Lactobacilli and memory
Intestinal lactobacilli linked to good memory in mice
Alice Bakhareva, N+1
Mice with a lot of bacteria from four families in their intestines remembered the dangerous compartment better in the passive avoidance test. The animals injected with lactobacilli or pure lactate (lactic acid) had better memory than the control mice. The proportion of cells expressing the mediator gamma-aminobutyric acid in the hippocampus of these animals was increased. A study published in the journal Microbiome (Mao et al., Genetic and metabolic links between the murine microbiome and memory) opens up the prospect for a new approach to the treatment of memory disorders.
The gut microbiome is associated not only with general health, but also with behavior and memory. Probiotics with lactobacilli and bifidobacteria have been shown in mice to reduce anxiety and improve animal memory. How gut bacteria affect brain processes is not clear. It is only known that taking lactobacilli increases the amount of the inhibitory mediator gamma-aminobutyric acid (GABA) and its receptors in the brain.
Scientists from Luxembourg and the USA, led by Antoine Snijders from the Lawrence Berkeley National Laboratory, studied the memory of mice of various lines of the Collaborative Cross project. The genetic diversity of these animals is much higher than that of conventional laboratory lines – this allows us to find new genes that are associated with various processes in the body.
535 mice of 29 lines were trained in passive avoidance: in one of the two compartments of the experimental chamber, the animals were electrocuted, and three days later they were checked which compartment they would prefer. The better the mice's memory of the event, the more time passed before the mice entered the compartment where they were electrocuted.
The memory of mice varied significantly between the lines, and scientists identified 222 genes, the differences in which correlated with memory. About a third of these genes are already known to be associated with memory; expression of another 65 was found in the brain. So, 65 new genes have been found that can participate in memory processes.
The time of entry into the "dangerous" compartment of mice of various lines (blue – on the day of the electric shock, green – three days after). Drawings from an article in Microbiome.
The researchers then sequenced the ribosomal RNA of the intestinal bacteria of mice in which memory was tested. The number of bacteria from four families (Lactobacillaceae, Deferribacteraceae, Bacteroidaceae and Clostridiaceae) correlated with high rates of passive avoidance (p<0.05). Further studies were conducted with lactobacilli, since their connection with memory was found in previous studies on mice, rats and humans.
Mice were fed with bacteria of the following species Lactobacillus reuteri, L.plantarum and L.brevis, and then performed memory tests. To understand which bacterial substances affect the cognitive abilities of animals, the metabolome of their feces, blood plasma and brain was analyzed. The amount of GABA in the same assays and the proportion of hippocampal cells that express this mediator were also evaluated. The hippocampus is the area of the brain necessary for the formation of short–term memory, and GABA is its main mediator.
The memory of mice vaccinated with lactobacilli was better than that of control animals (p=0.00021). The concentration of only one substance – lactate – was increased in the intestines, blood plasma and brain of animals with lactobacilli. The GABA content in the assays was not increased, except in the hippocampus of mice with L.plantarum. And the proportion of hippocampal cells that express this mediator was significantly increased in mice that were vaccinated with all three types of lactobacilli.
Green – GABA-positive hippocampal cells of control mice (top left) and animals that were vaccinated with lactobacilli.
Lactate was added to the drinking water of mice of a line that performed poorly in primary memory tests. After five weeks, the time of entering the "dangerous compartment" with passive avoidance in these animals increased from 92 seconds to 210 (p=0.01). The percentage of GABA-positive hippocampal cells in these mice was also higher than in control (p=0.042).
Perhaps lactobacilli as probiotics will be useful for the treatment of memory disorders in humans. However, before applying the method to humans, it is necessary to conduct a number of additional studies.
The microbiome affects the behavior of not only mice. The absence of microorganisms in the intestines of fruit flies makes them hyperactive, and the presence of some bacteria is associated with the quality of life and a tendency to depression in humans.
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