Improving and humanizing animal models by microbiomic techniques

Published on February 11, 2015   42 min

Other Talks in the Series: Animal Models in Biomedical Research

0:00
Hello, my name is Axel Kornerup Hansen. I'm a professor and the board chairman of science at the University of Copenhagen. In this lecture, I will introduce you to the impact that the microbiome has on animal models, and how we can improve your work with these models by considering these aspects. In principle, this could be about models in various species. But I will focus on rodents, because they outnumber other model species, because there are those who are primarily used for their low variation, and high potential for standardisation, and also because this is what I'm actually working with in my own research group.
0:36
In this lecture, I will start out by talking about how bacteriological monitoring is done in laboratory rodents today. And after that, I will introduce to the fascinating world of the gut microbiota. I will talk about the impact that this microbiota has in rodent models, and give a short and very incomplete impression on how this interaction between the host and the microbiota may take place. And introduce you to how much variation actually causes in your rodent models, and I will end up presenting some plausible ways to deal with this impact.
1:13
Bacteria are a source of variation in laboratory animal work. This is not a new issue, and the systematic handling of the variation caused by bacteria has developed from the beginning of the 20th century, through the millennium, and up till today. However, there's still much which can be done. So let me start out by shedding a critical light on the states at which we are today in laboratory animal breeders, be it facilities, or be it scientists.
1:40
A major step forward in animal experimentation came with this book by Russel and Burch in 1959, when they introduce the concept of the three R's. These principles, which today forms the basis for laboratory animal use in a global scale, tells us that whenever using laboratory animals, we should aim at replacement; that means we should strive for planning the studies without using live animals. Refinement; that means we should develop our procedures to progressively less discomfort for the animals. And reduction; that means in relation to the amount of knowledge we create, we should use fewer animals. This was a step forward for animal welfare, but was also a step forward for science, because it made scientists and animal care staff focus on avoiding the use of those animals which never added to the scientific output, for example, because they suffered from various infectious diseases.
2:33
In 1959, when Russell and Burch wrote their book rodents in laboratories suffered from a range of diseases, many of these which were at-risk clinical signs, as illustrated by the rat with sarcoptic mange in this picture. Henry Foster was a veterinarian in Boston who founded the Charles River breeding laboratories in the '40s. In the late '50s, as part of this new free-out trend, he started producing rats and mice which were free of a range of well-defined infectious diseases. Today the commercial breeders have developed from low-tech family-run businesses, into high-tech multinational companies. And those who have survived the competition are those who have been able to fulfill the claims for the delivery of pathogen-free animals, which as you can see from the 2015 picture, have no obvious clinical diseases, but which are also free of a range of latent, research-interfering microorganisms.
3:31
Today, in-house standard of the commercial breeders, as well as common international guideline for health monitoring, such as those you can see here, issued by the Federation of European Laboratory Animal Science Associations, FELASA, which came into utlization in 2014, lists which agents to test for when doing routine microbiological monitoring on laboratory animals. As can be seen, this also includes some well-defined bacterial species, such as helicobacter, pasteurella, and streptococcal in mice, as we can see here.
4:07
The key question in relation to this bacteriological monitoring is, will it still, in 2015, make sense to monitor for these bacterial pathogens? Several surveys published over the last decade show that the prevalence of these bacteria in rodent colonies has declined. This is expected, as most research rodents today derive from commercial breeders, which over the last five decades, have developed the protection measured to a very high standard. And when used for research, these animals are placed in well-protected facilities under strict regimes, supervised by specialized veterinarians. In this survey, published from the Charles River Laboratory, was the outcome of screenings of all non-Charles River Laboratory sent to the laboratory has been compiled. Most of the bacteriological species screened for are never found. Still found today is helicobacter, and pasteurella, and streptococcal species. Helicobacter can easily be screened for by an easy, non-laborious and quick PCR. So what is found by the huge time consuming, laborious, and in terms of working hours, expensive work on cultivation, from all of the animals, especially pasteurella pneumotropica, and staphylococcus aureus. The latter is not recommended for screening by international guidelines, such as those of FELASA. So the net result is that animal facilities and breeders spend a substantial amount of resources for screening for pasteurella pneumotropica, and then we are back at the key question, does this make sense at all?
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Improving and humanizing animal models by microbiomic techniques

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