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

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

By: Brian Henderson (editor), Luigi Nibali (editor)Hardback

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Description

Microbiota-associated pathology can be a direct result of changes in general bacterial composition, such as might be found in periodontitis and bacterial vaginosis, and/or as the result of colonization and/or overgrowth of so called keystone species. The disruption in the composition of the normal human microbiota, or dysbiosis, plays an integral role in human health and human disease. The Human Microbiota and Human Chronic Disease: Dysbioses as a Cause of Human Pathology discusses the role of the microbiota in maintaining human health. The text introduces the reader to the biology of microbial dysbiosis and its potential role in both bacterial disease and in idiopathic chronic disease states. Divided into five sections, the text delineates the concept of the human bacterial microbiota with particular attention being paid to the microbiotae of the gut, oral cavity and skin. A key methodology for exploring the microbiota, metagenomics, is also described. The book then shows the reader the cellular, molecular and genetic complexities of the bacterial microbiota, its myriad connections with the host and how these can maintain tissue homeostasis. Chapters then consider the role of dysbioses in human disease states, dealing with two of the commonest bacterial diseases of humanity periodontitis and bacterial vaginosis. The composition of some, if not all microbiotas can be controlled by the diet and this is also dealt with in this section. The discussion moves on to the major idiopathic diseases afflicting humans, and the potential role that dysbiosis could play in their induction and chronicity. The book then concludes with the therapeutic potential of manipulating the microbiota, introducing the concepts of probiotics, prebiotics and the administration of healthy human faeces (faecal microbiota transplantation), and then hypothesizes as to the future of medical treatment viewed from a microbiota-centric position. * Provides an introduction to dysbiosis, or a disruption in the composition of the normal human microbiota * Explains how microbiota-associated pathology and other chronic diseases can result from changes in general bacterial composition * Explores the relationship humans have with their microbiota, and its significance in human health and disease * Covers host genetic variants and their role in the composition of human microbial biofilms, integral to the relationship between human health and human disease Authored and edited by leaders in the field, The Human Microbiota and Human Chronic Disease will be an invaluable resource for clinicians, pathologists, immunologists, cell and molecular biologists, biochemists, and system biologists studying cellular and molecular bases of human diseases.

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About Author

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.

Contents

List of contributors, xvii Preface, xxi Section 1 An introduction to the human tissue microbiome, 1 1 The human microbiota: an historical perspective, 3 Mike 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 1.2.1 The indigenous microbiota and human disease, 4 1.2.2 The indigenous microbiota and human health, 4 1.3 The development of technologies for characterising the indigenous microbiota, 8 1.3.1 Light microscopy, 9 1.3.2 Electron microscopy, 11 1.3.3 Culture ]based approaches to microbial community analysis, 12 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, 37 Mike 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, 55 Herve M. Blottiere and Joel Dore 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, 67 W. G. Wade 4.1 Introduction, 67 4.2 Composition of the oral microbiome, 68 4.2.1 Archaea, 68 4.2.2 Fungi, 68 4.2.3 Protozoa, 68 4.2.4 Viruses, 69 4.2.5 Bacteria, 69 4.3 The oral microbiota in health, 71 4.3.1 Evolution of the oral microbiota, 71 4.3.2 Role of oral bacteria in health, 72 4.4 Role of oral microbiome in disease, 73 4.4.1 Dental caries, 73 4.4.2 Gingivitis, 74 4.4.3 Oral bacteria and non ]oral disease, 74 4.5 Future outlook, 75 Take ]home message, 75 References, 76 5 The skin microbiota, 81 P.L.J.M. Zeeuwen and J. Schalkwijk 5.1 Normal skin, 81 5.2 Skin diseases, 83 5.2.1 Atopic dermatitis, 83 5.2.2 Psoriasis, 84 5.2.3 Acne, 85 5.2.4 Rosacea, 85 5.2.5 Seborrheic dermatitis and dandruff, 86 5.2.6 Primary immunodeficiencies, 86 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, 95 Luis G. Bermudez ]Humaran 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 6.5.1 The skin microbiota, 99 6.5.2 The airway microbiome, 99 6.5.3 Vaginal microbiome, 100 6.5.4 Gut microbiota and disease, 101 6.5.5 Metabolic disorders (obesity/diabetes), 103 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 bacteria ]host interactions, 115 Almut Heinken, Dmitry A. Ravcheev and Ines Thiele 7.1 Introduction, 115 7.2 Computational analysis of host ]microbe interactions, 118 7.2.1 Analysis of metagenomic data, 118 7.2.2 Metabolic reconstruction through comparative genomics, 119 7.3 Network ]based modeling, 121 7.3.1 Topological network modeling, 121 7.3.2 Constraint ]based modeling, 123 7.3.3 Metabolic reconstructions of human metabolism, 124 7.3.4 Constraint ]based modeling of host ]microbe interactions, 124 7.4 Other computational modeling approaches, 127 7.4.1 Ordinary differential equation (ODE) models, 127 7.4.2 Kinetic modeling, 128 7.5 Conclusion, 129 Take ]home message, 130 Acknowledgments, 130 References, 131 8 Bacterial biofilm formation and immune evasion mechanisms, 139 Jessica Snowden 8.1 Introduction, 139 8.2 Biofilms in human disease, 139 8.3 Biofilm formation, 141 8.4 Immune responses to biofilms, 143 8.4.1 Innate immune responses, 144 8.4.2 Adaptive immune responses, 146 8.4.3 Fibroblasts, epithelial cells and other immune responses, 147 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, 155 Markus B. Geuking 9.1 Introduction, 155 9.2 Symbiosis in eukaryotic evolution, 156 9.3 Evolution of the (innate and adaptive) immune system, 157 9.3.1 Immune proteins, 157 9.3.2 Evolution of adaptive immunity, 158 9.3.3 Two separate adaptive immune systems evolved, 158 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, 165 Frank Ryan 10.1 Genetic symbiosis, 165 10.2 Mitochondria: symbiogenesis in the human, 167 10.3 Virus symbiogenesis, 169 10.4 HERV proteins, 172 Take ]home message, 174 References, 174 11 The microbiota as an epigenetic control mechanism, 179 Boris 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, 199 Holger Bruggemann 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 12.7.1 Innate immune responses, 206 12.7.2 Adaptive immune responses, 207 12.7.3 Host cell tropism of P. acnes, 208 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?, 217 Luigi 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, 227 George 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: ef-fects of oral bacteria on the gut microbiota and metabolism, 243 Kazuhisa Yamazaki 15.1 Introduction, 243 15.2 Association between periodontal and systemic diseases, 244 15.2.1 Periodontal disease and diabetes, 244 15.2.2 Periodontal disease and atherosclerotic vascular diseases, 245 15.2.3 Periodontal disease and rheumatoid arthritis, 246 15.2.4 Periodontal disease and non ]alcoholic fatty liver disease, 246 15.2.5 Periodontal disease and pre ]term birth, 247 15.2.6 Periodontal disease and obesity, 248 15.2.7 Periodontal disease and cancer, 248 15.2.8 Periodontal disease and inflammatory bowel disease, 249 15.3 Issues in causal mechanisms of periodontal disease for systemic disease, 249 15.3.1 Endotoxemia (bacteremia), 249 15.3.2 Inflammatory mediators, 251 15.3.3 Autoimmune response from molecular mimicry, 251 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, 263 S. Tariq Sadiq and Phillip Hay 16.1 What makes a healthy microbiota, 263 16.1.1 How does the vaginal microbiota mediate healthiness?, 264 16.1.2 Establishment of the vaginal microbiota, 264 16.1.3 The role of host genetic variation on vaginal health, 264 16.1.4 Impact of age, menstrual cycle and environmental factors on vaginal health, 265 16.2 The Vaginal Microbiota in Disease, 265 16.2.1 Bacterial vaginosis, 265 16.2.2 Clinical consequences of altered vaginal microbiota (see Figure 1), 268 16.2.3 Vaginal microbiota and transmission and susceptibility to HIV infection, 269 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, 275 John 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, 283 Jacqueline 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, 301 Nik 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 19.3.1 Diet, 302 19.3.2 Age, 303 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 19.6.1 Potentiators, 306 19.6.2 Protectors, 307 19.6.3 Anti ]inflammatory effects of microbiota (functional dysbiosis), 308 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, 317 Alan 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, 327 Lionel Fry 21.1 Introduction, 327 21.2 Microbiota in psoriasis, 329 21.2.1 Bacteria, 329 21.2.2 Fungi, 330 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 21.7.1 Psoriasis and crohn s disease, 332 21.7.2 Genetic factors, 333 21.7.3 Innate immunity, 333 21.8 New hypothesis on the pathogenesis of psoriasis, 334 Take ]home message, 334 References, 335 22 Liver disease: interactions with the intestinal microbiota, 339 Katharina 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 22.7.1 Qualitative and quantitative changes in the intestinal microbiome, 343 22.7.2 Contribution of dysbiosis to alcoholic liver disease, 344 Take ]home message, 346 References, 346 23 The gut microbiota: a predisposing factor in obesity, diabetes and atherosclerosis, 351 Frida Fak 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 23.9.1 Type I diabetes and the gut microbiota, 355 23.9.2 Type II diabetes, 355 23.10 The atherosclerotic microbiota, 356 23.11 Conclusions, 357 Take ]home message, 357 References, 357 24 The microbiota and susceptibility to asthma, 361 O. Salami and B J. Marsland 24.1 Introduction, 361 24.2 The microenvironment of the lower airways, 361 24.3 Development of the airway microbiota in the neonate, 362 24.3.1 Intrauterine microbial exposure and airway microbiota, 362 24.3.2 Perinatal events and airway microbiota, 363 24.3.3 Breast milk as a source of airway microbiota, 364 24.3.4 Airborne microbiota and airway microbiota, 364 24.4 Upper airway microbiota, 364 24.5 What constitutes a healthy airway microbiota, 365 24.6 Microbiota and asthma, 365 24.7 Dietary metabolites and asthma, 366 24.8 Conclusion, future perspectives and clinical implications, 367 Take ]home message, 367 References, 367 25 Microbiome and cancer, 371 Ralph Francescone and Debora B. Vendramini ]Costa 25.1 Introduction, 371 25.2 Microbiome and cancer: where is the link?, 374 25.3 Microbiome and barrier disruption, 376 25.4 Microbiome and different types of cancer, 377 25.4.1 Colon cancer, 377 25.4.2 Skin cancer, 378 25.4.3 Breast cancer, 379 25.4.4 Liver cancer, 379 25.4.5 Local microbes affecting distant cancers, 381 25.5 Microbiota and metabolism: the good and the bad sides, 382 25.6 Chemotherapy, the microbiome and the immune system, 384 25.7 Therapeutic avenues, 385 25.7.1 Modulation of bacterial enzyme activity, 385 25.7.2 Antibiotics, 386 25.7.3 Pre ] and probiotics, 386 25.7.4 Fecal transplantation, 386 25.8 Unresolved questions and future work, 387 Take ]home message, 387 References, 387 26 Colorectal cancer and the microbiota, 391 Iradj Sobhani and Severine Couffin 26.1 Introduction, 391 26.2 Colon carcinogenesis and epidemiological data, 392 26.2.1 Human carcinogenesis model, 392 26.2.2 Age ]related risk in the general population, 393 26.2.3 Gene ] and familial ]related risks, 393 26.2.4 Environment ]related risk, 394 26.3 The microbiota, 394 26.4 Bacteria and CRCs links, 395 26.4.1 Historical data, 395 26.4.2 Clinical data, 396 26.4.3 Experimental data and mechanisms involved, 397 26.5 Hypotheses and perspectives, 402 Take ]home message, 405 References, 405 27 The gut microbiota and the CNS: an old story witha new beginning, 409 Aadil Bharwani and Paul Forsythe 27.1 Introduction, 409 27.2 The microbiota ]gut ]brain axis: a historical framework, 410 27.3 The microbiota ]gut ]brain axis: an evolutionary perspective, 411 27.4 The gut microbiota influence on brain and behavior, 413 27.5 Microbes and the hardwired gut brain axis, 415 27.5.1 The vagus, 416 27.5.2 The enteric nervous system, 417 27.6 Hormonal pathways to the brain, 418 27.7 Microbes and immune pathways to the brain, 420 27.8 Metabolites of the microbiota: short ]chain fatty acids, 421 27.9 Clinical implications of the microbiota ]gut ]brain axis, 422 27.10 Conclusion, 422 Take ]home message, 423 References, 423 28 Genetic dysbiosis: how host genetic variants may affect microbial b-iofilms, 431 Luigi Nibali 28.1 The holobiont: humans as supra ]organisms, 431 28.2 Genetic variants in the host response to microbes, 432 28.2.1 Bacterial recognition pathway, 432 28.2.2 Bacterial proliferation, 433 28.3 Genetic dysbiosis, 434 28.3.1 Genetic dysbiosis of oral biofilm, 435 28.3.2 Genetic dysbiosis of gut biofilm, 435 28.3.3 Genetic dysbiosis of skin biofilm, 436 28.3.4 Genetic dysbiosis of vaginal biofilm, 437 28.4 Summary and conclusions, 438 Take ]home message, 438 References, 438 Section 5 Mirroring the future: dysbiosis therapy, 443 29 Diet and dysbiosis, 445 M. Estaki, C. Quin and D.L. Gibson 29.1 Introduction, 445 29.2 Coevolution of the host ]microbiota super ]organism, 445 29.3 Gut microbiota in personalized diets, 446 29.4 The evolution of diet, 447 29.5 Plasticity of the microbiota and diet, 447 29.6 Interaction among gut microbiota, host and food, 448 29.7 Consequences of diet ]induced dysbiosis for host health, 450 29.8 The role of gut microbes on the digestion of macronutrients, 451 29.8.1 Carbohydrates, 451 29.8.2 Proteins, 451 29.8.3 Lipids, 452 29.9 Diet induces dysbiosis in the host, 452 29.9.1 Protein, 453 29.9.2 Carbohydrates, 453 29.9.3 Lipids, 454 29.10 The effect of maternal diet on offspring microbiota, 456 29.11 The effects of post ]natal diet on the developing microbiota of neonates, 457 29.11.1 Breast milk, 457 29.11.2 Formula, 458 29.12 Conclusion, 459 Take ]home message, 459 Host-food, 460 References, 460 30 Probiotics and prebiotics: what are they and what can they do for us?, 467 Marie Jose Butel, Anne ]Judith and Waligora ]Dupriet 30.1 The gut microbiota, a partnership with the host, 467 30.2 Probiotics, 467 30.2.1 Probiotics, a story that began a long time ago, 467 30.2.2 What are probiotics?, 468 30.2.3 How do probiotics work?, 468 30.2.4 Safety of probiotics, 469 30.3 Prebiotics, 470 30.3.1 What are prebiotics?, 470 30.3.2 How do prebiotics work?, 471 30.4 Synbiotics, 471 30.5 Pro ], pre ], and synbiotics in human medicine today, 471 30.5.1 Pro ] and prebiotics and infectious diarrhea, 471 30.5.2 Pro ] and prebiotics and inflammatory bowel diseases, 472 30.5.3 Pro ] and prebiotics and irritable bowel syndrome, 473 30.5.4 Pro ] and prebiotics and allergy, 474 30.5.5 Pro ] and prebiotics and obesity and diabetes, 475 30.5.6 Other indications, 475 30.5.7 Pre ] and probiotics in pediatrics, 476 30.6 Concluding remarks, 477 Take-home message, 478 References, 47831 The microbiota as target for therapeutic intervention in pediatric intestinal diseases, 483 Andrea Lo Vecchio and Alfredo Guarino 31.1 Introduction, 483 31.2 Use of probiotics in pediatric intestinal diseases, 484 31.2.1 Acute diarrhea, 484 31.2.2 Inflammatory bowel diseases, 486 31.2.3 Irritable bowel syndrome, 487 31.2.4 Infant colic, 487 31.2.5 Necrotizing enterocolitis, 488 31.3 Fecal microbiota transplantation for treatment of intestinal diseases, 488 31.3.1 Preparation and administration, 488 31.3.2 Advantages and barriers, 490 31.3.3 The use of FMT in specific intestinal diseases, 490 31.4 Conclusion, 492 Take ]home message, 493 References, 493 32 Microbial therapy for cystic fibrosis, 497 Eugenia Bruzzese, Vittoria Buccigrossi, Giusy Ranucci and Alfredo Guarino 32.1 Introduction: pathophysiology of cystic fibrosis, 497 32.2 Intestinal inflammation in CF, 498 32.3 Dysbiosis in CF, 499 32.4 Microbial therapy in CF, 502 32.5 Conclusion, 504 Take home message, 504 References, 504 Index, 000

Product Details

  • publication date: 30/09/2016
  • ISBN13: 9781118982877
  • Format: Hardback
  • Number Of Pages: 544
  • ID: 9781118982877
  • weight: 1102
  • ISBN10: 1118982878

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