Laboratory Animals - June Issue - 239

Basic and Bleich
studied using a model organism that recapitulates the
human disease phenotypes and aetiology.

The future of gnotobiotics
Gnotobiotic animal models provide an excellent in vivo
model to investigate the causality and functionality of
host-microbiota interactions, and these animals represent an important step in translating associations into
functions. Additionally, gnotobiology provides a valuable platform for establishing standardized conditions
that can reduce experimental variability and increase
experimental reproducibility. Furthermore, the development of novel minimal bacterial consortia will
increase the power of gnotobiotic approaches by providing the possibility of selecting specific microbiota
members based on their function and by allowing targeted mechanistic studies. However, a substantial fraction of the bacterial taxa in the mouse intestine are still
unknown.65 Therefore, it is important to isolate, cultivate and describe novel bacteria as a prerequisite for
developing representative minimal bacterial consortia.
Further studies should also investigate the impacts of
other microbiota members such as viruses, fungi and
archaea on host physiology. The generation of 'humanized mouse models' can support translational aspects
of research by creating human-like conditions in the
mouse gut. Based on these capabilities, gnotobiotic
models will be indispensable for further advancements
in the microbiome research field, especially when such
models are combined with 'omics' approaches such as
genomics, transcriptomics, metabolomics and proteomics. These approaches may support the discovery
of the exact mechanisms that underlie host colonization
and the interaction and communication of specific
microbiota representatives among themselves and
with their host. Moreover, these discoveries will contribute to the development of new therapeutic
approaches.
As advances in the microbiome research field are
tightly bound to the use of gnotobiotic animals, we
believe that gnotobiotic facilities will be confronted
with increased demand for the use of these models.
Furthermore, as building and maintaining a gnotobiotic facility is expensive and requires a well-trained
staff, we think that the establishment of regional or
national core gnotobiotic centres is advisable. These
core centres could serve as central repositories of
animal models, rederive new models and provide training for scientists who want to use gnotobiotic models.
For research groups that do not have suitable infrastructure for conducting gnotobiotic experiments,
these experiments could be performed in a collaborative
manner at the core facility. Furthermore, for researchers who have available isolators or short-term housing

239
systems, germ-free or gnotobiotic animals could be sent
to their facilities. Our facility successfully implemented
this model in collaborative projects within the
Germany-wide Priority Program 'Intestinal microbiota'. Moreover, development of national funding
programmes that would support gnotobiotic facilities
as resource centres would be valuable in the future. In
addition, the creation of a network of regional, national
and international gnotobiotic facilities would allow the
facilities to share their expertise and protocols as well as
increase the availability of different models.

Conclusion
Gnotobiotic animal husbandry is laborious, expensive
and requires well-trained staff. However, it provides a
fundamental tool for analysing the impact of the microbiome on host physiology and disease development
under highly standardized conditions. Association of
gnotobiotic animal models with single microorganisms
or defined 'allogenic' or 'xenogenic' communities will
help unravel the mechanistic pathways driving human
microbiota-dependent diseases. Therefore, the use of
gnotobiotic animal models will probably grow continuously over the next few years, likely causing inundation
of current gnotobiotic sites with increasing numbers of
service requests. An approach to handling this demand
in facilities lacking gnotobiotic capabilities might be
through collaboration with existing gnotobiotics centres or through the local use of individualized maintenance systems (gnotocage/isocage systems) for
experiments.
Declaration of Conflicting Interest
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) disclosed receipt of the following financial support for the research, authorship, and/or publication of this
article: This work was supported by the German Research
Foundation (DFG) Priority Program SPP1656 [grant
number BL 953/5-2].

ORCID iD
Andre´ Bleich

http://orcid.org/0000-0002-3438-0254

References
1. Macpherson AJ and McCoy KD. Standardised animal
models of host microbial mutualism. Mucosal Immunol
2015; 8: 476-486.
2. Ursell LK, Metcalf JL, Parfrey LW, et al. Defining the
human microbiome. Nutr Rev 2012; 70(1): S38-44.


http://www.orcid.org/0000-0002-3438-0254 http://www.orcid.org/0000-0002-3438-0254

Laboratory Animals - June Issue

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Contents
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