Human Ocular Microbiome: Bacteria, Fungi and Viruses in the Human Eye

Description

This book provides an integrated review of the human ocular microbiome. It documents the discovery of ocular surface microbes by the conventional cultivable method and next generation sequencing technologies in both healthy and diseased (keratitis, uveitis, endophthalmitis, blepharitis, conjunctivitis etc.) eyes. The book further discusses the confounding factors that influence the microbiome, mycobiome and virome. The chapters cover niche-specificity with reference to skin, eyelid- margin, hands etc. It highlights the concept of core genera, dysbiosis and discriminating genera and covers the functional relevance of the dysbiotic microbiome, mycobiome and virome with respect to ocular diseases. The book includes topics on the relevance of molecular mechanisms, including quorum-sensing and mucin metabolism to ocular disorders, such as dry eye; and, microbiome-based therapies for treating of ocular disorders like vernal keratoconjunctivitis.  The book is essential for microbiologists studying the human eye, ophthalmologists treating eye infection and trauma. It also caters to students of medical microbiology and medicine. Foreword Preface The Beginning of Microbiome Research The Human Ocular Microbiome Contents of the Book Human Ocular Microbiome: Bacteria, Fungi and Viruses in the Human Eye Target Audience and Importance Acknowledgements Contents About the Author Abbreviations Chapter 1: Introduction: From the Gut Microbiome to the Ocular Surface Microbiome-Are They Associated? 1.1 Introduction 1.2 Gut Microbiome Functions 1.3 Core Gut Microbiome and `Dysbiosis´ 1.4 Gut Microbiome Is Associated with Disease 1.5 Gut Microbiome Dysbiosis and Human Health 1.5.1 Gut Microbiome Dysbiosis and Intestinal Diseases 1.5.2 Gut Microbiome Dysbiosis and Extra-intestinal Diseases 1.5.3 Gut Microbiome Dysbiosis and Ocular Diseases 1.5.3.1 Gut Microbiome Dysbiosis and Uveitis 1.5.3.2 Gut Microbiome Dysbiosis and Bacterial Keratitis (BK) 1.5.3.3 Gut Microbiome Dysbiosis and Fungal Keratitis (FK) 1.5.3.4 Gut Microbiome Dysbiosis and Ocular Mucosal Disease 1.5.3.5 Gut Microbiome Dysbiosis and Age-Related Macular Degeneration (AMD) 1.5.3.6 Gut Microbiome Dysbiosis and Diabetic Retinopathy 1.6 Modulation of the Gut Microbiome as a Therapy 1.7 What Needs to Be Done References Chapter 2: The Cultivable Bacteria of the Human Eye 2.1 Introduction 2.2 Commensal Microbes of the Ocular Surface 2.2.1 Bacterial Load on the Ocular Surface 2.2.2 Viable Community of Bacteria on the Ocular Surface 2.2.3 Impact of Age on the Ocular Surface Cultivable Microbiome 2.2.4 Impact of Sex on Ocular Surface Cultivable Microbiome 2.2.5 Impact of Geographical Location on Ocular Surface Cultivable Microbiome 2.3 Cultivable Microbiome of Eyelids and Tears 2.4 Ocular Microbiota Changes in the Diseased Eye 2.4.1 Keratitis 2.4.2 Conjunctivitis 2.4.3 Blepharitis 2.4.4 Scleritis 2.4.5 Orbital Cellulitis 2.4.6 Endophthalmitis 2.4.7 Uveitis 2.4.8 Retinitis 2.4.9 Post-fever Retinitis 2.4.10 Dacryocystitis 2.4.11 Meibomian Gland Dysfunction 2.4.12 Dry Eye Disease 2.4.13 Stevens-Johnson Syndrome 2.4.14 Sjogren´s Syndrome 2.4.15 Lax Eyelid Syndrome 2.4.16 Ocular Graft vs. Host Disease 2.4.17 Prior to Cataract Surgery 2.4.18 Diabetes 2.4.19 Contact Lens Use 2.4.20 Alcoholism 2.4.21 Chronic Limbal Stem Cell Deficiency 2.4.22 Behçet´s Disease 2.5 Treatment of Ocular Infectious Diseases 2.6 Conclusions References Chapter 3: The Microbiome of the Human Eye 3.1 Introduction 3.2 What Is a Microbiome? 3.3 The Microbiome Approach 3.3.1 Amplicon Sequencing 3.3.2 Metagenome Sequencing 3.3.3 Data Analysis 3.3.3.1 Amplicon Sequencing Reads 3.3.3.2 Metagenome Sequencing Reads 3.4 Culture-independent Methods to Identify Ocular Bacteria 3.4.1 The Ocular Surface Microbiome Using Amplicon Sequencing 3.4.2 Impact of Age on Ocular Surface Microbiome 3.4.3 Impact of Sex on Ocular Surface Microbiome 3.4.4 Impact of Geographical Location on Ocular Surface Cultivable Microbiome 3.5 Microbiome of Various Microhabitats of the Eye 3.6 The Effect of Sampling Depth on the Ocular Surface Microbiome 3.7 Ocular Microbiome Changes in the Diseased Eye 3.7.1 Ocular Microbiome of Individuals with Fungal Keratitis 3.7.2 Ocular Microbiome of Individuals with Bacterial Keratitis 3.7.3 Ocular Surface Microbiome of Individuals with Endophthalmitis 3.7.4 Ocular Surface Microbiome of Individuals with Conjunctivitis 3.7.5 Ocular Surface Microbiome of Individuals with Blepharitis 3.7.6 Ocular Surface Microbiome of Individuals with Retinitis 3.7.7 Ocular Surface Microbiome of Individuals with Meibomian Gland Dysfunction 3.7.8 Ocular Surface Microbiome of Individuals with Dry Eye Disease 3.7.9 Ocular Surface Microbiome of Individuals with Stevens-Johnson Syndrome 3.7.10 Ocular Surface Microbiome of Individuals with Sjogren´s Syndrome 3.7.11 Ocular Surface Microbiome of Individuals with Ocular Graft Versus Host Disease 3.7.12 Ocular Surface Microbiome of Individuals with Diabetes Mellitus 3.7.13 Ocular Surface Microbiome of Individuals with Contact Lens Use 3.7.14 Ocular Surface Microbiome of Individuals with Floppy Eyelid Syndrome 3.7.15 Ocular Surface Microbiome of Individuals with Trachoma 3.8 Conclusions References Chapter 4: Antimicrobial Resistance in Ocular Bacteria 4.1 Introduction 4.2 AMR in Ocular Bacteria 4.3 Factors Driving Antibiotic Resistance in Ocular Bacteria 4.4 What Is a Biofilm? 4.4.1 Adhesion 4.4.2 Microcolony Formation 4.4.3 Maturation 4.4.4 Dispersal 4.5 Biofilm Formation in Ocular Bacteria 4.6 AMR in Ocular Bacteria Is Associated with Biofilm Formation 4.7 Biofilm in the Diseased Eye 4.7.1 Biofilms in Endophthalmitis 4.7.1.1 Genes Associated with Biofilm Formation in Endophthalmitis 4.7.2 Biofilms in Keratitis 4.7.2.1 Factors Associated with Contact Lens Keratitis 4.7.3 Biofilms in Infectious Crystalline Keratopathy 4.8 Biofilms Associated with Ocular Implants 4.8.1 Biofilms Associated with Scleral Buckles 4.8.2 Biofilms Associated with Conjunctival Plug 4.8.3 Biofilms Associated with Lacrimal Intubation Devices and Orbital Implants 4.9 Quorum Sensing and Biofilm Formation in Ocular Bacteria 4.10 Candidate Genes Involved in Biofilm Formation in Ocular Bacteria 4.11 Comparison of Candidate Genes Involved in Biofilm Formation in Non-ocular Bacteria 4.12 Hacking Biofilms to Overcome AMR 4.12.1 Using Inhibitors of Quorum Sensing 4.12.2 CRISPRi Technology to Mitigate Quorum Sensing 4.12.3 Use of Biocides to Inhibit Adhesion 4.12.4 Use of Antimicrobial Compounds Including Peptides to Inhibit Adhesion 4.12.5 Modifying the Surface Structure of Ocular Devices to Inhibit Adhesion 4.12.6 d-amino Acids to Disperse Biofilms 4.12.7 Antibiotics to Disperse Biofilms 4.12.8 Enzymatic Degradation of the Biofilm Matrix to Disperse Biofilms 4.12.9 Use of Natural Products to Disperse Biofilms 4.12.10 Use of Signalling Molecules to Disperse Biofilms 4.12.11 Suppression of Enzymes and Inhibition of Biofilm Formation 4.12.12 Use of Photodynamic Therapy to Eliminate Biofilms 4.12.13 Phage Therapy to Inhibit Biofilm Formation 4.12.14 Other Strategies to Inhibit Biofilm Formation 4.12.15 Limitations in Hacking Strategies 4.13 The Gap Areas 4.14 Conclusions References Chapter 5: The Cultivable Fungi of the Human Eye 5.1 Introduction 5.2 Collection and Processing of Clinical Samples for Ocular Fungi 5.3 Direct Microscopy Examination of Clinical Samples 5.4 Molecular Methods in the Diagnosis of Ocular Infections 5.5 Confocal Microscopy in the Diagnosis of Ocular Infections 5.6 Experimental In Vivo Models for Ocular Infections 5.6.1 Mouse Models 5.6.2 Rabbit Models 5.6.3 Rat Models 5.6.4 Other Models 5.7 Cultivable Fungi of the Normal Human Eye 5.8 Cultivable Fungi of the Diseased Human Eye 5.8.1 Fungi Associated with Fungal Keratitis 5.8.2 Fungi Associated with Blepharitis 5.8.3 Fungi Associated with Conjunctivitis 5.8.4 Fungi Associated with Scleritis 5.8.5 Fungi Associated with Endophthalmitis 5.8.5.1 Exogenous Endophthalmitis 5.8.5.2 Endogenous Endophthalmitis 5.8.6 Fungi Associated with Retinitis 5.8.7 Fungi Associated with Chorioretinitis 5.8.8 Fungi Associated with Post-fever Retinitis (PFR) 5.8.9 Fungi Associated with Orbital cellulitis 5.8.10 Fungi Associated with Dry Eye Disease 5.8.11 Fungi Associated with Meibomian Gland Dysfunction 5.8.12 Fungi Associated with Uveitis 5.8.13 Fungi Associated with Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis 5.8.14 Fungi Associated with Sjögren´s Syndrome 5.8.15 Fungi Associated with Lax Eyelid Syndrome 5.8.16 Fungi Associated with Ocular Graft Vs Host Disease 5.9 Treatment of Ocular Infectious Diseases 5.10 The Gap Areas 5.11 Conclusions References Chapter 6: The Mycobiome of the Human Eye 6.1 Introduction 6.2 What Is a Mycobiome? 6.2.1 Amplicon Sequencing 6.2.2 Metagenome Sequencing 6.2.3 Data Analysis 6.2.3.1 Taxonomic Classification of Amplicon Sequencing Reads 6.2.3.2 Annotation of Metagenome Sequencing Reads 6.3 Mycobiome of the Normal Human Eye 6.3.1 Core Ocular Mycobiome 6.4 Mycobiome of the Diseased Human Eye: Next-Generation Sequencing Approach 6.4.1 Mycobiome Associated with Keratitis 6.4.2 Mycobiome Associated with Endophthalmitis 6.4.3 Mycobiome Associated with Post-Fever Retinitis (PFR) 6.5 Conclusions References Chapter 7: Viruses of the Human Eye 7.1 Introduction 7.2 Enumeration of Viruses 7.3 Challenges in Studying Human Virome 7.4 Viral Infections of the Eye 7.4.1 Viral Conjunctivitis 7.4.2 Viral Keratitis 7.4.2.1 Herpes Simplex Virus Keratitis 7.4.2.1.1 Epidemiological Features of HSV Keratitis 7.4.2.2 Congenital and Neonatal HSV Keratitis 7.4.2.3 Epidemics of HSV 7.4.2.4 Necrotizing Stromal Keratitis 7.4.2.5 Immune Stromal Keratitis or Interstitial Keratitis 7.4.2.6 Other Diseases Caused by HSV 7.4.2.6.1 Acute Retinal Necrosis 7.4.2.6.2 HSV Involvement in Various Syndromes 7.4.2.6.3 HSV in Blepharitis 7.4.3 Ocular Complications of AIDS 7.4.4 Ocular Diseases Caused by Varicella Zoster Virus 7.4.4.1 Retinal Involvement of HZV 7.4.5 Ocular Diseases Caused by Cytomegalovirus 7.4.6 Ocular Diseases Caused by Adenovirus 7.4.7 Ocular Diseases Caused by Molluscum Contagiosum Virus 7.4.8 Ocular Diseases Caused by Epstein-Barr Virus 7.4.9 Ocular Diseases Caused by Rubeola Virus 7.4.10 Conclusions References Chapter 8: Virome of the Healthy Human Eye 8.1 Introduction 8.2 Diversity of the Human Virome 8.3 Virome of Different Body Sites 8.3.1 Virome of Gastrointestinal Tract 8.3.2 Virome of Respiratory Tract 8.3.3 Virome of the Blood 8.3.4 Virome of the Skin 8.3.5 Virome of the Urogenital System 8.3.6 Virome of the Nervous System 8.3.7 Viromes of Other Tissues 8.3.8 The Human Megavirome 8.4 Development of the Human Virome 8.5 Virome of the Eye 8.5.1 Viruses on the Ocular Surface 8.5.2 Ocular Surface Virome of Children 8.5.3 Viruses in the Anophthalmic Conjunctiva 8.5.4 Virome of the Ocular Fluids 8.6 Factors that Shape the Ocular Virome 8.7 Conclusions References Chapter 9: Virome of the Diseased Human Eye 9.1 Introduction 9.2 Viral Communities in the Vitreous Fluid of Patients with Post-Fever Retinitis 9.2.1 Viral Abundance in PFR 9.2.2 Discriminating Families and Genera in PFR 9.2.3 Functional Attributes of Ocular Viruses 9.3 Conclusions References Chapter 10: Cellular and Molecular Basis of Ocular Diseases 10.1 Introduction 10.2 Innate Immunity on the Ocular Surface 10.2.1 Toll-Like Receptors in Innate and Adaptive Immune Responses at the Ocular Surface 10.3 Cell-Mediated Immunity on the Ocular Surface 10.4 Cellular and Molecular Basis of Bacterial Keratitis 10.4.1 Pseudomonas aeruginosa Keratitis 10.4.2 Streptococcus pneumoniae Keratitis 10.4.3 Serratia marcescens Keratitis 10.4.4 Staphylococcus aureus Keratitis 10.5 Cellular and Molecular Basis of Mycotic Keratitis 10.6 Cellular and Molecular Basis of Herpes Simplex Keratitis 10.7 Cellular and Molecular Basis of Acanthamoeba Keratitis 10.8 Cellular and Molecular Basis of Helminthic Keratitis 10.9 Cellular and Molecular Basis of Sterile Corneal Inflammation 10.10 Cellular and Molecular Basis of Uveitis 10.11 Cellular and Molecular Basis of Scleritis 10.12 Cellular and Molecular Basis of Conjunctivitis 10.13 Molecular Basis of Blepharitis 10.14 Cellular and Molecular Basis of Endophthalmitis 10.15 Cellular and Molecular Basis of Retinitis 10.16 Cellular and Molecular Basis of Dry Eye Disease 10.17 Cellular and Molecular Basis of Meibomian Gland Dysfunction 10.18 Conclusions References Chapter 11: What We Need to Know About the Human Ocular Microbiome 11.1 Introduction 11.2 Gaps in Ocular Surface Microbiome 11.3 Conclusions References