A study reports that laboratory mice that are given the gut bacteria of wild mice can survive a deadly flu virus infection and fight colorectal cancer dramatically better than laboratory mice with their own gut bacteria. This could explain why results in lab mice are so different than studies in humans or other animals. The work comes from scientists at the NIH and was published yesterday in Cell.
"We think that by restoring the natural 'microbial identity' of laboratory mice, we will improve the modeling of complex diseases of free-living mammals, which includes humans and their diseases," said Barbara Rehermann, M.D., senior author of the paper.
"By being so different, natural microbiota will help us to discover protective mechanisms that are relevant in the natural world and absent in the laboratory," said Stephan Rosshart, M.D., first author of the paper.
Laboratory mice are so carefully bred, fed, and raised so that each mouse's traits are genetic are predictable. While this could be a great advantage, this also does not reflect what is actually occurring in the natural environment.
"We hypothesized that this might explain why laboratory mice, while paramount for understanding basic biological phenomena, are limited in their predictive utility for modeling complex diseases of humans and other free-living mammals," said Rosshart.
So, the researchers took wild mice from different locations and gave the lab mice a gut microbiota donation from the wild mice. They then tested and compared the gut microbiomes of the wild mice and the laboratory mice. They also confirmed that the laboratory mice had different gut microbiomes than the wild mice.
Researchers then engrafted the microbiota of wild mice to pregnant, germ-free mice and as a control, the microbiota from regular lab mice to germ-free mice.
When the mice were exposed to a high dose of influenza virus, 92 percent of the laboratory mice with wild microbiomes survived, whereas only 17 percent of laboratory mice and mice in the control group survived. In other experiments, the laboratory mice with wild microbiomes had better outcomes in tumor-related disease too.
The researchers note that more work and evaluation is needed for definitive results, and they hope to improve and expand upon the method of using natural microbiomes in laboratory mice.
Image: The process of transferring gut microbiota from wild mice to laboratory mice. Image courtesy of Rosshart et al.