Role of Microorganisms in Pathogenesis and Management of Autoimmune Diseases: Volume II: Kidney, Central Nervous System, Eye, Blood, Blood Vessels & Bowel

Foreword
Preface
Contents
Editors and Contributors
Part I: Human Microbiome, Vaccines and Autoimmunity
	1: Autoimmunity and Microbiome
		1.1 Introduction
		1.2 Microbiota and Immune System Interaction
		1.3 Microbiota and Autoimmunity
		1.4 Mechanisms of Autoimmunity Induced by Microbiota
			1.4.1 Microbiome Translocation
			1.4.2 Molecular Mimicry
			1.4.3 Dysregulated Immune Response
				1.4.3.1 Secretion of Immunosuppressive Cytokines
				1.4.3.2 Cytolysis
				1.4.3.3 Metabolic Disruption
				1.4.3.4 Suppression of DC Maturation and Function
		1.5 Conclusion
		References
	2: The Vaccines Induced Autoimmunity
		2.1 Introduction
		2.2 Vaccines
			2.2.1 How Do Vaccines Work?
			2.2.2 Types of Vaccines
				2.2.2.1 Live Attenuated Vaccine
				2.2.2.2 Inactivated Vaccine
				2.2.2.3 Subunit and Conjugate Vaccines
				2.2.2.4 Virus Like Particles
				2.2.2.5 Viral Vector Vaccines
				2.2.2.6 Nucleic Acid Vaccine
				2.2.2.7 Toxoids
		2.3 Autoimmune Diseases
			2.3.1 Types of Autoimmune Disease
				2.3.1.1 Systemic Autoimmune Disease
					2.3.1.1.1 Rheumatoid Arthritis (RA)
					2.3.1.1.2 Systemic Lupus Erythematosus
					2.3.1.1.3 Multiple Sclerosis
					2.3.1.1.4 Ankylosing Spondylitis
					2.3.1.1.5 Scleroderma
					2.3.1.1.6 Sjogren´s Syndrome
				2.3.1.2 Organ-Specific Autoimmune Diseases
					2.3.1.2.1 Type-1 Diabetes Mellitus (T1DM)
					2.3.1.2.2 Hashimoto´s Thyroiditis
					2.3.1.2.3 Vitiligo
					2.3.1.2.4 Graves´ Disease
					2.3.1.2.5 Autoimmune Anemia
					2.3.1.2.6 Goodpasture´s Syndrome
					2.3.1.2.7 Myasthenia Gravis
		2.4 Mechanism of Vaccine Triggered Autoimmunity
			2.4.1 Adjuvants
			2.4.2 Molecular Mimicry
			2.4.3 mRNA-Based Vaccines: a Trigger to Autoimmunity
			2.4.4 Other Mechanisms
		2.5 Vaccines Reported for Development of Autoimmunity
			2.5.1 Hepatitis B Vaccines
			2.5.2 Measles, Mumps, and Rubella (MMR) Vaccines
			2.5.3 Influenza Vaccine
			2.5.4 Human Papilloma Virus (HPV) Vaccine
			2.5.5 SARS-CoV-2 Vaccines
			2.5.6 Other Vaccines
		2.6 Conclusions
		References
	3: COVID-19 and Autoimmunity
		3.1 Introduction
		3.2 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
		3.3 Virus Infection and Autoimmunity
			3.3.1 SARS-CoV-2 Induced Autoimmunity
				3.3.1.1 Molecular Mimicry
				3.3.1.2 Bystander Activation
				3.3.1.3 Cytokine Storm
				3.3.1.4 Autoantibodies
				3.3.1.5 Innate Immune Mechanisms
				3.3.1.6 Genetic Susceptibility
		3.4 Similarities Between COVID-19 Manifestations and Autoimmunity
		3.5 Autoimmune Complications of COVID-19
			3.5.1 Guillain-Barre Syndrome
			3.5.2 Immune Thrombocytopenic Purpura
			3.5.3 Kawasaki Disease
			3.5.4 Autoimmune Thyroid Diseases
			3.5.5 Rheumatoid Arthritis
			3.5.6 Systemic Lupus Erythematosus
			3.5.7 Type 1 Diabetes
			3.5.8 Vitiligo
			3.5.9 Alopecia areata
			3.5.10 Cold Agglutinin Syndrome (CAS)
			3.5.11 Antiphospholipid Syndrome
		3.6 Autoimmune Disease: A Risk Factor for Severe COVID-19?
		3.7 Conclusions
		References
	4: The Protective Discourse Between Infections and Autoimmunity
		4.1 Introduction
		4.2 Autoimmune Diseases
		4.3 Proposed Mechanisms for Protective Effect of Infections on Autoimmune Diseases
			4.3.1 Antigenic Competition
			4.3.2 Innate Immune Mechanisms
			4.3.3 Infections Induced Immunoregulation
		4.4 Epidemiological Evidence for the Protective Role of Infections in Human Autoimmune Diseases
		4.5 Animal Model Studies for Exploring the Protective Effects of Infections on Autoimmune Diseases
			4.5.1 Type 1 Diabetes Mellitus
			4.5.2 Rheumatoid Arthritis
			4.5.3 Multiple Sclerosis
			4.5.4 Inflammatory Bowel Disease (IBD)
		4.6 Conclusions
		References
Part II: Microorganisms in Pathogenesis and Management of Autoimmune Kidney Diseases and Adrenal Insufficiency
	5: Microorganisms in Pathogenesis and Management of IgA Vasculitis and IgA Nephropathy
		5.1 Introduction
		5.2 Role of Microorganisms in the Pathogenesis of IgA Vasculitis
			5.2.1 Bacteria
			5.2.2 Viruses
				5.2.2.1 SARS-CoV-2
		5.3 Role of Gut Microbiota in IgA Vasculitis
		5.4 Role of Microorganisms in IgA Nephropathy
		5.5 Therapeutic Aspects of Gut Microbiota in IgA Nephropathy
			5.5.1 Modulation of Gut Microbiota
			5.5.2 Suppression of Excessive Mucosal Immune Responses
		5.6 Conclusions
		References
	6: Microorganisms in Pathogenesis and Management of Immune-Mediated Glomerulopathies
		6.1 Introduction
		6.2 Glomerulopathies
			6.2.1 Glomerulopathies Associated with Bacterial Infections
			6.2.2 Glomerulopathies Associated with Viral Infections
				6.2.2.1 COVID-19 and Immune-Mediated Glomerulopathies
		6.3 Immune-Mediated Nephropathies
		6.4 Glomerulonephritis Caused by Immune Complex Deposits
		6.5 Glomerulopathies and Gut Microflora
		6.6 Management of Glomerulopathies
		6.7 Conclusions
		References
	7: Microorganisms in Pathogenesis and Management of Autoimmune Addison´s Disease (AAD)
		7.1 Introduction
		7.2 Role of Microorganisms in the Pathogenesis of Autoimmune Addison´s Disease
			7.2.1 Bacteria
			7.2.2 Viruses
				7.2.2.1 SARS-CoV-2
		7.3 Role of Gut Microbiota in Autoimmune Addison´s Disease
		7.4 Role of Probiotics in Autoimmune Addison´s Disease
		7.5 Conclusion
		References
Part III: Microorganisms in Pathogenesis and Management of Central Nervous System (CNS) Demyelinating Autoimmune Diseases
	8: Microorganisms in Pathogenesis and Management of Multiple Sclerosis (MS)
		8.1 Introduction
		8.2 Microbiota
		8.3 Multiple Sclerosis and Gut Microbiota
		8.4 Multiple Sclerosis, Microbiota, and the Immune System
			8.4.1 Smad7 Protein
		8.5 Viruses and Multiple Sclerosis
			8.5.1 Epstein-Barr Virus
			8.5.2 Human Herpesvirus 6
			8.5.3 Human Endogenous Retroviruses
			8.5.4 Measles, Rubella, and Varicella-Zoster Viruses
		8.6 Probiotics and Multiple Sclerosis
		8.7 Conclusion
		References
	9: Microorganisms in Pathogenesis and Management of Guillain-Barré Syndrome (GBS)
		9.1 Introduction
		9.2 Microorganisms in the Pathogenesis of Guillain-Barré Syndrome
			9.2.1 Bacterial Infections
			9.2.2 Viral Infections
				9.2.2.1 Link Between SARS-CoV-2 and Guillain-Barré Syndrome
			9.2.3 Protozoan Infections
		9.3 Vaccine-Induced Guillain-Barré Syndrome
		9.4 Role of Gut Microbiota in Guillain-Barré Syndrome
		9.5 Management of Guillain-Barré Syndrome
			9.5.1 Immunotherapy for Guillain-Barré Syndrome
				9.5.1.1 Plasma Exchange
				9.5.1.2 Intravenous Immunoglobulin
				9.5.1.3 Monoclonal Antibody
			9.5.2 Role of Probiotics and Prebiotics in Guillain-Barré Syndrome
		9.6 Future Perspectives
		9.7 Conclusions
		References
	10: Microorganisms in Pathogenesis and Management of Neuromyelitis Optica Spectrum Disorder
		10.1 Introduction
		10.2 Pathogenesis
		10.3 Risk Factors
		10.4 The Role of Microorganisms in the Pathogenesis of Neuromyelitis Optica
			10.4.1 Bacteria
				10.4.1.1 Mycobacterium tuberculosis
				10.4.1.2 Gut Microbiome
				10.4.1.3 Helicobacter pylori
			10.4.2 Viruses
				10.4.2.1 Epstein-Barr Virus (EBV)
				10.4.2.2 SARS-CoV-2
				10.4.2.3 Varicella Zoster Virus (VZV)
				10.4.2.4 Dengue Virus
				10.4.2.5 Cytomegalovirus (CMV)
				10.4.2.6 Herpes Simplex Virus 2 (HSV2)
				10.4.2.7 Zika
		10.5 Diagnostic of NMOSD
		10.6 The Role of Infections in Causing an Attack in Patients with NMOSD
		10.7 Infection of NMOSD Patients with Infectious Diseases and Its Complications
		10.8 Management of NMOSD Through Microorganisms
		10.9 Conclusion
		References
	11: Microorganisms in Pathogenesis and Management of Acute Disseminated Encephalomyelitis (ADEM)
		11.1 Introduction
		11.2 Mechanisms of Microorganism-Induced Autoimmunity
		11.3 Evidence in Illnesses
			11.3.1 Demyelinating Disease: Guillain-Barre Syndrome (GBS)
			11.3.2 Acute Disseminated Encephalomyelitis (ADEM)
			11.3.3 Definitions
			11.3.4 Epidemiology
		11.4 ADEM and Microbial Link
			11.4.1 Viral Causes
			11.4.2 SARS-CoV-2 and Other Coronaviruses
			11.4.3 Bacterial Causes
			11.4.4 Parasitic Causes
			11.4.5 Vaccination-Induced ADEM
			11.4.6 Other Causes of ADEM
		11.5 Pathogenesis of ADEM
		11.6 ADEM and Gut Microbiota
		11.7 Pathological Findings of ADEM
		11.8 Clinical Features of ADEM
		11.9 Diagnosis of ADEM
			11.9.1 Neuroimaging
			11.9.2 CSF Analysis
			11.9.3 CNS Angiography
			11.9.4 EEG
			11.9.5 Serological Tests
			11.9.6 Multiphasic Disseminated Encephalomyelitis (MDEM)
			11.9.7 Differential Diagnosis
		11.10 Treatment of ADEM
			11.10.1 Probiotics as a Potential Therapeutic Option
			11.10.2 Prognosis
			11.10.3 Sequelae
			11.10.4 Prevention
		11.11 Conclusion
		References
Part IV: Microorganisms in Pathogenesis and Management of Inflammatory Bowel Diseases (IBDs)
	12: Microorganisms in Pathogenesis and Management of Ulcerative Colitis (UC)
		12.1 Introduction
		12.2 Role of Microorganism in the Pathophysiology of Ulcerative Colitis
		12.3 Role of Microorganisms in the Management of Ulcerative Colitis
		12.4 Conclusion
		References
	13: Microorganisms in the Pathogenesis and Management of Crohn´s Disease (CD)
		13.1 Introduction
		13.2 Role of Gut Microbiota in the Pathogenesis of Crohn´s Disease
			13.2.1 Microbe-Host Interactions in Crohn´s Disease
			13.2.2 Intestinal Permeability
		13.3 Microorganisms in the Pathogenesis of Crohn´s Disease
			13.3.1 Bacteria
			13.3.2 Viruses
				13.3.2.1 SARS-CoV-2
		13.4 Therapeutic Role of Microorganisms in the Management of Crohn´s Disease
			13.4.1 Role of Prebiotics and Probiotics in the Treatment of Crohn´s Disease
			13.4.2 Fecal Microbiota Transplantation
		13.5 Future Perspectives
		13.6 Conclusion
		References
	14: Microorganisms in the Pathogenesis and Management of Pouchitis
		14.1 Introduction
			14.1.1 Inflammatory Bowel Diseases
			14.1.2 Basics of Pouchitis
		14.2 Microorganisms in Pathogenesis of Pouchitis
		14.3 Gut Microbiota Dysbiosis in Pouchitis
		14.4 SARS-CoV2 and Pouchitis
		14.5 Probiotics in the Management of Pouchitis
		14.6 Fecal Microbiota Transplant in the Treatment of Pouchitis
		14.7 Conclusions
		References
	15: Microorganisms in the Pathogenesis and Management of Celiac Disease(CeD)
		15.1 Introduction
		15.2 Pathogenesis of Celiac Disease
		15.3 Dysbiosis in CeD
		15.4 Role of Intestinal Microbiota in the Pathogenesis of CeD
			15.4.1 Interactions Between HLA DQ Haplotypes and Microbiome
			15.4.2 Interactions Between Gluten and Microbiome
			15.4.3 Interactions Between Microbiome and Intestinal Barrier
			15.4.4 Interactions Between Microbiome and Immune Response in Celiac Disease
		15.5 Role of Infections in the Development of CeD
		15.6 Microbiota Targeted Therapy for CeD
			15.6.1 Dietary Intervention: GFD
			15.6.2 Probiotics
			15.6.3 Prebiotics
			15.6.4 Microbiota-Derived Glutenases
			15.6.5 Hookworms
			15.6.6 Fecal Microbiome Transfer (FMT)
		15.7 Conclusion
		References
Part V: Microorganisms in Pathogenesis and Management of Autoimmune Blood and Blood Vessel Disorders
	16: Microorganisms in Pathogenesis and Management of Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis
		16.1 Introduction
		16.2 Classification of AAVs
		16.3 Epidemiology of AAVs
		16.4 Microbial Pathogenesis of ANCA-Associated Vasculitis
		16.5 Cells and Pathways Involved in AAVs
			16.5.1 Neutrophils
			16.5.2 Lymphocytes (T and B Cells)
			16.5.3 Complement
			16.5.4 Cytokines and Chemokines
		16.6 Major Steps Involved in AAVs
			16.6.1 Priming of Neutrophils and Monocytes
			16.6.2 Activation of Neutrophils and Monocytes
			16.6.3 T cell Activation
			16.6.4 B cell Activation
			16.6.5 Tissue Damage and Repair
			16.6.6 Endothelial Injury and Repair
			16.6.7 Role of Proteinase-3
		16.7 Gut Microbial Dysbiosis in AAVs
		16.8 Diagnosis of AAVs
		16.9 General Treatment Methods
			16.9.1 Remission Induction
			16.9.2 Maintenance Therapy and Relapse Prevention
			16.9.3 Following Up and Withdrawing Therapy
		16.10 Role of Gut Microbes in AAVs Treatment
		16.11 Conclusion and Future Perspectives
		References
	17: Microorganisms in the Pathogenesis and Management of Anti-phospholipid Syndrome (Hughes Syndrome)
		17.1 Introduction
		17.2 Origin and Development of Antiphospholipid Antibodies
		17.3 Infections and Antiphospholipid Antibodies
			17.3.1 Infectious Agents and APS
			17.3.2 Infections and Catastrophic APS (CAPS)
		17.4 Infectious Origin of Antiphospholipid Antibodies
			17.4.1 The Role of Molecular Mimicry
			17.4.2 The Link Between Innate Immunity and APS
			17.4.3 Commensal Microbiota in APS
			17.4.4 Vaccines and APS
		17.5 Therapeutic Implications
		17.6 Conclusions
		References
	18: Microorganisms in Pathogenesis and Management of Behçet Disease (BD)
		18.1 Introduction
		18.2 The Microbiome and Immunity
		18.3 Behcet´s Syndrome and the Microbiome
			18.3.1 The Intestinal Microbiome in BD
			18.3.2 The Salivary Microbiome in BD
			18.3.3 The Role of Dysbiosis
			18.3.4 The Role of the SCFAs
			18.3.5 The Role of Smoking
		18.4 Therapy
			18.4.1 Diet
			18.4.2 Antibiotics
			18.4.3 Oral Health and Dental Interventions
		18.5 Conclusion
		References
	19: Microorganisms in the Pathogenesis and Management of Immune Thrombocytopenia (ITP)
		19.1 Introduction
		19.2 Bacteria and ITP
			19.2.1 Helicobacter pylori and ITP
			19.2.2 Gut Microbiota and ITP
		19.3 Viruses and ITP
			19.3.1 HIV and ITP
			19.3.2 HCV and ITP
			19.3.3 HBV and ITP
			19.3.4 SARS-CoV-2 and ITP
		19.4 Vaccination and ITP
		19.5 Probiotics, Prebiotics, and Synbiotics: Can We Exploit Their Health Benefits in the Management of ITP?
		19.6 Conclusions
		References
Part VI: Microorganisms in Pathogenesis and Management of Autoimmune Eye Diseases
	20: Microorganisms in Pathogenesis and Management of Autoimmune Uveitis
		20.1 Introduction
		20.2 Correlations Between the Intestine Microbe and Autoimmune Uveitis
			20.2.1 Animal Models of Experimental Autoimmune Uveitis
			20.2.2 Clinical Observation of Uveitis Patients
			20.2.3 Immunosuppressive Medications Can Affect Gut Microbes
		20.3 How Gut Microbiota Affect the Development of Autoimmune Uveitis
			20.3.1 Antigenic Mimicry
			20.3.2 Disruption of Gut Immune Homeostasis
			20.3.3 Loss of the Intestinal Barrier
			20.3.4 Metabolic Pathway
		20.4 Targeting the Gut Microbiota to Treat Uveitis
			20.4.1 Antibiotics
			20.4.2 Probiotics
		20.5 Conclusion
		References
	21: Role of Microorganisms in Pathogenesis and Management of Autoimmune Retinopathy (AIR)
		21.1 Introduction
		21.2 Pathophysiology of AIR
		21.3 The Gut Microbiota
		21.4 The Gut-Retina Axis
		21.5 Experimental Autoimmune Uveitis (EAU)
		21.6 Spontaneous Autoimmune Uveitis Model (SAIU)
			21.6.1 Specific Pathogen Free (SPF) and Germ Free (GF)Mice Models
		21.7 Clinical Implications of EAU Models
		21.8 Translational Science
		21.9 Commensal Microbiota as a Trigger of Uveitis
		21.10 Mechanism for Dybiosis Causing AIR
			21.10.1 Antigenic (Molecular) Mimicry
			21.10.2 Loss of Intestinal Immune Homeostasis (Imbalance Between Th17 and Tregs)
			21.10.3 Destruction of Intestinal Barrier (Increased Intestinal Permeability)
			21.10.4 Microbial Metabolites
		21.11 All the Way from the Gut to the Retina
		21.12 Current Management Options
		21.13 Future Therapeutic Considerations
			21.13.1 Dietary Modifications
			21.13.2 Prebiotics and Probiotics
			21.13.3 Antibiotics
			21.13.4 FMT
			21.13.5 Cytokines
		21.14 Conclusion
		References
Part VII: Microorganisms in Pathogenesis and Management of Autoimmune Diabetes
	22: Microorganisms in the Pathogenesis and Management of Type 1 Diabetes (T1D)
		22.1 Introduction
		22.2 Gut Microorganisms and Metabolic Profile
		22.3 Gut Microorganisms and Type 1 Diabetes
		22.4 Other Microorganisms and Type 1 Diabetes
			22.4.1 Viruses and Type 1 Diabetes
		22.5 The Mechanisms Through Which Gut Microorganisms Influence the Development of Type 1 Diabetes
			22.5.1 Intestinal Permeability
			22.5.2 Molecular Mimicry
			22.5.3 Impact of Immune System
				22.5.3.1 Impact on Innate Immunity
				22.5.3.2 Impact on Adaptive Immunity
		22.6 Management Possibilities for Type 1 Diabetes Prevention
		22.7 Diabetes and Dysbiosis: A Causal or Contemporary Phenomenon
		22.8 Conclusion
		References
Part VIII: Current Challenges and Future Prospects in Research Towards Microbial Pathomechanisms and Therapeutic Aspects of Au...
	23: The Influence of the Microbiome and Genetic Associations on Immune Functions and on Autoimmune and Autoinflammatory Diseas...
		23.1 Introduction
		23.2 Autoimmunity and Autoinflammation
			23.2.1 Some Immunological Facts to Consider
			23.2.2 Immune Tolerance
			23.2.3 Genetic Susceptibility to Autoimmune and Autoinflammatory Diseases
		23.3 The Microbiome and the Development and Tunning of the Immune System (Fig. 23.1)
		23.4 The Impact of the Microbiome on Autoimmune and Autoinflammatory Diseases
		23.5 Conclusions
		References
	24: Current Challenges in Research with Exploring the Microbial Pathomechanisms of Autoimmune Diseases
		24.1 Introduction
		24.2 Unanswered Questions Regarding Symbiosis
		24.3 Confounding Factors
		24.4 Technical Difficulties
		24.5 The Multiomics Approach
		24.6 Drug-Microbiome Interactions and Translatability
		24.7 Difficulties of Studying Microbial Pathomechanisms in Autoimmune Diseases
		24.8 Concluding Remarks
		References
	25: Future Therapeutic Prospects in Dealing with Autoimmune Diseases: Treatment Based on the Microbiome Model
		25.1 Introduction
		25.2 The Era of Microbiome
			25.2.1 The Current Knowledge of the Human Microbiome with the emfasis on the Gut
			25.2.2 From Eubiosis to Gut Dysbiosis and Inflammation
			25.2.3 The Chicken and Egg Situation-Proof of Causality?
			25.2.4 The Emerging Role of Microbiome in Autoimmune Diseases-Mechanisms and Interactions
				25.2.4.1 Microbiome-Immune Axis
				25.2.4.2 Leaky Gut Syndrome (LGS)
				25.2.4.3 Molecular Mimicry
			25.2.5 Gut Microbiome Alterations in Certain Autoimmune Conditions
			25.2.6 From Microbiome to Infectome-Autoinfectome: A New Platform
		25.3 Dealing with Autoimmune Diseases: Where Are We Standing?
			25.3.1 Current `Old-Fashioned´ Therapies
				25.3.1.1 Disease-Modifying Antirheumatic Drugs (DMARDs)
				25.3.1.2 Methotrexate (MTX)
				25.3.1.3 Leflunomide
				25.3.1.4 Hydroxychloroquine
				25.3.1.5 Biological Therapies
			25.3.2 Peaking in the Future of Autoimmune Disorders´ Treatment
			25.3.3 New Target Acquisition: The Microbiome
		25.4 Microbiota-Based Interventions
			25.4.1 Probiotic Applications
			25.4.2 The New Concept of BRUGs
			25.4.3 Prebiotics and Diet: `Let Food be Thy Medicine and Let Medicine be Thy Food´ (Hippocrates 400 BC)
			25.4.4 Bacteria Used as Drug-Engineered Microbes: Pharmacomicrobiomics
			25.4.5 Faecal Microbiota Transplantation: A Superior Option?
		25.5 Conclusions
		References
Index