Luigi Nibali is a Senior Clinical Lecturer in the Clinical Oral Research Centre, Institute of Dentistry, Queen Mary University London in London, UK.

Brian Henderson is a Professor of Microbial Diseases in the School of Life and Medical Sciences at University College London in London, UK.

List of contributors xvii Preface xxi Section 1 An introduction to the human tissue microbiome 1 1 The human microbiota: an historical perspective 3Michael Wilson 1.1 Introduction: the discovery of the human microbiota: why do we care? 3 1.2 The importance of the indigenous microbiota in health and disease 3 1.3 The development of technologies for characterising the indigenous microbiota 8 1.4 Culture¿independent approaches to microbial community analysis 29 1.5 Determination of microbial community functions 31 1.6 Closing remarks 32 Take¿home message 32 References 33 2 An introduction to microbial dysbiosis 37Mike Curtis 2.1 Definition of dysbiosis 37 2.2 The 'normal' microbiota 38 2.3 Main features of dysbiosis 45 2.4 Conclusions 49 Take¿home message 53 Acknowledgment 53 References 53 3 The gut microbiota: an integrated interactive system 55Hervé M. Blottière and Joël Doré 3.1 Introduction 55 3.2 Who is there how is it composed? 56 3.3 A system in interaction with food 58 3.4 A system highly impacted by the host 61 3.5 A system in interaction with human cells 62 3.6 Conclusion: an intriguing integrated interactive system deserving further study 63 Take¿home message 63 References 63 4 The oral microbiota 67William G. Wade 4.1 Introduction 67 4.2 Composition of the oral microbiome 68 4.3 The oral microbiota in health 71 4.4 Role of oral microbiome in disease 73 4.5 Future outlook 75 Take¿home message 75 References 76 5 The skin microbiota 81Patrick L.J.M. Zeeuwen and Joost Schalkwijk 5.1 Normal skin 81 5.2 Skin diseases 83 5.3 Experimental studies 87 5.4 Dynamics of the skin microbiome 87 5.5 Axillary skin microbiome transplantation 89 5.6 Mouse skin microbiome studies 89 5.7 Concluding remarks 90 Take¿home message 90 References 90 6 Metagenomic analysis of the human microbiome 95Luis G. Bermúdez¿Humarán 6.1 Introduction 95 6.2 The human microbiome 96 6.3 Changes in microbiota composition during host life cycles 97 6.4 The human microbiome and the environment 98 6.5 Disease and health implications of microbiome 99 6.6 Conclusions 105 Take¿home message 105 References 106 Section 2 Microbiota-microbiota and microbiota-host interactions in health and disease 113 7 Systems biology of bacteriähost interactions 115Almut Heinken Dmitry A. Ravcheev and Ines Thiele 7.1 Introduction 115 7.2 Computational analysis of host¿microbe interactions 118 7.3 Network¿based modeling 121 7.4 Other computational modeling approaches 127 7.5 Conclusion 129 Take¿home message 130 Acknowledgments 130 References 131 8 Bacterial biofilm formation and immune evasion mechanisms 139Jessica Snowden 8.1 Introduction 139 8.2 Biofilms in human disease 139 8.3 Biofilm formation 141 8.4 Immune responses to biofilms 143 8.5 Biofilm immune evasion strategies 147 8.6 Vaccines and biofilm therapeutics 148 8.7 Conclusions 149 Take¿home message 149 References 150 9 Co¿evolution of microbes and immunity and its consequences for modern¿day life 155Markus B. Geuking 9.1 Introduction 155 9.2 Symbiosis in eukaryotic evolution 156 9.3 Evolution of the (innate and adaptive) immune system 157 9.4 Hygiene hypothesis 159 9.5 What drives the composition of the microbiota? 160 9.6 The pace of evolution 161 Take¿home message 162 References 162 10 How viruses and bacteria have shaped the human genome: the implications for disease 165Frank Ryan 10.1 Genetic symbiosis 165 10.2 Mitochondria: symbiogenesis in the human 167 10.3 Viral symbiogenesis 169 10.4 HERV proteins 172 Take¿home message 174 References 174 11 The microbiota as an epigenetic control mechanism 179Boris A. Shenderov 11.1 Introduction 179 11.2 Background on epigenetics and epigenomic programming/ reprograming 180 11.3 Epigenomics and link with energy metabolism 184 11.4 The microbiota as a potential epigenetic modifier 185 11.5 Epigenetic control of the host genes by pathogenic and opportunistic microorganisms 188 11.6 Epigenetic control of the host genes by indigenous (probiotic) microorganisms 189 11.7 Concluding remarks and future directions 191 Take¿home message 193 References 193 12 The emerging role of propionibacteria in human health and disease 199Holger Brüggemann 12.1 Introduction 199 12.2 Microbiological features of propionibacteria 199 12.3 Population structure of P. acnes 201 12.4 Propionibacteria as indigenous probiotics of the skin 202 12.5 Propionibacteria as opportunistic pathogens 203 12.6 Host interacting traits and factors of propionibacteria 205 12.7 Host responses to P. acnes 206 12.8 Propionibacterium¿specific bacteriophages 208 12.9 Concluding remarks 209 Take¿home message 210 References 210 Section 3 Dysbioses and bacterial diseases: Metchnikoff's legacy 215 13 The periodontal diseases: microbial diseases or diseases of the host response? 217Luigi Nibali 13.1 The tooth: a potential breach in the mucosal barrier 217 13.2 The periodontium from health to disease 217 13.3 Periodontitis: one of the most common human diseases 219 13.4 Periodontal treatment: a non¿specific biofilm disruption 220 13.5 Microbial etiology 220 13.6 The host response in periodontitis 221 13.7 Conclusions 223 Take¿home message 223 References 223 14 The polymicrobial synergy and dysbiosis model of periodontal disease pathogenesis 227George Hajishengallis and Richard J. Lamont 14.1 Introduction 227 14.2 A (very) polymicrobial etiology of periodontitis 229 14.3 Synergism among periodontal bacteria 230 14.4 Interactions between bacterial communities and epithelial cells 232 14.5 Manipulation of host immunity 233 14.6 Conclusions 237 Take¿home message 238 References 239 15 New paradigm in the relationship between periodontal disease and systemic diseases: effects of oral bacteria on the gut microbiota and metabolism 243Kazuhisa Yamazaki 15.1 Introduction 243 15.2 Association between periodontal and systemic diseases 244 15.3 Issues in causal mechanisms of periodontal disease for systemic disease 249 15.4 New insights into the mechanisms linking periodontal disease and s ystemic disease 252 15.5 Effect of oral administration of P. gingivalis on metabolic change and gut microbiota 252 15.6 Conclusions 254 Take¿home message 255 References 255 16 The vaginal microbiota in health and disease 263S. Tariq Sadiq and Phillip Hay 16.1 What makes a healthy microbiota 263 16.2 The vaginal microbiota in disease 265 16.3 Conclusions 269 Take¿home message 269 References 270 Section 4 Dysbioses and chronic diseases: is there a connection? 273 17 Reactive arthritis: the hidden bacterial connection 275John D. Carter 17.1 Introduction 275 17.2 Reactive arthritis 276 17.3 Pathophysiology of ReA 277 17.4 Questions remain 279 17.5 Conclusion 280 Take¿home message 280 References 280 18 Rheumatoid arthritis: the bacterial connection 283Jacqueline Detert 18.1 Preclinical rheumatoid arthritis 283 18.2 Predisposition to RA 284 18.3 MCH¿HLA and genetic predisposition to RA 284 18.4 Molecular mimicry in RA 285 18.5 Innate immune system and RA 285 18.6 Bystander activation and pattern recognition receptors 286 18.7 Antibodies and neoepitopes 287 18.8 Superantigens 287 18.9 Lps 287 18.10 Bacterial DNA and peptidoglycans 288 18.11 Heat¿shock proteins 288 18.12 Toll¿like and bacterial infections 288 18.13 Proteus mirabilis 288 18.14 Porphyromonas gingivalis and RA 289 18.15 Gastrointestinal flora and RA 290 18.16 Smoking lung infection and RA 291 18.17 Where to go from here? 291 Take¿home message 291 References 292 19 Inflammatory bowel disease and the gut microbiota 301Nik Ding and Ailsa Hart 19.1 The microbiota in inflammatory bowel disease 301 19.2 Dysbiosis and IBD pathogenesis 301 19.3 Environmental factors affecting microbiome composition 302 19.4 Genetics and application to the immune system and dysbiosis in IBD 303 19.5 An overview of gut microbiota studies in IBD 305 19.6 Specific bacterial changes in IBD 306 19.7 Functional composition of microbiota in IBD 308 19.8 Challenges 310 19.9 Conclusion 310 Take¿home message 310 References 310 20 Ankylosing spondylitis klebsiella and the low¿starch diet 317Alan Ebringer, Taha Rashid and Clyde Wilson 20.1 Introduction 317 20.2 Clinical features of AS 317 20.3 Gut bacteria and total serum IgA 318 20.4 Molecular mimicry in AS 319 20.5 Pullulanase system and collagens 320 20.6 Specific antibodies to Klebsiella in AS patients 321 20.7 The low¿starch diet in AS 322 20.8 Conclusions 324 Take¿home message 325 References 325 21 Microbiome of chronic plaque psoriasis 327Lionel Fry 21.1 Introduction 327 21.2 Microbiota in psoriasis 329 21.3 Variation of microbiota with site 331 21.4 Swabs versus biopsies 331 21.5 Psoriatic arthritis 331 21.6 Microbiome and immunity 332 21.7 Evidence that the skin microbiome may be involved in the pathogenesis of psoriasis 332 21.8 New hypothesis on the pathogenesis of psoriasis 334 Take¿home message 334 References 335 22 Liver disease: interactions with the intestinal microbiota 339Katharina Brandl and Bernd Schnabl 22.1 Introduction 339 22.2 Non¿alcoholic fatty liver disease 339 22.3 Qualitative and quantitative changes in the intestinal microbiota 340 22.4 Endotoxin 341 22.5 Ethanol 342 22.6 Choline 342 22.7 Alcoholic liver disease 343 Take¿home message 346 References 346 23 The gut microbiota: a predisposing factor in obesity diabetes and atherosclerosis 351Frida Fåk 23.1 Introduction 351 23.2 The "obesogenic" microbiota: evidence from animal models 351 23.3 The "obesogenic" microbiota in humans 352 23.4 A leaky gut contributing to inflammation and adiposity 352 23.5 Obesity¿proneness: mediated by the gut microbiota? 353 23.6 Bacterial metabolites provide a link between bacteria and host metabolism 353 23.7 Fecal microbiota transplants: can we change our gut bacterial profiles? 354 23.8 What happens with the gut microbiota during weight loss? 354 23.9 The "diabetic" microbiota 355 23.10 The "atherosclerotic" microbiota 356 23.11 Conclusions 357 Take¿home message 357 References 357 24 The microbiota and susceptibility to asthma 361Olawale Salami and Benjamin J....