Laboratory Animals - June Issue - 261

Ericsson

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Table 1. Summary of the advantages, common uses, and limitations of various non-rodent species for research
investigating host-associated microbiota.
Model
organism(s)

Advantages/uses

Limitations

Invertebrates






High throughput and sample sizes
Genetic tractability (variable)
Cost effective; efficient
Studies of symbiosis and aging

 Simplified GIT anatomy
 Simplified GM composition; dominant
phyla different than in human
 Inability to model many diseases

Zebrafish






High throughput and sample sizes
Genetic tractability
Cost effective; efficient
Similarities to human endocrine and
neural systems
 Developmental studies, gnotobiotics,
gut-brain axis

 Aquatic environment
 Simplified GIT anatomy
 Dominant GI phyla different than in
human
 Inability to model many diseases

Dogs

 Outbred population with similar
environment to humans
 GM composition similar to humans
 GI and respiratory anatomy similar to
humans
 Periodontal disease, IBD, neoplasia






Pigs

 Outbred population with similar environment to humans
 GM composition similar to humans
 GI and respiratory anatomy similar to
humans
 Genetic tractability

 Expensive to house and maintain
 High throughput studies not feasible

Rabbits

 GI anatomy similar to humans
 Pathogen challenge in ligated GIT
 Sinus and periodontal microbiota studies

 Expensive to house and maintain
 GM dominated by Firmicutes phylum

Expensive to house and maintain
High throughput studies not feasible
Genetics not easily manipulated
Public perception of research using
purpose-bred dogs

IBD: inflammatory bowel disease; GI: gastrointestinal; GIT: GI tract; GM: gut microbiota.

Limitations of the zebrafish model in microbiotarelated research include differences in environmental
conditions and exposures when compared to humans
and other model organisms. Perhaps not surprisingly,
the intestinal microbiota of zebrafish is thus quite different from that of mammalian hosts and, unlike most
other host species, differs dramatically between institutions (and depending on diet) at the phylum
level.36,55-58 Although the fecal microbiota of humans
and rodents may vary significantly at the genus level
depending on host genetics, geography, age, and environmental factors, it is consistently dominated by the
phyla Firmicutes and Bacteroidetes. Depending on the
source, the GM of zebrafish is dominated by
Proteobacteria and Fusobacteria, with variable presence
of Firmicutes, Cyanobacteria, Actinobacteria, and other
phyla;55,57 Bacteroidetes are usually, but not
always,36,58 negligible. Although they are beyond the
scope of the current review, there are also considerable
differences between zebrafish and mammalian hosts in
gut anatomy that may be of relevance to particular

studies such as a lack of Paneth cells and organized
lymphoid structures.59 Specifically, the intestinal microbiota stimulates Myd88-mediated signaling in Paneth
cells to induce the production of antimicrobial peptides
(e.g. defensins),60 which, in turn, modulate microbial
ecology within the gut.61,62 Additionally, the GIT of
zebrafish lacks the clearly differentiated segments (e.g.
stomach, small and large intestines) found in higher
vertebrates. In higher vertebrates, there is a distinct
division between the small and large intestines with
regard to bacterial composition63,64 and the lack of a
clear anatomic division between these regions in zebrafish should be considered a limitation with regard to
translational research.

Dogs (Canis familiaris)
Companion animals such as dogs possess attributes that
make them an appropriate model species for certain
microbiota-focused studies. First, the canine GIT is
more similar in size and structure to that of humans



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