Molecule produced by gut microbes could improve memory

Lactate, a molecule produced by all species of one gut microbe, was found to be a key memory-boosting molecular messenger, according to a new study published in the journal BMC Microbiome.

Researchers know that mice that have been fed probiotics experience several positive benefits. They also know that microbes produce molecules that travel through the blood and act as chemical messengers that influence other parts of the body, including the brain. However, it wasn't clear which specific microorganisms and microbial molecular messengers might influence memory.

The microbiome's impact on memory is a very active research area, with more than 100 papers published in the last five years on links between common probiotics and memory.

The researchers started with a collection of mice called the Collaborative Cross. They bred 29 different strains of mice to mimic the genetic and physical diversity of a human population. It includes mice of different sizes, coat colors, and disposition. Researchers also know the genome sequences of each strain.

First, the team gave each strain of mice a memory test. Then they screened each strain for genetic variations and correlated these variations to the memory results. They found two sets of genes associated with memory. One was a set of new candidate genes for influencing cognition, while the other set of genes was already known.

Next, the researchers analyzed the gut microbiome of each strain so they could make microbial connections to the genetics and memory links they already had. They identified four families of microbes that were associated with improved memory. The most common of those was a species of Lactobacillus, L. reuteri.

To test this association, the researchers fed L. reuteri to germ-free mice without any gut microbes and then tested the mice's memory. They saw a significant improvement relative to germ-free mice not fed microbes. They also found the same improvement when they fed germ-free mice one of two other Lactobacillus species.

Finally, the researchers wanted to identify which microbe-related molecules might be involved with memory enhancement. They analyzed stool, blood and brain tissue from germ-free mice each fed a specific species of Lactobacillus. Lactate was one of the common metabolic molecular byproducts; it is also a molecule that all Lactobacillus strains produce.

The team fed lactate to mice previously identified to have poor memory and noticed that their memory improved. Mice fed lactate or Lactobacillus microbes also had increased levels of gamma-aminobutyric acid (GABA), a molecular messenger linked to memory formation in their brains.

To see if the same molecular mechanism might apply in humans too, the researchers developed a tiny chip that mimics where microbes interact with human intestinal tissue. When the researchers tested L. reuteri in this chip, they saw that lactate produced by the microbes traveled through the human gut tissue, indicating that it could enter the bloodstream and potentially travel to the brain.

The researchers said it might be possible one day to use probiotics to improve memory in targeted populations, such as people with learning disabilities and neurodegenerative disorders.