JP2024026407A - Composition for maintaining and/or improving memory and learning ability and food, medicine and feed containing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide medicines, foods and feeds that are effective in preventing and/or improving the decline in memory and learning ability that occurs with aging (senescence).

SOLUTION: A novel microorganism having an effect in preventing and/or improving the decline in memory and learning ability that occurs with aging (senescence) is provided. More specifically, the microorganism is a microorganism belonging to a genus Lactobacillus, and more specifically, the microorganism is a microorganism belonging to one of Lactobacillus acidophilus, Lactobacillus gallinarum, or Lactobacillus delbrueckii subspecies delbrueckii.

SELECTED DRAWING: Figure 2

COPYRIGHT: (C)2024,JPO&INPIT

Description

The present invention provides an agent for preventing and improving the decline in memory and learning ability that occurs with aging (senescence) and/or an agent that prevents and improves the decline in memory and learning ability that occurs with aging (senescence). Regarding food and beverages that have

In 2010, Japan entered a super-aging society, with the number of people aged 65 and over exceeding 21% of the total population. The proportion of elderly people is expected to continue to increase, reaching 40% by 2060. Under these circumstances, responding to medical and welfare issues related to the increasing elderly population has become an urgent issue.

With the increase in the elderly population, the increase in cognitive dysfunction and dementia, such as decline in memory and learning ability, among middle-aged and elderly people is becoming a problem. Generally, as we age, changes occur in the fine structure of neurons in the brain, and the brain atrophies through the deposition of abnormal proteins and shedding of cells, which is thought to lead to a decline in cognitive function. ing. In addition to these age-related changes, factors such as cerebral infarction, cerebral hemorrhage, and excessive accumulation of abnormal proteins are added, resulting in a pathological decline in cognitive function, resulting in dementia.

As of 2012, there were an estimated 4.62 million people, or 15%, of the elderly aged 65 and over who had dementia, and about 4 million people with mild cognitive impairment, known as those with dementia. This is said to be the era of 8 million people suffering from dementia.

The development of therapeutic drugs for dementia is progressing, but at present they are only used to delay the progression of dementia, and no fundamental treatment has yet been achieved. On the other hand, in healthy elderly people and elderly people with mild cognitive impairment, which is considered a precursor to dementia, cognitive functions such as memory and learning ability can be improved through appropriate interventions such as reviewing dietary habits and exercising. It has been shown that it is possible to prevent or ameliorate the decline of dementia, and even to reduce the risk of developing dementia (Shinkyokeishi 111, 26-30, (2009)). For this reason, there is increasing interest in foods and drinks that can be continuously consumed in daily life, are highly safe, and have no side effects.

Microorganisms used in foods such as lactic acid bacteria are used in a wide range of fields, including fermented foods such as cheese, yogurt, and pickles, as well as lactic acid bacteria drinks.They can be supplied at relatively low prices, and due to their high palatability, they have been used in large quantities around the world for a long time. It is produced in Recently, it has attracted attention as a health food that has favorable health effects such as intestinal regulation effects such as preventing constipation and improving diarrhea, prevention of infectious diseases, and immune activation effects. Regarding aging and cognitive function, Lactobacillus gasseri and Bifidobacterium longum are effective against age-related metabolic abnormalities (Patent No. 5155961, Patent No. 5155960), and Lactobacillus reuteri DSM 17938 strain. It has been disclosed that this is effective for the development of cognitive functions in young mammals (Special Publication No. 2015-503913).

However, the effect of microorganisms on the decline in memory and learning ability that occurs with aging is still unclear.

The nematode Caenorhabditis elegans (hereinafter referred to as C. elegans) uses a simple neural circuit consisting of 302 neurons to sense various external stimuli and can take various response behaviors. When nematodes are reared at a constant temperature, they remember the rearing temperature as a comfortable temperature, so when placed on a temperature gradient, they tend to move towards the previous rearing temperature. For example, C. When P. elegans is placed on a temperature gradient from 17°C to 23°C without food, it will move to around 23°C after one hour. Furthermore, C., who remembered 23℃. If P. elegans is reared at a new temperature of 17°C, it will acquire a memory of the new temperature of 17°C in about 4 hours and will move up the temperature gradient to around 17°C (Proc. Natl. Acad. Sci. USA, 72, 4061-4065 (1975); Genetics, 169, 1437-1450 (2005); J. Neurosci. Methods, 154, 45-52 (2006)). This behavior is called thermotaxis, and it is known to be an excellent model system that reflects the plasticity of neural functions such as memory and learning (Curr. Opin. Neurobiol., 17, 712-719 (2007)).

Previous experiments by the inventors to destroy neurons using lasers have revealed the neurons necessary for thermotactic behavior, and it is known that thermotactic behavior is based on extremely simple neural circuits ( Nature, 376, 344-348 (1995)). The research group of the inventors also analyzed the process by which temperature memory is formed using genome-wide microarray analysis, molecular genetic methods, and imaging technology. As a result, C. It was discovered that when P. elegans memorizes the rearing temperature, the whole body receives the surrounding temperature through the transcription factor HSF-1. Furthermore, it was shown that the reception of this temperature causes a change in gene expression, and as a result, the temperature signal is stored as a memory in the AFD neuron, which is a thermoreceptive neuron in the neural circuit, via the female hormone estrogen. (Nat. Neurosci., 14, 984-92 (2011)).

Furthermore, the inventors discovered that C.I. of CREB, a typical transcription factor responsible for memory. As a result of searching for cells in which the ortholog functions in C. elegans, it was found that only one ortholog of CREB functions only in AFD neurons (EMBO Rep., 12, 855-862 (2011)). In other words, C. Among all neurons in C. elegans, AFD neurons were shown to be the only neurons with CREB-mediated temperature memory. These studies have revealed part of the molecular mechanism by which temperature memory is formed.

Although nematodes and mammals are separated in terms of evolutionary lineage, they share many common molecular mechanisms at the cellular level. It has been reported that molecules known to be involved in memory in mammals are also involved in thermotaxis in C. elegans. For example, the factor CREB (CRH-1 in C. elegans), which is involved in memory in mammals, is involved in the acquisition of temperature memory in C. elegans (EMBO Rep., 12, 855-862 (2011)); Serotonin, a brain transmitter, controls thermotaxis in C. elegans (PLoS One., 8, 1-10 (2013)), and calcineurin, a factor involved in memory in mammals (RCAN-1 in C. elegans) ) has been reported to be involved in the thermotactic behavior of nematodes (J. Mol. Biol., 427, 3457-3468 (2015)).

Furthermore, there have been reports of cases where ingredients that have been shown to be effective on the nervous system in nematodes also show effects on the brain and nervous system in mammals. That is, orally ingested alpha-lipoic acid improves the associative learning behavior of nematodes and mammals that deteriorates with age (Neurobiol. Aging., 26, 899-905 (2005); J. Med. Food., 15, 713-7 (2012)), orally ingested curcumin improves age-related cognitive impairment in nematodes and mammals (Neurobiol Aging., 39, 69-81 (2016); Geroscience., 40, 73-95 (2018)) have been reported.

From these things, C. The thermotactic behavior of P. elegans is considered to be a suitable model system for analyzing the molecular mechanisms of temperature reception and memory.

Patent 5155961 Patent 5155960 Special table 2015-503913

Katsuyoshi Mizukami, Shinkyokeishi 111, 26-30, (2009) Hedgecock, E. M. & Russell, R. L.: Normal and mutant thermotaxis in the nematode Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA, 72, 4061-4065 (1975) Mohri, A., Kodama, E., Kimura, K. D. et al.: Genetic control of temperature preference in the nematode Caenorhabditis elegans. Genetics, 169, 1437-1450 (2005) Ito, H., Inada, H. & Mori, I.: Quantitative analysis of thermotaxis in the nematode Caenorhabditis elegans. J. Neurosci. Methods, 154, 45-52 (2006) Mori, I., Sasakura, H. & Kuhara, A.: Worm thermotaxis: a model system for analyzing thermosensation and neural plasticity. Curr. Opin. Neurobiol., 17, 712-719 (2007) Mori, I. & Ohshima, Y.: Neural regulation of thermotaxis in Caenorhabditis elegans. Nature, 376, 344-348 (1995) Sugi, T., Nishida, Y., & Mori, I.: Regulation of behavioral plasticity by systemic temperature signaling in Caenorhabditis elegans. Nat. Neurosci., 14, 984-92 (2011) Nishida, Y., Sugi, T., Nonomura, M. et al.: Identification of the AFD neuron as the site of action of the CREB protein in Caenorhabditis elegans thermotaxis. EMBO Rep., 12, 855-862 (2011) Li, Y., Zhao, Y., Huang, X., et al.: Serotonin control of thermotaxis memory behavior in nematode Caenorhabditis elegans. PLoS One., 8, 1-10 (2013) Li, W., Bell, H. W., Ahnn, J., Lee, S. K.: Regulator of Calcineurin (RCAN-1) Regulates Thermotaxis Behavior in Caenorhabditis elegans. J. Mol. Biol., 427, 3457-3468 (2015) Murakami, S., Murakami, H.: The effects of aging and oxidative stress on learning behavior in C. elegans. Neurobiol. Aging., 26, 899-905 (2005) Cui, Y., Shu ,Y., Zhu, Y., Shi, Y., Le, G.: High-fat diets impair spatial learning of mice in the Y-maze paradigm: ameliorative potential of α-lipoic acid. J . Med. Food., 15, 713-7 (2012) Miyasaka, T., Xie, C., Yoshimura, S., et al.: Curcumin improves tau-induced neuronal dysfunction of nematodes. Neurobiol. Aging., 39, 69-81 (2016) Sarker, M. R., Franks, S. F..: Efficacy of curcumin for age-associated cognitive decline: a narrative review of preclinical and clinical studies. Geroscience., 40, 73-95 (2018)

The present invention relates to providing a novel microorganism that has the effect of preventing and/or improving the decline in memory and learning ability that occurs with aging.

The present inventors focused on the microorganisms used in foods and the components contained therein, from the perspective of whether it is possible to prevent or improve various functional abnormalities in living organisms using food materials that can be ingested on a daily basis. As a result of intensive research to solve this problem, we have found that bacteria or cultures of microorganisms from multiple different genera have the ability to prevent and/or improve the decline in memory and learning ability that occurs with aging. They discovered this and completed the present invention. That is, the present invention has the following configuration.
(1) Memory/learning ability maintenance and/or containing cells or cultures of one or more microorganisms belonging to the genus Lactobacillus, Bifidobacterium, Streptococcus, Leuconostoc, or Pediococcus or enhancing compositions.
(2) The genus Lactobacillus is Lactobacillus acidophilus, Lactobacillus gasseri, Lactobacillus gallinarum, Lactobacillus spp. Lactobacillus johnsonii, Lactobacillus delbrueckii subsp. The composition for maintaining and/or improving memory and learning ability according to (1), characterized in that the composition is one or more selected from Lactobacillus delbruekii subsp. delbruekii.
(3) The Bifidobacterium genus is Bifidobacterium catenulatum, Bifidobacterium pseudolongum, Bifidobacterium b. ifidum), Bifidobacterium The composition for maintaining and/or improving memory and learning ability according to (1), characterized in that the composition is one or more selected from Bifidobacterium breve and Bifidobacterium longum.
(4) The composition for maintaining and/or improving memory and learning ability according to (1), wherein the Streptococcus genus is Streptococcus thermophilus.
(5) The genus Leuconostoc is one or more selected from Leuconostoc mesenteroides subsp. dextranicum and Leuconostoc lactis (1) ) The composition for maintaining and/or improving memory/learning ability.
(6) As described in (1), wherein the Pediococcus genus is one or more selected from Pediococcus acidilactici and Pediococcus pentosaceus. A composition for maintaining and/or improving memory and learning ability.
(7) The genus Lactobacillus is selected from Lactobacillus acidophilus SBT1921 strain, Lactobacillus gasseri SBT2056 strain, Lactobacillus gallinarum SBT0316 strain, Lactobacillus johnsonii SBT0307 strain, and Lactobacillus delbrueckii subsp. delbrueckii SBT0413 strain. The composition for maintaining and/or improving memory/learning ability according to (2), characterized in that the composition contains at least one.
(8) The Bifidobacterium genus is Bifidobacterium catenulatum SBT11114 strain, Bifidobacterium pseudolongum SBT2922 strain, Bifidobacterium bifidum SBT10550 strain, Bifidobacterium breve SBT10532 strain, Bifidobacterium breve SBT10532 strain, The composition for maintaining and/or improving memory and learning ability according to (3), characterized in that the composition is one or more selected from Bacterium longum SBT10527 strain.
(9) The composition for maintaining and/or improving memory and learning ability according to (4), wherein the Streptococcus genus is Streptococcus thermophilus strain SBT0118.
(10) The memory/learning according to (5), wherein the Leuconostoc genus is one or more selected from Leuconostoc mesenteroides subsp. Dextranicum strain SBT0096 and Leuconostoc lactis SBT2561 strain. A composition for maintaining and/or improving performance.
(11) The memory/learning according to (6), wherein the Pediococcus genus is one or more selected from Pediococcus acidilactici SBT3331 strain and Pediococcus pentosaceus SBT2229 strain. A composition for maintaining and/or improving performance.
(12) A food for maintaining and/or improving memory/learning ability, characterized by containing the composition for maintaining and/or improving memory/learning ability according to any one of (1) to (11); Pharmaceuticals for maintaining and/or improving memory/learning ability, feed for maintaining and/or improving memory/learning ability.
(13) Lactobacillus acidophilus SBT1921 strain whose accession number is NITE P-02980, Lactobacillus gallinarum SBT0316 strain whose accession number is NITE P-02981, Lactobacillus johnsonii SBT0307 strain whose accession number is NITE P-02982 , Bifidobacterium catenulatum SBT11114 strain whose accession number is NITE P-02983, Bifidobacterium pseudolongum SBT2922 strain whose accession number is NITE P-02984, Bifidobacterium pseudolongum SBT2922 strain whose accession number is NITE P-02985 Bacterium bifidum SBT10550 strain, Bifidobacterium breve SBT10532 strain with accession number NITE P-02986, Bifidobacterium longum SBT10527 strain with accession number NITE P-02987, accession number NITE P-02988 Streptococcus thermophilus strain SBT0118, whose accession number is NITE P-02989, Leuconostoc mesenteroides subsp. Pediococcus acidilactici strain SBT3331, which is P-02991, or Pediococcus pentosaceus strain SBT2229, whose accession number is NITE P-02992.

According to the present invention, it is possible to prevent and/or improve the decline in memory and learning ability that occurs with aging. The present invention is effective in improving the quality of life in daily life of elderly people who are concerned about decline in memory and learning ability.

C. FIG. 2 is a diagram showing an outline of a thermotaxis test using P. elegans. C. FIG. 3 is a diagram showing changes in the memory index of C. elegans with aging and the memory index of aged adults that ingested lactic acid bacteria.

As used herein, "maintaining and/or improving memory/learning ability" preferably means preventing and/or improving the decline in memory/learning ability that occurs with aging, More preferably, it means preventing and/or improving the decline in memory ability that occurs with aging. Furthermore, in this specification, when referring to "decrease in memory and learning ability that occurs with aging (senescence)" or "decrease in memory ability that occurs with aging (senescence)", preferably Alzheimer's disease and brain diseases, including dementia such as Huntington's disease and basal ganglia diseases such as Parkinson's disease, as well as amnesia, amnesia, and memory disorders such as Korsakoff's syndrome, as well as depression, anxiety, bipolar disorder, and schizophrenia. It does not include declines in memory and learning ability that occur with mental illnesses such as ataxia, sleep abnormalities, and stress disorders, or declines in memory ability.

The term "composition" as used herein preferably means a pharmaceutical composition or a food composition.

The composition for maintaining and/or improving memory and learning ability of the present invention contains any microorganism belonging to the genus Lactobacillus, Bifidobacterium, Streptococcus, Leuconostoc, or Pediococcus as an active ingredient. It is characterized by Microorganisms belonging to the genus Lactobacillus, Bifidobacterium, Streptococcus, Leuconostoc, and Pediococcus include Lactobacillus acidophilus, Lactobacillus gasseri, Lactobacillus gallinarum, and Lactobacillus johnsonii. Species, Lactobacillus delbrueckii subsp. delbrueckii, Bifidobacterium catenulatum spp., Bifidobacterium pseudolongum spp., Bifidobacterium bifidum spp., Bifidobacterium breve spp., Bifidobacterium longum spp. Preferred species are Streptococcus thermophilus sp., Leuconostoc mesenteroides subsp. Dextranicum, Leuconostoc lactis sp., Pediococcus acidilactici sp., Pediococcus pentosaceus. More preferred are Lactobacillus acidophilus SBT1921 strain, Lactobacillus gasseri SBT2056 strain, Lactobacillus gallinarum SBT0316 strain, Lactobacillus johnsonii SBT0307 strain, Lactobacillus delbrueckii subsp. delbrueckii SBT0413 strain, and Bifidobacterium catenulatum SBT11114. stocks , Bifidobacterium pseudolongum SBT2922 strain, Bifidobacterium bifidum SBT10550 strain, Bifidobacterium breve SBT10532 strain, Bifidobacterium longum SBT10527 strain, Streptococcus thermophilus SBT0118 strain, Leuconostoc. Mesenteroides subspecies Dextranicum SBT0096 strain, Leuconostoc lactis SBT2561 strain, Pediococcus acidilactici SBT3331 strain, and Pediococcus pentosaceus SBT2229 strain, which maintain and/or improve the memory and learning ability of the present invention. The microorganism is not particularly limited as long as it is a microorganism belonging to the genus Lactobacillus, Bifidobacterium, Streptococcus, Leuconostoc, or Pediococcus that has the effect of

These microorganisms belonging to the genus Lactobacillus, Bifidobacterium, Streptococcus, Leuconostoc, and Pediococcus can be used alone, or two or more lactic acid bacteria can be used in combination as appropriate. . Furthermore, these microorganisms belonging to the genus Lactobacillus, Bifidobacterium, Streptococcus, Leuconostoc, and Pediococcus can be cultured according to a conventional method for culturing lactic acid bacteria. Various media can be used as the culture medium, such as a milk medium, a medium containing milk components, and a semi-synthetic medium that does not contain milk components. Examples of such a medium include reduced skim milk medium and MRS medium.

Bacterial cells separated from the obtained culture by a bacterial collection means such as centrifugation can be used as they are as the active ingredient of the present invention. Bacterial cells that have been concentrated, dried, freeze-dried, etc. may be used, or may be killed by heating and drying. In addition to pure isolated bacterial cells, cultures, suspensions, and other bacterial cell-containing substances, as well as cytoplasm and cell wall fractions obtained by treating bacterial cells with enzymes or physical means, can be used. can. The forms of cultures include not only those using media commonly used for culturing lactic acid bacteria, such as the synthetic medium MRS medium (manufactured by DIFCO) and reduced skim milk medium, but also cheese, fermented milk, and milk. Examples include dairy products such as lactic acid bacteria drinks, but are not particularly limited.

When formulating the agent for maintaining and/or improving memory and learning ability of the present invention, excipients, stabilizers, flavoring agents, etc. that are permitted in the formulation are appropriately mixed, concentrated, freeze-dried, and heat-dried. The cells may also be killed. Dried products, concentrates, and paste-like products of these products are also included. In addition, to the extent that it does not interfere with the memory/learning ability maintenance and/or improvement effect of microorganisms or cultures belonging to the genus Lactobacillus, Bifidobacterium, Streptococcus, Leuconostoc, and Pediococcus, The formulation can also be prepared by mixing excipients, binders, disintegrants, lubricants, flavoring agents, suspending agents, coating agents, and other arbitrary agents. The dosage form can be tablets, capsules, granules, powders, powders, syrups, etc., and it is desirable to administer these orally.

The composition for maintaining and/or improving memory and learning ability of the present invention may be incorporated into any food or drink, or may be added to raw materials during the manufacturing process of the food or drink. Examples of food and beverages include cheese, fermented milk, dairy products, lactic acid bacteria drinks, dairy products such as butter and margarine, milk drinks, fruit juice drinks, soft drinks and other beverages, and eggs such as jelly, candy, pudding, and mayonnaise. Examples include processed products, sweets and breads such as butter cake, various powdered milks, infant foods, nutritional compositions, etc., but are not particularly limited. Furthermore, the composition for maintaining and/or improving memory and learning ability of the present invention can be incorporated into feed. As with the above-mentioned food and drink products, it may be incorporated into any feed, or may be added to raw materials during the feed manufacturing process.

A composition for maintaining and/or improving memory and learning ability, which contains cells or cultures of microorganisms belonging to the genus Lactobacillus, Bifidobacterium, Streptococcus, Leuconostoc, and Pediococcus, or When used in combination with materials such as food and beverages, nutritional compositions, feeds, etc. for maintaining and/or improving memory and learning ability, or processed products of these materials, Lactobacillus, Bifidobacterium, Streptococcus, Leuconobacterium spp. The blending ratio of microbial cells or cultures of microorganisms belonging to the genus Stock and Pediococcus is not particularly limited, and may be adjusted as appropriate depending on ease of production and preferred daily dosage. This is determined individually taking into account the symptoms and age of the recipient, but for adults, for example, 10 to 200 g of Lactobacillus gasseri culture, or 0.1 to 0.1 g of the bacterial cells themselves. The amount may be adjusted so that 5,000 mg can be taken. By ingesting it in this way, the desired effects can be exerted.

In the present invention, as a method for screening lactic acid bacteria that prevent and/or improve the decline in memory and learning ability that occurs with aging, C. A thermotaxis test was conducted using P. elegans. Generally, higher animals such as mice, rats, dogs, and monkeys are used to verify the physiological functions of food ingredients and drugs, but this requires a great deal of effort, time, and money, and also has ethical issues. It is necessary to give sufficient consideration to As an alternative to animal experiments, tests are also being conducted using cultured cells isolated from animal tissues.

C. P. elegans is a non-parasitic multicellular organism that lives in the soil, and in addition to being easy to handle as a laboratory animal, the cell lineages of the approximately 1,000 somatic cells that make up its body have all been clarified. They are widely used as model organisms in a variety of research fields because of their unique features such as vertebrates and nervous systems. In particular, he has made significant contributions to various research fields such as cell death, nerves, development, and aging. Furthermore, in recent years, C.I. elegans is being used to search for pharmaceuticals and food ingredients that are effective in preventing and improving these neurodegenerative diseases.

C. Although P. elegans has a simple neural circuit, it is known that they memorize and learn by associating information such as the presence or absence of food with the salt concentration and temperature of the environment in which they were placed, and are capable of learning and remembering information such as associative learning and memory. It can be used as a model system for evaluating the cognitive functions of humans (Nature, 376, 344-348 (1995)).

Hereinafter, the present invention will be described in more detail based on examples, but the present invention is not to be interpreted as being limited to these examples.

[Test Example 1] Evaluation of lactic acid bacteria that prevent and/or improve the decline in cognitive function that occurs with aging (aging). C. elegans was bred using the wild type N2 strain according to the "Nematode Lab Manual."
1. Test method (1) Test bacteria The strains shown in Table 1 were subjected to screening.

(2) Test procedure
(i) Preparation of evaluation samples Each of the test bacteria described in (1) above was cultured under the conditions shown in Table 2. The cultured cells were centrifuged (7,000×g, 4° C., 15 minutes), and the supernatant was discarded. After washing the bacterial cells with physiological saline, the wet weight of the bacterial cells was determined and the weight was adjusted to 0.05 g/ml using NG buffer (0.3% NaCl, 1mM CaCl ₂ , 1mM MgSO ₄ , 25mM phosphate buffer). [pH 6.0]) and resuspended in C.I. A sample plate was prepared by inoculating 200 μl of each sample onto a P. elegans breeding plate (NGM plate). As a control, C. Escherichia coli OP50 strain, which is commonly used as food for P. elegans, was used.

(ii) C. nigra recovered by preparative bleaching of aged adults that had ingested lactic acid bacteria. C. elegans eggs were sown on a plate seeded with OP50, and allowed to stand at 23° C. for 3 days to obtain young adults. The adult worms were collected in NG buffer, transferred to a plate inoculated with lactic acid bacteria or a plate inoculated with OP50, and reared at 23°C for 4 days to obtain aged adults.

(iii) Screening by thermotaxis test The thermotaxis test was performed using ItoH. (J. Neurosci. Methods, 154, 45-52 (2006)). Prepare two thermostats, and place one leg of a U-shaped aluminum stand (21.5cm x 60cm x 1.5cm thick) on the low temperature side (5℃) and the other on the high temperature side (35℃). A linear temperature gradient from approximately 5°C to 35°C was created on the aluminum stand by immersing it in a constant temperature bath. An agar plate placed in a square petri dish is placed on an aluminum stand so that the center is at 20°C, the young adult or aged adult described above is released into the center of the plate, and C. The distribution of P. elegans was evaluated. Memory and learning ability was determined by C.I. The proportion of C. elegans was evaluated as a memory index (Figure 1). In addition, Dunnett's multiple test was used to evaluate whether there was a significant difference when using aged adults that had ingested OP50 as a control (p<0.05 was determined to be a significant difference).

2. Test Results Figure 2 shows the screening results. Memory index decreased in older adults compared to young adults.
Lactobacillus acidophilus SBT1921 strain, Lactobacillus gasseri SBT2056 strain, Lactobacillus gallinarum SBT0316 strain, Lactobacillus johnsonii SBT0307 strain, Lactobacillus delbrueckii subsp. delbrueckii SBT0413 strain, Bifidobacterium catenulatum SBT11114 strain, Bifidobacterium catenulatum SBT11114 strain bacteria Bifidobacterium pseudolongum SBT2922 strain, Bifidobacterium bifidum SBT10550 strain, Bifidobacterium breve SBT10532 strain, Bifidobacterium longum SBT10527 strain, Streptococcus thermophilus SBT0118 strain, Leuconostoc mesenteroides subspecies dextranicum Memory index was significantly increased in aged adults that ingested SBT0096 strain, Leuconostoc lactis SBT2561 strain, Pediococcus acidilactici SBT3331 strain, and Pediococcus pentosaceus SBT2229 strain compared to those that ingested OP50. did. In other words, it was found that by ingesting the above bacteria, it is possible to prevent and/or improve the decline in memory and learning ability that occurs with aging.

(Example 1) Production of an agent (granules) for maintaining and/or improving memory and learning ability ) was ingested at 5% by weight, and after culturing at 38°C for 15 hours, the bacterial cells were collected by centrifugation. The collected cells were freeze-dried to obtain a freeze-dried powder of early-stage cells. 1 g of this freeze-dried powder was mixed with 5 g of lactose and formed into granules to obtain the agent for maintaining and/or improving memory and learning ability of the present invention.

(Example 2) Production of an agent (powder) for maintaining and/or improving memory and learning ability Lactobacillus obtained in Example 1 above was prepared in accordance with the provisions of the 13th revised Japanese Pharmacopoeia Explanation General Rules for Preparations "Powder" - To 10 g of freeze-dried powder of Gallinarum SBT0316 strain, 400 g of lactose (Japanese Pharmacopoeia) and 600 g of potato starch (Japanese Pharmacopoeia) were added and mixed uniformly to produce the agent for maintaining and/or improving memory and learning ability of the present invention.

(Example 3) Production of nutritional composition for maintaining and/or improving memory/learning ability Synthetic medium edible for Lactobacillus gallinarum SBT0316 strain (0.5% yeast extract, 0.1% trypticase peptone added) After culturing at 38° C. for 15 hours, the cells were collected by centrifugation, and the collected cells were freeze-dried. 40 g of this freeze-dried powder was added to 40 g of vitamin C or 40 g of a mixture of equal amounts of vitamin C and citric acid, 100 g of granulated sugar, and 60 g of a mixture of equal amounts of corn starch and lactose and mixed. The mixture was packed in a bag to produce a nutritional composition for maintaining and/or improving memory and learning ability of the present invention.

(Example 4) Production of beverage for maintaining and/or improving memory/learning ability 1 g of Lactobacillus gallinarum SBT0316 strain obtained in Example 3 above was dissolved in 699 g of deionized water, and then heated to 40°C. The mixture was stirred and mixed for 20 minutes at 9,500 rpm using an Ultra Disperser (ULTRA-TURRAX T-25; manufactured by IKA Japan). After adding 100 g of maltitol, 2 g of acidulant, 20 g of reduced starch syrup, 2 g of fragrance, and 176 g of deionized water, the mixture was filled into a 100 ml glass bottle, sterilized at 95°C for 15 seconds, and then sealed tightly. and/or 10 bottles (100 ml) of the enhancing beverage were produced.

(Example 5) Production of feed for maintaining and/or improving memory and learning ability 12 kg of soybean meal, 14 kg of skim milk powder, 4 kg of soybean oil, 2 kg of corn oil, 23.2 kg of palm oil, 14 kg of corn starch, 9 kg of wheat flour, 2 kg of bran, 5 kg of vitamin mixture, 2.8 kg of cellulose, and 2 kg of mineral mixture were blended, sterilized at 120°C for 4 minutes, and 10 kg of Lactobacillus gallinarum SBT0316 strain obtained in Example 3 was blended to improve the memory and learning of the present invention. A feed for maintaining and/or improving performance was produced.

(Example 6) Production of fermented milk for maintaining and/or improving memory and learning ability Lactobacillus gallinarum SBT0316 strain was added to an edible synthetic medium (added with 0.5% yeast extract and 0.1% trypticase peptone). After ingesting 5% by weight and culturing at 37°C for 17 hours, the bacterial cells were collected by centrifugation and freeze-dried. 5 g of the freeze-dried bacterial cells, 1700 g of skim milk powder, 300 g of glucose, and 7695 g of deionized water were mixed and heat sterilized by holding at 95° C. for 2 hours. This was cooled to 37°C, 300g of lactic acid bacteria starter (Lb. casei) was inoculated, and after stirring and mixing, fermentation was carried out to pH 4.0 in an incubator maintained at 37°C. After reaching pH 4.0, it was cooled to 10° C. or lower to produce 10 kg of fermented milk for maintaining and/or improving memory and learning ability of the present invention.

(1) Lactobacillus acidophilus SBT1921 strain (accession number: NITE P-02980, accession date: June 26, 2019), accession address: 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan 292-0818 , Japan National Institute of Technology and Evaluation, Patent Microorganism Depositary (NPMD).
(2) Lactobacillus gallinarum SBT0316 strain (accession number: NITE P-02981, accession date: June 26, 2019), accession address: 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan 292-0818 , Japan National Institute of Technology and Evaluation, Patent Microorganism Depositary (NPMD).
(3) Lactobacillus johnsonii SBT0307 strain (accession number: NITE P-02982, accession date: June 26, 2019), accession address: 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan 292-0818 , Japan National Institute of Technology and Evaluation, Patent Microorganism Depositary (NPMD).
(4) Bifidobacterium catenulatum SBT11114 strain (accession number: NITE P-02983, accession date: June 26, 2019), accession address: 2-5 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan 292-0818 -8, National Institute of Technology and Evaluation, Japan Patent Microorganisms Depositary (NPMD).
(5) Bifidobacterium pseudolongum SBT2922 strain (accession number: NITE P-02984, accession date: June 26, 2019), accession address: 2 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan 292-0818 -5-8, National Institute of Technology and Evaluation, Japan Patent Microorganisms Depositary (NPMD).
(6) Bifidobacterium bifidum SBT10550 strain (accession number: NITE P-02985, accession date: June 26, 2019), accession address: 2-5 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan 292-0818 -8, National Institute of Technology and Evaluation, Japan Patent Microorganisms Depositary (NPMD).
(7) Bifidobacterium breve SBT10532 strain (accession number: NITE P-02986, accession date: June 26, 2019), accession address: 2-5 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan 292-0818 -8, National Institute of Technology and Evaluation, Japan Patent Microorganisms Depositary (NPMD).
(8) Bifidobacterium longum SBT10527 strain (accession number: NITE P-02987, accession date: June 26, 2019), accession address: 2-5 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan 292-0818 -8, National Institute of Technology and Evaluation, Japan Patent Microorganisms Depositary (NPMD).
(9) Streptococcus thermophilus SBT0118 strain (accession number: NITE P-02988, accession date: June 26, 2019), accession address: 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan 292-0818 , Japan National Institute of Technology and Evaluation, Patent Microorganism Depositary (NPMD).
(10) Leuconostoc mesenteroides subsp. Dextranicum strain SBT0096 (accession number: NITE P-02989, accession date: June 26, 2019), accession address: 2 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan 292-0818 -5-8, National Institute of Technology and Evaluation, Japan Patent Microorganisms Depositary (NPMD).
(11) Leuconostoc lactis SBT2561 strain (accession number: NITE P-02990, accession date: June 26, 2019), accession address: 2-5 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan 292-0818 8. National Institute of Technology and Evaluation, Japan Patent Microorganism Depositary (NPMD).
(12) Pediococcus acidilactici SBT3331 strain (accession number: NITE P-02991, accession date: June 26, 2019), accession address: 2 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan 292-0818 -5-8, National Institute of Technology and Evaluation, Japan Patent Microorganisms Depositary (NPMD).
(13) Pediococcus pentosaceus SBT2229 strain (accession number: NITE P-02992, accession date: June 26, 2019), accession address: 2-5 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan 292-0818 8. National Institute of Technology and Evaluation, Japan Patent Microorganism Depositary (NPMD).
(14) Lactobacillus gasseri SBT2056 strain (accession number: FERM BP-11038, accession date: April 22, 1986), accession address: 2-5 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan 292-0818 8. National Institute of Technology and Evaluation, Japan Patent Organism Depositary (IPOD).

Claims (5)

A composition for maintaining and/or improving memory and learning ability, which contains cells or cultures of one or more microorganisms belonging to the genus Lactobacillus. The genus Lactobacillus includes Lactobacillus acidophilus, Lactobacillus gallinarum, and Lactobacillus delbruekii subsp. ubsp. delbruekii) The composition for maintaining and/or improving memory/learning ability according to claim 1. The memory/learning according to claim 2, wherein the genus Lactobacillus is one or more selected from Lactobacillus acidophilus SBT1921 strain, Lactobacillus gallinarum SBT0316 strain, and Lactobacillus delbrueckii subsp. delbrueckii SBT0413 strain. A composition for maintaining and/or improving performance. A food for maintaining and/or improving memory/learning ability, comprising the composition for maintaining and/or improving memory/learning ability according to any one of claims 1 to 3, and a food for maintaining and/or improving memory/learning ability. /Or medicines for improving memory/learning ability and/or feed for maintaining and/or improving memory/learning ability. Lactobacillus acidophilus SBT1921 strain, whose accession number is NITE P-02980, and Lactobacillus gallinarum SBT0316 strain, whose accession number is NITE P-02981.