New research from an international team of scientists has tracked a compelling series of connections between the gut microbiome and memory. Using a novel mouse model engineered to simulate the genetic diversity of a human population, the study illustrates how genetics can influence memory via bacterial metabolites produced in the gut.
Over the past few years there has been significant research interest in the relationship between memory, cognition and the gut microbiome. While certain families of bacteria that live in our gut have been implicated in memory function, this new study set out to investigate the connection from a different angle, starting with the role genetics play in this relationship.
“To know if a microbial molecule influenced memory, we needed to understand the interaction between genetics and the microbiome,” explains co-corresponding author on the study, Antoine Snijders.
To do this the researchers worked with a mouse model known as the Collaborative Cross, which was developed to address the broad genetic variations that occur in human populations. Mimicking the genetic diversity of a human population, the new research began with 29 different strains of mice.
Each strain was administered memory tests, and subsequent work homed in on the specific genetic characteristics that accompanied those mice that performed best on the tests. Two sets of genes were identified as linked to memory in the mice. One of these sets comprised 135 genes that have never previously been linked to memory or cognition.
The next step in the research was to examine the gut microbiome of the different mouse strains. Lactobacillus was the most common family of microbes to correlate with better memory, with the species L. reuteri specifically seeming to offer the strongest association with memory in the animals.
Subsequent tests administering L. reuteri to germ-free mice resulted in improved memory compared to germ-free mice administered other microbes. The relationship between Lactobacillus and memory is not novel to this study, however, Snijders suggests his team’s results come from unbiased genome screening processes, implying a genetic role may underpin the relationship between the gut microbiome and memory.
“While a link between Lactobacillus and memory was previously reported, we also found it independently in this unbiased genetic screen,” says Snijders. “These results suggest that genetic variation in large part controls memory, as well as the differences in the composition of the gut microbiome across strains.”
The final part of the robust study homed in on what particular molecular process could be generating this association between the gut bacteria and memory. Lactate seemed to appear as the main metabolite these bacteria were producing, a molecule commonly produced in different volumes by all strains of Lactobacillus.
Feeding lactate directly to mice with poor memory led to notable memory improvements. In the study the researchers reference a number of prior studies exploring the effects of lactate on cognitive processes, hypothesizing this molecular mechanism may be how gut bacteria can influence memory function. Prior research has also suggested lactate can cross the blood-brain barrier, validating a possible pathway from gut to brain.
It is unclear at this stage exactly how the observed genetic patterns could be influencing this microbiome activity. Janet Jansson, co-corresponding author on the study, notes more work is needed to validate these mechanisms in human subjects, but the research does fundamentally highlight a complex interplay between genetics, the microbiome and cognition.
“Our study shows that the microbiome might partner with genetics to affect memory,” says Jansson, but also adding, “While this research strengthens the idea that diet, genetics, and behaviors – like memory – are connected, further work is needed to show if Lactobacillus can improve memory in humans.”
The new study was published in the journal Microbiome.
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