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Introduction

The surface of the human body and its mucous membranes are heavily colonized by microorganisms. Our understanding of the contributions that complex microbial communities, such as Archaea, bacteria, and eukaryotes, and their viruses (Hugon et al., 2017; Parker, 2016), make to health and disease is advancing rapidly (Cho and Blaser, 2012; Eloe-Fadrosh and Rasko, 2013; Hooper et al., 2012; Lloyd-Price et al., 2016; Lynch and Pedersen, 2016). These projects have produced experimental and computational resources that are enabling investigators to analyze microbial community functions and begin to understand the role that microbial and viral genomes play in normal and disease biology. To capitalize on these new resources and to aggressively explore the relationship between microbiomes and their hosts, including humans, the White House launched the National Microbiome Initiative¹ in May 2016 to “foster the integrated study of microbiomes across different ecosystems” by pulling together federal agencies, academic institutions, and private entities.

Most microbiome research to date has focused on the mouse as a model organism for delineating the mechanisms that shape the assembly and dynamic operations of microbial communities. Mouse microbiome models have also been the primary choice for performing preclinical proof-of-concept tests of causal relationships between given community configurations/memberships and host physiological, metabolic, immune, and neurologic phenotypes and for developing methods to repair or prevent functional abnormalities in these communities that contribute to disease pathogenesis. The mouse, however, is not a perfect surrogate for studying different aspects of the microbiome and how it responds to various environmental and host stimuli. As a result, researchers have been conducting microbiome studies in other animals as well, for instance, zebrafish, piglets, and Drosophila.

To examine the different animal models researchers employ in microbiome studies and to better understand the strengths and weaknesses of each of these model organisms as they relate to human and nonhuman health and disease, the Roundtable on Science and Welfare in Laboratory Animal Use of the

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¹ See https://obamawhitehouse.archives.gov/the-press-office/2016/05/12/fact-sheet-announcing-national-microbiome-initiative (accessed February 28, 2017).

National Academies of Sciences, Engineering, and Medicine convened a workshop on December 19-20, 2016, in Washington, DC, to discuss animal models of microbiome research. An ad hoc committee (see the committee roster and Appendix B for their biographies) planned this workshop to (1) explore how to improve the depth and breadth of analysis of microbial communities using various model organisms; (2) address the challenges of standardization and biological variability that are inherent in gnotobiotic animal-based research; (3) examine the predictability and translatability of preclinical studies to humans; and (4) discuss strategies for expanding the infrastructure and tools for conducting studies in these types of models (see Box 1-1 for the full Statement of Task). Invited speakers and stakeholders discussed gaps, challenges, and opportunities in this rapidly expanding field, paying particular attention to the care, use, and welfare of the gnotobiotic animals.

This Proceedings of a Workshop was prepared by the rapporteurs as a factual summary of what occurred at the workshop. The planning committee’s role was limited to planning and convening the workshop (see Appendix A for the agenda and Appendix B for the biographies of the planning committee members). The views contained in the publication are those of individual workshop participants and do not necessarily represent the views of all workshop participants, the planning committee, or the National Academies of Sciences, Engineering, and Medicine.