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appropriate model species for certain lines of investigation and, in the case of dogs and pigs, may serve as
more relevant models for humans due to their shared
environmental exposure. With that in mind, readers are
also directed to more focused reviews on the aforementioned model species1-4 as well as other species not discussed here, such as non-human primates5,6 and other
non-murine rodent species.7

Laboratory Animals 53(3)
community structure at the most basic taxonomic
levels, and an inability to model many of the immunemediated and neoplastic conditions occurring in
humans such as those reliant on the adaptive immune
system. Table 1 summarizes these benefits and limitations, alongside those of the host species discussed
below.

Zebrafish (Danio rerio)
Invertebrates
Invertebrate hosts such as worms and insects represent
multicellular in vivo systems with variably compartmentalized digestive tracts and homologs of many of the
differentiated cell types found in vertebrate hosts.
There are several invertebrate model species that are
frequently used to study certain interactions between
the host and its microbiota. Frequently, invertebrate
species are used in studies focused on symbioses
between the host and microbiota and the mechanisms
by which those interdependent relationships are established and maintained. Two characteristics of invertebrates making them particularly amenable to such
research are their reliance on the innate immune
system8 and a highly restricted (i.e., low a-diversity)
gut microbiota.9 Much work has been done in this
regard using entomopathogenic nematode hosts such
as Heterorhabditis bacteriophora and Steinernema carpocapsae and their respective symbionts. Photorhabdus
luminescens and Xenorhabdus nematophila,10-13 as well
as marine organisms such as the freshwater leech
(Hirudo verbana)14,15 and bobtail squid (Euprymna scolopes) and their respective symbionts Aeromonas veronii
and Vibrio fischeri.16,17
For studies necessitating genetically tractable model
organisms, Drosophila melanogaster and Caenorhabditis
elegans are the two most commonly used invertebrate
models. Although these host species can also be used to
study the nature of microbial symbioses, their relatively
short lifespan and the aforementioned ability to
manipulate their well-characterized genomes18-23 make
them attractive models to study the influence of the
microbiota on host aging, including methods involving
caloric restriction.24-28 Additionally, it is possible to
render both Drosophila sp. and C. elegans axenic or
germfree (GF) for use in gnotobiotic experiments.29,30
Moreover, their small size allows for well-powered studies and high-throughput whole animal testing including in vivo fluorescent imaging in the case of C. elegans.
As one final advantage, the use of invertebrate models
abrogates much of the regulatory concerns associated
with vertebrate animal research. The primary limitations associated with invertebrate models include the
stark differences in gastrointestinal anatomy relative
to mammalian hosts, differences in microbial

The use of zebrafish in biomedical research in general
has been increasing steadily over the last couple of decades. As in mice, the limited requirements related to
housing space and cost and high fecundity allow studies
with larger sample sizes. Physiologically, zebrafish also
possess several basic similarities to mammalian hosts
including a well-differentiated adaptive immune
system,31 a stress response axis typified by the same
neuronal transmitters,32 corticosteroid mediators,33
and responses to pharmaceutical interventions in
accordance with the responses observed in humans.34
Zebrafish first gained popularity in the field of developmental biology and teratology due to their transparent body wall during embryonic and larval stages,
allowing direct visualization of events during organogenesis. That same trait, along with their ex utero development, can be exploited to directly study early events
during colonization by the gastrointestinal tract (GIT).
Specifically, surface sterilization of embryos with various antibiotic cocktails results in GF zebrafish
larvae,35,36 and whole mount larvae can be labeled
with in situ hybridization or other assays to localize
gene expression or specific cell types in GF and colonized fish.37 Alternatively, fluorescently labeled bacteria
can be visualized directly through the transparent body
wall.38,39
Zebrafish are also increasingly being used to determine the role of the microbiota in disease models,40
including chemically induced models of inflammatory
bowel disease (IBD).41,42 In these and other studies,
their aquatic environment allows test compounds and
antibiotics to be delivered directly into the tank
water.43,44 Notably, zebrafish have gained considerable
attention over the last decade for their utility in determining the influence of probiotic bacteria, such as
Lactobacillus spp., on stress- and anxiety-related behaviour,45 appetite and feeding behaviour,46 metabolism,
reproduction,47,48 immunity and pathogen resistance,49,50 and candidate microbial taxa with possible
effects on these parameters can also be delivered via
the tank water.36,45,51 Allowing for investigations of
the effect of host gene expression on the GM, genetic
manipulation can be accomplished in zebrafish using
any of the recently developed platforms employed in
rodents.52-54



Laboratory Animals - June Issue

Table of Contents for the Digital Edition of Laboratory Animals - June Issue

Contents
Laboratory Animals - June Issue - Cover1
Laboratory Animals - June Issue - Cover2
Laboratory Animals - June Issue - Contents
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