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264
to their rodent predecessors, particularly in the areas of
nutrition and digestion.137-139 However, the same factors that drive the use of mice and rats as experimental
models in general (i.e. low costs and high fecundity)
likely explain the relative dearth of research being performed with GF rabbits; it is simply more cost effective
to work with GF mice or rats than it is to work with
GF rabbits. That said, there are still investigators
taking advantage of the precocious nature of rabbits
and hand-rearing cesarean-born rabbits as GF
models.140,141
Prior to the development of GF rabbits (or mice),142
rabbits had gained favor as model organisms in investigations of cultivable infectious agents. Specifically, in
1953 De and Chatterje pioneered an acute rabbit
model to study GI pathogens wherein a portion of the
small intestine was ligated intra-operatively, injected
with a pure culture of the candidate bacteria, and
placed back in the abdomen with the ligations
intact.143 At 24 hours post-surgery, rabbits were euthanized and the ligated section was removed and evaluated
to assess in vivo effects of the bacteria in question. Since
that initial study on the effects of Vibrio cholerae, numerous pathogenic agents have been studied using similar
techniques.144-148 As this approach completely stops
intestinal transit of ingesta and the associated microbiota, rabbits must be sacrificed shortly after the procedure. Recently, however, a related approach has been
developed that allows for longer studies and can be
used to investigate complex microbial communities.
Specifically, within 24 hours of birth, the appendix is
flushed with a broad-spectrum antibiotic cocktail and
ligated at the cecal-appendix junction to prevent influx
and colonization of commensal bacteria. At 4 weeks
post-ligation, the sterile lumen of the appendix can
then be inoculated with cecal contents or pure isolates
to assess influence on the immune system and inflammatory responses.140,149-151 Although undeniably artificial,
this model is somewhat unique in that it renders only a
portion of the gut a sterile environment and allows
otherwise normal gut development and physiology.
There are, of course, limitations of rabbits as model
species in microbiota-focused research including their cost
relative to rodents. As with dogs and pigs, this often precludes large sample sizes. Also, as in swine, although the
technology to create knockout and transgenic rabbits
does exist, these are not commonly performed procedures
and existing mutant rabbit models are few.

Conclusion
In translational medicine, model species are selected
based on some similarity to humans with regard to
anatomy, molecular basis, pathogenesis, or response
to treatment. In studies of host-associated microbiota

Laboratory Animals 53(3)
and interactions between host and microbes, the investigator must now consider other factors. For example,
traditional rodent models may be less preferable than
dogs when studying the effects of environmental factors
on the GM of an outbred population. Similarly, larger
omnivorous animals such as pigs may be preferable to
rodents for nutrition research or certain procedures.
The question of which host species harbors a GM
most similar to humans may be, to some degree, irrelevant. Although it is difficult to argue against the possible merits of working with host species in which the
GM resembles humans, it is also well established that
each host has co-evolved with its cognate GM and
xenotransplantation of the GM usually fails to recapitulate the same effects as the ''correct'' GM on development of the immune system and other physiological
parameters.114 Moreover, the concept of a ''core microbiota'' of any host species, humans included, has largely
been supplanted by the concept of a core microbiome.
In other words, although the GM composition may
vary widely between and within a host species, the functions provided by those microbes are highly conserved.
As such, readers are encouraged to fully consider the
experimental question being asked during study design
and consider whether alternative model species might
better serve their goals.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.

Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.

ORCID iD
Aaron C. Ericsson

http://orcid.org/0000-0002-3053-7269

References
1. Douglas AE. The Drosophila model for microbiome
research. Lab Anim (NY) 2018; 47: 157-164.
2. Gerbaba TK, Green-Harrison L and Buret AG. Modeling
host-microbiome interactions in Caenorhabditis elegans.
J Nematol 2017; 49: 348-356.
3. Zhang F, Berg M, Dierking K, et al. Caenorhabditis elegans as a model for microbiome research. Frontiers
Microbiol 2017; 8: 485.
4. Chandler JA, Lang JM, Bhatnagar S, et al. Bacterial communities of diverse Drosophila species: Ecological context
of a host-microbe model system. PLoS Genet 2011; 7:
e1002272.
5. Amato KR. Incorporating the gut microbiota into models
of human and non-human primate ecology and evolution.
Am J Phys Anthropol 2016; 159: S196-215.


http://www.orcid.org/0000-0002-3053-7269 http://www.orcid.org/0000-0002-3053-7269

Laboratory Animals - June Issue

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

Contents
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