A recent study by Lawrence Berkeley National Laboratory researchers found that lactate produced by Lactobacillus bacteria in the gut microbiome improved memory in mice.
In collaboration with Pacific Northwest National Laboratory, the researchers used a population-based mouse model system known as “collaborative cross,” which has a genetic and phenotypic diversity similar to that of the human population. According to the study, through this model, researchers identified necessary controls on genetic and environmental factors to better analyze the relationship between host genetics and the microbiome on memory.
To understand these linkages, researchers examined a total of 535 mice from 29 collaborative cross strains by assessing their memory, their gut microbiome and the effect of Lactobacillus strains on memory, according to the study.
“The microbiome has been linked to host health and behavior including memory,” said study co-author and Berkeley Lab scientist Antoine Snijders in an email. “However, the mechanism and metabolic mediators of the link between the gut and the brain are not well understood.”
Using a passive avoidance memory test based on the mice’s hesitation to enter a compartment three days after feeling a mild foot shock, researchers tested their memory, according to the study. Across the mice cohorts, the researchers observed reproducible variations in memory potential, which suggests genetics are an important factor of memory.
Through gut microbiome analysis, researchers also found that four bacterial families — Lactobacillaceae, Deferribacteraceae, Bacteroidaceae and Clostridiaceae — are significantly correlated with memory. Lactobacillus, in particular the L. reuteri strain, became the main focus, as strains of the bacteria have been previously linked to improving memory in mice, humans and rats, according to the study.
“We are finding evidence that some of the genetic effects on different phenotypes like memory are indirect and are in fact mediated by alterations in the composition of the gut microbiome,” Snijders said in the email.
To examine Lactobacillus effects, researchers fed L. reuteri to a separate cohort of germ-free mice and then tested their memory through passive avoidance with the shocks. According to the study, mice that were fed with Lactobacillus saw significant memory improvement compared to those that were not.
Researchers also analyzed germ-free mice’s stool, plasma and brain tissue to identify molecules that might impact memory enhancement and found that lactate, which is produced by all Lactobacillus strains, was a common byproduct.
Researchers then fed lactate to mice with poor memory and noticed that their memory improved. They also saw increased levels of gamma-aminobutyric acid, or GABA, a neurotransmitter associated with memory, in the brain.
“One potential outcome of this research is the support of use of probiotic Lactobacillus strains to promote memory through their production of lactate and through their promotion of GABA accumulation in the hippocampus,” Snijders said in the email. “This could potentially have an impact on people with learning disabilities and neurodegenerative disorders.”