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

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.

About the Authors
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.

 

Preface

SECTION 1 AN INTRODUCTION TO THE HUMAN TISSUE MICROBIOME

Chapter 1 The Human Microbiota System: A Brief History
Mike Wilson

1.1. Introduction– The discovery of the human microbiota: why do we care?

1.2. The importance of the indigenous microbiota in health and disease

1.3. The development of technologies for characterising the indigenous microbiota

1.4. Culture–independent approaches to microbial community analysis

1.5. Determination of microbial community functions

1.6. Closing Remarks

Take–home message

Chapter 2 An introduction to Microbial Dysbiosis
Mike Curtis

2.1 Definition of dysbiosis

2.2 The normal microbiota

2.3 Main features of dysbiosis

2.4 Conclusions

Take–home message

Acknowledgement

References

Chapter 3 The Gut Microbiota: An Integrated Interactive System
Hervé Blottiere and Joel Doré

3.1 Introduction

3.2 Who is there, how is it composed?

3.3 A system in interaction with food

3.4 A system highly impacted by the host

3.5 A system in interaction with human cells

3.6 Conclusion: an intriguing integrated interactive system deserving further studies

Take–home message

References

Chapter 4 The Oral Microbiota
David J. Spratt and Luigi Nibali

4.1 Introduction

4.2 Composition of the oral microbiota

4.2.1 Archaea

4.3 The oral microbiota in health

4.4 Role of oral microbiota in disease

4.5 Future outlook

Take–home message

References

Chapter 5 The Skin Microbiot
P. Zeeuwen and J. Schalkwjik

5.1 Normal Skin

5.2 Skin Diseases

5.3 Experimental Studies

Take–home message

References

Chapter 6 Metagenomic Analysis of the Human Microbiome
L. G. Bermúdez–Humarán

6.1 Introduction

6.2 The human microbiome

6.3 Changes in microbiota composition during host life cycles

6.4 The human microbiome and the environment

6.5 Disease and health implications of Microbiome

6.6 Conclusions

Take–home message

References

SECTION 2 MICROBIOTA–MICROBIOTA AND MICROBIOTA–HOST INTERACTIONS IN HEALTH AND DISEASE

Chapter 7 Systems Biology of Bacteria–Host Interactions
Ines Thiele

7.1 Introduction

7.2 Computational analysis of host–microbe interactions

7.3 Network–based modeling

7.4 Other computational modeling approaches

7.5 Conclusion

Take–home message

Acknowledgements

References

Chapter 8 Bacterial Biofilm Formation and Immune evasion mechanisms
Jessica Snowden

8.1 Introduction

8.2 Biofilms in human disease

8.3 Biofilm formation

8.4 Immune responses to biofilms

8.5 Biofilm immune evasion strategies

8.6 Vaccines and Biofilm Therapeutics

8.7 Conclusions

Take–home message

References

Chapter 9 Co–evolution of microbes and immunity and consequences for modern–day life
Markus Geuking

9.1 Introduction

9.2 Symbiosis in eukaryotic evolution

9.3 Evolution of the (innate and adaptive) immune system

9.4 Hygiene Hypothesis

9.5 What drives the composition of the microbiota?

9.6 The pace of evolution

Take–home messages

References

Chapter 10 How viruses and bacteria have shaped the human genome
Frank Ryan

10.1 Genetic symbiosis

10.2 Mitochondria: symbiogenesis in the human

10.3 Virus symbiogenesis

10.4 HERV proteins

Take–home messages

References

Chapter 11 The Microbiota as an Epigenetic Control Mechanism
B. A. Shenderov

11.1 Introduction

11.2 Background on epigenetics and epigenomic programming/reprograming

11.3 Epigenomics and link with energy metabolism

11.4 The Microbiota as a potential epigenetic modifier

11.5 Epigenetic control of the host genes by pathogenic and opportunistic microorganisms

11.6 Epigenetic control of the host genes by indigenous (probiotic) microorganisms

11.7 Concluding remarks and future directions

Take–home message

References

Chapter 12 The emerging role of Propionibacteria in human health and disease
H. Bruggemann

12.1 Introduction

12.2 Microbiological features of propionibacteria

12.3 Population structure of P. acnes

12.4 Propionibacteria as indigenous probiotics of the skin

12.5 Propionibacteria as opportunistic pathogens

12.6 Host interacting traits and factors of propionibacteria

12.7 Host responses to P. acnes

12.8 Propionibacterium–specific bacteriophages

12.9 Concluding remarks

Take–home message

References

SECTION 3 DYSBIOSES AND BACTERIAL DISEASES: METCHNIKOFF S LEGACY

Chapter 13 The Periodontal Diseases: Microbial disease or a disease of the host response
Luigi Nibali

13.1 The tooth: a potential breach in the mucosal barrier

13.2 The Periodontium from health to disease

13.3 Periodontitis: one of the commonest human diseases

13.4 Periodontal treatment: a non–specific biofilm disruption

13.5 Microbial aetiology

13.6 The host response in periodontitis

13.7 Conclusions

Take–home message

References

Chapter 14 The polymicrobial synergy and dysbiosis model of periodontal disease pathogenesis
G. Hajishengallis and Richard J. Lamont

14.1 Introduction

14.2 A (very) polymicrobial etiology of periodontitis

14.3 Synergism among periodontal bacteria

14.4 Interactions between bacterial communities and epithelial cells

14.5 Manipulation of host immunity

14.6 Conclusions

Take–home message

References

Chapter 15 New paradigm in the relationship between periodontal disease and systemic diseases– Effects of oral bacteria on the gut microbiota and metabolism
K. Yamazaki

15.1 Introduction

15.2 Association between periodontal and systemic diseases

15.3 Issues about causal mechanisms of periodontal disease for systemic disease

15.4 New insights into the mechanisms linking periodontal disease and systemic disease

15.5 Effect of oral administration of P. gingivalis on metabolic change and gut microbiota

15.6 Conclusions

Take–home messages

References

Chapter 16 The Vaginal Microbiota in health and disease
T. Sadiq and P. Hay

16.1 What makes a healthy microbiota

16.2 The Vaginal Microbiota in Disease

16.3 Conclusions

SECTION 4 DYSBIOSES AND CHRONIC DISEASES: IS THERE A CONNECTION?

Chapter 17 Reactive Arthritis: The Hidden Bacterial Connection
John Carter

17.1 Introduction

17.2 Reactive Arthritis

17.3 Pathophysiology of ReA

17.4 Questions Remain

17.5 Conclusion

Chapter 18 Rheumatoid arthritis: The Bacterial Connection
J. Detert

18.1 Preclinical rheumatoid arthritis

18.2 Predisposition to RA

18.3 MCH–HLA and genetic predisposition to RA

18.4 Molecular mimicry in RA

18.5 Innate immune system and RA

18.6 Bystander activation and pattern recognition receptors

18.7 Antibodies and neoepitopes

18.8 Superantigens

18.9 LPS

18.10 Bacterial DNA and peptidoglycans

18.11 Heat shock proteins

18.12 Toll–like and bacterial infections

18.13 Proteus mirabilis

18.14 Porphyromonas gingivalis and RA

18.15 Gastrointestinal flora and RA

18.16 Smoking, lung infection and RA

18.17 Where to go from here?

Chapter 19 Inflammatory bowel disease and the gut microbiota
A. Hart

19.1 The microbiota in inflammatory bowel disease

19.2 Dysbiosis and IBD pathogenesis

19.3 Environmental factors affecting microbiome composition

19.4 Genetics and application to the immune system and dysbiosis in IBD

19.5 An overview of gut microbiota studies in IBD

19.6 Specific bacterial changes in IBD

19.6.1 Potentiators

19.6.2 Protectors

19.6.3 Anti–inflammatory effects of microbiota (functional dysbiosis)

19.7 Functional composition of microbiota in IBD

19.8 Challenges

19.9 Conclusion

Chapter 20 Ankylosing Spondylitis, Klebsiella pneumonia and the low starch diet
Alan Ebringer and C. Wilson

20.1 Introduction

20.2 Clinical features of AS

20.3 Gut bacteria and total serum IgA

20.4. Molecular mimicry in AS

20.5 Pullulanase system and collagens

20.6 Specific antibodies to Klebsiella in AS patients.

20.6 The low starch diet in AS

20.7 Conclusions

Chapter 21 Microbiome of Chronic Plaque Psoriasis
Lionel Fry

21.1 Introduction

21.2 Microbiota in Psoriasis

21.3 Variation of microbiota with site

21.4 Swabs versus biopsies

21.5 Psoriatic arthritis

21.6 Microbiome and immunity

21.7 Evidence that the skin microbiome may be involved in the pathogenesis of psoriasis

21.8 New hypothesis on the pathogenesis of psoriasis

Chapter 22 Liver Disease: Interactions with the Intestinal Microbiota
B. Schnabl

22.1 Introduction

22.2 Non–alcoholic fatty liver disease

22.3 Qualitative and quantitative changes in the intestinal microbiota

22.4 Endotoxin

22.5 Ethanol

22.6 Choline

22.7 Alcoholic liver disease

Chapter 23 The Gut Microbiota: A Predisposing Factor in Obesity, Diabetes, Metabolic syndrome and Atherosclerosis
F. Fåk

23.1 Introduction

23.2 The obesogenic microbiota: evidence from animal models

23.3 The obesogenic microbiota in humans

23.4 A leaky gut contributing to inflammation and adiposity

23.5 Obesity–proneness: mediated by the gut microbiota?

23.6 Bacterial metabolites provide a link between bacteria and host metabolism

23.7 Fecal microbiota transplants: can we change our gut bacterial profiles?

23.8 What happens with the gut microbiota during weight loss?

23.9 The diabetic microbiota

23.10 The atherosclerotic microbiota

23.11 Conclusions

Chapter 24 The Airway Microbiota and Susceptibility to Asthma
B. J. Marsland and O. Salami

24.1 Introduction

24.2 The microenvironment of the lower airways

24.3 Development of the airway microbiota in the neonate

24.4 Upper airway microbiota

24.5 What constitutes a healthy airway microbiota

24.6 Microbiota and asthma

24.7 Dietary metabolites and asthma

24.8 Conclusion, future perspectives and clinical implications

Chapter 25 The Microbiota and Cancer
R. Francescone

25.1 Introduction

25.2 Microbiome and cancer: where is the link?

25.3 Microbiome and Barrier Disruption

25.4 Microbiome and different types of cancer

25.5 Microbiota and Metabolism: the good and the bad sides

25.6 Chemotherapy, Microbiome and the Immune System

25.7 Therapeutic Avenues

25.8 Unresolved Questions and Future Work

Chapter 26 Is colorectal cancer a result of dysbiosis?
I. Sobhani

26.1 Introduction

26.2 Colon carcinogenesis and epidemiological data

26.3 The Microbiota

26.4 Bacteria and CRCs links

26.5 Hypotheses and perspectives

26.6 Take–home message

Chapter 27 The Gut Microbiota and the CNS: An Old Story with a New Beginning
P. Forsythe

27.1 Introduction

27.2 The Microbiota–Gut–Brain Axis: A Historical Framework

27.3 The Microbiota–Gut–Brain Axis: An Evolutionary Perspective

27.4 The gut microbiota influence on brain and behavior

27.5 Microbes and the hardwired gut brain axis

27.6 Hormonal pathways to the brain

27.7 Microbes and Immune pathways to the brain

27.8 Metabolites of the microbiota: Short chain fatty acids

27.9 Clinical implications of the microbiota–gut–brain axis

27.10 Conclusion

Chapter 28 Genetic dysbiosis: how host genetic variants may affect microbial biofilms
L. Nibali

28.1 The holobiont: humans as supra–organisms

28.2 Genetic variants in the host response to microbes

28.3 Genetic dysbiosis

28.4 Summary and conclusions

SECTION 5 MIRRORING THE FUTURE: DYSBIOSIS THERAPY

Chapter 29 Diet and Dysbiosis
D. L. Gibson

29.1 Introduction

29.2 Coevolution of the host–microbiota super–organism

29.3 Gut microbiota in personalized diets

29.4 The evolution of diet

29.5 Plasticity of the microbiota and diet

29.6 Interaction between gut microbiota, host and food

29.7 Consequences of diet–induced dysbiosis on host health

29.8 The role of gut microbes on the digestion of macronutrients

29.9 Diet induces dysbiosis in the host

29.10 The effect of maternal diet on offspring microbiota

29.11 The effects of post–natal diet on the developing microbiota of neonates

29.12 Conclusion

Chapter 30 Probiotics and Prebiotics: What Are They And What Can They Do For Us?
Marie–Jose Butel

30.1 The gut microbiota, a partnership with the host

30.2 Probiotics

30.3 Prebiotics

30.4 Synbiotics

30.5 Pro–, pre–, and synbiotics today in human medicine

30.6 Concluding remarks

Chapter 31 The microbiota as target for therapeutic interventions in pediatric intestinal diseases
Andrea Lo Vecchio and Alfredo Guarino

31.1 Introduction

31.2 Use of Probiotics in pediatric intestinal diseases

31.3 Fecal microbiota transplantation for treatment of intestinal diseases

31.4 CONCLUSION

Chapter 32 Microbial therapeutics for cystic fibrosis: correction of intestinal dysbiosis
Eugenia Bruzzese, Giusy Ranucci and Alfredo Guarino

32.1 Introduction–Pathophysiology of Cystic Fibrosis

32.2 Intestinal inflammation in CF

32.3 Dysbiosis in CF

32.4 Microbial therapy in CF

32.5 Conclusion

Index