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Gnotobiosis (from Greek roots gnostos "known" and bios "life") is a condition in which all the forms of life present within an organism can be accounted for. Typically gnotobiotic organisms are germ-free or gnotophoric (having only one contaminant).

History
The first discussion of the concept of gnotobiotics is generally attributed to the postulations of Louis Pasteur in the late 19th century, in which he questioned whether animals could survive without microbes. From the late 1890's through the 1920's, numerous scientists attempted gnotobiotic experiments with limited success. The success of these experiments was limited mostly due to the lack of knowledge surrounding nutrition and the biochemical implications of steam sterilizing food, which can degrade essential vitamins. Major accomplishments in the field of gnotobiotics in the early years (1930-1950s) came from primarily Notre Dame University, The University of Lund, and Nagoya University.

The Laboratories of Bacteriology, University of Notre Dame (known as LOBUND), founded by James Reyniers, is cited for making some of the most notable achievements in the field of gnotobiotic research by conducting more expansive tests on some of the first germ-free rats in 1939 and by reducing the cost of isolators. Early isolators were bulky and costly steel containers that were designed to withstand high pressure steam sterilization techniques. Refined sterilization techniques and manufacturing changes from LOBUND significantly reduced the size and cost of isolators, making gnotobiotic research more universally accessible.

Despite numerous advances in gnotobiotic research and technologies, setting up and maintaining a gnotobiotic research facility remains relatively expensive. In 2015 the costs of maintaining gnotobiotic mice cages was greater than 4 times the cost of rearing non-gnotobiotic mice. This increased cost remains a challenge for starting and operating gnotobiotic laboratories, especially if the main source of funds is through federal grants from institutions such as the NIH.

Gnotobiotic animals
A gnotobiotic animal is an animal in which only certain known strains of bacteria and other microorganisms are present. Technically, the term also includes germ-free animals, as the status of their microbial communities is also known. However, the term gnotobiotic is often incorrectly contrasted with germ-free.

Gnotobiotic animals (also "gnotobiotes" or "gnotobionts") are born in aseptic conditions, which may include removal from the mother by Caesarean section and immediate transfer of the newborn to an isolator where all incoming air, food and water is sterilized. Such animals are normally reared in a sterile or microbially-controlled laboratory environment, and they are only exposed to those microorganisms that the researchers wish to have present in the animal. These gnotobiotes are used to study the symbiotic relationships between an animal and one or more of the microorganisms that may inhabit its body. This technique is important for microbiologists because it allows them to study only a select few symbiotic interactions at a time (see Scientific control), whereas animals that develop under normal conditions may quickly acquire a microbiota that includes hundreds or thousands of unique organisms.

Animals reared in a gnotobiotic colony often have poorly developed immune systems, lower cardiac output, thin intestinal walls and high susceptibility to infectious pathogens.

Such animals may also be used in animal production, especially in the rearing of pigs. After the Caesarean birth, these animals are introduced to their natural microflora in a stepwise fashion. This avoids undesired infections and leads to faster growth.

Gnotobiotic Fish
Fish have a numerous advantages as model organisms for gnotobiotic research. Overall fish generally have a significantly higher number of offspring per reproductive event compared to mammals. This can range upwards of thousands of eggs, each of which is contained in a protective outer membrane, the chorion. This chorion membrane allows for the eggs to be easily sanitized prior to rearing in a gnotobiotic environment, removing the need to preform invasive surgeries such as a caesarean section. Another advantage is that fish eggs develop quickly, easily allowing for multi-generational studies. Like in mammals, the microbiota of fish have been attributed to nutrient digestion, immune system stimulation, intestinal development, and other important physiological processes. Thus fish raised in a gnotobiotic environment can display numerous physiological changes compared to those exposed to normal environmental microorganisms.

Historically gnotobiotic fish have been used for human research because of their importance as a model organism. However, with the increased prevalence of aquaculture for sustainable food production, gnotobiotic studies focused on maximizing production and maintaining healthy captive populations are becoming more prevalent. Though these studies are becoming of increasing importance for their implications on farm raised fish dietary and immunological processes, the majority of research is still only conducted on a few species of fish, such as the zebra fish. Since there are many species of fish currently raised in aquaculture, the small number of fish species used in gnotobiotic research is still a known limitation for this growing field.