Microbial Ecology in States of Health and Disease: Workshop Summary (2014)

MICROBIAL ECOLOGY
IN STATES OF HEALTH
AND DISEASE

WORKSHOP SUMMARY

Eileen R. Choffnes, LeighAnne Olsen, and Alison Mack,
Rapporteurs

Forum on Microbial Threats

Board on Global Health

INSTITUTE OF MEDICINE
              OF THE NATIONAL ACADEMIES

THE NATIONAL ACADEMIES PRESS

Washington, D.C.

www.nap.edu

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NOTICE: The workshop that is the subject of this workshop summary was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine.

Financial support for this activity was provided by the U.S. Department of Health and Human Services: National Institutes of Health, National Institute of Allergy and Infectious Diseases, Centers for Disease Control and Prevention, Food and Drug Administration, and the Fogarty International Center; U.S. Department of Defense: Armed Forces Health Surveillance Center, Defense Threat Reduction Agency, and Medical Research and Materiel Command; U.S. Department of Justice: Federal Bureau of Investigation; U.S. Department of Veterans Affairs; U.S. Department of Homeland Security; U.S. Agency for International Development; Uniformed Services University of the Health Sciences; Alfred P. Sloan Foundation; American Society for Microbiology; Burroughs Wellcome Fund; GlaxoSmithKline; Infectious Diseases Society of America; Johnson & Johnson; Merck Company Foundation; and sanofi pasteur. The views presented in this publication do not necessarily reflect the views of the organizations or agencies that provided support for this activity.

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Cover images: (Front, upper) Medical illustration of methicillin-resistant Staphylococcus aureus (MRSA); (Front, lower) Medical Illustration of Clostridium difficile; (Back) Medical illustration of Streptococcus pneumoniae. Photo Credits: All photos courtesy of the Centers for Disease Control and Prevention, www.cdc.gov.

Suggested citation: IOM (Institute of Medicine). 2014. Microbial ecology in states of health and disease: Workshop summary. Washington, DC: The National Academies Press.

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INSTITUTE OF MEDICINE
              OF THE NATIONAL ACADEMIES

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www.national-academies.org

PLANNING COMMITTEE FOR A WORKSHOP ON MICROBIAL ECOLOGY IN STATES OF HEALTH AND DISEASE¹

ARTURO CASADEVALL, Albert Einstein College of Medicine, Bronx, New York

EDUARDO GOTUZZO, Instituto de Medicina Tropical–Alexander von Humboldt, Universidad Peruaña Cayetano Heredia, Lima, Peru

JO HANDELSMAN, Yale University, New Haven, Connecticut

JAMES M. HUGHES, Emory University, Atlanta, Georgia

DAVID A. RELMAN, Stanford University and Veterans Affairs Palo Alto Health Care System, Palo Alto, California

P. FREDERICK SPARLING, University of North Carolina, Chapel Hill, North Carolina

________________

¹ Institute of Medicine planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published workshop summary rests solely with the workshop rapporteurs and the institution.

FORUM ON MICROBIAL THREATS¹

DAVID A. RELMAN (Chair), Stanford University, and Veterans Affairs Palo Alto Health Care System, Palo Alto, California

JAMES M. HUGHES (Vice-Chair), Global Infectious Diseases Program, Emory University, Atlanta, Georgia

LONNIE J. KING (Vice-Chair), Ohio State University, Columbus, Ohio

KEVIN ANDERSON, Biological and Chemical Defense Division, Science and Technology Directorate, Department of Homeland Security, Washington, DC

ENRIQUETA C. BOND, Burroughs Wellcome Fund (Emeritus), QE Philanthropic Advisors, Marshall, Virginia

ROGER G. BREEZE, Lawrence Livermore National Laboratory, Livermore, California

JOHN E. BURRIS,² Burroughs Wellcome Fund, Research Triangle Park, North Carolina

ARTURO CASADEVALL, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York

ANDREW CLEMENTS, U.S. Agency for International Development, Washington, DC

PETER DASZAK, EcoHealth Alliance, New York, New York

JEFFREY S. DUCHIN, Public Health–Seattle and King County, Seattle, Washington

JONATHAN EISEN, Genome Center, University of California, Davis, California

RALPH L. ERICKSON,³ Walter Reed Army Institute of Research, Silver Spring, Maryland

MARK B. FEINBERG, Merck Vaccine Division, Merck & Co., Inc., West Point, Pennsylvania

JACQUELINE FLETCHER, Oklahoma State University, Stillwater, Oklahoma

CLAIRE FRASER, Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland

JESSE L. GOODMAN, Food and Drug Administration, Rockville, Maryland

EDUARDO GOTUZZO, Instituto de Medicina Tropical–Alexander von Humboldt, Universidad Peruaña Cayetano Heredia, Lima, Peru

CAROLE A. HEILMAN, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland

DAVID L. HEYMANN, Public Health England, London, United Kingdom

________________

¹ Institute of Medicine forums and roundtables do not issue, review, or approve individual documents. The responsibility for the published workshop summary rests with the workshop rapporteurs and the institution.

² Forum member until October 18, 2013.

³ Forum member until June 30, 2013.

ZHI HONG,⁴ GlaxoSmithKline, Research Triangle Park, North Carolina

PHILIP HOSBACH, sanofi pasteur, Swiftwater, Pennsylvania

STEPHEN ALBERT JOHNSTON, Arizona BioDesign Institute, Arizona State University, Tempe, Arizona

KENT KESTER,⁵ Uniformed Services University of the Health Sciences, Bethesda, Maryland

GERALD T. KEUSCH, Boston University School of Medicine and Boston University School of Public Health, Boston, Massachusetts

RIMA F. KHABBAZ, Centers for Disease Control and Prevention, Atlanta, Georgia

MARK KORTEPETER,⁶ Uniformed Services University of the Health Sciences, Bethesda, Maryland

STANLEY M. LEMON, University of North Carolina, Chapel Hill, North Carolina

MARGARET J. McFALL-NGAI, University of Wisconsin, Madison, Wisconsin

EDWARD McSWEEGAN, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland

PAULA J. OLSIEWSKI, Alfred P. Sloan Foundation, New York, New York

JULIE PAVLIN, Armed Forces Health Surveillance Center, Silver Spring, Maryland

GEORGE POSTE, Complex Adaptive Systems Initiative, Arizona State University, SkySong, Scottsdale, Arizona

DAVID RIZZO, University of California, Davis, California

GARY A. ROSELLE, Veterans Health Administration, Department of Veterans Affairs, Cincinnati, Ohio

KEVIN RUSSELL, Armed Forces Health Surveillance Center, Silver Spring, Maryland

JANET SHOEMAKER, American Society for Microbiology, Washington, DC

JAY P. SIEGEL,⁷ Johnson & Johnson, Radnor, Pennsylvania

P. FREDERICK SPARLING, University of North Carolina, Chapel Hill, North Carolina

MARY E. WILSON, Harvard School of Public Health, Harvard University, Boston, Massachusetts

EDWARD H. YOU,⁸ Federal Bureau of Investigation, Washington, DC

________________

⁴ Forum member until October 18, 2013.

⁵ Retired as of December 31, 2013.

⁶ Forum member since January 15, 2014.

⁷ Forum member since January 15, 2014.

⁸ Forum member since July 1, 2013.

IOM Staff

EILEEN CHOFFNES, Scholar and Director

LEIGHANNE OLSEN,⁹ Program Officer

KATHERINE McCLURE, Associate Program Officer

REBEKAH HUTTON, Research Associate

CHARLEE ALEXANDER,¹⁰ Senior Program Assistant

JOANNA ROBERTS,¹¹ Senior Program Assistant (Temp)

________________

⁹ Staff member until August 15, 2013.

¹⁰ Staff member from April 1 to November 15, 2013.

¹¹ Staff member since November 1, 2013.

BOARD ON GLOBAL HEALTH¹

THOMAS C. QUINN (Chair), Associate Director for International Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Professor of Medicine, International Health, Epidemiology, and Molecular Biology and Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland

JO IVEY BOUFFORD (IOM Foreign Secretary), President, New York Academy of Medicine, New York

CLAIRE V. BROOME, Adjunct Professor, Division of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia

JACQUELYN C. CAMPBELL, Anna D. Wolf Chair, and Professor, Johns Hopkins University School of Nursing, Baltimore, Maryland

THOMAS J. COATES, Michael and Sue Steinberg Professor of Global AIDS, Research Co-Director, UC Global Health Institute, David Geffen School of Medicine, University of California, Los Angeles, California

GARY DARMSTADT, Director, Family Health Division, Global Health Program, Bill & Melinda Gates Foundation, Seattle, Washington

VALENTIN FUSTER, Director, Wiener Cardiovascular Institute, Kravis Cardiovascular Health Center, Professor of Cardiology, Mount Sinai School of Medicine, Mount Sinai Medical Center, New York, New York

JACOB A. GAYLE, Vice President, Community Affairs, Executive Director, Medtronic Foundation, Minneapolis, Minnesota

GLENDA E. GRAY, Executive Director, Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, University of the Witwatersrand, Diepkloof, South Africa

STEPHEN W. HARGARTEN, Associate Dean, Global Health Program, Medical College of Wisconsin, Milwaukee, Wisconsin

PETER J. HOTEZ, Professor of Pediatrics and Molecular Virology and Microbiology, Texas Children’s Hospital Endowed Chair of Tropical Pediatrics, President, Sabin Vaccine Institute and Texas Children’s Center for Vaccine Development, Dean, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas

CLARION JOHNSON, Consultant, Exxon Mobil, Fairfax, Virginia

FITZHUGH MULLAN, Professor, Department of Health Policy, The George Washington University, Washington, DC

OLUFUNMILAYO F. OLOPADE, Walter L. Palmer Distinguished Service Professor of Medicine, The University of Chicago, Chicago, Illinois

________________

¹ Institute of Medicine boards do not review or approve individual workshop summaries. The responsibility for the content of the workshop summary rests with the workshop rapporteurs and the institution.

GUY PALMER, Regents Professor of Pathology and Infectious Diseases, Director of the School for Global Animal Health, Washington State University, Pullman, Washington

IOM Staff

PATRICK KELLEY, Director

ANGELA CHRISTIAN, Program Associate

Reviewers

This workshop summary has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the National Research Council’s Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published workshop summary as sound as possible and to ensure that the workshop summary meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the process. We wish to thank the following individuals for their review of this workshop summary:

Jeffrey L. Dangl, University of North Carolina, Chapel Hill, North Carolina

Maria Dominguez-Bello, New York University Langone Medical Center, New York, New York

Jesse L. Goodman, Food and Drug Administration, Rockville, Maryland

Margaret J. McFall-Ngai, University of Wisconsin, Madison, Wisconsin

Although the reviewers listed above have provided many constructive comments and suggestions, they did not see the final draft of the workshop summary before its release. The review of this workshop summary was overseen by Melvin Worth. Appointed by the Institute of Medicine, he was responsible for making certain that an independent examination of this workshop summary was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this workshop summary rests entirely with the rapporteurs and the institution.

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Acknowledgments

The Forum on Emerging Infections was created by the Institute of Medicine (IOM) in 1996 in response to a request from the Centers for Disease Control and Prevention (CDC) and the National Institutes of Health (NIH). The purpose of the Forum is to provide structured opportunities for leaders from government, academia, and industry to regularly meet and examine issues of shared concern regarding research, prevention, detection, and management of emerging, reemerging, and novel infectious diseases in humans, plants, and animals. In pursuing this task, the Forum provides a venue to foster the exchange of information and ideas, identify areas in need of greater attention, clarify policy issues by enhancing knowledge and identifying points of agreement, and inform decision makers about science and policy issues. The Forum seeks to illuminate issues rather than resolve them. For this reason, it does not provide advice or recommendations on any specific policy initiative pending before any agency or organization. Its value derives instead from the diversity of its membership and from the contributions that individual members make throughout the activities of the Forum. In September 2003, the Forum changed its name to the Forum on Microbial Threats.

The Forum on Microbial Threats and the IOM wish to express their warmest appreciation to the individuals and organizations who gave their valuable time to provide information and advice to the Forum through their participation in the planning and execution of this workshop. A full list of presenters, and their biographical information, may be found in Appendixes B and E, respectively.

The forum gratefully acknowledges the contributions of the members of the planning committee¹: Arturo Casadevall (Albert Einstein College of Medicine),

________________

¹ Institute of Medicine planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published workshop summary rests solely with the workshop rapporteurs and the institution.

Eduardo Gotuzzo (Universidad Peruaña Cayetano Heredia), Jo Handelsman (Yale University), James M. Hughes (Emory University), David A. Relman (Stanford University), and P. Frederick Sparling (University of North Carolina, Chapel Hill).

The Forum is also indebted to the IOM staff who tirelessly contributed throughout the planning and execution of the workshop and the production of this workshop summary report. On behalf of the Forum, we gratefully acknowledge these efforts led by Dr. Eileen Choffnes, Scholar and Director of the Forum; Dr. LeighAnne Olsen,² Program Officer; Katherine McClure, Associate Program Officer; Rebekah Hutton, Research Associate; and Charlee Alexander,³ Senior Program Assistant for dedicating much effort and time to developing this workshop’s agenda and for their thoughtful and insightful approach and skill in planning for the workshop and in translating the workshop’s proceedings and discussion into this workshop summary report. We would also like to thank the following IOM staff and consultants for their valuable contributions to this activity: Daniel Bethea, Laura Harbold DeStefano, Chelsea Frakes, Alison Mack, Erika Vijh, and Julie Wiltshire.

Finally, the Forum wishes to recognize the sponsors that supported this activity. Financial support for this project was provided by the U.S. Department of Health and Human Services: National Institutes of Health, National Institute of Allergy and Infectious Diseases, Centers for Disease Control and Prevention, Food and Drug Administration, and the Fogarty International Center; U.S. Department of Defense: Armed Forces Health Surveillance Center, Defense Threat Reduction Agency, and Medical Research and Materiel Command; U.S. Department of Justice: Federal Bureau of Investigation; U.S. Department of Veterans Affairs; U.S. Department of Homeland Security; U.S. Agency for International Development; Uniformed Services University of the Health Sciences; Alfred P. Sloan Foundation; American Society for Microbiology; Burroughs Wellcome Fund;⁴ GlaxoSmithKline;⁵ Infectious Diseases Society of America; Johnson & Johnson; Merck Company Foundation; and sanofi pasteur. The views presented in this workshop summary are those of the workshop participants and have been summarized by the rapporteurs. They do not necessarily reflect the views of the Forum on Microbial Threats, its sponsors, or the IOM.

________________

² Staff member until August 15, 2013.

³ Staff member from April 1 to November 15, 2013.

⁴ Sponsor until October 18, 2013.

⁵ Sponsor until October 18, 2013.

Contents

Workshop Overview

Workshop Overview References

Appendixes

A     Contributed Manuscripts

A1     Effector and Memory T Cell Responses to Commensal Bacteria

Yasmine Belkaid, Nicolas Bouladoux, and Timothy W. Hand

A2     What Are the Consequences of the Disappearing Human Microbiota?

Martin J. Blaser and Stanley Falkow

A3     Pathways in Microbe-Induced Obesity

Laura M. Cox and Martin J. Blaser

A4     Microbial Exposure During Early Life Has Persistent Effects on Natural Killer T Cell Function

Torsten Olszak, Dingding An, Sebastian Zeissig, Miguel Penilla Vera, Julia Richter, Andre Franke, Jonathan N. Glickman, Reiner Siebert, Rebecca M. Barron, Dennis L. Kasper, and Richard S. Blumberg

A5     The Application of Ecological Theory Toward an Understanding of the Human Microbiome

Elizabeth K. Costello, Keaton Stagaman, Les Dethlefsen, Brendan J. M. Bohannan, and David A. Relman

A6     Seasonal Restructuring of the Ground Squirrel Gut Microbiota Over the Annual Hibernation Cycle

Hannah V. Carey, William A. Walters, and Rob Knight

A7     Lessons from Studying Insect Symbioses

Angela E. Douglas

A8     A New Vision of Immunity: Homeostasis of the Superorganism

Gérard Eberl

A9     Host Defense and Immunomodulation of Mucosal Candidiasis

Paul J. Fidel, Jr., and Mairi C. Noverr

A10   Microbiota-Targeted Therapies: An Ecological Perspective

Katherine P. Lemon, Gary C. Armitage, David A. Relman, and Michael Fischbach

A11   Community Ecology and the Vaginal Microbiome

Larry J. Forney and Jacques Ravel

A12   Investigating Bacterial-Animal Symbioses with Light Sheet Microscopy

Michael J. Taormina, Matthew Jemielita, W. Zac Stephens, Adam R. Burns, Joshua V. Troll, Raghuveer Parthasarathy, and Karen Guillemin

A13   Clinical Application of Fecal Microbiota Transplantation in Clostridium difficile Infection and Beyond

Josbert J. Keller and Els van Nood

A14   Consumption of Human Milk Glycoconjugates by Infant-Associated Bifidobacteria: Mechanisms and Implications

Daniel Garrido, David C. Dallas, and David A. Mills

A15   Bacteriophage Adhering to Mucus Provide a Non–Host-Derived Immunity

Jeremy J. Barr, Rita Auro, Mike Furlan, Katrine L. Whiteson, Marcella L. Erb, Joe Pogliano, Aleksandr Stotland, Roland Wolkowicz, Andrew S. Cutting, Kelly S. Doran, Peter Salamon, Merry Youle, and Forest Rohwer

A16   Topographic Diversity of Fungal and Bacterial Communities in Human Skin

Keisha Findley, Julia Oh, Joy Yang, Sean Conlan, Clayton Deming, Jennifer A. Meyer, Deborah Schoenfeld, Effie Nomicos, Morgan Park, NIH Intramural Sequencing Center Comparative Sequencing Program, Heidi H. Kong, and Julia A. Segre

A17   Distinct Microbial Communities Within the Endosphere and Rhizosphere of Populus deltoides Roots Across Contrasting Soil Types

Neil R. Gottel, Hector F. Castro, Marilyn Kerley, Zamin Yang, Dale A. Pelletier, Mircea Podar, Tatiana Karpinets, Ed Uberbacher, Gerald A. Tuskan, Rytas Vilgalys, Mitchel J. Doktycz, and Christopher W. Schadt

A18   Interactions Between Commensal Fungi and the C-Type Lectin Receptor Dectin-1 Influence Colitis

Iliyan D. Iliev, Vincent A. Funari, Kent D. Taylor, Quoclinh Nguyen, Christopher N. Reyes, Samuel P. Strom, Jordan Brown, Courtney A. Becker, Phillip R. Fleshner, Marla Dubinsky, Jerome I. Rotter, Hanlin L. Wang, Dermot P. B. McGovern, Gordon D. Brown, and David M. Underhill

A19   Metagenomics and Personalized Medicine

Herbert W. Virgin and John A. Todd

A20   From Genetics of Inflammatory Bowel Disease Towards Mechanistic Insights

Daniel B. Graham and Ramnik J. Xavier

A21   Antimicrobial Peptides and the Microbiome

Michael Zasloff

B     Agenda

C     Acronyms

D     Glossary

E     Speaker Biographies

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Tables, Figures, and Boxes

TABLES

WO-1    Microbial Ecology Definitions

WO-2    Changes in Human Ecology That Might Affect Microbiota Composition

A2-1    Changes in Human Ecology That Might Affect Microbiota Composition

A3-1    Metabolic Consequences of Specified Host and Dietary Interactions with the Microbiome

A6-1    Ground Squirrel Body Mass, Cecal Tissue Mass, Body Temperature, and Torpor Characteristics

A6-2    Short-Chain Fatty Acid and Ammonia Concentrations and Molar Proportions of SCFA in Ground Squirrel Cecal Contents

A6-3    Correlations Between SCFA Levels and Microbial Taxa in Squirrel Cecal Contents

A11-1   Median Vaginal pH by Community State Types Within Ethnic Background

A12-1   List of Key Parts for the Author’s Light Sheet Microscope

A13-1   Donor Screening

A17-1   Selected Tree Dendrometric Measurements and Soil Physicochemical Characteristics for Bottomland and Upland Sites

A20-1   Candidate IBD Genes

FIGURES

WO-1   Model for early colonization

WO-2   Illustration of the chemical communication that exists between plant roots and other organisms in the complex rhizosphere

WO-3   Host–microbe systems biology

WO-4   Monoassociation with zebrafish gut bacterial isolates elicits a wide range of neutrophil influx

WO-5   The gut microbial community composition changes over developmental time

WO-6   Positive and negative selection of colonizing microbial species in the gut

WO-7   The dynamic interfaces that exist between plants, microbes, and the environment

WO-8   Constructed communities based on functional diversity

WO-9   The ancestry of humans reflected in the genomic signature

WO-10   The metabolic network of Buchnera aphidicola APS1, illustrating the flow of carbon from the main precursors to essential amino acids

WO-11   Annual cycles of body temperature, gut morphology, and feeding behavior

WO-12   Compositional differences in the microbiota by anatomical site

WO-13   The development of the microbiota from the first inoculum as an infant through continued change, modified by diet, genetics, and environment, throughout life

WO-14   The continuum of microbial states and immune responses: a dynamic equilibrium

WO-15   The intestinal mucosa in states of health and disease

WO-16   Physiological differences observed between the ancient (H. pylori–colonized) stomach and the postmodern (H. pylori–free) stomach

WO-17   Bacterial diversity increases with age in populations from distinct cultural traditions

WO-18   Factors modifying mother-to-child microbial transmission

WO-19   Influence of birth cohort on risk of breast cancer among BRCA-1 and BRCA-2 mutation carriers

WO-20   Phylogenetic surveys of the vaginal microbiome of healthy women identified five distinct clusters

WO-21   Epithelial cell sensitivity—organism threshold hypothesis

WO-22   Potential consequences of commensal-specific memory T cells

WO-23   Chronic viral infections in humans

WO-24   The Bacteriophage Adherence to Mucus Immunity model

WO-25   Worldwide Crohn’s disease incidence rates and/or prevalence for countries reporting data before 1960, from 1960 to 1979, and after 1980

WO-26   Bacterial phyla identified in the human gut microbiota

WO-27   IBD as a multifactorial disorder

WO-28   Potential mechanisms of NKT cell control in mucosal tissues by commensal microbiota during early life

WO-29   Proposed metabolic roles of the gut microbiome in IBD

WO-30   Therapeutic modulation of the gut microbiota: from the cradle to the grave

WO-31   Natural products with medicinal relevance

WO-32   Genomics can reveal cryptic natural products

WO-33   The secreted anti-infective protein/peptide arsenal of innate immunity

WO-34   Wound healing in a severely wounded bottlenose dolphin

WO-35   Atopic dermatitis (AD) progression hypothesis

WO-36   Fecal microbiota transplantation for patients with recalcitrant Clostridium difficile infection

WO-37   Rates of cure without relapse during 10 weeks of follow-up for recurrent Clostridium difficile infection

A1-1      Commensal-specific T cells at homeostasis and during infection

A1-2      Potential consequences of commensal-specific memory T cells

A2-1      The effect of maternal status on the resident microbiota of the next generation

A2-2      Helicobacter pylori prevalence in the United States by age and year of birth

A2-3     Interactions between host and microbiota

A3-1     Pathways in microbe-induced obesity

A3-2     Pathways involving microbiome and immunity that contribute to obesity

A3-3     Response of r- and K-selected species to environmental stress

A3-4     Microbial equilibrium and host effects in relation to energy substrates

A4-1     Intestinal bacteria-dependent accumulation of colonic iNKT cells in GF mice leads to high mortality in oxazolone-induced colitis

A4-2     Microbial colonization during early life prevents the CD1d/iNKT celldependent high mortality in oxazolone colitis in GF mice

A4-3     The increased CD1d/iNKT cell-mediated allergic response sensitivity of GF mice is dependent on age of colonization

A4-4     Microbiota affects tissue specific iNKT cell accumulation by genetic modifications of Cxcl16

A5-1     Alternative community assembly scenarios could give rise to the compositional variations observed in the human microbiota

A5-2     Disturbance can be illustrated using a stability landscape schematic

A6-1     Principal coordinate analysis plots of unweighted UniFrac metrics for squirrel microbiotas

A6-2     Alpha diversity rarefaction plots of squirrel cecal microbiotas

A6-3     Phylogenetic trees of squirrel cecal microbiotas colored by seasonal taxa

A6-4     Relative abundance of major taxa in squirrel cecal microbiotas

A6-5     Schematic illustrating major changes in the ground squirrel gut microbiota over the annual hibernation

A7-1     The insect IMD pathway and persistence of resident microorganisms

A7-2     Coevolution of amino acid biosynthesis in plant sap–feeding insects and their bacterial symbionts

A8-1     The superorganism

A8-2     The dualistic and the continuum models of the microbial and immunological worlds

A8-3     The continuum of microbial states and immune responses: a dynamic equilibrium

A9-1     OPC: Protection, susceptibility, and results of treatment with ART/PI or IFN-g

A9-2     Schematic diagrams representing the mechanism for the effects of vaginal S100 alarmins on PMN migration during VVC

A9-3     Proposed model of immunopathogenesis of Candida-associated denture stomatitis

A10-1    Microbial communities as networks

A10-2   New opportunities in treatment and diagnostics

A10-3   Microbiota-targeted therapy can shift a community to a healthier stable state

A11-1   Heat map of log₁₀ transformed proportions of microbial taxa found in the vaginal bacterial communities of 394 women of reproductive age

A11-2   Representation of vaginal bacterial community groups within each ethnic group of women

A11-3   Contribution of ethnicity to each of the five vaginal community groups expressed as percentage

A11-4   Relationships among vaginal bacterial communities visualized by principal component analysis in which the relative abundances are expressed as proportions of the total community and displayed in three-dimensional (3-D) space

A11-5   Assignment of vaginal community state types

A11-6   Dynamics of vaginal community state types in 32 women over 16 weeks

A11-7   Graphical representation of community state type transitions observed between all consecutive pairs of time points (905 transitions) and their frequencies among all women

A11-8   Heat maps and interpolated bar plots of phylotype relative abundance observed in four selected subjects over 16 weeks

A11-9   Temporal dynamics of vaginal bacterial communities in two women over 16 weeks

A11-10   Modeling the dependence of the log of Jensen-Shannon divergence rate of change over the menstrual cycle

A12-1   A zebrafish larva at 7 dpf (days post-fertilization)

A12-2   Schematic illustrations of fluorescence imaging techniques

A12-3   Schematic illustration of our light sheet microscope setup

A12-4   Colonization of a larval zebrafish gut by GFP-expressing and dTomato-expressing Aeromonas veronii bacteria

A12-5   Fluorescently labeled enteroendocrine cells in a larval zebrafish gut

A12-6   Population distributions as a function of time for the two coinoculated bacterial populations illustrated in Figure A12-4

A12-7   Image auto- and cross-correlations

A14-1   Structural diversity of glycans in human milk and corresponding glycosyl hydrolases in infant-gut associated bifidobacteria

A14-2   Clusters of genes in B. infantis ATCC 15697 with assigned or putative functions in the utilization of milk glycans

A15-1   Phage adhere to cell-associated mucus layers and mucin glycoprotein

A15-2   Effect of phage adsorption on subsequent bacterial infection of epithelial cells

A15-3   Effect of Hoc protein on phage–mucin interactions

A15-4   Hoc-mediated glycan binding and Hoc-related phylogeny

A15-5   The BAM model

A16-1   Relative abundance of fungal genera and Malassezia species at different human skin sites

A16-2   Median richness of fungal and bacterial genera

A16-3   Forces that shape fungal and bacterial communities

A16-4   Clinical involvement alters shared fungal community structure

A17-1   Rarefaction curves for bacterial OTUs, clustering at 97% rRNA sequence similarity

A17-2   Rarefaction curves for fungal OTUs, clustering at 95% rRNA sequence similarity

A17-3   Bacterial classifications using the RDP classifier at 80% identity as implemented in mothur, shown at the phylum level except for Proteobacteria, which are classified by class

A17-4   Fungal sequence classifications as identified from a consensus among the top BLAST scores against the SILVA LSU database

A17-5   Principle coordinate analysis of bacterial and fungal communities, based on Fast UniFrac analysis

A17-6   Heat map and hierarchical cluster analysis based on the relative abundances of the top OTUs identified in >5 samples in the bacterial and fungal data sets

A18-1   Commensal fungi are present in the intestine and are recognized by Dectin-1

A18-2   Dectin-1 regulates the severity of colitis

A18-3   Defining the fungal microbiome and characterizing the specific role of Dectin-1–mediated host defense during colitis

A18-4   Anti-fungal therapy ameliorates colitis in Clec7a^-/- mice and CLEC7A associates with ulcerative colitis severity in humans

A19-1   Perfect storms for developing Crohn’s disease and type 1 diabetes

A19-2   Refining the relationship between genotype and phenotype in complex inflammatory diseases

A19-3   The iterative redefinition of mechanism-based disease subtypes

A19-4   Microbe plus gene interactions determine inflammatory bowel disease phenotypes

A19-5   A metagenetic view of developing normal and pathological immune responses

A20-1   From genetics to disease mechanisms

A20-2   Inflammatory bowel disease (IBD) pathways and key cell types

A20-3   Molecular pathogenesis of inflammatory bowel disease (IBD): assembling the evidence

BOXES

WO-1    Human Microbiome Research Projects

A2-1      The Human Microbiome Project

A2-2     What Is a Pathogen?

A2-3     The Gastric Microbiome

A8-1     Definitions

A8-2     Predictions

A19-1   Definition of Terms

A20-1   Key Genes Implicated in IBD

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