Gnotobiotic technology in laboratory animal science is the processes and systems employed for maintaining gnotobiotic and germfree research
animals. Through sterilization of feed
and other husbandry supplies, and by
housing in systems that completely protect the animals from the surrounding
environment and human caretakers, the
intent is to create and maintain animal
models with fully controlled and known
Gnotobiotics in animal research has
been known for more than a century.
Researchers initially studied the absence
of microbes in germfree animals to learn
about the microbiome’s impact on the
host’s anatomy, physiology, and metabolism. Later, germfree rodents and other
Housing Systems for Rodents
Used in Microbiome Research
Solutions for Gnotobiotic and Germfree Animals
Alexander Maue, Ph.D. and Randi Lundberg, DVM, Ph.D.
The microbiome of laboratory animals
is now recognized as an important variable and experimental factor, even in
studies not focusing on the microbiome.
By sourcing study animals from gnotobiotic breeding colonies, gnotobiotic technology helps researchers regain control
over the microbiome to avoid confounding of studies.
TRADITIONAL GNOTOBIOTIC HOUSING
Historically, isolator housing has been
the gold standard for gnotobiotic rodents
and still is the safest solution for minimizing contamination risk. The first
isolators, developed in the early 1940s,
were made of stainless steel, with separate sections for surgery, examination,
and storage, for example. Some of the
early steel isolators even had an integrated food autoclave.1
The early isolator types were heavy,
inconvenient, and costly. In the 1950s,
the less expensive and easier to use flexible film “bubble” isolators were invented,
and, in the 1990s, the sturdier semi-rigid
isolators with a rigid plastic frame and
flexible film front panel were developed. Other isolator types have been
marketed, but these remain the most
popular designs used globally in gnotobiotic animal facilities. The basic principle of both types is a double-door lock
system to enter and exit materials without exposing the isolator chamber to the
exterior. Cages and animals are manually
handled via long, thick plastic gloves.
A gnotobiotic isolator provides bio-
exclusion for the inhabitants, as only
sterile feed, water, bedding, enrichment
items, and other materials are entered
into the isolator. The safest way to intro-
or very few bacterial strains to dissect
the effects of these specific organisms or
complex microbiota when transplanted
into the germfree hosts. Most biomedi-
cal researchers were not knowledgeable
about or interested in the microbiome,
and only a few carried out these special-
ized, technically demanding experiments.
The late 2000s onward has seen
extreme, continuous growth in the use
of gnotobiotic technology in biomedical
research, spurring insight into how the
microbiome is key to health and disease.
Germfree and gnotobiotic animals are
recognized as invaluable experimental
tools for examining the host-microbiome
interface and play a pivotal part in demonstrating the causal role of the microbiome
on the host phenotype through microbiota transplantation studies conceptually
known as phenotype transfers.
Semi-rigid isolators are among the most popular designs used globally in gnotobiotic animal