Drug Discovery
specific research application. Once a knockout or humanised germ-free model is colonised with the microbiota of choice, strict procedures for hus- bandry and housing must be followed to ensure the microbial composition remains intact. Another approach gaining traction is custom microbiota associations, which involves performing FMT from a patient donor to a germ-free mouse to study patient-specific gut bacteria and their effects on disease and to test drug candidates in the clinic. Finally, the use of a wild-type microbiome in a mouse model is an emerging approach that pro- vides the advantages of studying disease develop- ment or therapeutic efficacy in a model with a more natural immune response than is found in lab animals. Additionally, ensuring the microbiome of the
selected model does not change over time is vital for research of any kind, but particularly when the microbiome is a key variable of interest. A wide range of factors can impact a mouse model’s microbiome unintentionally, ranging from hus- bandry practices, to mouse-specific factors such as gender and genetics, to the health standard and mode of birth. As a result, it is essential to employ globally harmonised health standards and stan- dard operating procedures to maintain the desired microbial composition. As investigators endeavour to learn more about
the microbiome’s role in improving human health and strive to find new ways to harness its potential, investment in this field will likely continue its upward trend. New approaches and strategies will be required to fully realise the promise of the microbiome to elucidate the mechanisms of disease and help answer questions about why patient response to a therapeutic can vary so widely. The mouse model will remain front and centre as a tool for advancing researchers’ understanding of the microbiome and taking disease treatment to new levels.
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Continued from page 18
9 Rekdal, V et al. Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism. Science. 14 Jun 2019: Vol. 364, Issue 6445, eaau6323.
Dr Alexander Maue is Director of Microbiome Research Services at Taconic Biosciences. Previously he was Head of the Campylobacter Immunology Laboratory at the Naval Medical Research Center. Trained as an immunologist, his research focus was on enteric diseases and the development of vaccines and therapies to prevent illness.
Drug Discovery World Fall 2019 19
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