Our guts are industrious factories, supplying our bodies with nutrients and energy. Much of the work is completed by our own cells; however, a large portion of the labour is outsourced to the millions of bacteria that colonise our intestines. Regardless of who does the job, communication between the gut's bacterial lodgers and the brain must be excellent, yet the links between these two systems are unclear. Mélanie Gareau and colleagues from the Hospital for Sick Children in Canada have looked at the effect of stress on memory formation in mice with and without normal gut flora to find new links between the two.

First, the team altered the animals' gut flora by infecting them with a pathogen and looked for changes in the animals' intestines. They found changes in the size of colonic cells — an indicator of bowel inflammation — changes in gene expression of several factors involved with the immune response of the intestine, and they identified the effects of these changes on gut bacterial inhabitants and their population size.

Then the team used a stress test, where the mice were suspended over a shallow bowl of water, followed by a series of memory tests on mice with altered intestinal bacterial communities and ‘germ-free’ mice that were raised without exposure to bacteria. Memory formation was shown by the recognition of objects the mice had previously been introduced to, as well as recognition of paths previously taken through a maze. Interestingly, the unstressed mice with altered gut flora showed normal memory formation but the mice with altered gut flora that were stressed had trouble forming new memories. What is more, the germ-free mice had memory problems even without being stressed. This suggests that the intestine and its many inhabitants influence the ability to form memories, implying that there is a novel line of communication between the two organs.

Next, the team looked at new memory formation in the brain using fluorescent labels that bind to cell markers indicative of the formation of new memories. They found a decreased expression of cell markers in the brain that are associated with novel memory formation in stressed mice with altered gut flora 30 days following infection. This suggests that there are long-lasting consequences to changes in the intestine, which are reflected by changes in the brain.

Finally, the team investigated whether daily treatment with probiotics — living microorganisms such as Lactobacillus helveticus, which is commonly used to make some cheeses — would protect against these memory abnormalities. Not only did probiotics appear to reverse the effects of stress on memory in infected mice, they also blunted the increase in cell swelling as well as the increase in the immune response. The decrease in cell markers associated with memory formation seen in mice carrying the gut flora-damaging infection was erased as well. Probiotics seem to be able to fill in for native bacteria found in the gut.

So a healthy gut helps prevent memory problems in stressed mice. Probiotics appear to prevent these memory abnormalities when the gut isn't so healthy. When all gut bacteria are lost, memory formation is compromised even without stress. This unexpected and exciting connection between the brain and the belly illustrates just how interconnected biological systems are. Employing a multi-disciplinary attack has revealed a hitherto unrecognised link between two apparently unrelated systems.

M. G.
D. M.
J. H.
M. T.
D. J.
P. M.
Bacterial infection causes stress-induced memory dysfunction in mice