The Human Microbiota E-Book

David N. Fredricks

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch
• Veröffentlichungsjahr: 2013

Seitenzahl: 752

Beschreibung

The Human Microbiota offers a comprehensive review of all human-associated microbial niches in a single volume, focusing on what modern tools in molecular microbiology are revealing about human microbiota, and how specific microbial communities can be associated with either beneficial effects or diseases. An excellent resource for microbiologists, physicians, infectious disease specialists, and others in the field, the book describes the latest research findings and evaluates the most innovative research approaches and technologies. Perspectives from pioneers in human microbial ecology are provided throughout.

Leseprobe

Table of Contents

Title page

Copyright page

Preface

Contributors

1: The NIH Human Microbiome Project

1.1. Introduction

1.2. Genesis of Human Microbiome Research and the Human Microbiome Project (HMP)

1.3. Guiding Principles, Structure, and Initiatives of the HMP Program

1.4. Products from the Human Microbiome Project

1.5. Other NIH-Supported Human Microbiome Research Activities

1.6. Future Directions for Human Microbiome Research

Acknowledgments

2: Methods for Characterizing Microbial Communities Associated with the Human Body

2.1. Introduction

2.2. Cultivation-Independent Techniques

2.3. Cultivation

2.4. Choosing an approach

Acknowledgments

3: Phyloarrays

3.1. Introduction

3.2. Phylogenetic Microarray Design

3.3. Sample Preparation for Phylogenetic Microarray Profiling

3.4. The Utility of Phylogenetic Microarrays

Acknowledgments

4: Mathematical Approaches for Describing Microbial Populations: Practice and Theory for Extrapolation of Rich Environments

4.1. Introduction: Practice for Extrapolation of Environments

4.2. Theory for Extrapolation of Environments

4.3. Average Analysis of Sample Coverage

4.4. Conditional Analysis of Sample Coverage

4.5. Conclusions

5: Tension at the Border: How Host Genetics and the Enteric Microbiota Conspire to Promote Crohn’s Disease

5.1. Introduction and Overview

5.2. Human Inflammatory Bowel Diseases

5.3. The Enteric Microbiota and IBD

5.4. Human Genetic Loci Associated with IBD

5.5. How Host Genetics Shapes Enteric Microbiota

5.6. Modeling Dysbiosis and Crohn’s Disease

Acknowledgments

6: The Human Airway Microbiome

6.1. Introduction

6.2. Lung-Characteristics and Conditions

6.3. Outlook for Respiratory Tract Microbiome Studies

7: Microbiota of the Mouth: A BLESSING OR A CURSE?

7.1. Introduction

7.2. From Colonization to Communities

7.3. Communities in Health and Disease

7.4. Oral Communities and Systemic Disease

7.5. Summary

8: Microbiota of the Genitourinary Tract

8.1. Introduction

8.2. Microbial Ecosystems of the Female Reproductive Tract: A Biogeographic Perspective of Their Impact on Reproduction

8.3. Scientific Controversy Regarding Bacterial Vaginosis

8.4. Perspectives on the Vaginal Microbiome in the Age of High-Throughput Sequencing

8.5. Vaginal Health In 2025: How Understanding the Microbiome Will Shape the Future of Women’s Healthcare

8.6. The Male Microbiota: Two Sides of the Same Coin or a Different Currency?

8.7. Conclusion

9: Functional Structure of Intestinal Microbiota in Health and Disease

9.1. Introduction

9.2. Intestinal Microbiota

9.3. Changes of the Colonic Microbiota in Disease

9.4. Possible Ways to Remodel the Mucus Barrier

9.5. Biostructure of Fecal Microbiota in Health, Inflammatory Bowel Disease, and Other GI Diseases

9.6. Site-Dependent Changes of Colonic Microbial Biostructure

9.7. Conclusions

10: From Fly to Human: Understanding How Commensal Microorganisms Influence Host Immunity and Health

10.1. Introduction

10.2. Microbial Diversity in Humans and Animal Models

10.3. Comparative Immunity: Immune System Development in Animals

10.4. Maintaining Intestinal Homeostasis

10.5. The Role of Commensal Bacteria in Host Health

10.6. Finding the Right Mix of Bacteria: Harnessing Our Understanding of Commensal Host Relationships for Therapeutic Benefit

11: Insights into the Human Microbiome from Animal Models

11.1. Introduction

11.2. Animal Model Systems

11.3. Establishment of Host-Associated Microbial Communities

11.4. The Function of Resident Microbial Communities in Host Biology

11.5. Concluding Remarks

12: To Grow or Not to Grow: Isolation and Cultivation Procedures in the Genomic Age

12.1. Introduction

12.2. Isolation, Growth, And Cultivation

12.3. Changes in a Changing World

13: New Approaches to Cultivation of Human Microbiota

13.1. Introduction

13.2. Microbiota Cultivation Methodology

13.3. Application to Human Microbiota

13.4. Looking Ahead

Acknowledgments

14: Manipulating the Indigenous Microbiota in Humans: Prebiotics, Probiotics, and Synbiotics

14.1. Introduction

14.2. Probiotics

14.3. Prebiotics

14.4. Synbiotics

14.5. Conclusion

Index

Cover Design: Michael Rutkowski

Cover Illustrations: top five panels © courtesy of David N. Fredricks; right side art © Mads Abildgaard/iStockphoto

Copyright © 2013 by John Wiley & Sons, Inc. All rights reserved.

Published by John Wiley & Sons, Inc., Hoboken, New Jersey

Published simultaneously in Canada

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Library of Congress Cataloging-in-Publication Data:

The human microbiota: how microbial communities affect health and disease / edited by David N. Fredricks.

p. cm.

 Includes bibliographical references and index.

 ISBN 978-0-470-47989-6 (cloth)

 1. Human body–Microbiology. 2. Microorganisms. I. Fredricks, David N.

 QR46.H86 2013

 579–dc23

2012015251

Preface

The human body is a marvelously intricate machine, and the parts list includes trillions of microbial cells that colonize epithelial surfaces such as those found in the mouth and gut. There is increasing evidence that these microbes do more than just reside on tissues—they play key roles in human physiology and organ function. Indeed, there are 100 times more genes in our microbiome compared to our human genome, and these microbial genes code for proteins that impact diverse processes such as digestion, immunity, and development. The goal of this book is to provide an overview of the microbial diversity found in humans and to describe efforts linking microbial communities to human health. Attempts to understand human-associated microbial communities were given a boost by Human Microbiome Project (HMP) initiatives in the United States, Canada, Europe, and Asia. The National Institutes of Health in the United States has devoted more than $150 million to support these studies that are now maturing with release of data and a flurry of publications. This is a time of unprecedented discovery, and although still young, the field is sufficiently advanced to warrant a book summarizing progress. Answers to many questions are now emerging. How do microbial communities differ across body sites? What is the variability in microbial composition across healthy and diseased humans at the same body site? How do certain microbial communities foster healthy tissues? What are the microbial community profiles associated with disease states, and are these communities markers of disease or causes of disease? How can microbial communities be manipulated to optimize health and minimize disease risk? How do microbial communities change over the course of human development? What are the internal factors (genetic, anatomic, hormonal, physiologic) and external environmental factors (diet, sexual activity, hygiene) that shape human-associated microbial communities? With partial answers to these questions come many additional questions about the intimate relationships between human and microbial cells in our bodies.

Our excursion into the human microbiome begins with an introduction to the Human Microbiome Project by Lita Proctor and colleagues from the NIH (Chapter 1). This chapter provides an excellent description of the HMP with its many research initiatives and early progress. It also provides some historical context and a vision for future research. We then shift to chapters focused on tools for studying the human microbiome, including a methodological overview chapter (Chapter 2) by Christine Bassis, Vincent Young, and Tom Schmidt that lays the groundwork for later chapters. Bassis and colleagues compare different genomic cultivation-independent methods for characterizing microbial communities, highlighting the advantages and limitations of commonly used techniques. They also consider the role of cultivation methods in the genomic era, and provide advice about designing microbiome studies. In their chapter, Susan Lynch and Eoin Brodie delve more deeply into the use of phyloarrays for microbial community analysis (Chapter 3), a technique that has some distinct advantages for microbial community profiling. Manuel Lladser and Rob Knight round out our methods section by providing a mathematical perspective on interpreting microbial community structure and diversity. This chapter (Chapter 4) is highly relevant in the era of high-throughput sequencing of phylogenetically informative microbial gene sequences [generated by polymerase chain reaction (PCR) or from metagenomic methods] for describing microbial populations.

We then begin a tour of various microbial niches of the human body, such as the gut, respiratory tract, mouth, and genital tract. These chapters highlight the different microbial populations found in different human tissues, and describe how microbial communities change with conditions such as gingivitis, inflammatory bowel disease, and bacterial vaginosis. Dan Frank and Ellen Li start this tour with a description of how host genetics (immune response) and the gut microbiota may interact to facilitate Crohn’s disease (Chapter 5). They also introduce the concept of dysbiosis that will be used in other chapters. Edith Zemanick and J. Kirk Harris then describe the microbiota of the human respiratory tract (Chapter 6), focusing on the normal microbiota and alterations in conditions such as cystic fibrosis and ventilator-associated pneumonia. The oral microbiota is described in a chapter by Angela Nobbs, David Dymock, and Howard Jenkinson (Chapter 7). Here they note some of the physical and metabolic interactions among the 600 different bacteria species that live in the mouth. They also describe the connections between some oral microbial communities and local conditions such as caries, and systemic diseases such as endocarditis. Laura Sycuro and myself review the genital tract microbiota of women and men, with a particular focus on the condition bacterial vaginosis that is associated with numerous adverse health outcomes in women and neonates (Chapter 8). Alexander Swidsinski and Vera Loening-Baucke end this section with a chapter on use of in situ hybridization methods combined with fluorescence microscopy for describing the spatial relationships of microbes and human cells in the gut. This chapter (Chapter 9) is notable for moving beyond the description of “who’s there” to a description of the structural and functional features of the gut microbiota. Note that not every human body niche is covered in these chapters.

Two chapters focus on the use of animal models to manipulate the microbiota and understand how changes impact health. June Round tackles the use of a variety of animal models to study host immunity, including the fruit fly, zebrafish, and mouse (Chapter 10). She highlights key lessons that can be learned from these models regarding human immune responses to our indigenous microbiota. The team of Bethany Rader and Karen Guillemin describe new insights that have been produced by animal models, including fish (Chapter 11). Several important questions are more easily answered with animal models, including how microbial communities assemble in space and time, and identifying the relative contributions of host genetics, environmental factors (such as diet), and stochastic sampling. Microbes and animals can be studied in the laboratory in ways that are not possible in human studies.

The use of cultivation-independent methods suggests that many human-associated microbes still resist cultivation in the laboratory. Karsten Zengler tackles this issue in his chapter on cultivation procedures in the genomic age (Chapter 12), reinforcing the challenges and rewards of cultivating microbes from the human body. So, how can we cultivate fastidious members of the human microbiota? The chapter by Slava Epstein, Maria Sizova, and Amanda Hazen (Chapter 13) provides many novel approaches for cultivating human microbes using cutting-edge techniques in order to resolve the “great plate count anomaly.”

Finally, George and Sandra Macfarlane (Chapter 14) address a key issue in the microbiome field: how one can manipulate the human microbiota. These investigators provide a thoughtful and balanced review on the use of prebiotics, probiotics, and synbiotics to alter the human indigenous microbiota for the purpose of enhancing health.

What does it mean to be human? The authors of these chapters provide a compelling argument that we are far from alone, and that our microbiota helps mold the human form. Please enjoy the insights from this outstanding collection of investigators who are unraveling the mysteries of the human microbiome.

Special thanks to Sue Bartlett for helping to bring these chapters together and assisting the editors with organization of the project.

David N. Fredricks, MD

Fred Hutchinson Cancer Research Center Seattle, Washington

Contributors

Carl Baker, MD, PhD National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, Maryland 20892

Christine Bassis, PhD Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109

Eoin L. Brodie, PhD Ecology Department, Earth Sciences Division, 1 Cyclotron Road, Lawrence Berkeley National Laboratory, Berkeley, California 94720

Shaila Chhibba National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), Bethesda, Maryland 20892

David Dymock, PhD School of Oral and Dental Sciences, University of Bristol, Lower Maudlin Street, Bristol BS1 2LY, United Kingdom

Slava S. Epstein, PhD Department of Biology, Northeastern University, Boston, Massachusetts 02115

Daniel N. Frank, PhD Division of Infectious Diseases, School of Medicine, University of Colorado, Mucosal and Vaccine Research Program Colorado (MAVRC), and UC-Denver Microbiome Research Consortium (MiRC), Denver, Colorado 80045

David N. Fredricks, MD Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109

Maria Giovanni, PhD National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland 20892

Karen Guillemin, PhD Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403

J. Kirk Harris, PhD Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045

Amanda Hazen, MS Department of Biology, Northeastern University, Boston, Massachusetts 02115

Howard F. Jenkinson, PhD School of Oral and Dental Sciences, University of Bristol, Lower Maudlin Street, Bristol BS1 2LY, United Kingdom

Rob Knight, PhD Howard Hughes Medical Institute and Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309

Ellen Li, MD, PhD Department of Medicine, Stony Brook University, Stony Brook, New York 11790

Manuel E. Lladser, PhD Department of Applied Mathematics, University of Colorado, Boulder, Colorado 80309

Vera Loening-Baucke, MD The University Hospital Charité of the Humboldt University at Berlin, Charitéplatz 1, 10117 Berlin, Germany

R. Dwayne Lunsford, PhD Program Director, Microbiology Program, Integrative Biology and Infectious Disease Branch, Division of Extramural Research, National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), Bethesda, Maryland 20892

Susan V. Lynch, PhD Division of Gastroenterology, Department of Medicine, University of California, 513 Parnassus Avenue, San Francisco, California 94143

George T. Macfarlane, PhD The University of Dundee, Microbiology and Gut Biology Group, Ninewells Hospital Medical School, Dundee DD1 9SY, United Kingdom

Sandra Macfarlane, PhD The University of Dundee, Microbiology and Gut Biology Group, Ninewells Hospital Medical School, Dundee DD1 9SY, United Kingdom

Jean McEwen, JD, PhD National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), Bethesda, Maryland 20892

Pamela McInnes, DDS, MSc National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), Bethesda, Maryland 20892

Angela H. Nobbs, PhD School of Oral and Dental Sciences, University of Bristol, Lower Maudlin Street, Bristol BS1 2LY, United Kingdom

Jane Peterson, PhD National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), Bethesda, Maryland 20892

Lita M. Proctor, PhD National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), Bethesda, Maryland 20892

Bethany A. Rader, PhD Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut 06269

June L. Round, PhD Department of Pathology, Division of Microbiology and Immunology, University of Utah, Salt Lake City, Utah 84112

Thomas Schmidt, PhD Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan 48824

Maria Sizova, PhD Department of Biology, Northeastern University, Boston, Massachusetts 02115

Alexander Swidsinski, MD, PhD The University Hospital Charité of the Humboldt University at Berlin, Charitéplatz 1, 10117 Berlin, Germany

Laura K. Sycuro, PhD, MSc Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109

Chris Wellington National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), Bethesda, Maryland 20892

Vincent Young, MD, PhD Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109

Edith T. Zemanick, MD Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045

Karsten Zengler, PhD Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093

1

The NIH Human Microbiome Project

Lita M. Proctor, Shaila Chhibba, Jean McEwen, Jane Peterson, and Chris Wellington

NHGRI/NIH, Bethesda, Maryland

Carl Baker

NIAMS/NIH, Bethesda, Maryland

Maria Giovanni

NIAID/NIH, Bethesda, Maryland

Pamela McInnes and R. Dwayne Lunsford

NIDCR/NIH, Bethesda, Maryland

1.1. Introduction

The human microbiome is the full complement of microbial species and their genes and genomes that inhabit the human body. The National Institutes of Health (NIH) Human Microbiome Project (HMP) is a community resource project designed to promote the study of complex microbial communities involved in human health and disease. The HMP has increased the appreciation for the features of the human microbiome that all people share as well as the features that are highly personalized. Host genetics, the environment, diet, the immune system, and many other factors all interact with the human microbiota to regulate the composition and function of the microbiome. As a scientific resource, the HMP has publically deposited to date or made available over 800 reference microbial genome sequences, hundreds of microbial isolates from the human microbiome, over 3 terabases (Tbp) of metagenomic microbial sequence, over 70 million 16S rRNA reads, close to 700 microbiome metagenome assemblies, over 5 million unique predicted genes, and a comprehensive bodywide survey of the human microbiome in hundreds of individuals from a healthy adult cohort. A number of demonstration projects are contributing a wealth of knowledge about the association of the microbiome with specific gut, skin, and urogenital diseases. Other key resources include the development of new computational tools, technologies, and scientific approaches to investigate the microbiome, and studies of the ethical, legal, and social implications of human microbiome research. This chapter captures the historical context of the HMP and other international research endeavors in the human microbiome, highlights the multiple initiatives of the HMP program and the products from this activity, and closes with some suggestions for future research needs in this emerging field.

1.2. Genesis of Human Microbiome Research and the Human Microbiome Project (HMP)

It sometimes seems that research on the human microbiome blossomed overnight. However, the conceptual and technological foundations for the study of the human microbiome began to emerge before the 1990s and can be found within many disciplines. Microbial ecologists who studied microorganisms and microbial communities in the environment recognized early on that most microorganisms in nature were not culturable and so developed alternate approaches to the study of microbial communities. An early and broadly adopted approach for investigating microorganisms in the environment, based on the three-domain system for biological classification [1], was the use of the 16S ribosomal RNA gene as a taxonomic marker for interrogating microbial diversity in nature [2]. With the growth of non-culture-based, molecular techniques in the 1980s and 1990s for study of environmental microorganisms and communities, some medical microbiologists turned these tools to the human body and found far greater microbial diversity than expected, even in well-studied sites such as the oral cavity [3–5].

In the infectious disease field, recognition was growing that many diseases could not satisfy Koch’s postulates as the pathogenesis of many of these diseases appeared to involve multiple microorganisms. The term polymicrobial diseases was coined to describe those diseases with multiple infectious agents [6]. We now recognize that many of these formerly classified polymicrobial diseases, such as abscesses, AIDS-related opportunistic infections, conjunctivitis, gastroenteritis, hepatitis, multiple sclerosis, otitis media, periodontal diseases, respiratory diseases, and genital infections, are associated with multiple microbial factors, that is, with the entire microbiome. In an essay on the history of microbiology and infectious disease, Lederberg [7], who coined the term microbiome, called for “a more ecologically informed metaphor” to understand the relationship between humans and microbes.

The field of immunology was also undergoing its own revolution with the recognition that the innate and adaptive immune systems not only evolved to eliminate specific pathogens but are also intimately involved in shaping the composition of the commensal intestinal microbiota [8–10]. Recognition was also growing in this field that the microbiota is involved in regulating gut development and function [11,12].

Another key catalyst for discussions about the inclusion of the microbiome in the study of human health and disease was the publication of the first drafts of the human genome sequence. Relman and Falkow [13] noted on this occasion that a “second human genome project” should be undertaken to produce a comprehensive inventory of microbial genes and genomes associated with the human body. Lead by Davies [14], they renewed a call for considering the role of the human-associated microorganisms in development and in health and disease. Also, by 2005 or so, as sequencing costs began to drop, sequencing technology offered the opportunity to consider extensive surveys of the microbial communities associated with the human. Early human studies focusing on the most complex of human microbiomes, the digestive tract [15,16], demonstrated the tremendous complexity as well as the functional potential of the human microbiome.