Stress-relieving composition, food and drink, medicine, and feed

Abstract

The present invention addresses the problem of providing: a stress-relieving composition that can relieve stress, and is excellent in stability and safety; and food and drink, medicine, and feed that contain the stress-relieving composition.　Provided are: a stress-relieving composition characterized by containing Bifidobacterium adolescentis as an active ingredient; and food and drink, stress-relieving medicine, and stress-relieving feed that are characterized by containing the stress-relieving composition.

Description

Stress-reducing compositions, foods, beverages, medicines, and feeds

[0001] The present invention relates to a composition for reducing stress, and to a food, drink, pharmaceutical, and feed containing the composition for reducing stress.

[0002] It is said that we live in a stressful society today, and we experience various stresses every day due to our physical condition, financial situation, workplace and home environment, etc.

[0003] Being exposed to strong, sustained stress can cause a variety of physical and psychological disorders, and in severe cases can lead to depression and other conditions.

[0004] In fact, according to the Ministry of Health, Labor and Welfare's 2019 Basic Survey on National Life, 47.9% of men and women aged 12 and over responded that they felt stressed, and 10.3% of men and women aged 20 and over responded that they felt psychological distress equivalent to a mood disorder or anxiety disorder (Non-Patent Document 1).

[0005] To alleviate this stress, various stress-reducing agents have been developed. For example, a stress response-reducing agent containing Lactococcus lactis subsp. cremoris (Patent Document 1) and an anti-stress composition containing Bifidobacterium breve (Patent Document 2) have been reported.

[0006] However, it cannot be said that there are enough options available to satisfy the diverse needs of consumers.

[0007] JP 2023-091935 A JP 2021-153446 A

[0008] Ministry of Health, Labour and Welfare 2019 Comprehensive Survey on Living Conditions of the People

[0009] An object of the present invention is to provide a stress-reducing composition that can reduce stress and has excellent stability and safety. Another object of the present invention is to provide a food or drink, a pharmaceutical product, or a feed containing the stress-reducing composition.

[0010] The present inventors have conducted extensive research to solve the above-mentioned problems and have found that ingestion of Bifidobacterium adolescentis, particularly Bifidobacterium adolescentis SBT2786 strain (NITE BP-03102), significantly reduces stress. That is, the present invention includes the following aspects.

[0011] (1) A stress-reducing composition characterized by containing Bifidobacterium adolescentis as an active ingredient. (2) The stress-reducing composition according to (1), characterized in that the Bifidobacterium adolescentis is Bifidobacterium adolescentis SBT2786 strain (NITE BP-03102). (3) A food or drink characterized by containing the stress-reducing composition according to (1) or (2). (4) A pharmaceutical characterized by containing the stress-reducing composition according to (1) or (2). (5) A feed characterized by containing the stress-reducing composition according to (1) or (2). (6) A method for reducing stress, comprising administering Bifidobacterium adolescentis to a human. (7) A method for using Bifidobacterium adolescentis, characterized by being used for the purpose of stress reduction. (8) A composition comprising Bifidobacterium adolescentis for use in the treatment of stress reduction. (9) Non-therapeutic use of Bifidobacterium adolescentis for stress reduction. (10) Use of Bifidobacterium adolescentis in the manufacture of a therapeutic agent for stress reduction.

[0012] According to the present invention, it is possible to provide a stress-reducing composition that can reduce stress and has excellent stability and safety, as well as foods, beverages, pharmaceuticals, and feed containing the stress-reducing composition.

[0013] 1 is a graph comparing the stress-reducing effect of the present invention with the amount of NPF expression in Drosophila.

[0014] Hereinafter, a mode for carrying out the present invention (hereinafter simply referred to as "the present embodiment") will be described in detail. The following present embodiment is an example for explaining the present invention, and is not intended to limit the present invention to the following content. The present invention can be carried out by appropriately modifying it within the scope of its gist.

[0015] (Stress-reducing composition) The stress-reducing composition of the present invention is characterized by containing Bifidobacterium adolescentis as an active ingredient. Bifidobacterium adolescentis is one of the predominant species of bifidobacteria (genus Bifidobacterium) that live in the intestinal tract of adult humans, and its stability and safety when ingested from outside the body by humans have been confirmed.

[0016] The Bifidobacterium adolescentis contained in the stress-reducing composition is not particularly limited to a strain as long as it is of the Bifidobacterium adolescentis species, but a preferred example is the SBT2786 strain of Bifidobacterium adolescentis.

[0017] The Bifidobacterium adolescentis SBT2786 strain has been deposited at the National Institute of Technology and Evaluation, National Patent Microorganisms Depositary (NPMD), Biotechnology Center, and is available from the institution. The accession number is shown in Table 1.

[0018]

[0019] In the present invention, stress reduction refers to making one less susceptible to stress, reducing stress responses, or controlling stress responses themselves, and also includes improving or suppressing part or all of the physical or mental abnormalities that occur as a result of exposure to stress.

[0020] "Stress" in the present invention encompasses physical stress, chemical stress, mental stress, etc., and is preferably mental stress. The stress-reducing effect of the present invention can be used to prevent and / or treat symptoms and diseases that occur under stress by alleviating stress, and can also be used to improve energy, vitality, concentration, etc. Furthermore, by alleviating stress under specific circumstances, it can be used to alleviate tension, maintain mental well-being under those circumstances, and enable normal performance.

[0021] In the present invention, stress can be evaluated using a questionnaire for evaluating mood states, such as the Profile of Mood States (POMS) or the Profile of Mood States 2nd Edition (POMS2). These psychological tests include those for different ages of test subjects, such as those for adults and those for adolescents, and those with different numbers of questions, such as full-item versions and shortened versions, and can be selected appropriately depending on the condition of the test subject.

[0022] Specifically, POMS2 measures the factors of "Anger-Hostility (AH)," "Confusion-Bewilderment (CB)," "Depression-Dejection (DD)," "Fatigue-Inertia (FI)," "Tension-Anxiety (TA)," "Vigor-Activity (VA)," "Friendliness (F)," and "Total Mood Disturbance (TMD)." TMD is an index that comprehensively represents negative mood states and can represent mood disorders, emotional or psychological distress, and subjective well-being.

[0023] The content of Bifidobacterium adolescentis in the stress-reducing composition of the present invention can be freely set to a level that achieves the effects of the present invention, but is preferably 100 million to 1,000 billion cells / g. The daily dosage varies depending on age, body weight, etc., but for example, for an adult, it is preferably 100 million to 100 billion cells / day, and more preferably 1,000 million to 100 billion cells / day. Regarding the amount of bacterial cells, when the bacterial cells are disrupted, it can be expressed as a weight conversion from the number of bacteria (cells / g) before disruption.

[0024] The administration period of the stress-reducing composition of the present invention can be freely set to a degree that ensures the effects of the present invention, but is preferably 1 to 120 days, more preferably 14 to 60 days. The administration period can be adjusted appropriately depending on the content of Bifidobacterium adolescentis in the stress-reducing composition.

[0025] The subject to which the stress-reducing composition of the present invention is applied is not particularly limited, and it can be applied to humans or mammals other than humans. Examples of subjects to which the composition can be applied include healthy adults and healthy middle-aged and elderly people who are feeling stressed. It can also be applied to healthy adults and healthy middle-aged and elderly people who are not feeling any particular stress and who are living their daily lives without any problems.

[0026] The Bifidobacterium adolescentis contained in the stress-reducing composition of the present invention can be cultured under conditions suitable for each bacterium. For example, various media can be used, such as a milk medium or a medium containing milk components, a semi-synthetic medium not containing milk components, or a chemically defined synthetic medium. Examples of such media include reconstituted skim milk and MRS medium. The culture temperature is preferably 35 to 42°C. Furthermore, the culture is preferably carried out under anaerobic conditions.

[0027] The Bifidobacterium adolescentis contained in the stress-reducing composition of the present invention can be used as an active ingredient of the present invention as it is, after being separated from the culture by a collection method such as centrifugation. The cells may be subjected to some kind of treatment, such as concentration, drying, or freeze-drying, or may be killed by heat drying or the like, and the treatment method is not particularly limited.

[0028] The Bifidobacterium adolescentis contained in the stress-reducing composition of the present invention can be separated from the culture by a collection method such as centrifugation and used as the active ingredient of the present invention. The cells may also be subjected to some kind of treatment. For example, cells that have been subjected to treatments such as concentration, drying, or freeze-drying may be used, or the cells may be killed by heat drying or the like, and the treatment method is not particularly limited.

[0029] Furthermore, not only purely isolated bacterial cells but also 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. Examples of the form of the culture include, but are not limited to, cultures using media generally used for culturing lactic acid bacteria, such as synthetic MRS medium (manufactured by DIFCO) and reduced skim milk medium, as well as dairy products such as cheese, fermented milk, and dairy lactic acid bacteria drinks.

[0030] (Foods, beverages, medicines, and feed) The stress-reducing composition of the present invention can be added to foods, beverages, medicines, feed, etc. Furthermore, foods, beverages, medicines, and feed containing the stress-reducing composition of the present invention may contain various auxiliary ingredients as long as the effects of the present invention are not impaired. Examples of foods and beverages include general foods, as well as functional foods, nutritional supplements, and foods for specified health uses. The form of the stress-reducing composition of the present invention is not particularly limited, and examples include powders, granules, tablets, capsules, and oral liquids.

[0031] Although the present invention has been described above using embodiments, it goes without saying that the technical scope of the present invention is not limited to the scope described in the above embodiments. It will be apparent to those skilled in the art that various modifications and improvements can be made to the above embodiments. Furthermore, it is clear from the claims that such modifications and improvements can also be included within the technical scope of the present invention.

[0032] The present invention will be described in detail below with reference to examples and test examples, but these are merely illustrative and the present invention is not limited to them in any way.

[0033] Test Example 1 The composition for reducing stress of the present invention was administered to humans, and the stress-reducing effect was evaluated based on the TMD score of the POMS2 short version.

[0034] Example 1 Bacterial powder of Bifidobacterium adolescentis SBT2786 strain was mixed with starch and filled into commercially available hard capsules so that the mixture contained 100 billion cells per 4 capsules.

[0035] Comparative Example 1 Capsules were produced in the same manner as in Example 1, except that starch was used instead of Bifidobacterium adolescentis SBT2786 strain.

[0036] (Evaluation Test 1) Healthy Japanese men and women aged 30 to 60 years were used as subjects. 126 subjects were divided into two groups (61 subjects in the Example 1 intake group and 65 subjects in the Comparative Example 1 intake group) and a placebo-controlled, randomized, double-blind, parallel-group study was conducted. Four capsules of either the Example 1 or Comparative Example 1 capsules were orally ingested daily. The intake period was 4 weeks. To evaluate the stress state of the subjects, the TMD scores of the POMS2 short version were evaluated before and after the intake period. The scores were evaluated using T-scores (values ​​converted to approximate a normal distribution with a generation mean of 50 and a standard deviation of 10). This TMD score comprehensively represents the negative mood state, with a lower score indicating a greater improvement in the subject's mood state.

[0037] The average scores and standard errors before and after intake are shown in Table 2. It was shown that the TMD score after the intake period was significantly reduced in the group taking Example 1 compared to the group taking Comparative Example 1. This indicates that the stress state was improved in the group taking Example 1.

[0038]

[0039] Test Example 2 A number of different bifidobacteria were administered to fruit flies, and the stress-reducing effect was evaluated based on the expression level of NPF.

[0040] (Preparation of Administration Samples) The following donor bacteria (Example 2, Comparative Examples 2 to 4) were cultured in GAM medium (manufactured by Nissui Pharmaceutical Co., Ltd.) + 1% glucose (Fujifilm Wako Pure Chemical Industries, Ltd.) medium, and then the bacterial cells were separated by centrifugation. The bacterial cells were washed twice with physiological saline and once with ultrapure water, and then freeze-dried to prepare freeze-dried powder. Example 2: Bifidobacterium strain SBT2786 Comparative Example 2: Bifidobacterium strain SBT0430 (NITEP-03103) Comparative Example 3: Bifidobacterium strain JCM1275 (reference strain) Comparative Example 4: Bifidobacterium strain NK98 (KCCM12297P)

[0041] (3) Test Procedure (1) Wild-type Drosophila were reared at 25°C under a 12-hour light / dark cycle, and virgin female individuals 5 days after eclosion were used for evaluation. (2) The administration sample (lyophilized powder) was mixed with food to a final concentration of 10 mg / mL and administered to the Drosophila. As a control, food without bifidobacteria was administered. (3) On the third day after administration, the intestines were removed from the Drosophila, and RNA was collected using an RNeasy mini kit (QIAGEN). (4) cDNA was synthesized from RNA using ReverTra Ace qPCR RT Master Mix with gDNA Remover (TOYOBO), and gene expression levels were quantified by real-time PCR using THUNDERBIRD Next SYBR qPCR Mix (TOYOBO). (5) Primers shown in Table 3 were used. Using rp49 as an endogenous control gene, the expression levels of NPF were compared using the ΔΔCt method.

[0042] NPF is a Drosophila homolog of mammalian neuropeptide Y (NPY), and NPY has been reported to have anti-stress effects.

[0043]

[0044] (Test Results) The NPF expression levels are shown in Table 4 and Figure 1. In the group of Example 2, the NPF expression level was significantly increased compared to the control group. On the other hand, in the groups of Comparative Examples 2 to 4, the NPF expression level also increased compared to the control group, but the increase was not as great as in Example 2. These results indicate that, among bifidobacteria, the Bifidobacterium adolescentis SBT2786 strain has a stronger anti-stress effect than other Bifidobacterium adolescentis strains.

[0045]

[0046] The present invention provides a novel composition having a stress-reducing effect, which is a microorganism belonging to the species Bifidobacterium adolescentis, a composition containing the microorganism, and a food, drink, pharmaceutical, and feed containing the composition. By ingesting the composition of the present invention, the stress-reducing effect can be exerted.

[0047] [Reference to deposited biological materials] Bifidobacterium adolescentis SBT2786 strain (accession number: NITE BP-03102, date of deposit: January 14, 2020), depository address: 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, 292-0818, Japan, National Institute of Technology and Evaluation, Biotechnology Center, Patent Microorganism Deposit Center (NPMD).

Claims

1. A composition for reducing stress, characterized by containing Bifidobacterium adolescentis as an active ingredient.

2. The composition for reducing stress according to claim 1, wherein the Bifidobacterium adolescentis is Bifidobacterium adolescentis SBT2786 strain (NITE BP-03102).

3. A food or drink containing the stress-reducing composition according to claim 1 or 2.

4. A pharmaceutical comprising the stress-reducing composition according to claim 1 or 2.

5. A feed characterized by containing the stress-reducing composition according to claim 1 or 2.

6. A method for reducing stress, comprising administering Bifidobacterium adolescentis to a human.

7. A method of using Bifidobacterium adolescentis, characterized in that it is used for the purpose of reducing stress.

8. A composition comprising Bifidobacterium adolescentis for use in the treatment of stress reduction.

9. Non-therapeutic use of Bifidobacterium adolescentis for stress reduction.

10. Use of Bifidobacterium adolescentis in the manufacture of a therapeutic drug for stress reduction.

Images