Laboratory Animals - June Issue - 232

Special Issue: Microbiota

Gnotobiotics: Past, present and future
´ Bleich
Marijana Basic and Andre

Laboratory Animals
2019, Vol. 53(3) 232-243
! The Author(s) 2019
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DOI: 10.1177/0023677219836715
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Abstract
Gnotobiotics or gnotobiology is a research field exploring organisms with a known microbiological state. In
animal research, the development of gnotobiotics started in the late 19th century with the rederivation of
germ-free guinea pigs. Cutting-edge achievements were accomplished by scientists in the Laboratories of
Bacteriology at the University of Notre Dame (LOBUND). The primary goals of gnotobiotics were not only the
development of the equipment required for long-term husbandry but also phenotypic characterization of
germ-free animals. The first isolators were designed by Reynolds and Gustafsson as rigid-wall stainless
steel autoclave-like chambers, which were subsequently replaced by Trexler's flexible-film polyvinyl plastic
isolators. Flexible-film or semi-rigid isolators are commonly used today. The long-term maintenance of
gnotobiotic rodents is performed in positive-pressure isolators. However, to facilitate gnotobiotic experimental procedures, short-term husbandry systems have been developed. Gnotobiotic animal husbandry is laborious and requires experienced staff. Germ-free animals can be rederived from existing rodent colonies by
hysterectomy or embryo transfer. The physiology and anatomy of germ-free rodents are different from those
of specified pathogen-free (SPF) rodents. Furthermore, to guarantee gnotobiotic status, the colonies need to
be regularly microbiologically monitored. Today, gnotobiotics provides a powerful tool to analyse functional
effects of host-microbe interactions, especially in complex disease models. Gnotobiotic models combined
with 'omics' approaches will be indispensable for future advances in microbiome research. Furthermore,
these approaches will contribute to the development of novel therapeutic targets. In addition, regional or
national gnotobiotic core facilities should be established in the future to support further applications of
gnotobiotic models.

Keywords
gnotobiotics, gnotobiology, germ-free, gnotobiotic, microbiota, microbiome, isolators, short-term housing
Date received: 13 April 2018; accepted: 14 February 2019

Introduction
The mammalian gut harbours approximately 1014
microorganisms (consisting mostly of bacteria but
also including some protozoa, fungi, archaea and
viruses) that coevolved over millions of years together
with their host.1 The entire collection of microorganisms inhabiting a specific niche is called the microbiota.2 The two major bacterial phyla dominating the
gut are Bacteroidetes and Firmicutes, followed by
Actinobacteria and Proteobacteria.3 The striking influence of the microbiota on host health and disease was
recognized within the last few decades. The intestinal
microbiota is important for host physiology as it participates in many processes such as degradation of
xenobiotic substances, synthesis of vitamins, production of short chain fatty acids (SCFAs) and the

development of the immune system.4 Furthermore,
the intestinal microbiota is also associated not only
with diverse intestinal disorders but also with autoimmune and metabolic diseases.5-8 The detrimental
effects of the intestinal microbiota are mainly associated with alterations in the composition and function
of the microbiota, which can be triggered by infections,
immune defects, diet, antibiotic treatments or metabolic changes.4
Institute for Laboratory Animal Science, Hannover Medical School,
Germany
Corresponding author:
Prof. Andre
´ Bleich, Institute for Laboratory Animal Science,
Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover,
Germany.
Email: bleich.andre@mh-hannover.de


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Laboratory Animals - June Issue

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