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Hansen et al.
mice and rats are closely related but different from one
another.131 Mouse colonies differ in terms of SFB
status,93,132 which is crucial to know, as SFBs strongly
influence immune functions such as IgA production,
T-cell response and intestinal T helper cell type 17
(TH17) induction.132-135 The recolonization of germfree mice with SFBs induces a full reconstitution of
all CD4-positive T cells136 and increases the expression
of the major histocompatibility complex (MHC) class
II.134 Since TH17 is important in models of Crohn's
disease, an impact of SFBs on IBD models should be
expected, for example reconstituting the SCID adoptive
transfer model with a SFB-containing microbiota
enhances intestinal inflammation.137 SFBs also promote arthritis development in K/BxN mice138 and
enhance experimental allergic encephalomyelitis development in myelin oligodendrocyte glycoproteininjected mice,115 while they reduce the incidence of
type 1 diabetes in female NOD mice.139

Discussion
To select specific bacteria for consideration before
using animals for a specific study, it seems relevant to
consider agents if (a) the animals are in reality at risk
and (b) if infections in the animals will make a difference for animal research or welfare, for example
because the agent regulates clinical disease progression
or in other ways has an impact on animal models.
To this should be added that it is relevant to consider
a zoonotic potential. This also implies that if neither (a)
or (b) are fulfilled, then there is no need for specific
screening. C. rodentium, C. kutscheri, Salmonella spp.
and S. pneumonia are, in reality, absent in laboratory
rats and mice. Furthermore, a single reported case on
b-haemolytic streptococcal disease56 is questionable as
a justification for frequent global screening in favour of
some of the other agents presented here. All of the bacteria listed in Tables 2 and 3 fulfil requirements (a) and
(b), but they are obviously not equally relevant for all
types of research and, therefore, it may be up to the
individual facilities and the needs of their research
groups to decide which ones should be routinely
screened for. However, it is no longer sufficient only
to secure the sole absence of pathogens. Some bacteria
are crucial for some models but ruin other models, for
example SFBs facilitate IBD132 but counteract type 1
diabetes,139 F. prausnitzii and A. muciniphila reduce
severity in IBD124 and type 1 diabetes models,98
respectively, but this is precisely why they are targets
for intervention.99,123 F. rodentium, C. piliforme,
Mycoplasma spp., Helicobacter spp. and Rodentibacter
spp. also fulfil requirements (a) and (b). In addition, it
may be argued that F. rodentium, C. piliforme, and
Mycoplasma spp. represent organisms for which there

285
is a real risk of outbreak of clinical disease with a high
prevalence in a colony. It may also be argued that S.
aureus is as important as Rodentibacter spp., since
reports about abscesses are more or less similar.140
However, laboratory rodents probably catch this
agent from their human caretakers, as it is extremely
rare in wild rodents,141 and, therefore, it is far more
difficult to keep out of barrier facilities. Zoonotic
agents, such as S. moniliformis, despite presenting a
low risk, may be included; however, it could be
argued that Leptospira spp., also latently present in
the wild rodent population,142,143 are equally important
as a zoonosis, and it is unlikely to isolate any of these
two agents in modern animal facilities.
Sequencing costs are rapidly declining, and the
fast, cost-effective screening of samples for unknown
species using portable, real-time sequencers will soon
change molecular diagnostics.103,144 Even if sequencing is not an option, most bacteria can still be monitored simply by using PCR. Since it is likely that the
list of bacteria with a research impact will continue to
grow, it may well be best to reduce the number of
organisms routinely screened for at breeders and to
allow local needs to direct what should be included in
further testing. On the other hand, with the use of
multiplex PCRs it may be possible to screen for a
longer list of bacteria, routinely or on request,
which may be seen as a competitive move for a commercial breeder. As positive results for wanted organisms need less frequent re-confirmation and as
laborious cultivations are no longer required, which
also eliminates the need for transporting live animals
to laboratories, the costs of bacteriology will be
reduced dramatically.
In conclusion, research groups may benefit from
having a short list of the presence or absence of
defined and relevant bacterial species for the animals
they use. The list will probably need current revision,
as new bacteria with an impact will be involved, and
as increase in knowledge and technology will lead
to a higher resolution in identification. Routine
screening can be performed using cost-effective sequencing or simple multiple PCR approaches. With fewer
pathogens on the list and with the transition from cultivation to molecular methods, this is likely to be costneutral.
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.



Laboratory Animals - June Issue

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Contents
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Laboratory Animals - June Issue - Contents
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