Laboratory Animals - June Issue - 247

Lundberg

247

Table 2. Examples of human GM bacteria associated with human health that are showing variable colonization success in
germ-free animal studies.
Organism

Colonization efficiency of organism

Bifidobacteriaceae

Completely lost 2 days post-colonization despite high abundance in
inoculum (72.8%)
Almost completely lost
Was transferred but to lower
abundance than in inoculum
Was not compared with the inoculum, but established well and at
higher abundance than pigs with
pig microbiota
Was not compared with the inoculum, but established in the mice
and increased in response to
feeding a high-bran diet
Almost completely lost
Established well in recipient rats
Was not compared to the inoculum,
but was established in mice
Increased abundance from inoculum to recipient mice
Disappeared 7 days postcolonization
Disappeared 14 days post-colonization, but colonized long term if
monocolonized prior to fecal
transfer
Almost completely lost

Bifidobacterium spp.

Faecalibacterium spp.

Lactobacillus spp.

Pseudobutyrivibrio spp.

Recipient

Detection method

Reference

#

Mouse

16S rRNA sequencing

7

#
#

Mouse
Mouse

16S rRNA sequencing
qPCR

18

$

Pig

qPCR

37

$

Mouse

Culturing

44

#
$
$

Mouse
Rat
Mouse

16S rRNA sequencing
DGGE þ sequencing
16S rRNA sequencing

18

"

Mouse

qPCR

43

#

Mouse

Culturing

11

#

Mouse

qPCR

29

#

Mouse

16S rRNA sequencing

18

43

45
22

": increased abundance in recipient animals compared with the donor inoculum; #: decreased abundance in recipient animals compared
with the donor inoculum; $: similar abundance in donor inoculum and recipients, or established in recipients but abundance not
compared with inoculum.

and found that the colonization efficiency was significantly higher in the rats (76% versus 44%).19 Another
study demonstrated that 75% of a human GM was
established in GF rats.8
Table 2 summarizes examples of bacterial genera
containing known health-beneficial species and strains
which are difficult to establish in GF mice. Loss of specific bacteria is problematic when they are necessary for
the outcome of the study, for example, for studying
prebiotic metabolism by these bacteria. In other cases,
the study concept is not compromised by the loss and
seems to rely more on the complexity of the transferred
GM or the presence of other organisms that were successfully established. For instance, induction of oral
tolerance and protection against infection occurred in
mice with human GM despite total loss of
Bifidobacterium.21
Despite the immunological naivety characterizing
mice harboring a human GM, the concept has

demonstrated the ability to elicit differential and translationally relevant immune responses. Recently, GF
mice with cancer patient GM replicated patient
responses to checkpoint inhibitor immunotherapy
through mechanisms hypothesized to happen via
immunological stimulation by the transplanted microbiota.22-24 Mice with GM from patients responding
well to therapy recruited more CD4þ T cells23 and
CD8þ T cells22,24 to the tumor microenvironment
than mice with a non-responder GM. However, one
of the studies found that only a portion of the GF
mice with patient GM recapitulated the human responder phenotype, and these were the same mice whose
GM was most different from the donor GM.24 This
may illustrate an element of luck and suggest that the
desired outcome may simply be reached by including
enough study replicates and hoping for the best. In a
model of induced lung inflammation, mice with human
GM mounted study-relevant and measurable



Laboratory Animals - June Issue

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Laboratory Animals - June Issue - Cover1
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Laboratory Animals - June Issue - Contents
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Laboratory Animals - June Issue - Cover3
Laboratory Animals - June Issue - Cover4
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