Laboratory Animals - June Issue - 229

Special Issue: Microbiota

Microbiota, laboratory animals, and
research
Axel Kornerup Hansen1

Laboratory Animals
2019, Vol. 53(3) 229-231
! The Author(s) 2019
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DOI: 10.1177/0023677219844538
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and Craig Franklin2

Back in the 19th century, working with laboratory
rodents was dangerous. There was a certain risk of
catching hazardous zoonoses such as Yersinia pestis,
Leptospira, Salmonella, and Streptobacillus moniliformis.1 It was, therefore, common, to decontaminate
rodents with strong chemicals before studies.2 This progressed to efforts that were made to eliminate such
infections from rodent colonies in the last half of the
19th century.
In the beginning of the 20th century, scientists
described some fatal rodent diseases, such as
Bordetella bronchiseptica in guinea pigs3 and
Clostridium piliforme in mice,4 which were not dangerous for humans, but were detrimental to research
because of unanticipated loss of animals. Also in the
early 20th century, it became evident that animals
could be rendered free of all microbial organisms
(germ-free, axenic) without fatal consequences if maintained in closed isolators.5,6 In 1947, Henry Foster
founded the United States breeding company later
known as Charles River. With the concurrent introduction of the 3Rs (refinement, reduction, replacement)7 to
animal-based research, he started the use of cesarean
section and barrier protection as a way to refine rodent
models by producing them free of well-defined specific
pathogens.8 Disease-provoking rodent infections were
all eliminated, while new ones, such as Citrobacter
rodentium9 and Filobacterium rodentium (cilia-associated
respiratory bacillus)10 were described and subsequently
also fully eliminated.11-13 Nowadays laboratory rodents
are produced only behind barriers subjected to thorough health monitoring programs and, should any of
the previously experienced bacterial agents be found,
depopulation is often the only viable solution.
Early attempts to move rederived germ-free rodents
from isolators to barrier-protected facilities were often
confounded by opportunistic infections. To circumvent
this, Russell W. Schaedler explored whether limiting
the number of commensal bacterial species could minimize clinical disease in reconstituted rodents.14 He
selected known commensal (i.e. not associated with disease) bacteria, which could be cultivated, and this collection became known as the Schaedler flora.15 After a

redesign it became ''The altered Schaedler flora''
(ASF),16 which today is the initial microbiota of most
commercial laboratory rodent-breeding colonies. ASF
bacteria can be recovered from rodents several years
after the initial colonization.17,18
Although ASF provides a valuable tool for controlled studies of the role of microbes in models of disease, the translatability of such studies must be viewed
with caution as ASF does not recapitulate the complexity of microbiota that exist in human populations. As a
result, we must interpret such studies in combination
with studies performed in rodents with complex microbiota.19 However, the latter are also potentially flawed
as during 70 years of rederivation and barrier protection key microorganisms crucial to the function of the
animals as models for human beings may have been
lost, or at least found in only some rodent colonies.
An example can be found with the anti-inflammatory
bacterium Akkermansia muciniphila,20 whose presence
in contemporary rodent colonies is now inconsistent
and thus may be affecting reproducibility of inflammatory models of disease. This phenomenon is also well
known in human medicine, in which it has been
hypothesized that the ''loss of old friends'' has affected
the incidence of a number of diseases, such as allergies
and type 1 diabetes.21 To address this there is growing
interest in using pet store or wild mice, which possess
microbiota that have evolved in a more complex and
antigen-experienced environment. While such studies
may have merit, they are also complicated by lack of
controlled microbiota and adventitious pathogens that
most research facilities strive to exclude.22 A happy
1

Department of Veterinary and Animal Sciences, Faculty of Health
and Medical Sciences, University of Copenhagen, Denmark
2
Mouse Resource and Research Center, College of Veterinary
Medicine, University of Missouri, USA
Corresponding author:
Axel Kornerup Hansen, University of Copenhagen, Faculty of
Health and Medical Sciences, Department of Veterinary and
Animal Sciences, Thorvaldsensvej 57, Frederiksberg, DK-1871,
Denmark.
Email: akh@sund.ku.dk


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Laboratory Animals - June Issue

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

Contents
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