Metagenomics of the Human Body (eBook)

Foreword The Human Genome and the Human Microbiome 6
Contents 9
Contributors 11
About the Editor 14
1 The Human Genome, Microbiomes, and Disease 15
Introduction: Variation in the Genome and Microbiome 15
Steps to Treatment 17
Factors in Experimental Design 18
The Gastrointestinal Microbiome 19
Crohn's Disease 19
Celiac Disease 20
Obesity 20
Colorectal Cancer 21
Vaginal Bacterial Biota 22
Oral 23
Skin Microbiome 24
Psoriasis 24
Acne 25
Conclusion 26
References 26
2 Host Genotype and the Effect on Microbial Communities 29
Introduction 29
Interactions in a Super-Organism 31
Host Genotype and Microbiota Selection 33
Dietary Influences 37
Obesity in Animal Models 38
Obesity in Humans 39
Diet: Transient or Permanent Effects? 40
Host--Microbiota Co-evolution: Selective Geographic Pressure? 41
Host-Genotype Polymorphisms 44
Host--Microbiota Communication: Innate Immune System 44
Host--Microbiota Communication: Non-immune-Related Mechanisms 46
Direct Interactions of Host Genome and Microbiome 47
Conclusions 48
References 50
3 The Human Microbiome and Host--Pathogen Interactions 56
Microbial Pathogenesis: Looking Beyond Koch 56
The Human Microbiota in Health and Disease 57
From Microbiota to Microbiome: Surveying the Unknown 59
Blurring the Boundaries Between Pathogen and Commensal 62
Immunological Crosstalk Between Microbiota and Host 63
The Human Microbiome: A Shield Against Pathogens 64
Diet, Antibiotics, the Human Microbiome and Risks of Infection 65
Pathogen-Induced Inflammation Perturbs the Microbiome 66
Clinical Metagenomics, Polymicrobial Sepsis and Dysbiosis 67
Conclusion 68
References 69
4 The Human Virome 75
Background 75
Metagenomics 76
Approximate Number and Distribution of Viruses in the Human Body 77
How Many Viruses Are There in a Human? 77
Abundance of Viruses at Specific Body Sites 78
What Types of Viruses Inhabit the Human Host? 78
Phage Community 79
Eukaryotic Viruses 81
Residence Time and Pathogenicity 82
Viral Metagenomics Methods 82
Recovery from Microarrays 83
Random RT-PCR 83
Virus Purification and Phi29 Amplification 83
Sequencing Methods 83
Bioinformatics 84
Similarity-Dependent Analyses 84
Metabolic Pathways 84
Similarity-Independent Analyses 84
Uncharacterized Viral Diversity 85
Implications for Medical Care 85
References 87
5 Selection and Sequencing of Strains as References for Human Microbiome Studies 90
First- and Next-Generation Human Microbiome Projects 90
The Human Microbiome Stability in Diversity 91
Reference Genomes and Strain Selection 92
Traditional Cultivation Methods 94
Microscale Cultivation Methods 94
Application of Sequencing from Single Cells and/or with Minute Quantities of DNA 95
Reverse Isolation of Reference Strains Using (Meta)Genomic Data 96
Genome Finishing and Annotation 96
Prospects for the Future 98
Concluding Remarks 98
References 99
6 The Human Vaginal Microbiome 102
The Impact of Vaginal Infections on Womens Health 102
BV as a Risk Factor for Urogenital Infections and STDs 103
BV as a Risk Factor for Pregnancy Complications and Preterm Birth 104
Microbial Diversity in the Vaginal Tract 105
Effect of Antibiotic and Probiotic Treatment on Vaginal Microbiota 109
The Role of Host Response in BV 111
Immunologic Impact on the Vaginal Microbiome 112
Microbial Metabolic Function and Vaginal Health 114
Future Prospectus 116
References 116
7 The Human Lung Microbiome 127
The Human Lung 127
Lung Microbiome Overview 127
Anatomical and Immunological Setting 129
Diseases of the Lower Respiratory Tract and Their Impact on the Lung Microbiome 129
Microbiome Characterization 130
Human Lung Sampling Methods 130
High-Throughput Sequencing of Bacterial Ribosomal RNA Subunits 131
Ribosomal RNA ITS Typing of Fungal Populations 132
Viral Identification via Genome Sequencing for Population Analysis 132
Metagenomics 133
The Lung Microbiome in Asthma 133
The Role of Infections in Asthma Exacerbations 134
The Role of Infections and Microbial Colonization in Asthma Development 135
The Role of Fungi in Severe Asthma 136
The Lung Microbiome in Cystic Fibrosis (CF) 137
Introduction 137
The Chronically Colonized CF Airways Represent a Surprising Complex and Diverse Ecosystem 138
The Microbiome of the CF Lung Contains Microbial Diversity Not Evaluable by Standard Culture Techniques 138
Fastidious or Noncultivatable Bacteria: An Emerging Concept in CF 139
The Lung Microbiome in Idiopathic Bronchiectasis 139
Introduction 139
Bronchiectasis Phenotype and Microbial Flora 139
Significance of Filamentous Fungi: A Novel Consideration in Bronchiectasis 140
Serologic Assessment of Fungal Response 140
The Lung Microbiome in COPD 141
Introduction 141
Role of Infections in COPD 141
Bacteria, Viruses, and Fungi Have All Been Linked to COPD 142
The Lung Microbiome and Human Immunodeficiency Virus Infections 143
Lung Diseases Remain a Leading Cause of Morbidity and Mortality in HIV Infection 143
Role of the Microbiome in Obstructive Lung Diseases in HIV 143
Role of Pneumocystis Colonization in HIV-Associated COPD 144
Conclusions 144
References 145
8 The Human Skin Microbiome in Health and Skin Diseases 154
Human Skin Microbiome 154
Bacterial Composition of the Skin Microbiota 155
Skin Microbiome Variation Among Different Body Sites 157
Left and Right Symmetry 158
Skin Microbiome Variation Among Individuals 158
Temporal Variation of the Skin Microbiome 159
Eukaryotes of the Skin Microbiota 159
Skin Microbiome and Diseases 160
Acne Vulgaris 160
Pathogenesis, Clinical Presentation, and Treatment of Acne Vulgaris 161
Propionibacterium acnes and Acne 162
Follicular Microbiota and Acne 163
Propionibacterium acnes Bacteriophages 163
Host Factors in Acne Pathogenesis 164
Atopic Dermatitis 165
Clinical Presentation and Pathogenesis of Atopic Dermatitis 165
Skin Microbiota and Atopic Dermatitis 166
Psoriasis 167
Clinical Presentation and Pathogenesis of Psoriasis 167
Skin Microbiota and Psoriasis 167
Other Skin Diseases and the Skin Microbiome 168
References 169
9 The Human Oral Metagenome 173
Introduction 173
Microbial Ecology of the Human Oral Cavity and Its Role in Health and Disease 173
Interactions Between Oral Bacteria 174
Physical Interactions 174
Chemical Interactions 175
Gene Transfer 175
Metagenomic Analysis of the Oral Cavity 176
Identifying Oral Organisms 176
Antibiotic Resistance in the Oral Metagenome 177
The ''Mobilome'' of the Oral Cavity 177
Discovery of New ICE in Oral Metagenomes 177
Discovery of Genomic Islands in Oral Metagenomes 178
Discovery of New Plasmids in Oral Metagenomes 178
Functional Analysis of the Oral Metagenome 179
References 179
10 The Human and His Microbiome Risk Factors for Infections 182
Introduction 182
The HostMicrobiota Ecosystem 183
Homeostasis 184
Resilience 185
Threshold 185
The Human Gut Microbiota 186
Intestinal Microbiota in Neonates and Preterm Infants 186
Physiological Colonization 188
The Process of Colonization 188
Peristalsis 189
The Environment of the Epithelial Surface 189
Mucus Secretion 189
Intestinal Permeability 190
Gradient from Stomach to Colon 191
Translocation 191
The Intestinal Mucosal Immune System 192
Context Influences and Pathology 193
Intestinal Microbiota and Allergy Development 193
Breast Milk 194
Type of Birth 194
Premature Neonatal Gut 195
The Problem of Low-Birth-Weight (LBW) Infants 195
Necrotizing Enterocolitis (NEC) 195
Antibiotics 196
Mechanism of Antibiotic Action 197
DNA Synthesis Inhibitors 198
RNA Synthesis Inhibitors 198
Protein Synthesis Inhibitors 199
Cell Wall Synthesis Inhibitors 199
Contribution of Structural Molecular Biology 199
The Example of -Lactam Antibiotics 200
The Synchrotron Radiation 201
Community Dynamics and Ecology 201
Biomolecular Science and Engineering 201
Resistance 202
Mechanism of Resistance 202
Impact of Resistance 203
Evolution of Resistance 204
Control of Resistance 207
Example of Resistant Organisms 208
The Pervasive Effects of Antibiotics 210
Common Side Effects 210
Antibiotherapy and Microbiota 211
Neonates 213
Microbiota and Microbiome Analysis Methods 214
Analytical Methodologies 214
Mathematical Network 216
Analytical Methodologies 216
Theories 217
Examples 218
Conclusion 218
References 219
11 Infectogenomics: Aspect of Host Responses to Microbes in Digestive Tract 224
Introduction 224
The Microecological Barrier of the Gastrointestinal Tract 225
HostBacterium Interactions in the Gastrointestinal Tract 229
Functional Genomics Approaches in Studying Host Immunoresponses 231
Host Responsiveness to Microbiota Metabonomic Approaches 232
References 234
12 Autoimmune Disease and the Human Metagenome 238
Background 238
Culture-Independent Methods for Identifying Microbes 240
The Human Metagenome 243
Microbial Complexity 245
Toward a More Nuanced View of the Human Microbiota 247
Pathogens Alter the Expression of Human Genes and Receptors 248
Successive Infection and Variability in Disease Onset and Presentation 253
Early Infections Predispose a Person to Later Chronic Disease 255
Comorbidity 257
Causation vs. Association 258
Microbial Interaction and Disease 259
Familial Aggregation 260
Is Autoimmune Disease Predisposition Mendelian? 261
SNPs and Autoimmune Disease 263
Potential Systematic Errors in the Interpretation of the Metagenome 264
Antibodies in Response to Microbial DNA 264
Therapies in the Era of the Metagenome 267
L-Form Bacteria: An Often Overlooked Component of the Microbiota 270
A Research Consideration: Men Are Not Tall MiceWithout Tails 271
Discussion 272
References 274
13 Metagenomic Applications and the Potential for Understanding Chronic Liver Disease 283
Introduction 283
Liver Fibrosis and Cirrhosis 283
Bacterial Translocation 284
Intestinal Symbiosis and Dysbiosis 284
Requirement of Bacterial Products for Liver Fibrogenesis 285
Nonalcoholic Fatty Liver Disease 286
Alcohol-Induced Liver Disease 287
Chronic Liver Disease 289
Dysbiosis and Bacterial Translocation in Experimental Models of Chronic Liver Disease 289
Intestinal Bacterial Overgrowth in Patients with Chronic Liver Disease 291
Bacterial Translocation in Cirrhotic Patients 292
Potential Interventions Using Antibiotics, Prebiotics, Probiotics, or Synbiotics 293
Animal Studies 294
Patients 294
Conclusion 295
References 296
14 Symbiotic Gut Microbiota and the Modulation of Human Metabolic Phenotypes 302
Gut Microbiota and the Symbiotic Relationship with Human Beings 302
The Composition and Diversity of the Gut Microbiota 302
The Function of Gut Microbiota 303
Gut Microbiota in Health and Disease 303
Gut Microbiota with Infectious Disease 303
Gut Microbiota in Other Chronic Diseases 304
Research Platforms and Technologies for Studying Gut Microbiota 305
Molecular Ecological Technologies Based on the 16S rRNA Gene 305
Metabonomics Study of ''Co-metabolism'' of Host and Microbiota 306
The Modulation of Gut Microbiota on the Host Metabolic Phenotype 307
Perspectives for Future Gut Microbiota-Oriented Studies 309
References 309
15 MetaHIT: The European Union Project on Metagenomics of the Human Intestinal Tract 312
Introduction 312
MetaHIT Objectives 313
MetaHIT Structure 313
MetaHIT Partnership and Funding 315
Gene Catalog of Gut Microbes 316
Microbial Gene Profiling 317
IBD and Obesity Patient Cohorts 317
Information Organization and Analysis 317
Function of Bacterial Genes Associated with Disease 318
Studies with Industry Transfer of Technology 318
MetaHIT Communication and Coordination 318
Expected Achievements 319
The MetaHIT Consortium Members 319
References 320
16 Implications of Human Microbiome Research for the Developing World 322
Introduction 322
The Promise of the Human Microbiome 324
NIH-Funded HMP and International Components of the HMP 325
Implications of the HMP for the Developing World 326
The Promise for Technology Development in the Developing World 328
Monitoring of Zoonotic Infections and Global Surveillance of Emerging and Reemerging Infectious Diseases 329
The Case of Selected Emerging Infectious Diseases: Tuberculosis (TB) and Leptospirosis 330
Potential for Understanding and Control of Diarrheal Diseases 332
Potential for Understanding Sexually Transmitted Diseases 333
Potential for Enhancement of Malaria Treatment Regimens 334
Challenges: Funding and Technology Transfer 335
References 337
Index 342