[6] Guinea pigs were the first germ-free animal model described in 1896 by George Nuttall and Hans Thierfelder, establishing techniques still used today in gnotobiology.
[7][8] The Laboratories of Bacteriology at the University of Notre Dame (known as LOBUND) was founded by John J. Cavanaugh and is cited for making some of the most notable achievements in the field of gnotobiotic research.
[4] The first germ-free rat colony was generated and maintained using a steam sterilized isolator in 1946 by Swedish scientist Bengt Gustafsson.
[4] Refined sterilization techniques and manufacturing changes from LOBUND significantly reduced the size and cost of isolators, making gnotobiotic research more universally accessible.
[9] In the early 1970s, gnotobiotes were used to study the role of microorganisms in host nutrition acquisition and immune response; however, this was limited because animals reared in a gnotobiotic colony often have poorly developed immune systems, lower cardiac output, and thin intestinal walls, which make them highly susceptible to infectious pathogens.
[13] Gnotobiotic animals are typically born under aseptic conditions, which may include removal from the mother by Caesarean section followed by immediate transfer of the newborn to an isolator where all incoming air, food and water is sterilized.
[7][16] Some of the advantages of gnotobiotic fish systems include high numbers of offspring per reproduction event coupled with fast generation times and eggs that can be sanitized.