Standardised animal models of host microbial mutualism

Abstract

An appreciation of the importance of interactions between microbes and multicellular organisms is currently driving research in biology and biomedicine. Many human diseases involve interactions between the host and the microbiota, so investigating the mechanisms involved is important for human health. Although microbial ecology measurements capture considerable diversity of the communities between individuals, this diversity is highly problematic for reproducible experimental animal models that seek to establish the mechanistic basis for interactions within the overall host-microbial superorganism. Conflicting experimental results may be explained away through unknown differences in the microbiota composition between vivaria or between the microenvironment of different isolated cages. In this position paper, we propose standardised criteria for stabilised and defined experimental animal microbiotas to generate reproducible models of human disease that are suitable for systematic experimentation and are reproducible across different institutions.

Figure 1

Time line of development of isobiotic mice in comparison with isogenic mice. The panel on the left highlights historical events in the development of gnotobiology. The panel on the right illustrates the huge progress made in the development of isogenic mice.

Figure 2

Sterile connection between a material drum and a flexible film isolator. The large steel drum contains sterile materials to be imported into the isolator, such as food, bedding, or cages. The drum is sealed and autoclaved and then connected to the isolator via a plastic sleeve that is sterilised by spraying with 2% peracetic acid, which then permits transfer of the sterile material into the isolator.

Figure 3

Experimental protocol for superovulation of embryo donor females followed by embryo transfer into germ-free or isobiotic pseudopregnant recipient females.

Figure 4

Specialised transport sleeve. The photo shows an example of a specialised transport sleeve developed to allow shipping of germ-free animals between facilities. The example shown is available from Taconic. Many germ-free facilities have developed their own transport devices that reflect the design of their isolators. Such transport containers allow importation of germ-free or isobiotic mice into isolators at the new facility and ensure hygiene is maintained during transport.