Laboratory mice given the gut bacteria of wild mice can survive flu virus infection and fight colorectal cancer much better. The wild mice’s immunological advantages may partly explain why disease experiments in lab mice often turn out very differently in humans or other animals.
Mammals depend on their microbiota: the collection of microorganisms they host in and on their bodies. Lab mice are carefully bred, fed and raised in tightly controlled conditions so that each mouse has predictable traits and genetics. While a great advantage in biology research, it means that a controlled environment - and not the survival pressures of the outside world - has shaped the microbiotas of lab mice.
To see if this might explain why lab mice are limited in how well they model mammalian diseases, the team trapped more than 800 wild mice from eight locations to find suitable candidates for gut microbiota donation. Then they compared the gut microbiomes - collective gut microbiota genomes - of the wild mice and a common strain of laboratory mice called C57BL/6.
Next, they introduced the microbiota of wild mice to pregnant, germ-free C57BL/6 mice. (Germ-free mice are raised in a sterile environment and don’t have microbiomes of their own.) For a control group comparison, the researchers also introduced microbiota from ordinary C57BL/6 mice into a separate group of pregnant, germ-free mice. Four generations later, the mice still carried either the wild microbiomes or the control lab microbiomes.
When exposed to a high dose of influenza virus, 92% of the lab mice with wild microbiomes survived, compared with only 17% of lab mice and control group mice (Cell, doi: http://dx.doi.org/10.1016/j.cell.2017.09.016). In other experiments, the lab mice without wild microbiomes had a greater number of tumours and more severe disease when induced with colorectal cancer. In both models, the beneficial effects of the wild microbiota were associated with reduced inflammation.
‘We think that by restoring the natural ‘microbial identity’ of laboratory mice, we will improve the modelling of complex diseases of free-living mammals, which includes humans,’ says senior author Barbara Rehermann of the National Institute of Health’s Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland. Natural microbiota could help researchers discover protective mechanisms relevant in the natural world.