Laboratory Animals - June Issue - 263

Ericsson
There are several limitations to the use of dogs as
research models. Clearly, dogs are quite expensive to
purchase and house relative to rodents, and studies
using purpose-bred research dogs often suffer from
poor statistical power owing to this burden.
Additionally, there is increased scrutiny of research performed in companion animals from an animal welfare
standpoint, and less acceptance by the general public.
Lastly, although the use of defined dog breeds can provide some degree of genetic homogeneity, they are
nonetheless outbred, and genetic manipulation of
dogs is not a readily available practice.

Pigs (Sus scrofa domesticus)
Domestic and miniature pigs have become standard
model species in several areas of translational research
including xenotransplantation,99 cardiovascular physiology,100,101 and more recently, gastrointestinal physiology102 and immuno-ontogeny.103 The appeal of pigs
as research models stems from their comparable size,
physiology, and developmental trajectories relative to
humans, as well as the ability to manipulate their
genome.104,105 As omnivores with a similar GIT structure to humans, the well-characterized fecal microbiota
of juvenile and adult domestic pigs106 and other select
strains used in research107-109 also possesses compositional similarities to that of humans. Notably, many
of these strains are used to study diet-induced obesity in
genetically susceptible individuals and the same differences (i.e. an increase in the ratio of Firmicutes to
Bacteroidetes) observed between lean and obese
humans110 are mirrored in these pig models during
the development of obesity.111 Moreover, when comparing the gut microbiota of humans and a wide
range of farm animals including horse, cow, goat,
sheep, rabbit, and pig via real-time polymerase chain
reaction (PCR), probes targeting the prominent butyrate-producing C. leptum (i.e. Clostridial cluster IV or
family Ruminococcaceae) and C. coccoides (i.e.
Clostridial cluster XIVa or family Lachnospiraceae)
groups, as well as the Bacteroides/Prevotella group,
were able to discriminate between humans and all
farm animals except for pigs and rabbits.112 Thus,
with regard to several metabolically active and physiologically relevant clades of gut bacteria, pigs appear to
harbor the most compositionally similar fecal microbiota relative to humans.
Aside from rodents, pigs appear to be the only other
host species that has been stably colonized with human
GM,113 and, unlike so-called ''humanized'' mice,114
cesarean-delivered pigs (i.e. not colonized with bacteria
at parturition) colonized with human GM at birth
develop relatively normal gastrointestinal morphology
with no overt deficiencies in immune system

263
development.115 In fact, pigs colonized with human GM
at birth develop the same or greater numbers of IgA- and
IgG-producing cells, CD4þ T helper cells, and MHC class
II antigen-presenting cells in the small and large intestines, when compared to control pigs colonized experimentally with porcine GM in a similar fashion.116
Based on these findings, other groups have now begun
using human GM-colonized pigs to evaluate the influence
of prebiotics and probiotics on community structure and
pathogen resistance.117-119 A more comprehensive review
of the use of pigs colonized with human GM is provided
by Wang and Donovan.113 Similarly, piglets delivered via
cesarean section can be monocolonized120,121 or colonized with a highly restricted defined microbiota similar
to Altered Schaedler Flora used in mice122,123 to tightly
control GM composition.
Given the financial implications of pigs as livestock,
the vast majority of GM-focused research in pigs has
been done from a production perspective, rather than as
biomedical or microbial ecology research. Numerous
studies have reported the effects of resistant starch,124
high- and low-fat diets,125 antibiotics126,127 prebiotics,128 probiotics,129,130 and myriad other compounds131 on the GM of pigs. That said, many of
these studies may have translational merit owing to
the similar functions of the GM, regardless of the host
(e.g. butyrate production, stimulation of the immune
system, and colonization resistance). A thorough
review of pigs as research models of dietary interventions in humans provides a more exhaustive discussion
of their beneficial attributes and limitations.132
The major limitations associated with pigs in studies
of the microbiota are related to their size and expense
to house and feed. These factors, in turn, make large
sample sizes difficult to achieve due to the necessary
physical space and budget. Moreover, although pigs
can be genetically manipulated, it is much more difficult
to generate knockout and transgenic pigs than rodents.

Rabbits (Oryctolagus cuniculus)
In general, rabbits are used sparingly and for select
purposes as animal models, and the same is true of
research targeting the GM. As herbivorous hindgut fermenters, rabbits possess a large and metabolically
active cecum, the contents of which have been characterized using culture-independent methods at different
stages of life.133-135 Within days of birth, rabbit kits
actively ingest fecal material from the doe and thus
inoculate their own GIT. Failure to do so results in
increased post-weaning mortality and a decreased rate
of GM maturation.136 Interestingly, GF rabbits fail to
practice coprophagy.137
Beginning in the mid-1960s, there was considerable
interest in GF rabbits as axenic models complementary



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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