Microbiology and Microbiome

A mammal harbours a vast number of microorganisms in the form of bacteria, viruses, protozoans, parasites, fungi and archaea, which is known as the microbiota. The animal host contains approximately 20,000 genes, while the microbiota contains more than 1 million genes. Therefore, many of the competences of a laboratory animal have arisen from the microbiota rather than the mammal genome. As there is substantial variation in composition between animals, animal units and commercial production sites and little information available on this, it is a challenge for experimental design, reproducibility and translatability of animal experiments. Some of the microorganisms are pathogens, i.e. they can induce spontaneous clinical disease in the animals, while others are commensals, i.e. their presence is latent. Traditionally, pathogens have been eradicated from so-called specific pathogen-free breeding colonies of research rodents to decrease mortality, disease incidence, inter-individual parameter variation and other forms of research interference. However, today it can also be argued that animals which have never been infected with pathogens have an under-stimulated immune system and, therefore, may be less translational compared to humans. Many of the commensals have been shown to be important for the induction of animal models, and variation in microbiota composition is responsible for a substantial part of the inter-individual variation in responses of many models and for different outcomes in different facilities. It is still a good principle that rodents for research only are bought from colonies bred behind a specific pathogen protecting barrier and that they are subjected to current health monitoring, which should be documented. However, it can also for individual studies be necessary to include a characterization of the microbiota, which has been made possible by modern sequencing techniques, which over the last decade have become more efficient and cheaper. Characterization can be done on a colony level, but eventually it can also be done on all animals in a specific study, which will allow the incorporation of the information in the data evaluation. It may also be important to ensure that specific bacteria needed for a proper model expression are present in the animals to be used. Before progressing from preclinical animal studies to clinical human studies, it might be considered wise to supplement the studies in SPF animals with animals infected with pathogens.