Animal Models for
Microbiome Research
Advancing Basic and Translational Science
PROCEEDINGS OF A WORKSHOP
Joe Alper, Lida Anestidou, and Jenna Ogilvie, Rapporteurs
Roundtable on Science and Welfare in Laboratory Animal Use
Institute for Laboratory Animal Research
Division on Earth and Life Studies
THE NATIONAL ACADEMIES PRESS
Washington, DC
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This project was supported by the American Veterinary Medical Association; Covance Laboratories, Inc.; Genentech; GlaxoSmithKline; Massachusetts General Hospital; Merck; National Primate Research Centers; National Science Foundation; Novartis; University of California, Davis; University of Michigan; University of Pittsburgh; University of Washington; U.S. Food and Drug Administration; and Yale University. Funding for this conference was made possible, in part, by the U.S. Food and Drug Administration through grant 5 R13 FD 005298-02. The views expressed in written conference materials or publications and by speakers or moderators do not necessarily reflect the official policies of the U.S. Department of Health and Human Services; nor does any mention of trade names, commercial practices, or organization imply endorsement by the U.S. government. This material is based on work supported by the National Science Foundation under Grant No. IOS-1639899. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.
International Standard Book Number-13: 978-0-309-46388-1
International Standard Book Number-10: 0-309-46388-2
Digital Object Identifier: https://doi.org/10.17226/24858
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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2018. Animal Models for Microbiome Research: Advancing Basic and Translational Science: Proceedings of a Workshop. Washington, DC: The National Academies Press. https://doi.org/10.17226/24858.
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PLANNING COMMITTEE FOR A WORKSHOP ON ANIMAL MODELS FOR MICROBIOME RESEARCH: ADVANCING BASIC SCIENCE AND TRANSLATIONAL RESEARCH
JAMES G. FOX (Co-Chair), Professor and Director, Division of Comparative Medicine, and Professor of Biomedical Engineering, Massachusetts Institute of Technology
JOSEPH T. NEWSOME (Co-Chair), Clinical Director, Division of Laboratory Animal Resources and Associate Professor, Pathology, University of Pittsburgh
WENDY S. GARRETT, Melvin J. and Geraldine L. Glimcher Associate Professor of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health
JEFFREY I. GORDON, Dr. Robert J. Glaser Distinguished University Professor and Director, Center for Genome Sciences and Systems Biology, Washington University in St. Louis
VINCENT B. YOUNG, Associate Professor, Department of Internal Medicine/Division of Infectious Diseases and Department of Microbiology and Immunology, University of Michigan
ROUNDTABLE ON SCIENCE AND WELFARE IN LABORATORY ANIMAL USE1
Co-Chairs
LYNN C. ANDERSON, Vice President, Global Animal Welfare and Comparative Medicine, Covance Laboratories, Inc.
ROBERT C. DYSKO, Professor and Director, Unit for Laboratory Animal Medicine, University of Michigan Medical School
Liaison to ILAR Council
PAUL A. LOCKE, Associate Professor, Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health
Members
DAVID M. ANDERSON, Executive Director, Health Sciences Administration, University of Washington
JILL ASCHER, Deputy Director, Division of Veterinary Services, U.S. Food and Drug Administration
BONNIE V. BEAVER, Professor, Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Texas A&M University
SAVERIO “BUDDY” CAPUANO III, Attending Veterinarian and Associate Director, Animal Services, Wisconsin National Primate Research Center, University of Wisconsin–Madison
CAROL CLARKE, Research Specialist Staff Officer, U.S. Department of Agriculture, Animal and Plant Health Inspection Service Animal Care
GAIL C. GOLAB, Director, Animal Welfare Division, American Veterinary Medical Association
DONNA MATHEWS JARRELL, Attending Veterinarian, Director, Center for Comparative Medicine, Massachusetts General Hospital
ESTELLA Z. JONES, Senior Regulatory Veterinarian and Acting Institutional Official, White Oak Animal Program, Office of Counterterrorism and Emerging Threats, Office of the Chief Scientist/Office of the Commissioner, U.S. Food and Drug Administration
BRUCE W. KENNEDY, Compliance Associate, Office of Research, California State Polytechnic University
DAVID M. KURTZ, Veterinary Staff Scientist, National Institute of Environmental Health Sciences, National Institutes of Health
___________________
1 Membership of the Roundtable and member affiliations current as of December 2016.
MARGARET S. LANDI, Chief of Animal Welfare, Ethics and Strategy, GlaxoSmithKline
K. C. KENT LLOYD, Professor and Director, Mouse Biology Program, University of California, Davis
JOSEPH T. NEWSOME, Clinical Director, Division of Laboratory Animal Resources and Associate Professor, Pathology, University of Pittsburgh
STEVEN NIEMI, Director, Office of Animal Resources, Harvard University Faculty of Arts and Sciences
PATRICIA PREISIG, Professor of Internal Medicine (Nephrology) and Cellular and Molecular Biology, Yale University
SUSAN BRUST SILK, Director, Division of Policy and Education, Office of Laboratory Animal Welfare, National Institutes of Health
EDDA (FLOH) THIELS, Program Director, Integrative Organismal Systems Division, Biological Sciences Directorate, National Science Foundation
RHONDA J. WILER, Senior Director, Transgenic Technology, Genentech
GINA P. WILKERSON, Global Animal Welfare Officer, Scientific Operations, Novartis Institute for Biomedical Research, Inc.
ROBERT H. WURTZ, NIH Distinguished Investigator, Laboratory of Sensorimotor Research, National Eye Institute, National Institutes of Health
National Academies of Sciences, Engineering, and Medicine Staff
LIDA ANESTIDOU, Director, Roundtable on Science and Welfare in Laboratory Animal Use
JENNA OGILVIE, Research Associate, Board on Life Sciences
ANGELA KOLESNIKOVA, Senior Program Assistant, Board on Life Sciences
INSTITUTE FOR LABORATORY ANIMAL RESEARCH1
Members
MARGARET S. LANDI (Chair), Chief of Animal Welfare, Ethics and Strategy, GlaxoSmithKline
KARIN BLUMER, Scientific Affairs, Novartis International AG
CORY BRAYTON, Associate Professor of Molecular and Comparative Pathobiology, Johns Hopkins University
JOSEPH J. DEGEORGE, Global Head of Safety Assessment and Laboratory Animal Resources, Merck Research Laboratories
MICHAEL DUVALL, Scientific Director, Head of Toxicology and Laboratory Animal Medicine, Johnson & Johnson, Janssen Pharmaceuticals
LEWIS B. KINTER, Independent Consultant
MALAK KOTB, Chair, Department of Basic Sciences, University of North Dakota
PAUL A. LOCKE, Associate Professor, Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health
DANIEL S. MARSMAN, Head, Safety and Regulatory Affairs, Procter & Gamble Health Care
MELINDA A. NOVAK, Professor of Psychology, Department of Psychology, University of Massachusetts
JAMES A. ROTH, Clarence Hartley Covault Distinguished Professor, Director, Center for Food Security and Public Health, College of Veterinary Medicine, Iowa State University
LAWRENCE B. SCHOOK, Vice President for Research, Edward William and Jane Marr Gutgsell Professor, University of Illinois
ROBERT S. SIKES, Professor of Biology, University of Arkansas at Little Rock
Staff
DOROTHY ZOLANDZ, Acting Director
LIDA ANESTIDOU, Senior Program Officer
___________________
1 Membership of the Roundtable and member affiliations current as of December 2016.
Acknowledgments
The support of the Roundtable on Science and Welfare in Laboratory Animal Use was vital to the planning and conduct of the workshop on Animal Models for Microbiome Research: Advancing Basic and Translational Science. Federal sponsors are the National Science Foundation and the U.S. Food and Drug Administration. Nonfederal sponsorship was provided by the American Veterinary Medical Association; Covance Laboratories, Inc.; Genentech; GlaxoSmithKline; Massachusetts General Hospital; Merck; National Primate Research Centers; Novartis; University of California, Davis; University of Michigan; University of Pittsburgh; University of Washington; and Yale University.
The Roundtable on Science and Welfare in Laboratory Animal Use wishes to express gratitude to the members of the planning committee for their work in developing a far-reaching workshop agenda and the expert speakers who took part in the workshop’s discussions.
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Reviewers
This Proceedings of a Workshop was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published proceedings as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the charge. The review comments and draft manuscript remain confidential to protect the integrity of the process.
We thank the following individuals for their review of this proceedings:
Angela Douglas, Cornell University
Robert Dysko, University of Michigan Medical School
Alton G. Swennes, Baylor College of Medicine
Tamara Tal, U.S. Environmental Protection Agency
Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the content of the proceedings nor did they see the final draft before its release. The review of this proceedings was overseen by Jeffrey Everitt, Duke University School of Medicine. He was responsible for making certain that an independent examination of this proceedings was carried out in accordance with standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the rapporteurs and the National Academies.
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Contents
2 A TRANS-KINGDOM PERSPECTIVE ON ANIMAL MODELS AND MICROBIOME RESEARCH
The Importance of Trans-Kingdom Interactions
3 NON-RODENT MODELS FOR MICROBIOME RESEARCH
In Vitro Systems for Characterizing Microbial Consortia
4 MODELING HUMAN MICROBIOTA IN ANIMAL SYSTEMS
Connecting Microbes to Metabolism Using Gnotobiotic Models
Revisiting Koch’s Postulates from a Microbial Community Perspective
The Interface Between Microbes and Neuroscience: Two Case Studies
5 EXPERIMENTAL REPRODUCIBILITY USING GNOTOBIOTIC ANIMAL MODELS
Creating Stabilized Microbiomes in Laboratory Animals
Complex Gnotobiology: An Emerging Paradigm in the Era of Next-Generation Sequencing
The Role of Immunological Variation
Standardizing and Characterizing Diets
6 ESTABLISHING AND EVOLVING GNOTOBIOTIC FACILITIES
Building and Maintaining a Gnotobiotic Facility
APPENDIXES
B BIOGRAPHICAL SKETCHES OF PLANNING COMMITTEE
C BIOGRAPHICAL SKETCHES OF WORKSHOP SPEAKERS AND MODERATORS
BOX, FIGURES, AND TABLE
BOX
1-1 Workshop Statement of Task
FIGURES
2-1 The enteric virome becomes more complex in patients with inflammatory bowel disease
3-1 Natural microbiome of C. elegans
3-2 The five major bacterial isolates from laboratory-grown Drosophila
4-1 The honeybee gut microbiome
5-2 Female and male differences in disease susceptibility related to immunological differences
TABLE
Acronyms and Abbreviations
BSL-2 | biosafety level 2 |
CCFA | Crohn’s & Colitis Foundation of America |
DGRP | Drosophila Genetic Resource Panel |
EEN | exclusive enteral nutrition |
IACUC | Institutional Animal Care and Use Committee |
IBD | inflammatory bowel disease |
LPS | lipopolysaccharide |
NAPE-PLD | N-acyl phosphatidylethanolamine phospholipase D |
NIH | National Institutes of Health |
NKT | natural killer T cells |
NOD | non-obese diabetic |
sDMDMm2 | Stable Defined Moderately Diverse Mouse Microbiota 2 |
SOP | standard operating procedure |
SPF | specific pathogen-free |
TMAO | trimethylamine-N-oxide |
USDA | U.S. Department of Agriculture |
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