Skin Microbiome Handbook

Nava Dayan Ph.D. Pharm D. is a research scientist who has specialized in skin product development for nearly 3 decades. She is the owner of Dr. Nava Dayan L.L.C, a skin science and research consultancy serving the pharmaceutical, cosmetic, and personal care industries; dermal and transdermal. The uniqueness of Dr. Dayan's approach is in its comprehensiveness since she covers biology, physics, efficacy, toxicology, formulations product development, and bio-availability. With her many years of experience in the skin care sector, she has produced more than 150 publication credits in numerous industry-respected journals and in four books. Her research focus is on feasibility in skin care, composition of R&D plans covering efficacy and toxicology; planning, execution and data interpretation into claims, formulations, delivery for improved efficacy and attenuated toxicity, drug-skin interaction, bio-markers, skin/age related sensitivities, inflammatory skin disorders, innate immunity and skin microbiome. This is her fifth book and her 2nd with the Wiley-Scrivener imprint.

• Preface xviiPart 1: Healthy Skin Microbiome and Oral-Skin Interactions 11 The Microbiome of Healthy Skin 3Samantha Samaras and Michael Hoptroff1.1 Introduction 31.1.1 Retrospective 31.1.2 Next Generation Sequencing 61.2 The Skin Microbiome in Health 71.2.1 Composition 71.2.2 Diversity 101.2.3 Uniqueness 131.3 Healthy Skin is the Foundation of a Balanced Skin Microbiome 141.3.1 Physical Aspects of Skin Impacting the Microbiome 141.3.2 Biochemical and Defensive Aspects of Skin Impacting the Microbiome 161.3.2.1 The Acid Mantle 161.3.2.2 Antimicrobial Lipids (AMLs) 161.3.2.3 Antimicrobial Peptides (AMPs) 171.3.3 Nutritional and Microenvironmental Aspects of Skin Impacting the Microbiome 181.3.3.1 Amino Acids 181.3.3.2 Sebaceous Lipids 191.3.3.3 Organic Acids and Other Materials 191.4 A Balanced Skin Microbiome Supports the Normal Functioning of Healthy Skin 201.4.1 Pathogen Exclusion 201.4.2 Contribution to Skin pH 201.4.3 Microbial Contribution to Skin Barrier Integrity 211.5 Conclusion 22Acknowledgments 23References 232 The Gut Microbiome-Skin Axis: Impact on Skin and Systemic Health 33David Drake2.1 Introduction 342.2 The Gut-Skin Microbiome Axis 352.3 The Gut-Skin Microbiome Axis: Principle Pathways 352.4 Dysbiosis of the Gut Microbiome and Skin Dyshomeostasis 372.4.1 Acne Vulgaris 382.4.2 Atopic Dermatitis 392.5 Summary and Future Directions 39References 403 The Skin and Oral Microbiome: An Examination of Overlap and Potential Interactions between Microbiome Communities 45Sandra Buerger3.1 Introduction 453.1.1 Focus of the Chapter 453.1.2 Definition of Skin Microbiome 473.1.3 Definition of Oral Microbiome 483.2 Characterization of the Microbiome 483.2.1 Variability and Stability of Skin and Oral Microbiome 483.2.2 Microbial Community 493.2.2.1 Permeant Mutualistic or Commensal Microbes 493.2.2.2 Non-Pathogenic Transient Microbes 503.2.2.3 Pathogenic Microbes 503.3 The Core Skin and Oral Microbiomes 513.3.1 Taxonomic Methodology 513.3.2 Subgroups of the Microbiome 523.3.2.1 Bacteriome 523.3.2.2 Mycobiome (and Other Eukaryotic Microbial Members) 523.3.2.3 Virome 533.4 Interactions Between Skin and Oral Microbiomes 543.4.1 Potential for Interactions 543.4.2 Quorum Sensing 543.4.3 Immune System Development 543.4.4 Future Directions 553.5 Conclusion 55Acknowledgments 56References 56Part 2: Skin Microbiome Observational Research 594 Skin Microbiome Alterations in Skin Diseases 61Travis Whitfill, Gilles R. Dubé and Julia Oh4.1 Introduction and Background 614.2 Interactions Between Microbes and Host 624.3 Summary of Known Associations Between Skin Dysbioses and Skin Diseases 644.3.1 The Role of S. Aureus in Skin Disease 644.3.2 Atopic Dermatitis 644.3.3 Acne Vulgaris 664.3.4 Psoriasis 674.4 Skin Dysbioses in Skin Health 684.5 Other Skin Conditions 684.6 Therapeutic Approaches to Dysbiosis-Associated Skin Diseases 694.6.1 Traditional Methods of Treating Dysbiosis-Associated Skin Diseases 694.6.1.1 Atopic Dermatitis 694.6.1.2 Acne Vulgaris 694.6.2 Emerging Therapeutic Approaches to Treating Dysbiosis-Associated Skin Diseases 704.7 Conclusion and Future Directions 71Acknowledgements 71References 715 The Axillary Microbiome and its Relationship with Underarm Odor 79Alexander Gordon James5.1 Introduction 805.2 Composition of the Axillary Microbiome 865.3 16-Androstene Steroids and Axillary Malodour 955.4 The Axillary Microbiome, VFAs and Malodour 965.5 The Axillary Microbiome, Thioalcohols and Malodour 1005.6 Perturbation of the Axillary Microbiome 1085.7 Human Genetics – Influence on Malodour and the Axillary Microbiome 1125.8 Conclusions and Future Perspectives 115Acknowledgements 122References 1226 Infant Skin Microbiome 131Georgios N. Stamatas6.1 Introduction 1316.2 Infant Skin Maturation 1326.3 Infant Immune System Maturation 1336.4 Infant Skin Microbiome Dynamics 1346.5 Mother-Infant Microbial Transmission 1376.6 Conclusion 138References 139Part 3: Skin Microbiome in Disequilibrium and Disease 1437 Microbiome of Compromised Skin 145Sara Farahmand7.1 Atopic Dermatitis 1467.2 Psoriasis 1487.2.1 Diversity 1497.2.2 Microbiome Composition 1517.3 Acne 1527.4 Rosacea 1537.5 Seborrheic Dermatitis and Dandruff 1557.6 Exposome, Skin Barrier, and Skin Microbiome 1577.6.1 Skin Irritation and Microbiome 1577.6.2 Diaper Dermatitis 1577.6.3 Occupational Hand Dermatitis 1587.6.4 Allergic Contact Dermatitis (ACD) and Skin Microbiome 1597.7 Conclusion 160References 1638 Human Cutaneous Ectoparasites: A Brief Overview and Potential Therapeutic Role for Demodex 171Stephen L. Strobel8.1 Introduction 1718.2 Chiggers (Trombiculidae) 1728.3 Bedbugs (Cimex lectularius and Hemipterus) 1738.4 Lice 1738.5 Scabies (Sarcoptes scabiei) 1748.6 Demodex 1758.7 The Association Between Demodex, Rosacea and Blepharitis 1768.8 Hypothesis 1778.9 Demodex Folliculorum as a Drug Delivery Agent for Early Skin Cancer 1778.10 Limitations 1798.11 Conclusion 1808.12 Future Considerations 181References 1829 Dysbiosis of the Skin Microbiome in Atopic Dermatitis 185Joyce Cheng and Tissa Hata9.1 Introduction 1859.2 The Healthy Skin Microbiome 1869.3 The Skin Microbiome in Atopic Dermatitis 1879.4 Microbiome-Targeted Treatment Strategies 1959.5 Conclusion 196References 19610 The Skin Microbiome of Inverse Psoriasis 203Jennifer Chung, Bruce E. Strober and George M. Weinstock10.1 Introduction 20410.2 Methods 20510.2.1 Subject Population 20510.2.2 Patient Diagnosis and Characteristics of Populations 20610.2.3 Specimen Collection 20610.2.4 Sample DNA Extraction and Sequencing 20710.2.5 Downstream Sequence Processing and Analysis 20710.3 Results 20810.3.1 Cohort Metadata 20810.3.2 Sequencing Information 20810.3.3 The Skin Microbiome of Intertriginous Lesion and Non-Lesional Sites on Inverse Psoriasis Subjects 20810.3.3.1 Psoriasis Lesional Status is Associated with Relative Abundance and Presence of Specific Species 20810.3.3.2 Psoriatic Lesions Trend to Decrease Taxonomic Diversity 21010.3.3.3 Psoriatic Lesions are Characterized by Greater Intragroup Variability 21210.3.4 Inverse Psoriasis vs. Plaque Psoriasis vs. Healthy (All Non-Lesion Sites) 21210.4 Conclusions & Future Plans 212Acknowledgements 213References 214Part 4: Skin’s Innate Immunity 21711 Effects of Endogenous Lipids on the Skin Microbiome 219Carol L. Fischer and Philip W. Wertz11.1 Introduction 21911.2 Sebaceous Lipids -- Source of Fatty Acids 22111.3 Stratum Corneum Lipids – Source of Long-Chain Bases 22311.4 Antimicrobial Activity of Fatty Acids 22611.5 Antimicrobial Activity of Long-Chain Bases 23011.6 Conclusion 231References 23112 Innate Immunity in Epidermis 237Miroslav Blumenberg12.1 Introduction 23712.2 Skin Acts as an Anatomical Physical and Chemical Barrier to Infectious Agents 23812.3 Epidermal Cells Recognize Conserved Features of Pathogens, as well as the Indicators of Tissue Damage 23912.4 Defensive Antimicrobial Proteins AMPs 24012.5 Cytokines, Specific Signals that Activate Inflammation and Further Cellular Protective Mechanisms 24212.6 Specialized White Blood Cells Identify and Remove Pathogens 24312.7 Complement System 24612.8 Innate Immune System Activates the Adaptive Immune System 24612.9 Antiviral Defenses 24712.10 Innate Immunity Memory? 24712.11 Cutaneous Microbiome: A Newly Surfaced Contributor to Innate Immunity 24812.12 Conclusion 25112.13 Future Perspectives 252References 254Part 5: Testing and Study Design 26113 Next Generation Sequencing Reveals the Skin Microbiome 263Niamh B O’Hara13.1 Introduction 26313.2 Current Approaches to Test the Microbiome 26513.3 The Genomics Revolution and Metagenomics 26613.4 Metagenomics and the Skin Microbiome 26713.5 Our Work at Biotia 26813.6 Challenges and Solutions in Metagenomics 26913.7 The Microbial World is our Oyster 27213.8 The Future of Metagenomics 273Acknowledgements 273References 27414 Three-Dimensional Human Skin Models to Investigate Skin Innate and Immune-Mediated Responses to Microorganisms 277Marisa Meloni and Silvia Balzaretti14.1 State-of-the-Art and Limits of Skin Microbiota Research 27714.2 Mechanism-Based Approach to Study Host Response to Associated Microbiome: 3D Skin Models 27914.3 Understanding S. epidermidis and S. aureus Behavior and Role on Reconstructed Human Epidermis (RHE) 28114.4 Immuno-Competent Atopic Dermatitis Model 28414.5 Conclusion and Future Perspectives 286References 28615 Cutibacterium acnes (formerly Propionibacterium acnes) In-Vivo Reduction Assay: A Pre-Clinical Pharmacodynamic Assay for Evaluating Antimicrobial/Antibiotic Agents in Development for Acne Treatment 289Stuart R. Lessin and James J. Leyden15.1 Acne Pathogenesis and the Role of Cutibacterium acnes  (formerly Propionibacterium acnes) 29015.1.1 Introduction 29015.1.2 Pathogenesis 29015.1.3 The Role of C. acnes and its Microbiome 29015.2 Current Therapies and Regulatory Approval 29315.3 In-Vivo C. acnes Reduction Assay 29415.4 Correlations of C. acnes Reduction and Clinical Efficacy 29715.5 Conclusion 300References 300Part 6: Regulatory and Legal Aspects for Skin Microbiome Related Products 30316 Intellectual Property Tools for Protecting, Developing and Growing a Skin Microbiome Brand 305Jeffrey K. Mills16.1 Introduction 30516.2 The Tools of Intellectual Property 30616.2.1 Patents 30616.2.2 Trademarks 30716.2.3 Copyrights 30816.2.4 Trade Secrets/Know-How 30916.3 Building an Intellectual Property Portfolio for a Skin Microbiome Brand 31016.3.1 Patents to Define “The Fence” 31016.3.1.1 Patents “As Sticks” – Enforcement of Infringement 31316.3.1.2 Patents “As Financial Boosts” – Licensing and Other Agreements 31416.3.2 Trademarks to Establish Brand Recognition 31516.3.3 Copyrights to Maintain Information 31716.3.4 Trade Secrets/Know-How to Keep A Competitive Edge 31816.4 Conclusion 32017 Regulatory Aspects of Probiotics and Other Microbial Products Intended for Skin Care: The European Approach 321Atte von Wright17.1 Introduction 32217.2 The Governing Bodies and Decision-Making in the EU 32217.2.1 The Legal Instruments of the EU 32317.3 Probiotic Foods and the European Regulations 32417.3.1 The Safety Assessment of Microorganisms by EFSA, The QPS Concept 32417.3.1.1 The Safety Assessment of Non-QPS Microorganisms 32717.3.2 The Case of GMMs 32817.3.3 Microorganisms as Novel Foods 32917.3.4 Human Probiotics and Functional Claims 32917.4 Probiotic Skin Care Products as Pharmaceuticals 33017.4.1 The Authorization Procedure for Medicines 33117.4.1.1 The Centralized Procedure 33217.4.1.2 National Authorizations and Authorizations by Mutual Recognition or Decentralized Procedures 33317.4.2 Bacteria as Medical Devices 33417.5 Probiotics in Cosmetics 33517.5.1 Safety Aspects 33617.5.1.1 Microorganisms on Skin – Problems of Safety Evaluation 33717.5.2 The Permissible Cosmetic Claims in the EU 33817.6 Conclusions 338References 340Legal Acts and Guidance Documents 34018 Regulation of Probiotic and Other Live Biologic Products: The United States Approach 343Ronie M. Schmelz18.1 Introduction 34318.1.1 U.S. Legislative Landscape 34418.1.2 Foods 34518.1.2.1 Permissible Food Claims 35018.1.2.2 Additional Regulatory Considerations 35418.1.3 Dietary Supplements 35518.1.3.1 Permissible Dietary Supplement Claims 35718.1.3.2 Additional Regulatory Considerations 35918.1.4 Drugs 36018.1.4.1 Drug Approval Process 36118.1.4.2 Additional Regulatory Considerations 36418.1.5 Cosmetics 36418.2 Summary of Product Categorization and Regulatory Requirements 36518.3 Resources 36918.4 Endnotes 36919 A Future Research Perspective Is There a Connection Between Sun Exposure, Microbiome and Skin Cancer? 377Nava Dayan19.1 Introduction 37819.2 Ultraviolet Light (UV) – The Skin Microbiome and Cancer 37819.3 Conclusion 386Acknowledgment 386References 387Glossary 389Index 399