A new study led by the University of Chicago shows that when they get sick, mice produce specialized sugars in the gut that feed their friendly bacteria. Reporting in Nature, the scientists describe how they also found mice unable to do this took longer to recover from illness.
Senior author Alexander Chervonsky, an Associate Professor in Chicago’s Department of Pathology and chair of the Committee on Immunology, says:
“Both hosts and their gut microbiota can suffer in the case of sickness, but this mutually beneficial relationship is guarded by the host.”
He and his colleagues suggest the mechanism they have discovered helps the host resist or be less harmed by pathogens or harmful microbes, and when it fails, it may lead to chronic diseases like Crohn’s.
When animals get sick, they tend to eat less – this helps conserve energy and deprives pathogens of nutrients. However, it also means beneficial bacteria – whose health is important to the host – can suffer from lack of nutrients.
To investigate this further, the team focused on a sugar called L-fucose that the body does not use for energy but when bound to proteins, it becomes a food source for gut bacteria.
When mice are healthy, their gut contains hardly any L-fucose. So the team made the mice sick by exposing them to a compound that produces a systemic reaction, causing illness all over the body. As they got sicker, the mice drank less water, ate less and lost weight.
However, within only a few hours of becoming sick, the mice also began to produce L-fucose in their gut – nearly all of their small intestine was lined with it.
In another experiment, the researchers bred mice lacking Fut2, the gene that controls L-fucose production, and also exposed them to the compound that induces systemic sickness.
As with the normal mice, the mice lacking Fut2 also drank and ate less and lost weight as they got sicker. But unlike normal mice, their gut contained no L-fucose and they took longer to recover.
Prof. Chervonsky explains, “Mice that can produce L-fucose recover better than those that can’t[…] if you remove bacteria the effect goes away.”
When they carried out a genetic analysis on the gut microbes in both groups of mice, the team found sick mice lacking Fut2 had more switched on harmful microbial genes than normal sick mice.
They then tested the idea that L-fucose somehow stops unfriendly bacteria from switching on the genes that make them more harmful. They exposed normal and Fut2-deficient mice to Citrobacter rodentium – a mild pathogen that causes a reaction similar to food poisoning – and then 4 days later exposed them to the chemical that gave them a systemic illness.
The Fut2-deficient mice lost more weight than the normal mice. The researchers suggest this shows the ability to produce L-fucose helped the normal mice somehow resist or tolerate the mild additional pathogen.
Prof. Chervonsky says about 20% of people don’t have a gene for producing L-fucose, and this has been linked to the inflammatory bowel disease known as Crohn’s.
He suggests perhaps not being able to make L-fucose means the gut cannot block the virulence genes in harmful pathogens explaining why bacteria are involved in Crohn’s disease:
“Whether we can use this toward therapeutics in the future requires further study,” he adds.
The study follows research recently published in PLOS ONE where a team from Boston’s Brigham and Women’s Hospital found gut bacteria changes may predict infection and inflammation. In that study, the team analyzed what happens to gut bacteria in mice during different stages of infection by C. rodentium.