The Human Microbiota and Chronic Disease – Dysbiosis as a Cause of Human Pathology

<p>List of&nbsp;contributors, xvii<br />Preface, xxi</p>
<p>Section 1 An introduction to the human tissue microbiome, 1<br />1&nbsp;&nbsp; The human microbiota: an historical perspective, 3<br />Mike Wilson<br />1.1 Introduction: the&nbsp;discovery of&nbsp;the&nbsp;human microbiota: why do we&nbsp;care?, 3<br />1.2 The importance of&nbsp;the&nbsp;indigenous microbiota in&nbsp;health and&nbsp;disease, 3<br />1.2.1 The indigenous microbiota and&nbsp;human disease, 4<br />1.2.2 The indigenous microbiota and&nbsp;human health, 4<br />1.3 The development of&nbsp;technologies for&nbsp;characterising the&nbsp;indigenous microbiota, 8<br />1.3.1 Light microscopy, 9<br />1.3.2 Electron microscopy, 11<br />1.3.3 Culture ]based approaches to&nbsp;microbial community analysis, 12<br />1.4 Culture ]independent approaches to&nbsp;microbial community analysis, 29<br />1.5 Determination of&nbsp;microbial community functions, 31<br />1.6 Closing remarks, 32<br />Take ]home message, 32<br />References, 33<br />2&nbsp; An introduction to microbial&nbsp;dysbiosis, 37<br />Mike Curtis<br />2.1 Definition of&nbsp;dysbiosis, 37<br />2.2 The normal microbiota, 38<br />2.3 Main features of&nbsp;dysbiosis, 45<br />2.4 Conclusions, 49<br />Take ]home message, 53<br />Acknowledgment, 53<br />References, 53<br />3&nbsp; The gut microbiota: an integrated interactive system, 55<br />Herv&eacute; M. Blotti&egrave;re and Jo&euml;l Dor&eacute;<br />3.1 Introduction, 55<br />3.2 Who is there, how is it composed?, 56<br />3.3 A system in&nbsp;interaction with&nbsp;food, 58<br />3.4 A system highly impacted by the&nbsp;host, 61<br />3.5 A system in&nbsp;interaction with&nbsp;human cells, 62<br />3.6 Conclusion: an&nbsp;intriguing integrated interactive system deserving&nbsp;further&nbsp;study, 63<br />Take ]home message, 63<br />References, 63<br />4&nbsp; The oral microbiota, 67<br />W. G. Wade<br />4.1 Introduction, 67<br />4.2 Composition of&nbsp;the&nbsp;oral microbiome, 68<br />4.2.1 Archaea, 68<br />4.2.2 Fungi, 68<br />4.2.3 Protozoa, 68<br />4.2.4 Viruses, 69<br />4.2.5 Bacteria, 69<br />4.3 The oral microbiota in&nbsp;health, 71<br />4.3.1 Evolution of&nbsp;the&nbsp;oral microbiota, 71<br />4.3.2 Role of&nbsp;oral bacteria in&nbsp;health, 72<br />4.4 Role of&nbsp;oral microbiome in&nbsp;disease, 73<br />4.4.1 Dental caries, 73<br />4.4.2 Gingivitis, 74<br />4.4.3 Oral bacteria and&nbsp;non ]oral disease, 74<br />4.5 Future outlook, 75<br />Take ]home message, 75<br />References, 76<br />5&nbsp; The skin microbiota, 81<br />P.L.J.M. Zeeuwen and J. Schalkwijk<br />5.1 Normal skin, 81<br />5.2 Skin diseases, 83<br />5.2.1 Atopic dermatitis, 83<br />5.2.2 Psoriasis, 84<br />5.2.3 Acne, 85<br />5.2.4 Rosacea, 85<br />5.2.5 Seborrheic dermatitis and&nbsp;dandruff, 86<br />5.2.6 Primary immunodeficiencies, 86<br />5.3 Experimental studies, 87<br />5.4 Dynamics of&nbsp;the&nbsp;skin microbiome, 87<br />5.5 Axillary skin microbiome transplantation, 89<br />5.6 Mouse skin microbiome studies, 89<br />5.7 Concluding remarks, 90<br />Take ]home message, 90<br />References, 90<br />6&nbsp; Metagenomic analysis of&nbsp;the&nbsp;human microbiome, 95<br />Luis G. Berm&uacute;dez ]Humar&aacute;n<br />6.1 Introduction, 95<br />6.2 The human microbiome, 96<br />6.3 Changes in&nbsp;microbiota composition during host life cycles, 97<br />6.4 The human microbiome and&nbsp;the&nbsp;environment, 98<br />6.5 Disease and&nbsp;health implications of&nbsp;microbiome, 99<br />6.5.1 The skin microbiota, 99<br />6.5.2 The airway microbiome, 99<br />6.5.3 Vaginal microbiome, 100<br />6.5.4 Gut microbiota and&nbsp;disease, 101<br />6.5.5 Metabolic disorders (obesity/diabetes), 103<br />6.6 Conclusions, 105<br />Take ]home message, 105<br />References, 106<br />Section 2 <br />Microbiota–microbiota and microbiota–host interactions in&nbsp;health and disease, 113<br />7&nbsp; Systems biology of&nbsp;bacteria ]host interactions, 115<br />Almut Heinken, Dmitry A. Ravcheev and Ines Thiele<br />7.1 Introduction, 115<br />7.2 Computational analysis of&nbsp;host ]microbe interactions, 118<br />7.2.1 Analysis of&nbsp;metagenomic data, 118<br />7.2.2 Metabolic reconstruction through comparative genomics, 119<br />7.3 Network ]based modeling, 121<br />7.3.1 Topological network modeling, 121<br />7.3.2 Constraint ]based modeling, 123<br />7.3.3 Metabolic reconstructions of&nbsp;human metabolism, 124<br />7.3.4 Constraint ]based modeling of&nbsp;host ]microbe interactions, 124<br />7.4 Other computational modeling approaches, 127<br />7.4.1 Ordinary differential equation (ODE) models, 127<br />7.4.2 Kinetic modeling, 128<br />7.5 Conclusion, 129<br />Take ]home message, 130<br />Acknowledgments, 130<br />References, 131<br />8&nbsp; Bacterial biofilm formation and&nbsp;immune evasion mechanisms, 139<br />Jessica Snowden<br />8.1 Introduction, 139<br />8.2 Biofilms in&nbsp;human disease, 139<br />8.3 Biofilm formation, 141<br />8.4 Immune responses to&nbsp;biofilms, 143<br />8.4.1 Innate immune responses, 144<br />8.4.2 Adaptive immune responses, 146<br />8.4.3 Fibroblasts, epithelial cells and&nbsp;other immune responses, 147<br />8.5 Biofilm immune evasion strategies, 147<br />8.6 Vaccines and&nbsp;biofilm therapeutics, 148<br />8.7 Conclusions, 149<br />Take ]home message, 149<br />References, 150<br />9&nbsp; Co ]evolution of&nbsp;microbes and&nbsp;immunity and&nbsp;its consequences<br />for&nbsp;modern ]day life, 155<br />Markus B. Geuking<br />9.1 Introduction, 155<br />9.2 Symbiosis in&nbsp;eukaryotic evolution, 156<br />9.3 Evolution of&nbsp;the&nbsp;(innate and&nbsp;adaptive) immune system, 157<br />9.3.1 Immune proteins, 157<br />9.3.2 Evolution of&nbsp;adaptive immunity, 158<br />9.3.3 Two separate adaptive immune systems evolved, 158<br />9.4 Hygiene hypothesis, 159<br />9.5 What drives the&nbsp;composition of&nbsp;the&nbsp;microbiota?, 160<br />9.6 The pace of&nbsp;evolution, 161<br />Take ]home message, 162<br />References, 162<br />10&nbsp; How viruses and&nbsp;bacteria have shaped the&nbsp;human genome: the implications for&nbsp;disease, 165<br />Frank Ryan<br />10.1 Genetic symbiosis, 165<br />10.2 Mitochondria: symbiogenesis in&nbsp;the&nbsp;human, 167<br />10.3 Virus symbiogenesis, 169<br />10.4 HERV proteins, 172<br />Take ]home message, 174<br />References, 174<br />11 The microbiota as&nbsp;an&nbsp;epigenetic control mechanism, 179<br />Boris A. Shenderov<br />11.1 Introduction, 179<br />11.2 Background on&nbsp;epigenetics and&nbsp;epigenomic programming/reprograming, 180<br />11.3 Epigenomics and&nbsp;link with&nbsp;energy metabolism, 184<br />11.4 The microbiota as&nbsp;a&nbsp;potential epigenetic modifier, 185<br />11.5 <br />Epigenetic control of&nbsp;the&nbsp;host genes by pathogenic and&nbsp;opportunistic microorganisms, 188<br />11.6 Epigenetic control of&nbsp;the&nbsp;host genes by indigenous (probiotic) microorganisms, 189<br />11.7 Concluding remarks and&nbsp;future directions, 191<br />Take home message, 193<br />References, 193<br />12 The emerging role of&nbsp;propionibacteria in&nbsp;human health<br />and&nbsp;disease, 199<br />Holger Br&uuml;ggemann<br />12.1 Introduction, 199<br />12.2 Microbiological features of&nbsp;propionibacteria, 199<br />12.3 Population structure of&nbsp;P. acnes, 201<br />12.4 Propionibacteria as&nbsp;indigenous probiotics of&nbsp;the&nbsp;skin, 202<br />12.5 Propionibacteria as&nbsp;opportunistic pathogens, 203<br />12.6 Host interacting traits and&nbsp;factors of propionibacteria, 205<br />12.7 Host responses to&nbsp;P. acnes, 206<br />12.7.1 Innate immune responses, 206<br />12.7.2 Adaptive immune responses, 207<br />12.7.3 Host cell tropism of&nbsp;P. acnes, 208<br />12.8 Propionibacterium ]specific bacteriophages, 208<br />12.9 Concluding remarks, 209<br />Take home message, 210<br />References, 210<br />Section 3 Dysbioses and bacterial diseases: metchnikoff s legacy, 215<br />13&nbsp; The periodontal diseases: microbial diseases or diseases of&nbsp;the&nbsp;host response?, 217<br />Luigi Nibali<br />13.1 The tooth: a&nbsp;potential breach in&nbsp;the&nbsp;mucosal barrier, 217<br />13.2 The periodontium from&nbsp;health to&nbsp;disease, 217<br />13.3 Periodontitis: one of&nbsp;the&nbsp;most common human diseases, 219<br />13.4 Periodontal treatment: a&nbsp;non ]specific biofilm disruption, 220<br />13.5 Microbial etiology, 220<br />13.6 The host response in&nbsp;periodontitis, 221<br />13.7 Conclusions, 223<br />Take home message, 223<br />References, 223<br />14&nbsp;The polymicrobial synergy and dysbiosis model of periodontal disease<br />pathogenesis, 227<br />George Hajishengallis and Richard J. Lamont<br />14.1 Introduction, 227<br />14.2 A (very) polymicrobial etiology of periodontitis, 229<br />14.3 Synergism among periodontal bacteria, 230<br />14.4 Interactions between bacterial communities and epithelial cells, 232<br />14.5 Manipulation of host immunity, 233<br />14.6 Conclusions, 237<br />Take ]home message, 238<br />References, 239<br />15&nbsp;New paradigm in the relationship between periodontal disease and systemic diseases: ef–fects of oral bacteria on the gut microbiota and metabolism, 243<br />Kazuhisa Yamazaki<br />15.1 Introduction, 243<br />15.2 Association between periodontal and systemic diseases, 244<br />15.2.1 Periodontal disease and diabetes, 244<br />15.2.2 Periodontal disease and atherosclerotic vascular diseases, 245<br />15.2.3 Periodontal disease and rheumatoid arthritis, 246<br />15.2.4 Periodontal disease and non ]alcoholic fatty liver disease, 246<br />15.2.5 Periodontal disease and pre ]term birth, 247<br />15.2.6 Periodontal disease and obesity, 248<br />15.2.7 Periodontal disease and cancer, 248<br />15.2.8 Periodontal disease and inflammatory bowel disease, 249<br />15.3 Issues in causal mechanisms of periodontal disease for systemic disease, 249<br />15.3.1 Endotoxemia (bacteremia), 249<br />15.3.2 Inflammatory mediators, 251<br />15.3.3 Autoimmune response from molecular mimicry, 251<br />15.4 New insights into the mechanisms linking periodontal disease and s&shy;ystemic disease, 252<br />15.5 Effect of oral administration of P. gingivalis on metabolic change <br />and gut microbiota, 252<br />15.6 Conclusions, 254<br />Take ]home message, 255<br />References, 255<br />16&nbsp;The vaginal microbiota in health and disease, 263<br />S. Tariq Sadiq and Phillip Hay<br />16.1 What makes a healthy microbiota, 263<br />16.1.1 How does the vaginal microbiota mediate healthiness?, 264<br />16.1.2 Establishment of the vaginal microbiota, 264<br />16.1.3 The role of host genetic variation on vaginal health, 264<br />16.1.4 <br />Impact of age, menstrual cycle and environmental factors on vaginal health, 265<br />16.2 The Vaginal Microbiota in Disease, 265<br />16.2.1 Bacterial vaginosis, 265<br />16.2.2 <br />Clinical consequences of altered vaginal microbiota <br />(see Figure 1), 268<br />16.2.3 <br />Vaginal microbiota and transmission and susceptibility to HIV infection, 269<br />16.3 Conclusions, 269<br />Take ]home message, 269<br />References, 270<br />Section 4 <br />Dysbioses and chronic diseases: is there <br />a connection?, 273<br />17&nbsp;Reactive arthritis: the hidden bacterial connection, 275<br />John D. Carter<br />17.1 Introduction, 275<br />17.2 Reactive arthritis, 276<br />17.3 Pathophysiology of ReA, 277<br />17.4 Questions remain, 279<br />17.5 Conclusion, 280<br />Take ]home message, 280<br />References, 280<br />18&nbsp;Rheumatoid arthritis: the bacterial connection, 283<br />Jacqueline Detert<br />18.1 Preclinical rheumatoid arthritis, 283<br />18.2 Predisposition to RA, 284<br />18.3 MCH ]HLA and genetic predisposition to RA, 284<br />18.4 Molecular mimicry in RA, 285<br />18.5 Innate immune system and RA, 285<br />18.6 Bystander activation and pattern recognition receptors, 286<br />18.7 Antibodies and neoepitopes, 287<br />18.8 Superantigens, 287<br />18.9 LPS, 287<br />18.10 Bacterial DNA and peptidoglycans, 288<br />18.11 Heat ]shock proteins, 288<br />18.12 Toll ]like and bacterial infections, 288<br />18.13 Proteus mirabilis, 288<br />18.14 Porphyromonas gingivalis and RA, 289<br />18.15 Gastrointestinal flora and RA, 290<br />18.16 Smoking, lung infection and RA, 291<br />18.17 Where to go from here?, 291<br />Take ]home message, 291<br />References, 292<br />19&nbsp;Inflammatory bowel disease and the gut microbiota, 301<br />Nik Ding and Ailsa Hart<br />19.1 The microbiota in inflammatory bowel disease, 301<br />19.2 Dysbiosis and IBD pathogenesis, 301<br />19.3 Environmental factors affecting microbiome composition, 302<br />19.3.1 Diet, 302<br />19.3.2 Age, 303<br />19.4 <br />Genetics and application to the immune system and dysbiosis in IBD, 303<br />19.5 An overview of gut microbiota studies in IBD, 305<br />19.6 Specific bacterial changes in IBD, 306<br />19.6.1 Potentiators, 306<br />19.6.2 Protectors, 307<br />19.6.3 <br />Anti ]inflammatory effects of microbiota (functional dysbiosis), 308<br />19.7 Functional composition of microbiota in IBD, 308<br />19.8 Challenges, 310<br />19.9 Conclusion, 310<br />Take ]home message, 310<br />References, 310<br />20&nbsp;Ankylosing spondylitis, klebsiella and the low ]starch diet, 317<br />Alan Ebringer, Taha Rashid and Clyde Wilson<br />20.1 Introduction, 317<br />20.2 Clinical features of AS, 317<br />20.3 Gut bacteria and total serum IgA, 318<br />20.4 Molecular mimicry in AS, 319<br />20.5 Pullulanase system and collagens, 320<br />20.6 Specific antibodies to Klebsiella in AS patients, 321<br />20.7 The low ]starch diet in AS, 322<br />20.8 Conclusions, 324<br />Take ]home message, 325<br />References, 325<br />21&nbsp;Microbiome of chronic plaque psoriasis, 327<br />Lionel Fry<br />21.1 Introduction, 327<br />21.2 Microbiota in psoriasis, 329<br />21.2.1 Bacteria, 329<br />21.2.2 Fungi, 330<br />21.3 Variation of microbiota with site, 331<br />21.4 Swabs versus biopsies, 331<br />21.5 Psoriatic arthritis, 331<br />21.6 Microbiome and immunity, 332<br />21.7 Evidence that the skin microbiome may be involved in the pathogenesis of psoriasis, 332<br />21.7.1 Psoriasis and crohn s disease, 332<br />21.7.2 Genetic factors, 333<br />21.7.3 Innate immunity, 333<br />21.8 New hypothesis on the pathogenesis of psoriasis, 334<br />Take ]home message, 334<br />References, 335<br />22&nbsp;Liver disease: interactions with the intestinal microbiota, 339<br />Katharina Brandl and Bernd Schnabl<br />22.1 Introduction, 339<br />22.2 Non ]alcoholic fatty liver disease, 339<br />22.3 Qualitative and quantitative changes in the intestinal microbiota, 340<br />22.4 Endotoxin, 341<br />22.5 Ethanol, 342<br />22.6 Choline, 342<br />22.7 Alcoholic liver disease, 343<br />22.7.1 Qualitative and quantitative changes in the intestinal microbiome, 343<br />22.7.2 Contribution of dysbiosis to alcoholic liver disease, 344<br />Take ]home message, 346<br />References, 346<br />23&nbsp;The gut microbiota: a predisposing factor in obesity, diabetes<br />and atherosclerosis, 351<br />Frida F&aring;k<br />23.1 Introduction, 351<br />23.2 The obesogenic microbiota: evidence from animal models, 351<br />23.3 The obesogenic microbiota in humans, 352<br />23.4 A leaky gut contributing to inflammation and adiposity, 352<br />23.5 Obesity ]proneness: mediated by the gut microbiota?, 353<br />23.6 Bacterial metabolites provide a link between bacteria and host metabolism, 353<br />23.7 Fecal microbiota transplants: can we change our gut bacterial profiles?, 354<br />23.8 What happens with the gut microbiota during weight loss?, 354<br />23.9 The diabetic microbiota, 355<br />23.9.1 Type I diabetes and the gut microbiota, 355<br />23.9.2 Type II diabetes, 355<br />23.10 The atherosclerotic microbiota, 356<br />23.11 Conclusions, 357<br />Take ]home message, 357<br />References, 357<br />24&nbsp;The microbiota and susceptibility to asthma, 361<br />O. Salami and B J. Marsland<br />24.1 Introduction, 361<br />24.2 The microenvironment of the lower airways, 361<br />24.3 Development of the airway microbiota in the neonate, 362<br />24.3.1 Intrauterine microbial exposure and airway microbiota, 362<br />24.3.2 Perinatal events and airway microbiota, 363<br />24.3.3 Breast milk as a source of airway microbiota, 364<br />24.3.4 Airborne microbiota and airway microbiota, 364<br />24.4 Upper airway microbiota, 364<br />24.5 What constitutes a healthy airway microbiota, 365<br />24.6 Microbiota and asthma, 365<br />24.7 Dietary metabolites and asthma, 366<br />24.8 Conclusion, future perspectives and clinical implications, 367<br />Take ]home message, 367<br />References, 367<br />25&nbsp;Microbiome and cancer, 371<br />Ralph Francescone and D&eacute;bora B. Vendramini ]Costa<br />25.1 Introduction, 371<br />25.2 Microbiome and cancer: where is the link?, 374<br />25.3 Microbiome and barrier disruption, 376<br />25.4 Microbiome and different types of cancer, 377<br />25.4.1 Colon cancer, 377<br />25.4.2 Skin cancer, 378<br />25.4.3 Breast cancer, 379<br />25.4.4 Liver cancer, 379<br />25.4.5 Local microbes affecting distant cancers, 381<br />25.5 Microbiota and metabolism: the good and the bad sides, 382<br />25.6 Chemotherapy, the microbiome and the immune system, 384<br />25.7 Therapeutic avenues, 385<br />25.7.1 Modulation of bacterial enzyme activity, 385<br />25.7.2 Antibiotics, 386<br />25.7.3 Pre ] and probiotics, 386<br />25.7.4 Fecal transplantation, 386<br />25.8 Unresolved questions and future work, 387<br />Take ]home message, 387<br />References, 387<br />26&nbsp;Colorectal cancer and the microbiota, 391<br />Iradj Sobhani and S&eacute;verine Couffin<br />26.1 Introduction, 391<br />26.2 Colon carcinogenesis and epidemiological data, 392<br />26.2.1 Human carcinogenesis model, 392<br />26.2.2 Age ]related risk in the general population, 393<br />26.2.3 Gene ] and familial ]related risks, 393<br />26.2.4 Environment ]related risk, 394<br />26.3 The microbiota, 394<br />26.4 Bacteria and CRCs links, 395<br />26.4.1 Historical data, 395<br />26.4.2 Clinical data, 396<br />26.4.3 Experimental data and mechanisms involved, 397<br />26.5 Hypotheses and perspectives, 402<br />Take ]home message, 405<br />References, 405<br />27&nbsp;The gut microbiota and the CNS: an old story witha new beginning, 409<br />Aadil Bharwani and Paul Forsythe<br />27.1 Introduction, 409<br />27.2 The microbiota ]gut ]brain axis: a historical framework, 410<br />27.3 The microbiota ]gut ]brain axis: an evolutionary perspective, 411<br />27.4 The gut microbiota influence on brain and behavior, 413<br />27.5 Microbes and the hardwired gut brain axis, 415<br />27.5.1 The vagus, 416<br />27.5.2 The enteric nervous system, 417<br />27.6 Hormonal pathways to the brain, 418<br />27.7 Microbes and immune pathways to the brain, 420<br />27.8 Metabolites of the microbiota: short ]chain fatty acids, 421<br />27.9 Clinical implications of the microbiota ]gut ]brain axis, 422<br />27.10 Conclusion, 422<br />Take ]home message, 423<br />References, 423<br />28&nbsp;Genetic dysbiosis: how host genetic variants may affect microbial b&shy;iofilms, 431<br />Luigi Nibali<br />28.1 The holobiont: humans as supra ]organisms, 431<br />28.2 Genetic variants in the host response to microbes, 432<br />28.2.1 Bacterial recognition pathway, 432<br />28.2.2 Bacterial proliferation, 433<br />28.3 Genetic dysbiosis, 434<br />28.3.1 Genetic dysbiosis of oral biofilm, 435<br />28.3.2 Genetic dysbiosis of gut biofilm, 435<br />28.3.3 Genetic dysbiosis of skin biofilm, 436<br />28.3.4 Genetic dysbiosis of vaginal biofilm, 437<br />28.4 Summary and conclusions, 438<br />Take ]home message, 438<br />References, 438<br />Section 5 Mirroring the future: dysbiosis therapy, 443<br />29&nbsp;Diet and dysbiosis, 445<br />M. Estaki, C. Quin and D.L. Gibson<br />29.1 Introduction, 445<br />29.2 Coevolution of the host ]microbiota super ]organism, 445<br />29.3 Gut microbiota in personalized diets, 446<br />29.4 The evolution of diet, 447<br />29.5 Plasticity of the microbiota and diet, 447<br />29.6 Interaction among gut microbiota, host and food, 448<br />29.7 Consequences of diet ]induced dysbiosis for host health, 450<br />29.8 The role of gut microbes on the digestion of macronutrients, 451<br />29.8.1 Carbohydrates, 451<br />29.8.2 Proteins, 451<br />29.8.3 Lipids, 452<br />29.9 Diet induces dysbiosis in the host, 452<br />29.9.1 Protein, 453<br />29.9.2 Carbohydrates, 453<br />29.9.3 Lipids, 454<br />29.10 The effect of maternal diet on offspring microbiota, 456<br />29.11 The effects of post ]natal diet on the developing microbiota of neonates, 457<br />29.11.1 Breast milk, 457<br />29.11.2 Formula, 458<br />29.12 Conclusion, 459<br />Take ]home message, 459<br />Host–food, 460<br />References, 460<br />30&nbsp;Probiotics and prebiotics: what are they and<br />what can they do for us?, 467<br />Marie Jos&eacute; Butel, Anne ]Judith and Waligora ]Dupriet<br />30.1 The gut microbiota, a partnership with the host, 467<br />30.2 Probiotics, 467<br />30.2.1 Probiotics, a story that began a long time ago, 467<br />30.2.2 What are probiotics?, 468<br />30.2.3 How do probiotics work?, 468<br />30.2.4 Safety of probiotics, 469<br />30.3 Prebiotics, 470<br />30.3.1 What are prebiotics?, 470<br />30.3.2 How do prebiotics work?, 471<br />30.4 Synbiotics, 471<br />30.5 Pro ], pre ], and synbiotics in human medicine today, 471<br />30.5.1 Pro ] and prebiotics and infectious diarrhea, 471<br />30.5.2 Pro ] and prebiotics and inflammatory bowel diseases, 472<br />30.5.3 Pro ] and prebiotics and irritable bowel syndrome, 473<br />30.5.4 Pro ] and prebiotics and allergy, 474<br />30.5.5 Pro ] and prebiotics and obesity and diabetes, 475<br />30.5.6 Other indications, 475<br />30.5.7 Pre ] and probiotics in pediatrics, 476<br />30.6 Concluding remarks, 477<br />Take–home message, 478<br />References, 47831 The microbiota as target for therapeutic intervention in pediatric <br />intestinal diseases, 483<br />Andrea Lo Vecchio and Alfredo Guarino<br />31.1 Introduction, 483<br />31.2 Use of probiotics in pediatric intestinal diseases, 484<br />31.2.1 Acute diarrhea, 484<br />31.2.2 Inflammatory bowel diseases, 486<br />31.2.3 Irritable bowel syndrome, 487<br />31.2.4 Infant colic, 487<br />31.2.5 Necrotizing enterocolitis, 488<br />31.3 Fecal microbiota transplantation for treatment of intestinal diseases, 488<br />31.3.1 Preparation and administration, 488<br />31.3.2 Advantages and barriers, 490<br />31.3.3 The use of FMT in specific intestinal diseases, 490<br />31.4 Conclusion, 492<br />Take ]home message, 493<br />References, 493<br />32 Microbial therapy for cystic fibrosis, 497<br />Eugenia Bruzzese, Vittoria Buccigrossi, Giusy Ranucci and Alfredo Guarino<br />32.1 Introduction: pathophysiology of cystic fibrosis, 497<br />32.2 Intestinal inflammation in CF, 498<br />32.3 Dysbiosis in CF, 499<br />32.4 Microbial therapy in CF, 502<br />32.5 Conclusion, 504<br />Take home message, 504<br />References, 504<br />Index, 000</p>