Waseda University and Kyodo Milk find that combination of bifidobacteria and arginine shows potential for prevention of aging-related cognitive function decline

On July 24, Kyodo Milk Industry Co.,Ltd and Waseda University jointly announced the discovery that the co-administration of bifidobacteria and arginine to mice, experimental animals, improved their cognitive flexibility. This result was obtained by a research group led by Researcher Kayo Ikuta and Principal Researcher Mitsuharu Matsumoto of Kyodo Milk, and Professor Masaki Kakeyama of the Faculty of Human Sciences at Waseda University and published in the international academic journal Frontiers in Nutrition.

It is known that cognitive flexibility (i.e., the ability to adapt to a changing environment) declines rapidly just before the onset and during the early stages of dementia, depression, and other psychiatric disorders. Recent studies have revealed that the gut and brain influence each other through various signaling factors (gut-brain correlation), and it is becoming clear that gut microbiota is also involved in cognitive function.

A research group comprising researchers from Kyodo Milk and Waseda University had previously reported that disturbance of the gut microbiota by antibiotics reduced cognitive flexibility in mice. Polyamine, a physiologically active substance that Kyodo Milk has been researching, is present in all the cells of all living organisms and is essential for maintaining cellular health.

Studies have shown that exogenous polyamine administration improves learning memory in mice, and that an increase in intestinal polyamines improves the mice's spatial learning memory. Therefore, the research group investigated whether an increased level of polyamines could improve cognitive flexibility.

They used a 'Cognitive Flexibility Evaluation Test Using a Touch Screen Device,' which they had developed to evaluate cognitive flexibility in mice. Specifically, they examined the effect of the co-administration of bifidobacteria and arginine, which stimulate polyamine production in the gut microbiota. This test applies a touch screen operant device. With this device, when the mouse touches the correct spot on the panel with its nose, one grain of bait falls, which the animal can eat as a reward for choosing the correct answer. The cognitive flexibility evaluation test using this device is a reward-based learning-memory test in which four asymmetrical spots are visible on the touch screen. Selection of the correct spot from the four will result in a highly preferred food. The mouse first performs a behavioral formation of 'spot selection' by touching a spot on the touch screen with its nose and then proceeds to a learning test.

The learning test consists of (1) original learning to acquire a sequence of actions to select the correct spot that alternates on the diagonal, and (2) repeated reversal tasks to swap the correct and incorrect diagonals (repeated reversal learning).

In the experiment, mice were divided into two groups. One group was administered a mixture solution containing both bifidobacteria and arginine (Bifal + Arg group) and the other group was administered physiological saline only (control group). Both groups were then subjected to the learning tests. In tests (1) and (2), the adaptive behavior of the mice to rule changes (e.g., the diagonal of the correct answer changed) was evaluated as cognitive flexibility.

Compared with the mice in the control group, those in the Bifal + Arg group recognized changes in the rules more quickly and switched behavior in accordance with the new rule; that is, administration of Bifal + Arg improved cognitive flexibility, allowing the animal to respond flexibly to environmental changes. This is the first report showing that foods that improve the gut environment, such as probiotics, may be useful for enhancing cognitive flexibility.

The research group plans to conduct human application tests and mechanistic analysis to further develop the results of this study, aiming for future social implementation of new dementia prevention strategies based on scientific evidence.

Journal Information
Publication: Frontiers in Nutrition
Title: Bifidobacterium animalis subsp. lactis and arginine mixture intake improves cognitive flexibility in mice
DOI: 10.3389/fnut.2023.1164809