Animal Models for Microbiome Research Advancing Basic and Translational Science: Proceedings of a Workshop (2018) / Chapter Skim
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3 Non-Rodent Models for Microbiome Research
3 Non-Rodent Models for Microbiome Research
Pages 7-16
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From page 7... ...
The three speakers on the second panel were Robert Britton, professor in the Department of Molecular Virology and Microbiology at Baylor College of Medicine; Vincent Young, associate professor in the Department of Internal Medicine/Division of Infectious Diseases and Department of Microbiology and Immunology at the University of Michigan; and Donald Ingber, founding director of the Wyss Institute for Biologically Inspired Engineering at Harvard University and Judah Folkman Professor of Vascular Biology at Harvard Medical School. EUKARYOTIC MODELS Caenorhabditis elegans (C.
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From page 8... ...
elegans populations and can now recapitulate communities representing 80 percent of the core operational taxonomic units and 75 percent of the microbial abundance (see Figure 3-1)
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. Douglas described an elaborate set of feeding experiments with axenic drosophila as an example of how axenic insects can provide insights on nutritional interactions in the host digestive system.
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. They also observed the co-expression of pairs of genes differed significantly between axenic and gnotobiotic flies, leading Douglas to conclude that the microbiome promotes co-expression of specific transcriptional modules.
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Zebrafish Zebrafish studies benefit from an abundance of genetic and genomic tools and high-throughput functional assays. As vertebrates, zebrafish offer additional complexity in terms of the kinds of microbial communities they harbor, and their optical transparency provides some unique opportunities to observe dynamic microbial communities in the gut of a living animal.
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Subsequent experiments identified several Aeromonas strains and a Shewenalla strain that could reverse this effect and that a specific secreted protein -- beta cell expansion factor A, or BefA -- produced by the bacteria was responsible for stimulating beta cell production. Treating axenic fish with this protein, which has homologs in human-associated bacteria, triggered expansion of beta cells.
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Nonetheless, Gordon said he is enthusiastic about this model for select purposes, and particularly as a second species in a translational medicine pipeline for both proof of concept and mechanistic studies. IN VITRO SYSTEMS FOR CHARACTERIZING MICROBIAL CONSORTIA As a means of studying a microbiome's complex microbial community at both the structural and the functional level, investigators are developing a variety of in vitro systems, including the miniature bioreactor arrays that Britton and his colleagues have created to study how microbial communities resist invasion by pathogens without the need to use mice.
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From page 14... ...
Britton and his collaborators are also using the bioreactor array to establish microbial communities from body sites other than the gut and to grow hard-tocultivate microbes. Going forward, he plans to develop an interface between this device and human enteroids, grown from autopsy tissue, and organoids, produced from induced human pluripotent stem cells or embryonic stem cells, as an approach to introducing a host component into the system and to explore ways of establishing niches inside the bioreactors.
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From page 15... ...
To address this problem, he and his colleagues at the Wyss Institute are engineering microchips containing living human cells that reconstitute organ-level functions to accelerate drug development and replace animal testing. Manufacturing microchips using well-developed photolithographic etching allows control of various features in biocompatible materials at the size scale of living cells (Chen et al., 1997; Singhvi et al., 1994)
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Food and Drug Administration, which has provided substantial funding for this work, has said it will accept data from these systems as long as Ingber and his collaborators can demonstrate that the data are as good or better than the data from animal models. His group has already demonstrated the robustness of the organs-on-chips, and therefore Ingber's next step would be to obtain primary and induced pluripotent stem cells and microbiome samples from individual patients as a means of creating personalized medicine approaches to treating disease.
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