Anti-stress composition

Abstract

To provide a composition for improving depressive symptoms that can be administered over a long period of time and has high safety. [Solution] A composition for improving depressive symptoms is provided, comprising Lactobacillus helveticus as an active ingredient. The Lactobacillus helveticus may be Lactobacillus helveticus NITE BP-01671. Furthermore, the composition may be a pharmaceutical composition or a food or beverage composition.

Description

[Technical Field]

[0001] This technology relates to an anti-stress composition containing Lactobacillus helveticus as an active ingredient. [Background technology]

[0002] In today's stressful society, people are exposed to various forms of stress due to changes in their living and working environments, complex interpersonal relationships, and physical and mental fatigue.

[0003] To alleviate such stress, various anti-stress agents have been developed. For example, agents that alleviate or prevent stress symptoms using oxidized and / or reduced coenzymes as active ingredients are known (Patent Document 1). [Prior art documents] [Patent Documents]

[0004] [Patent Document 1] Japanese Patent Publication No. 2010-030901 [Overview of the Initiative] [Problems that the invention aims to solve]

[0005] Since this type of stress can occur on a daily basis, it is preferable that anti-stress medications be able to be administered over a long period and have a high level of safety. Therefore, the main objective of this technology is to provide an anti-stress composition that can be administered over a long period of time and has high safety. [Means for solving the problem]

[0006] In recent years, the increasing complexity of social structures and interpersonal relationships due to acts of power harassment and sexual harassment by those in positions of power has led to increased stress on vulnerable individuals, creating a new social problem. While there is a need to alleviate this stress, sufficient knowledge is currently lacking.

[0007] Therefore, the inventors set up an animal model to evaluate the stress experienced by weaker individuals due to attacks from stronger individuals, and after diligent research, they found that administering Lactobacillus helveticus has an anti-stress effect, specifically an effect of reducing mental stress.

[0008] In other words, this technology is as follows: [1] An anti-stress composition containing Lactobacillus helveticus as the active ingredient. [2] The composition according to [1], wherein the stress is mental stress. [3] The composition according to [1] or [2] above, wherein the composition is used to treat or prevent anxiety disorders, social phobias, social impairment, or adjustment disorders. [4] The composition according to any one of [1] to [3], wherein the Lactobacillus helveticus is Lactobacillus helveticus NITE BP-01671. [5] The composition according to any one of [1] to [4] above, wherein the composition is a pharmaceutical composition or a food or beverage composition. [Effects of the Invention]

[0009] This technology makes it possible to provide an anti-stress composition that has few side effects, can be administered for a long period of time, and is highly safe. However, the effects of this technology are not necessarily limited to those described herein, and may include any of the effects described herein. [Modes for carrying out the invention]

[0010] Preferred embodiments of the present technology are described below. However, the present technology is not limited to the embodiments described below and can be freely modified within the scope of the present technology. In this specification, percentages are based on mass unless otherwise specified.

[0011] The present technology can provide a stress - relieving composition containing Lactobacillus helveticus as an active ingredient.

[0012] As the bacteria classified as Lactobacillus helveticus in the present technology, among the bacteria belonging to the genus Lactobacillus, any lactic acid bacterium belonging to the species Lactobacillus helveticus, which is classified as helveticus, can be used. Among them, it is preferable to use Lactobacillus helveticus NITE BP - 01671. Lactobacillus helveticus NITE BP - 01671 was deposited as Lactobacillus helveticus MCC1848 at the Patent Microorganisms Depositary, National Institute of Technology and Evaluation (Room 122, 2 - 5 - 8 Kazusa Kamashima, Kisarazu City, Chiba Prefecture 292 - 0818) on July 29, 2013 (Accession Number: NITE BP - 01671). This bacterium is generally available from the above - mentioned depository institution.

[0013] Lactobacillus helveticus NITE BP - 01671 is not limited to the above - deposited bacterium, and bacteria substantially equivalent to the deposited bacterium may also be used. Substantially equivalent bacteria are bacteria classified as Lactobacillus helveticus, the nucleotide sequence of whose 16S rRNA gene is 99.5% or more, preferably 100% identical to that of the deposited bacterium, or having the same mycological properties as the deposited bacterium, and also include strains substantially identical to the deposited strain (Japanese Patent Laid - Open No. 2015 - 047114). Regarding the strain, "a strain substantially equivalent to the above - deposited strain" means a strain belonging to the same species as the above - deposited strain and capable of obtaining the stress - relieving effect, which is the effect of the present technology. A strain substantially equivalent to the above - deposited strain may be, for example, a derivative strain having the deposited strain as a parent strain. Examples of derivative strains include strains bred from the deposited strain and strains naturally occurring from the deposited strain.

[0014] Examples of substantially identical strains and derivative strains include the following strains. (1) Strains determined to be the same strain as Lactobacillus helveticus NITE BP-01671 by the RAPD method (Randomly Amplified Polymorphic DNA) and the PFGE method (Pulsed-field gel electrophoresis) (as described on page 43 of Probiotics in food / Health and nutritional properties and guidelines for evaluation, page 85) (2) Strains that possess only genes derived from Lactobacillus helveticus NITE BP-01671, have no foreign genes, and have a DNA identity of 95% or more with Lactobacillus helveticus NITE BP-01671. (3) Strains bred from Lactobacillus helveticus NITE BP-01671 (including strains bred through genetic engineering, mutation, or spontaneous mutation) that possess the traits of NITE BP-01671

[0015] The Lactobacillus helveticus of this technology can be propagated, for example, by culture. The culture method is not particularly limited as long as the Lactobacillus helveticus of this technology can grow, and methods commonly used for culturing lactic acid bacteria can be used, modified as needed. For example, the culture temperature is preferably 25 to 45°C, 30 to 42°C, and particularly preferably 37 to 42°C. Furthermore, it is preferable to carry out the culture under anaerobic conditions, for example, by aerating with an anaerobic gas such as carbon dioxide. Alternatively, it may be cultured under microaerophilic conditions such as liquid static culture.

[0016] As a culture medium for growing Lactobacillus helveticus using this technology, for example, a culture medium commonly used for culturing lactic acid bacteria can be used, with appropriate modifications as needed. Specifically, as a carbon source, sugars such as galactose, glucose, fructose, mannose, cellobiose, maltose, lactose, sucrose, trehalose, starch, starch hydrolysate, and molasses can be used depending on their assimilation properties. As a nitrogen source, ammonium salts such as ammonia, ammonium sulfate, ammonium chloride, and ammonium nitrate, as well as nitrates, can be used. Inorganic salts such as sodium chloride, potassium chloride, potassium sulfate, magnesium sulfate, calcium chloride, calcium nitrate, manganese chloride, and ferrous sulfate can be used. Organic components such as peptone, soybean flour, defatted soybean meal, meat extract, and yeast extract may also be used. Furthermore, culture media commonly used for culturing Bifidobacterium bacteria include, specifically, reinforced Clostridial medium, MRS medium (de Man, Rogosa, and Sharpe medium), mMRS medium (modified MRS medium), TOSP medium (TOS propionate medium), and TOSP Mup medium (TOS propionate mupirocin medium).

[0017] In this technology, the Lactobacillus helveticus obtained after culturing may be used as is, diluted or concentrated, or the bacterial cells recovered from the culture may be used. In addition, various additional operations such as heating and freeze-drying can be performed after culturing, as long as the effectiveness of this technology is not impaired. The bacterial cells may be live or dead, but dead cells are preferred, and dead cells include those sterilized by heating or freeze-drying. Other methods for preparing dead bacterial cells include spray drying, retort sterilization, freeze-drying, UHT sterilization, pressure sterilization, high-pressure steam sterilization, dry heat sterilization, flow-through steam sterilization, electromagnetic wave sterilization, electron beam sterilization, high-frequency sterilization, radiation sterilization, ultraviolet sterilization, ethylene oxide gas sterilization, hydrogen peroxide gas plasma sterilization, and chemical sterilization (alcohol sterilization, formalin fixation, electrolytic water treatment). The bacterial cells may also be crushed. The crushed material may be made from crushed live bacteria or crushed dead bacteria, and may also be subjected to heating or freeze-drying after crushing.

[0018] The anti-stress composition of this technology is highly useful because its active ingredient is Lactobacillus helveticus, a type of lactic acid bacteria, resulting in excellent safety and minimal risk of side effects even with long-term, continuous administration. Furthermore, it is highly safe when used in combination with other compositions.

[0019] As shown in the examples described below, Lactobacillus helveticus in this technology has an anti-stress effect, specifically an effect of reducing mental stress, and more specifically an effect of reducing interpersonal stress (e.g., social defeat stress). Therefore, Lactobacillus helveticus in this technology can be used as an anti-stress composition. It can also be used in various applications such as pharmaceuticals and food and beverages, or it may be used as a material or formulation incorporated into these.

[0020] In this technology, "anti-stress" means improvement, prevention, delay, reversal of progression, or treatment of symptoms or diseases caused by stress. Furthermore, "anti-stress" in this technology also encompasses the prevention of diseases caused by stress. In this technology, "prevention" means preventing or delaying the onset of symptoms or diseases in the target population, or reducing the risk of developing symptoms or diseases in the target population. Furthermore, "stress" in this technology encompasses physical stress, chemical stress, mental stress, etc. In this technology, "stress" preferably refers to mental stress. In this technology, "mental stress" refers to a situation in which a person experiences mental stress due to a specific circumstances, resulting in the manifestation of mental, physical, and behavioral symptoms. Symptoms may include a depressed mood, anxiety, decreased motivation and concentration, and irritability, while physical symptoms may include headaches, dizziness, palpitations, and fatigue.

[0021] The anti-stress compositions of this technology are preferably used to prevent, reduce, or suppress stress caused by environmental changes or interpersonal relationships. Furthermore, the compositions of this technology can preferably be used to treat or prevent diseases caused by stress experienced over the medium to long term due to environmental changes, specifically anxiety disorders, social phobias, social decline, or adjustment disorders.

[0022] The anti-stress composition of this technology can be administered to patients suffering from stress-related disorders such as those described below. 1) Depression, anxiety disorders, social phobia, decreased social skills, and adjustment disorders resulting from chronic, long-term exposure of aggressive language and intimidating behavior by individuals of lower social status to individuals of higher social status. 2) Depression, anxiety disorders, social phobia, decreased social skills, and adjustment disorders resulting from being subjected to various forms of harassment, such as power harassment, sexual harassment, and moral harassment, over the medium to long term and on a chronic basis. 3) Depression, anxiety disorders, social phobia, decreased social skills, and adjustment disorders resulting from being subjected to bullying or harassment at school or work over the medium to long term or chronically. 4) Depression, anxiety disorders, social phobia, decreased social skills, and adjustment disorders resulting from an inability to adapt to environmental changes. 5) Anhedonia caused by the above-mentioned diseases. 6) Excessive thirst (due to thirst) and excessive eating caused by the above-mentioned diseases. 7) Depression, anxiety disorders, social phobia, social decline, and adjustment disorders resulting from social defeat stress, where individuals feel defeated due to attacks from stronger parties, but are unable to resolve or alleviate this feeling due to their social position in the workplace, home, or relationships with neighbors.

[0023] Furthermore, the anti-stress composition of this technology is preferably administered to the following subjects. 1) People with personalities that are prone to depression, such as being meticulous, serious, responsible, hardworking, having a strong sense of justice, being unable to refuse requests, disliking conflict with others, and constantly worrying about what others think. 2) People who are vulnerable to changes in their environment. 3) People who are highly sensitive to stress. 4) Individuals who feel defeated due to attacks from stronger parties, but whose current sense of defeat cannot be resolved or mitigated due to their social position in the workplace, family, or relationships with neighbors. In this technology, "the strong" preferably refers to someone who has a relatively higher social status or physical strength than the person experiencing stress. Also, in this technology, "feeling of defeat" refers to feeling powerless, or believing that one has no ability or value.

[0024] The amount of Lactobacillus helveticus contained in or used in this technology can be freely determined according to age, symptoms, etc., as long as it does not impair the efficacy of this technology. In this technology, the amount of Lactobacillus helveticus used is 2 × 10 4 CFU / kg body weight / day or more, or 2 x 10 4 It is preferable to have cells / kg body weight / day or more. Note that "CFU" represents "colony forming unit" and "cells" represents the number of cells (including dead cells).

[0025] The interval between administrations or ingestions of Lactobacillus helveticus in this technology is not particularly limited; it may be once a day or divided into multiple doses. Furthermore, it is desirable to use this technology continuously every day (i.e., administer or ingeste). Since Lactobacillus helveticus used in this technology is empirically considered highly safe, it can be ingested continuously for a long period.

[0026] <Pharmaceutical composition> This technology can provide a pharmaceutical composition containing Lactobacillus helveticus as the active ingredient. This pharmaceutical composition can be applied to the prevention, reduction, or suppression of stress. Specifically, it can be used as an anti-stress drug, etc.

[0027] The pharmaceutical composition of this technology is not particularly limited as long as it contains Lactobacillus helveticus. The pharmaceutical composition of this technology may use Lactobacillus helveticus as is, or it may be formulated by incorporating a physiologically acceptable liquid or solid pharmaceutical carrier.

[0028] The pharmaceutical composition of this technology may be for oral administration. Because Lactobacillus helveticus of this technology is unlikely to cause side effects even with long-term, continuous administration, it can be administered with confidence.

[0029] The dosage form of the pharmaceutical composition of this technology is not particularly limited, but for oral administration, it can be formulated as a solid preparation such as powders, granules, tablets, lozenges, and capsules; or as a liquid preparation such as a solution, syrup, suspension, or emulsion. For parenteral administration, it can be formulated as a suppository, spray, inhalant, ointment, patch, or injection. In addition, when formulating, additives such as excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents, diluents, surfactants, or solvents for injections that are commonly used as formulation carriers can be used. These components may be appropriately selected by those skilled in the art depending on the dosage form.

[0030] The content of Lactobacillus helveticus of the present technology in the pharmaceutical composition of the present technology may be appropriately set according to dosage form, usage, patient's age, sex, disease type, disease degree, and other conditions. The content of Lactobacillus helveticus of the present technology in the pharmaceutical composition of the present technology is usually 1×10 6 ~1×10 12 CFU / g or 1×10 6 ~1×10 12 CFU / mL, or 1×10 6 ~1×10 12 cells / g or 1×10 6 ~1×10 12 cells / mL, and it is preferably within this range. When the Lactobacillus helveticus of the present technology is a dead bacterium, CFU / g or CFU / mL can be replaced with cells / g or cells / mL.

[0031] The administration time of the pharmaceutical composition of the present technology can be appropriately selected according to the treatment method of the target symptom or disease. Also, the pharmaceutical composition of the present technology may be administered prophylactically or may be used in maintenance therapy. The pharmaceutical composition of the present technology may be administered once a day or may be administered in multiple divided doses per day. Also, the pharmaceutical composition of the present technology may be administered once every few days or weeks.

[0032] <Food and beverage composition> The present technology can also provide a food and beverage composition containing Lactobacillus helveticus as an active ingredient. The food and beverage composition of the present technology can be applied to the use of preventing, reducing, or suppressing stress. Specifically, it is a health food, functional food, etc. with the concept of use such as for anti-stress.

[0033] The food and beverage composition of this technology is not particularly limited as long as it contains Lactobacillus helveticus. Examples of food and beverage compositions include beverages such as soft drinks, carbonated drinks, nutritional drinks, fruit juices, and lactic acid bacteria drinks (including concentrated stocks and powders for preparation of these beverages); frozen desserts such as ice cream, sherbet, and shaved ice; confectionery such as candy, chewing gum, chocolate, tablets, snacks, biscuits, jelly, jam, cream, and baked goods; dairy products such as processed milk, milk beverages, fermented milk, drinkable yogurt, and butter; bread; enteral nutrition foods, liquid foods such as porridge, baby food, infant formula, sports drinks; and other functional foods. Furthermore, the food and beverage composition of this technology may also be a supplement, for example, a tablet-shaped supplement. If it is a supplement, Lactobacillus helveticus of this technology can be ingested without being affected by other foods in terms of daily food intake and calorie intake. Other commercially available foods include, for example, baby food, furikake (rice seasoning), and tea-soaked seaweed. Food and beverage compositions produced using this technology can be manufactured by adding these microorganisms to the raw materials of ordinary food and beverages, and can be manufactured in the same manner as ordinary food and beverages except for the addition of these microorganisms. The addition of these microorganisms may be carried out at any stage in the manufacturing process of the food and beverage composition. Alternatively, the food and beverage composition may be manufactured through a fermentation process using the added microorganisms. Examples of such food and beverage compositions include lactic acid bacteria beverages and fermented milk.

[0034] Furthermore, the food and beverage compositions of this technology may use known or future-discovered ingredients that have probiotic effects or ingredients that support probiotic effects, as long as they do not impair the effects of this technology. Here, generally speaking, probiotics refer to bacteria that perform beneficial functions in the intestines. On the other hand, prebiotics are substances that serve as a selective nutrient source for bacteria that perform beneficial functions in the intestines and promote their growth. For example, the food and beverage compositions of this technology can be manufactured by combining the bacterial cells with various proteins or mixtures thereof, such as whey protein, casein protein, soy protein, or pea protein (pea protein); amino acids such as leucine, valine, isoleucine, or glutamine; vitamins such as vitamin B6 or vitamin C; creatine; citric acid; fish oil; or prebiotics such as oligosaccharides, including isomaltoligosaccharide, galactooligosaccharide, xylooligosaccharide, soy oligosaccharide, fructooligosaccharide, lactulose, and human milk oligosaccharide (HMO). The human milk oligosaccharides that can be used with this technology include 2'-fucosyl lactose, 3-fucosyl lactose, 2',3-difucosyl lactose, lacto-N-triose II, lacto-N-tetraose, lacto-N-neotetraose, lacto-N-fucopentaose I, lacto-N-neofucopentaose, lacto-N-fucopentaose II, lacto-N-fucopentaose III, lacto-N-fucopentaose V, and lacto-N-neofuco Neutral human milk oligosaccharides such as pentaose V, lacto-N-difucohexaose I, lacto-N-difucohexaose II, 6'-galactosyl lactose, 3'-galactosyl lactose, lacto-N-hexaose, and lacto-N-neohexaose, and acidic human milk oligosaccharides such as 3'-sialyl lactose, 6'-sialyl lactose, 3-fucosyl-3'-sialyl lactose, and disialyl-lacto-N-tetraose can be used.

[0035] Food and beverages defined in this technology can also be provided and sold as food and beverages with health claims. The act of "displaying" includes all acts that make consumers aware of the aforementioned uses, and any expression that can evoke or infer the aforementioned uses, regardless of the purpose of the display, the content of the display, or the object or medium to which it is displayed, all of these constitute an act of "displaying" the technology.

[0036] Furthermore, it is preferable that the "display" be made in a way that allows consumers to directly recognize the above-mentioned use. Specifically, this includes acts such as transferring, delivering, displaying for transfer or delivery, or importing food and beverage products or product packaging on which the above-mentioned use is described; displaying or distributing advertisements, price lists, or transaction documents related to products on which the above-mentioned use is described; or providing information containing such information on an electronic (internet, etc.) basis.

[0037] On the other hand, the content of the display is preferably a display approved by the government or other administrative body (for example, a display approved based on various systems established by the government and made in accordance with such approval). Furthermore, it is preferable to attach such display content to packaging, containers, catalogs, brochures, point-of-sale (POP) displays and other promotional materials used at sales sites, and other documents.

[0038] Furthermore, "labeling" also includes labels for health foods, functional foods, enteral nutrition foods, foods for special dietary uses, health functional foods, foods for specified health uses, nutrient function foods, foods with functional claims, quasi-drugs, etc. In particular, labels approved by the Consumer Affairs Agency include, for example, labels approved under the systems for foods for specified health uses, foods with nutrient function, or foods with functional claims, or similar systems. Specifically, these include labels for foods for specified health uses, labels for conditionally specified health uses, labels that affect the structure or function of the body, labels that reduce disease risk, and labels that show scientifically based functionality. More specifically, typical examples include labels for foods for specified health uses (especially labels for health uses) and similar labels as defined in the Cabinet Office Ordinance concerning the permission of special use labeling, etc., as stipulated in the Health Promotion Act (Cabinet Office Ordinance No. 57 of August 31, 2009).

[0039] Furthermore, the wording used to make the above-mentioned displays is not limited to phrases such as "treatment and / or prevention of stress." It goes without saying that any other wording that expresses the effect of treating and / or preventing various diseases and symptoms related to the treatment and / or prevention of stress is also included within the scope of this technology. For example, such wording could include "For those who are tired from work," "For those who are experiencing work-related stress," or "For those who are troubled by interpersonal relationships," and other displays based on various purposes that make consumers aware of the anti-stress effect.

[0040] The content of Lactobacillus helveticus in the food and beverage composition of this technology is set appropriately depending on the form of the food and beverage composition, but usually, 1 × 10⁻⁶ is contained in the food and beverage. 6 ~1 × 10 12 CFU / g or 1x10 6 ~1 × 10 12 CFU / mL, or 1 × 10 6 ~1 × 10 12 cells / g or 1 × 10 6 ~1 × 10 12 It is preferable that the cells / mL range is within the specified range.

[0041] The food and beverage composition of this technology can be manufactured by adding Lactobacillus helveticus of this technology to the raw materials of the food and beverage composition. The food and beverage composition of this technology can be manufactured by the same method as ordinary food and beverage compositions, except that it includes the step of adding Lactobacillus helveticus of this technology. As ingredients for food or beverages, ingredients commonly used in beverages and foods may be used. Furthermore, Lactobacillus helveticus, as used in this technology, can be used in combination with other lactic acid bacteria, such as those used in food and beverages, depending on the purpose. The food and beverage compositions of this technology include raw materials for manufacturing food and beverage compositions, as well as food additives and other materials that are added to food and beverages during or after the manufacturing process of the food and beverage compositions. In the production of food and beverage compositions using this technology, the addition of Lactobacillus helveticus using this technology may be carried out at any stage of the food and beverage composition production process. For example, Lactobacillus helveticus using this technology may be added in the process in which lactic acid bacteria are generally added.

[0042] The food and beverage compositions of this technology include powdered milk, and can be used in particular for infant formula and maternity formula for pregnant and breastfeeding mothers. Infant formula refers to infant formula for infants aged 0-12 months, follow-up formula for infants aged 6-9 months and older and young children (up to 3 years old), infant formula for newborns weighing less than 2500g at birth (low birth weight infants), and various therapeutic formulas used to treat children with pathological conditions such as milk allergy or lactose intolerance. Furthermore, this composition can be applied to health functional foods and foods for sick people. The health functional food system was established based on domestic and international trends and consistency with the conventional system for specified health foods, and targets not only regular foods but also foods in the form of tablets, capsules, etc., and consists of two types: specified health foods (individually approved type) and nutrient function foods (standard type).

[0043] Examples of food and beverage products related to this technology include formula milk (prepared milk powder) and nutritional supplements for mothers during pregnancy and lactation. Formula milk refers to milk and other products that contain a balanced blend of nutrients necessary during pregnancy and lactation.

[0044] The prepared milk powder of this technology may, specifically, be, for example, an anti-stress milk powder. An anti-stress milk powder can be manufactured, for example, by the following method.

[0045] In other words, this technology provides a method for producing anti-stress milk powder, comprising the following steps (A) to (C): (A) A step of culturing Lactobacillus helveticus bacteria in a culture medium containing milk components to obtain a culture; (B) A step of subjecting the culture to spray drying and / or freeze-drying to obtain a bacterial cell powder; (C) A step of mixing the bacterial cell powder with prebiotics to obtain a milk powder for stress relief. Here, milk components may be mixed simultaneously with step (C), before step (C), or after step (C).

[0046] Furthermore, this technology provides a method for producing anti-stress powdered milk, which includes the following step (A): (A) a step of mixing prebiotics, Lactobacillus helveticus bacteria, and milk components to obtain powdered milk.

[0047] Examples of the milk components include cow's milk, buffalo milk, sheep's milk, goat's milk, mare's milk, skim milk, skim condensed milk, skim milk powder, condensed milk, whole milk powder, cream, butter, buttermilk, condensed milk, and milk proteins. Examples of milk proteins include whey, casein, and their hydrolysates. These hydrolysates can be produced by hydrolyzing whey, casein, etc., with acid, alkali, or enzymes (e.g., proteolytic enzymes).

[0048] Furthermore, the food composition of this technology may specifically be, for example, an anti-stress supplement. An anti-stress supplement can be manufactured, for example, by the following method.

[0049] In other words, this technology provides a method for producing an anti-stress supplement, comprising the following steps (A) and (B): (A) A step of mixing Lactobacillus helveticus bacteria and excipients to obtain a mixture; (B) Step of compressing the mixture into tablets.

[0050] In any of the above manufacturing methods, other components besides those mentioned in the above steps may be used in combination as appropriate.

[0051] Furthermore, this technology can also employ the following configuration. [1] This technology provides an anti-stress composition containing Lactobacillus helveticus as the active ingredient. [2] A method for preventing, reducing, or suppressing stress by administering or ingesting Lactobacillus helveticus, as described in this technology. [3] Lactobacillus helveticus, or its use, for the prevention, reduction, or suppression of stress. [4] Use of Lactobacillus helveticus for the manufacture of anti-stress compositions. [5] The use of Lactobacillus helveticus in stress relievers, stress-relieving medicines, or stress-relieving foods and beverages. [6] A method of stress relief, comprising administering or ingesting Lactobacillus helveticus. [7] A method of stress relief, comprising administering Lactobacillus helveticus to a person with high susceptibility to stress. [8] The use of Lactobacillus helveticus for the treatment or prevention of anxiety disorders, social phobias, social impairment, or adjustment disorders occurring under stress. [9] A method for treating or preventing anxiety disorders, social phobias, social impairment, or adjustment disorders occurring under stress, by administering or ingesting Lactobacillus helveticus.

[10] Preferably, in any one of the above [1] to [9], the stress is mental stress.

[11] Preferably, in any one of the above [1] to

[10] , the Lactobacillus helveticus is Lactobacillus helveticus NITE BP-01671.

[12] Preferably, any one of the above [1] to

[11] is for pharmaceutical use or for food and beverage use.

[13] A method for producing an anti-stress composition, comprising the following steps (A) to (C): (A) A step of culturing Lactobacillus helveticus in a culture medium containing milk components to obtain a culture; (B) A step of subjecting the culture to spray drying and / or freeze-drying to obtain a bacterial cell powder; (C) A step of mixing the bacterial cell powder with prebiotics to obtain an anti-stress composition.

[14] A method for producing an anti-stress composition, comprising the following step (A): (A) A step of mixing prebiotics, Lactobacillus helveticus bacteria and milk components to obtain an anti-stress composition.

[15] The method according to

[13] or

[14] , wherein the milk component is milk protein.

[16] The method according to

[15] , wherein the milk protein is at least one component selected from the group consisting of whey, whey hydrolysate, and casein.

[17] A method for manufacturing an anti-stress supplement, comprising the following steps (A) and (B): (A) A step of mixing bacteria of the genus Lactobacillus helveticus and an excipient to obtain a mixture; (B) Step of compressing the mixture into tablets. [Examples]

[0052] The present technology will be described in more detail below based on the following examples. The examples described below are representative examples of the present technology and should not be interpreted as narrowing the scope of the present technology.

[0053] [Experimental Example 1] (1) Experimental method In this experiment, smaller mice were subjected to repeated bites by larger mice to induce social defeat. The effects of Lactobacillus helveticus on behavioral changes (decreased avoidance behavior, lethargy) caused by social defeat stress were then investigated.

[0054] In this experiment, C57BL / 6J mice were used as mice subjected to social defeat stress. Male and female ICR mice that had been living together for more than three weeks were kept in a cage with only the male parent mice, and the C57BL / 6J mice were placed in the cage. The time it took for the C57BL / 6J mice to be bitten 20 times by the male parent mice (escape time) was measured. An increase in escape time indicated that the C57BL / 6J mice were trying to escape from the ICR mice, and therefore it was judged that the social defeat stress was reduced.

[0055] From two days before the start of social defeat stress until the end of the behavioral test, experiments were conducted on mice administered milnacipran (Toledomin tablets: Janssen Pharma) (positive control), mice given nothing (medium control), and mice orally administered live Lactobacillus helveticus NITE BP-01671 once daily via a tube needle.

[0056] (2) Experimental results The results of this experiment are shown in Table 1 below.

[0057] [Table 1]

[0058] As shown in Table 1, in the control group, escape time decreased to approximately 17 seconds from day 4 onward due to social defeat stress. However, in mice administered milnacipran, escape time was significantly increased compared to the control group. Furthermore, mice administered Lactobacillus helveticus NITE BP-01671 showed similar behavior to those administered milnacipran. Therefore, it was found that ingesting Lactobacillus helveticus NITE BP-01671 has an effect of reducing social defeat stress.

[0059] [Experimental Example 2] (1) Experimental method In this experiment, smaller mice were subjected to repeated chronic social defeats by being attacked daily by larger mice. The effect of Lactobacillus helveticus on behavioral changes (anorexia) resulting from multiple exposures to social defeat stress was investigated.

[0060] In this experiment, C57BL / 6J mice were used as social defeat stress-inducing mice, and dead Lactobacillus helveticus NITE BP-01671 cells were administered from two days before the start of social defeat stress until the end of the behavioral test. Lactobacillus helveticus NITE BP-01671 was cultured in MRS medium at 37°C for 16 hours using a liquid static culture method. After collecting the cells by centrifugation, dead cells were obtained by suspending them in physiological saline and heating at 90°C for 30 minutes. The dead cells were administered to the mice by mixing them into the mouse feed (AIN-93G). C57BL / 6J mice were placed in the territory of ICR mice and made to fight for 5 minutes. After that, both mice were moved to an SD cage (M cage manufactured by Natsume Seisakusho) with a partition plate installed, and kept in the same cage for 24 hours. This rearing was continued for 9 days. Two days later, one bottle each of distilled water and 1% sucrose water was placed in the mouse cages, and the amount of water consumed by each mouse until the following day was measured. The ratio of 1% sucrose water intake to normal water intake (hereinafter referred to as the sucrose water intake rate) was calculated. Mice have a natural preference for sucrose water, but mice subjected to social defeat stress lose their pleasure and no longer prefer sweet water. Therefore, if the decrease in the sucrose water intake rate was suppressed, it was assumed that the loss of pleasure was mitigated, and thus the social defeat stress was judged to have been reduced.

[0061] (2) Experimental results The results of this experiment are shown in Table 2 below.

[0062] [Table 2]

[0063] As shown in Table 2, the positive control group, which was subjected to stress, showed a decrease in sucrose water intake compared to the negative control group, which was not subjected to stress. On the other hand, the group administered Lactobacillus helveticus NITE BP-01671 showed a suppressed decrease in sucrose water intake compared to the positive control group. Therefore, it was found that ingestion of dead Lactobacillus helveticus NITE BP-01671 has an effect of reducing social defeat stress.

[0064] [Experimental Example 3] (1) Experimental method In this experiment, smaller mice were subjected to repeated chronic social defeats by being attacked daily by larger mice. The effects of Lactobacillus helveticus on behavioral changes (loss of sociality) resulting from multiple exposures to social defeat stress were investigated.

[0065] In this experiment, C57BL / 6J mice were used as social defeat stress-inducing mice, and dead Lactobacillus helveticus NITE BP-01671 cells were administered from two days before the start of social defeat stress until the end of the behavioral test. The same dead cells used in [Experimental Example 2] were used. The dead cells were administered to the mice by mixing them with the mouse feed (AIN-93G). C57BL / 6J mice were placed in the territory of ICR mice and made to fight for 5 minutes. After that, both mice were moved to an SD cage (M cage manufactured by Natsume Seisakusho) with a partition plate installed, and kept in the same cage for 24 hours. This rearing was continued for 9 days. Two days later, C57BL / 6J mice were placed in the cage of the ICR mice, and their social behavior was examined based on the degree of contact. An interaction zone (a 10cm wide area surrounding the area where the ICR mice were located) was pre-defined around the area where the ICR mice were present. Changes in the social behavior of C57BL / 6J mice were measured by measuring the time the mice spent in this interaction zone. The time spent in the interaction zone was analyzed using a CCD camera with an automated tracing system (Time OFCR1 software; O'Hara & Co., Tokyo, Japan).

[0066] (2) Experimental results The results of this experiment are shown in Table 3 below. The values ​​shown in the table were obtained using the following formula. 100 × [Time spent in the interaction zone (with ICR mouse)] / [Time spent outside the interaction zone (without ICR mouse)]

[0067] [Table 3]

[0068] As shown in Table 3, the positive control group, which was subjected to stress, spent less time in the interaction zone compared to the negative control group, which was not subjected to stress. In other words, their social behavior was reduced. On the other hand, the group administered Lactobacillus helveticus NITE BP-01671 spent more time in the interaction zone compared to the positive control group. In other words, the decline in social behavior was suppressed. Therefore, it was found that ingesting dead Lactobacillus helveticus NITE BP-01671 has the effect of reducing social defeat stress.

[0069] [Production Example 1: Fermented Milk] 1000 mL of 10% (W / W) reduced skim milk powder medium, obtained by dissolving 10% (W / W) reduced skim milk powder (manufactured by Morinaga Milk Industry Co., Ltd.) in water, was sterilized at 90°C for 30 minutes, 30 mL of Lactobacillus helveticus NITE BP-01671 seed culture was inoculated, and the medium was cultured at 37°C for 16 hours. Separately, 50 L of a base consisting of 3.0% (W / W) milk fat and 9.0% (W / W) non-fat milk solids is heated to 70°C, homogenized under a pressure of 15 MPa, then sterilized at 90°C for 10 minutes and cooled to 40°C. 500 mL of Lactobacillus helveticus NITE BP-01671 culture, pre-cultured as described above, is inoculated into the sterilized base, filled into a 500 mL resin container, sealed, cultured at 37°C for 7 hours, and then immediately cooled to obtain an anti-stress composition (fermented milk) containing Lactobacillus helveticus NITE BP-01671. This fermented milk contains Lactobacillus helveticus with a daily intake of 2 × 10⁶ 4 By consuming a CFU / kg body weight / day or more, an anti-stress effect can be expected.

[0070] [Manufacturing Example 2: Powder Formulation] A reduced skim milk powder medium (containing 13% skim milk powder and 0.5% yeast extract by weight) is sterilized at 95°C for 30 minutes, then Lactobacillus helveticus NITE BP-01671 seed culture is inoculated, and the culture is incubated at 37°C for 16 hours. The resulting culture is freeze-dried to obtain a powder formulation of Lactobacillus helveticus NITE BP-01671 culture. This powder formulation allows for a daily dose of Lactobacillus helveticus of 2 × 10⁶ days. 4 By administering the drug at a rate of CFU / kg body weight / day or higher, an anti-stress effect can be expected.

[0071] [Manufacturing Example 3: Prepared Milk Powder] 10 kg of desalted milk whey protein powder (Mirai Co., Ltd.), 6 kg of milk casein powder (Fonterra Co., Ltd.), 48 kg of lactose (Mirai Co., Ltd.), 920 g of mineral mixture (Tomita Pharmaceutical Co., Ltd.), 32 g of vitamin mixture (Tanabe Pharmaceutical Co., Ltd.), 500 g of lactulose (Morinaga Milk Industry Co., Ltd.), 500 g of raffinose (Nippon Beet Sugar Manufacturing Co., Ltd.), and 900 g of galactooligosaccharide liquid sugar (Yakult Pharmaceutical Industry Co., Ltd.) were dissolved in 300 kg of warm water, and then heated and dissolved at 90°C for 10 minutes. 28 kg of prepared fat (Taiyo Oil Co., Ltd.) was added and homogenized. After that, sterilization and concentration processes were carried out and spray-dried to prepare approximately 95 kg of prepared milk powder. To this, Lactobacillus helveticus NITE BP-01671 cell powder (1.8 × 10) was added, which was dispersed in starch. 11 Add 100g of (cfu / g, manufactured by Morinaga Milk Industry Co., Ltd.) to prepare approximately 95kg of Bifidobacterium and oligosaccharide-containing formula milk powder. When the prepared formula milk is dissolved in water to make a formula solution with a total solids content of 14% (w / V), which is the standard formula concentration, the number of Bifidobacterium in the formula solution is 2.7 × 10⁶. 9 A cfu / 100mL can be obtained. By administering the modified milk powder obtained as described above, an anti-stress effect can be expected. [Industrial applicability]

[0072] Because the anti-stress composition of this technology contains Lactobacillus helveticus as its active ingredient, it is highly safe and has few side effects even when administered or ingested continuously for a long period of time, making it extremely useful. [Accession Number]

[0073] (1) Lactobacillus helveticus NITE BP-01671 (Accession number: NITE BP-01671, Date of accession: July 29, 2013), Deposited at: National Institute of Technology and Evaluation Patent Microorganism Depositary Center (NPMD), 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan 292-0818, Japan.

Claims

1. A composition for improving depressive symptoms, containing Lactobacillus helveticus NITE BP-01671 as the active ingredient.

2. The composition for improving depressive symptoms according to claim 1, wherein the composition is a pharmaceutical composition or a food or beverage composition.

3. A method for preventing, reducing, or suppressing depressive symptoms (excluding medical procedures performed on humans) that includes administering or ingesting Lactobacillus helveticus NITE BP-01671.

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