofilm Models 8.1 Introduction 8.2 Biofilms 8.2.1 The History of a Lifestyle 8.2.2 What Are Biofilms and Why They Are so Important? 8.2.3 Biofilm Structure 8.2.4 Genetic Control of Biofilms 8.3 Periodontal Disease 8.4 Biofilm Models 8.4.1 Monospecies Biofilms 8.4.2 Multispecies Biofilms 8.4.3 Dynamic Oral Biofilm Models 8.5 Conclusion and Perspectives References 9: Update on B Cell Response in Periodontitis 9.1 Introduction 9.2 B Cells in Periodontitis 9.3 B Cells in Periodontal Cellular Network 9.4 Abnormal Interactions Between B and T Cells in Periodontitis 9.5 Plasma Cells and B Cells Are Predominant in Periodontal Lesions 9.5.1 B1 Cells in Periodontitis 9.6 Regulatory B Cells (Breg/B10) in Periodontitis 9.7 B Cells and Bone Resorption 9.8 Circulating B Cells and Periodontitis 9.9 Discussion References 10: Polarization Profiles of T Lymphocytes and Macrophages Responses in Periodontitis 10.1 Introduction 10.2 Macrophage Polarization Profiles in Periodontitis 10.3 Lymphocyte Subpopulations in Periodontitis 10.4 Immune Reprogramming Intervention Strategies 10.5 Conclusion and Perspectives References 11: Complementary Experimental Methods in Genetics Open Up New Avenues of Research to Elucidate the Pathogenesis of Periodontitis 11.1 Meaning of Genetic Studies for Periodontal Diseases 11.1.1 The Causative Factors of Periodontal Diseases Seem Elusive 11.1.2 The Genetic Architecture Determines the Susceptibility to Periodontal Diseases 11.2 Current Strategies to Identify the Genetic Basis of Periodontal Diseases 11.2.1 Candidate Gene Studies 11.2.2 Genomewide Association Studies 11.2.2.1 Statistical Limitations of GWAS 11.2.2.2 Alternative Study Concepts to Increase Testing Power of GWAS 11.2.2.3 SIGLEC5 11.2.2.4 Alpha Defensin Genes 11.2.2.5 ATP6V1C1 11.2.3 Gene x Environment Interactions 11.2.4 Mouse Models 11.2.5 Genetic Susceptibility Variants That Are Shared Between Different Diseases 11.2.6 Severe Early-Onset Diseases Are Tools to Identify Susceptibility Genes of Common Disease Phenotypes 11.3 Conclusion and Perspectives References Part III: Periodontitis-Associated Conditions 12: Update on the Bidirectional Link Between Diabetes and Periodontitis 12.1 Introduction 12.2 Method 12.3 Results 12.3.1 Effect of Diabetes on Periodontitis 12.3.2 Effect of Periodontitis on Diabetes 12.3.3 Effect of Periodontal Non-surgical Treatment on Diabetes 12.4 Discussion 12.5 Conclusion References 13: Periodontitis as a Risk Factor for Alzheimer’s Disease: The Experimental Journey So Far, with Hope of Therapy 13.1 Introduction 13.2 Periodontal Disease 13.3 Alzheimer’s Disease (AD) 13.4 The Emerging Association Between Periodontal Disease and Alzheimer’s Disease Provides a Rationale for Therapy 13.5 The Experimental Journey Towards Risk Factor Identification Between Periodontitis and Alzheimer’s Disease 13.6 Does Peripheral inflammation Induce Cerebral Inflammation? 13.6.1 Systemic LPS and Its Effect on Cognition 13.6.2 Systemic Aβ; Does It Contribute to the Intracerebral Burden of This Hallmark in AD? 13.6.3 Evidence Supporting the Inflammatory Burden of Periodontitis Affecting Memory 13.7 AD Brain Amyloid-β: A Potentially Shared Pool from Peripheral and Intracerebral Sources Towards a Blood Biomarker for Clinical AD 13.7.1 The Inflammatory Hypothesis – A Potentially Shared Pathway 13.8 Therapeutic Advances – Are We Nearly There Yet? 13.8.1 Periodontal Therapy 13.8.2 AD Treatment Based on Cholinesterase Inhibitors 13.8.2 AD Treatment Based on Cholinesterase Inhibitors 13.8.3 AD Treatment Based on Targeting Aβ 13.8.4 AD Treatment Based on Targeting Tau Protein 13.8.5 AD Treatment Based on Targeting Neuroinflammation 13.8.6 AD Treatment Based on Targeting P. gingivalis 13.8.7 AD Treatment Based on Managing Lifestyles 13.9 Conclusions References 14: Cardiovascular Diseases and Periodontitis 14.1 Introduction 14.2 Periodontitis 14.3 Cardiovascular Disease 14.3.1 Residual Inflammatory Risk 14.3.2 Increased Risk of CVD in Other Chronic Inflammatory Diseases 14.4 Observational Studies Linking CVD with Periodontitis 14.5 Periodontitis and Risk Factors for CVD 14.5.1 Hypertension 14.5.2 Diabetes 14.5.3 Other Risk Factors for CVD 14.6 Pathogenic Mechanisms Linking CVD with Periodontitis 14.6.1 Shared Clinical, Environmental, and Genetic risk Factors 14.6.2 Overlap of Inflammatory Pathways 14.6.3 Transfer of Bacteria from Periodontal Pockets to the Circulation with Subsequent Colonization of Atheromatous Plaques 14.7 Results from Experimental Models 14.8 Clinical Interventional Studies 14.9 Conclusion References Part IV: Therapeutic Management of Periodontitis 15: Update on the Role of Cytokines as Oral Biomarkers in the Diagnosis of Periodontitis 15.1 Epidemiology of Periodontitis, its Clinical Characteristics, and its Impact on Oral and Systemic Health 15.2 Limitations of Clinical Parameters for Diagnosing Periodontitis 15.3 The Importance of Biomarkers in Oral Fluids: Diagnostic Accuracy Studies 15.4 Host Response in Periodontitis: Role of Cytokines 15.5 Diagnostic Accuracy of Cytokines in the Gingival Crevicular Fluid: Single and Multiple Biomarkers 15.6 Cytokines in Saliva for the Diagnosis of Periodontitis: Single or Multiple Biomarkers 15.7 Cytokines for the Diagnosis of Periodontitis: Implications for Practice 15.8 Conclusions and Perspectives References 16: Non-surgical Periodontal Treatment: SRP and Innovative Therapeutic Approaches 16.1 Introduction 16.2 Prerequisites for Non-surgical Periodontal Therapy 16.2.1 Oral hygiene Instructions 16.2.2 Risk Factor Control 16.2.2.1 General Risk Factors 16.2.2.2 Aggravating Local Risk Factors 16.3 Mechanical Instrumentation 16.3.1 Hand Instrumentation 16.3.2 Sonic and Ultrasonic Instruments 16.3.2.1 Sonic Instruments 16.3.2.2 Ultrasonic Instruments 16.3.2.3 Hand vs. Power-Driven Instrumentation 16.3.3 Full Mouth vs. Quadrant-Wise Scaling 16.3.4 Limits 16.4 Adjunctive and Innovative Therapeutic Approaches 16.4.1 Air polishing 16.4.2 Photodynamic Therapy 16.4.3 Antiseptics 16.4.3.1 Chlorhexidine (CHX) 16.4.3.2 Povidone Iodine 16.4.3.3 Cetylpyridinium Chloride (CPC) 16.4.3.4 Hydrogen Peroxyde (H2O2) 16.4.3.5 Clinical Recommendations and New Approaches (Table 16.5) 16.4.3.6 Antibiotics 16.4.3.7 Local Antibiotics 16.4.3.8 Systemic Antibiotics 16.4.3.9 Timing 16.4.3.10 Dose and Duration (Table 16.5) 16.5 Innovative Approaches in Periodontal Non-surgical Therapy (Table 16.6) 16.5.1 Cold Atmospheric Plasma 16.5.2 Host Modulation Therapy (HMT) 16.5.3 Antimicrobial Peptides (AMPs) 16.6 Conclusion and Perspectives References 17: Update on the Roles of Oral Hygiene and Plaque Control on Periodontal Disease 17.1 Introduction 17.2 Methods 17.3 Results 17.3.1 Effect of Plaque control on Periodontal Features-Periodontitis Genesis 17.3.2 Effect of Oral Hygiene Devices on Periodontal Features 17.3.3 Effect of OH Before Periodontitis Non-surgical Treatment -Periodontitis Treatment 17.3.4 Effect of OH on Periodontitis Prevention and Maintenance of Healthy Periodontium 17.4 Discussion 17.5 Conclusion References 18: Multi-photonic Adjunctive Therapy for the Management of Periodontitis: Recent Advances and New Treatment Approach 18.1 Photonic Therapy in Periodontics: A Yet Unsolved Controversy 18.2 How Photonic Therapies Can Work in Periodontal Disease 18.3 Multi-photonic Therapy in Periodontal Disease: ‘United We Stand, Divided We Fall’ 18.4 Conclusion and Perspectives References 19: Probiotics During the Therapeutic Management of Periodontitis 19.1 Periodontitis and Adjunctive Therapies 19.2 Probiotics 19.3 Effect of Probiotics on Oral Bacteria. In Vitro Studies 19.4 Immunomodulatory Properties of Probiotics. In Vitro Studies 19.5 In Vivo Animal Studies 19.6 Clinical Evidence 19.7 Future Approaches References 20: Periodontal Cell Therapy: A Systematic Review and Meta-analysis 20.1 Introduction 20.2 Materials and Methods 20.2.1 Data Sources and Research Strategy 20.2.2 Inclusion Criteria 20.2.3 Outcomes 20.2.4 Study Selection, Data Extraction and Quality Assessment 20.2.5 Statistical Analysis 20.3 Results 20.3.1 Characteristics of Included Studies 20.3.2 Efficacy of Periodontal Regeneration in Animal Studies 20.3.2.1 Bone Regeneration 20.3.2.2 Cementum Regeneration 20.3.2.3 Periodontal Ligament Regeneration 20.3.3 Efficacy of Periodontal Regeneration in Human Studies 20.4 Discussion 20.4.1 Methodology 20.4.2 Animal and Defect Models 20.4.3 Cell Sources and Auto/Allogeneic Grafting Strategies 20.4.4 Cell Carriers 20.4.5 Periodontal MSC Therapy Outcomes 20.4.6 Periodontal Cell Therapy in Human Studies 20.5 Conclusion and Perspectives 20.6 Author Contribution Appendix References Index