VANCOUVER, CANADA—Whether a mouse lives or dies can be a matter of what bugs dwell in its gut. Microbiologists have shown that mice with the right mixture of bacteria survive a potentially fatal infection that causes diarrhea. Researchers had thought the protected mice were hardier genetically. The findings add to the growing understanding of the complex relationship between our health and the bacteria living in and on our bodies. They also add to the growing conviction that it might one day be possible to curb diarrhea, and prevent other diseases, by making sure our guts have the right complement of bacteria.
In the body, microbes outnumber human cells 10 to 1. The same is true of mice. The highest concentrations are in the gut, where the bacteria form a thin layer on the lining. In mice, the pathogen Citrobacter rodentium can disrupt this layer and cause inflammation and diarrhea. This infection is fatal in some mouse strains but not others.
Some researchers thought the survival difference was due to genetics, but they could never find the gene responsible. Microbiologist B. Brett Finlay of the University of British Columbia, Vancouver, and colleagues wondered whether certain microbes in the gut provided protection. They tested the idea by switching out the gut bacteria in a susceptible strain of mice. They used a high dose of antibiotic to kill the native gut bacteria and then fed those mice fecal material from a protected strain.
They observed that microbes in the fecal material took up residence in a susceptible mouse's gut for about a month. These new residents shielded mice against Citrobacter infection, Finlay reported 9 March here at the International Human Microbiome Congress. He and his colleagues also discovered that the gut bacteria from the resistant mice caused an increase in an immune system messenger called IL-22, and when the researchers inhibited IL-22, the mice were more likely to die from diarrhea.
Finlay and colleagues further explored how changes in the gut bacteria affect the severity of an infection. They gave protected mice one of two antibiotic drugs in low doses that altered the abundance of various microbes but didn't kill the bugs. The team then exposed the mice to Citrobacter. One antibiotic had no obvious effect. But the other resulted in much more severe diarrhea. When the researchers dissected these now susceptible mice, they discovered that the mucous layer that typically lines the gut was only half as thick as in protected mice. The shift in the microbial makeup had led to this shrinkage. "By thinning this mucous [layer], we increased the susceptibility to infection," Finlay said at the meeting.
"We know very little about how the different pathogens interact with the bugs that don't cause disease," says immunologist Marcelo Sztein of the University of Maryland School of Medicine in Baltimore. "But we should really be looking at the whole system." He hopes that studies such as Finlay's will help clarify how antibiotics might be put to better use. "Different antibiotics might be more effective not just because of the effect on the pathogen but also because of the effect on the [body's natural bacteria]."