JP2023051312A - Proliferation promoter of short chain fatty acid producing bacteria in bowel, prophylactic agent or relaxant of digestive organ or respiratory infection, intensifier of bowel barrier function, and inhibitor of proliferation or growth of pathogen - Google Patents

Abstract

To provide a component capable of effectively proliferating and safely ingesting short-chained fatty acid productive bacteria such as butyric acid bacterium or acetic acid bacteria living in a bowel.SOLUTION: The present invention provides an agent for promoting proliferation of short-chain fatty acid-producing bacteria in the intestine, containing barley green leaves as an active ingredient. The present invention effectively proliferates short-chain fatty acid-producing bacteria in the intestine and contributes to the prevention or alleviation of respiratory or digestive tract infections, the intestinal barrier function enhancer, and the suppression of the proliferation or growth of pathogens. In addition, the agent of the present invention can be used as an agent for inhibiting the proliferation of spoilage product-producing bacteria.SELECTED DRAWING: None

Description

TECHNICAL FIELD The present invention relates to an agent for promoting the growth of short-chain fatty acid-producing bacteria in the intestinal tract, an agent for preventing or alleviating digestive or respiratory infections, an agent for enhancing intestinal barrier function, and an agent for suppressing the growth or development of pathogens.

Short-chain fatty acids such as butyric acid and acetic acid are known to keep the intestinal tract acidic, promote intestinal peristalsis and secretion of water from the intestinal tract, and contribute to defense against infection. For example, butyric acid is known to be a very important nutrient that provides energy to colonic mucosal epithelial cells. It is a cellular mediator that regulates various functions not only in the intestine.
The intestinal tract has an intestinal barrier function to properly eliminate unnecessary substances such as pathogenic bacteria while absorbing ingested food. Intestinal barrier functions include physical barriers such as tight junctions, environmental barriers such as intestinal bacteria, and biological barriers such as antimicrobial peptides and immune cells. Butyric acid is important for maintaining the normal functions of the large intestine as a major energy source for the large intestine mucosal epithelium. It is thought to suppress the growth of pathogenic bacteria. In addition, butyric acid enhances tight junctions, promotes differentiation of regulatory T cells, and contributes to maintenance of intestinal barrier function. It is also known that acetic acid produced in the intestinal tract has an inhibitory effect on Escherichia coli infection (Non-Patent Document 1).
In recent years, due to the spread of infections such as the new coronavirus, short-chain fatty acid-producing bacteria such as butyric acid-producing bacteria (hereinafter also referred to as "butyric acid bacteria") have been used as an immune mechanism that contributes to the prevention and improvement of respiratory and digestive infections. There is an increasing amount of research on
Butyric acid bacteria are highly sensitive bacteria to oxidative stress that are ubiquitous in the healthy human intestinal flora and produce butyric acid as the end product of anaerobic bacterial fermentation of dietary fiber. A decrease in butyric acid bacteria in the intestinal tract is thought to lead to an increased risk of infection and aggravation of the novel coronavirus (Non-Patent Documents 2-4). Butyric acid is an important protective molecule against inflammation, and is thought to reduce intestinal dysbiosis due to viral infection and the like (Non-Patent Document 2). In addition, the composition of the intestinal flora of patients with novel coronavirus shows changes that are dependent on the novel coronavirus. (Non-Patent Document 3). It is also known that humans suffering from respiratory infections have fewer major butyric bacteria, Faecalibacterium prausnitzii and Roseburia intestinalis, than humans not suffering from them (Non-Patent Document 4). Butyric acid activates antigen-specific CD8-positive T cells, and is found to enhance antiviral ability, suppress mortality, and alleviate symptoms caused by infection (Non-Patent Document 5). Furthermore, it is said that the risk of developing a viral respiratory infection that causes symptoms such as a runny nose and sore throat is five times higher when there is less butyric acid bacteria in the intestine than when there is more (Non-Patent Documents 6 and 7). ).

Furthermore, it is considered that the growth of short-chain fatty acid-producing bacteria such as butyric acid bacteria and acetic acid bacteria is related to oral immune function and an increase in secretory immunoglobulin A (Non-Patent Documents 8 and 9).

In addition, it is known that suppressing the growth of indole-producing bacteria has advantages such as improvement of the intestinal environment and enhancement of the intestinal barrier function.

On the other hand, barley green leaves are known to have various physiological activities such as active oxygen scavenging action (Patent Document 1).

Japanese Patent Application Laid-Open No. 2006-321735

Japanese Journal of Food Microbiology, Jpn. J. Food Microbiol.,36(1) p32-35, 2019 "New Insights Into the Physiopathology of COVID-19: SARS-CoV-2-Associated Gastrointestinal Illness," Frontiers in Medicine 2021 vol.8 Published online 2021 Feb 18, https://www.frontiersin.org/articles/10.3389/fmed. 2021.640073/full, retrieved on August 3, 2021 “Analysis of the intestinal microbiota in COVID-19 patients and its correlation with the inflammatory factor IL-18. Med Microecol. (2020) Vol.5”, https://www.researchgate.net/publication/347130206_Analysis_of_the_intestinal_microbiota_in_COVID-19_patients_and_its_correlation_with_the_inflammatory_factor_IL-18 /fulltext/5fddbd7e299bf1408822c631/Analysis-of-the-intestinal-microbiota-in-COVID-19-patients-and-its-correlation-with-the-inflammatory-factor-IL-18.pdf?origin=publication_detail, 20218 3rd day of the month search 2020;159(3):944-955. 2018;48(5):992-1005. Care Post Seven, https://www.news-postseven.com/kaigo/79333, retrieved August 3, 2021 Blood. 2018;131(26):2978-2986. Gut Microbial Metabolites Fuel Host Antibody Responses, Cell Host Microbe. 2016 Aug 10; 20(2): 202-214. Published online 2016 Jul 28, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982788 / , retrieved September 19, 2021 The Salivary IgA Flow Rate Is Increased by High Concentrations of Short-Chain Fatty Acids in the Cecum of Rats Ingesting Fructooligosaccharides, Nutrients 2016, 8(8), 500, Published: 17 August 2016 , https://www.mdpi.com/ 2072-6643/8/8/500, Retrieved September 19, 2021

From the above, from the viewpoint of preventing or alleviating infectious diseases, enhancing intestinal barrier function, and suppressing the growth or growth of pathogens, short-chain fatty acid-producing bacteria such as butyric acid bacteria and acetic acid bacteria living in the intestine can be effectively propagated. Ingredients that can be safely ingested are desired.
In addition, there is a demand for a component that can effectively suppress the growth of spoilage product-producing bacteria such as indole and that can be safely ingested.

In the course of researching the functions of barley green leaves, the present inventors found that barley green leaves can effectively propagate butyric bacteria such as Roseburia, Faecalibacterium, and Coprococcus, and acetic acid bacteria such as Paraprevotella in the intestines of mammals such as humans. They have found that they can contribute to the prevention or alleviation of infectious diseases such as respiratory infections, the enhancement of the intestinal barrier function, and the suppression of the proliferation or development of pathogens, leading to the completion of the present invention. The present inventors also found that barley green leaves can effectively inhibit the growth of an indole-producing fungus, Anaerotruncus, leading to a decrease in the production of intestinal spoilage products.

That is, the present invention is as follows.
[1] An agent for promoting the growth of short-chain fatty acid-producing bacteria in the intestine, characterized by containing barley green leaves.
[2] The agent according to [1], wherein the short-chain fatty acid-producing bacterium contains at least one selected from butyric acid bacteria and acetic acid bacteria.
[3] An agent for promoting the growth of butyric acid bacteria in the intestine, characterized by containing barley green leaves.
[4] The agent according to [3], wherein the butyric acid bacterium contains at least one selected from bacteria belonging to the genus Coprococcus, bacteria belonging to the genus Anaerostipes, bacteria belonging to the genus Roseburia, and bacteria belonging to the genus Faecalibacterium.
[5] A growth-promoting agent for acetic acid bacteria in the intestine, characterized by containing barley green leaves.
[6] The agent according to [5], wherein the acetic acid bacteria include bacteria belonging to the genus Paraprevotella.
[7] An agent for preventing or alleviating gastrointestinal infections, characterized by containing barley green leaves.
[8] An agent for preventing or alleviating respiratory infections, characterized by containing barley green leaves.
[9] An agent for preventing or alleviating viral respiratory or gastrointestinal infections, characterized by containing barley green leaves.
[10] An intestinal barrier function enhancer, characterized by containing barley green leaves.
[11] A pathogen growth or development inhibitor, characterized by containing barley green leaves.
[12] A growth inhibitor for spoilage product-producing bacteria, characterized by containing barley green leaves.
[13] The agent according to [12], wherein the spoilage product-producing bacteria include indole-producing bacteria.
[14] A growth inhibitor for indole-producing bacteria, characterized by containing barley green leaves.
[15] The agent according to [14], wherein the indole-producing bacteria include bacteria belonging to the genus Anaerotruncus.
[16] A composition used for assisting the growth of short-chain fatty acid-producing bacteria in the intestine, characterized by containing barley green leaves.
[17] A composition used for assisting the growth of butyric acid bacteria in the intestine, characterized by containing barley green leaves.
[18] A composition used for assisting the growth of acetic acid bacteria in the intestine, characterized by containing barley green leaves.
[19] A composition used to help prevent or alleviate gastrointestinal infections, characterized by containing barley green leaves.
[20] A composition used to help prevent or alleviate respiratory infections, characterized by containing barley green leaves.
[21] A composition used to help prevent or alleviate viral respiratory or gastrointestinal infections, characterized in that it contains barley green leaves.
[22] A composition used to help enhance intestinal barrier function, characterized by containing barley green leaves.
[23] A composition used to help suppress the growth or development of pathogens, characterized by containing barley green leaves.
[24] A composition used to help inhibit the growth of spoilage product-producing fungi, characterized by containing barley green leaves.
[25] A composition used to help inhibit growth of indole-producing bacteria, characterized by containing barley green leaves.
[26] A composition characterized by containing barley green leaves and labeled as useful for the growth of short-chain fatty acid-producing bacteria in the intestine.
[27] A composition characterized by containing barley green leaves and labeled as useful for the growth of butyric acid bacteria in the intestine.
[28] A composition characterized by containing barley green leaves and labeled as useful for the growth of acetic acid bacteria in the intestine.
[29] A composition characterized by containing barley green leaves and labeled as being useful for preventing or alleviating digestive tract infections.
[30] A composition comprising green barley leaves and labeled as useful for preventing or alleviating respiratory infections.
[31] A composition comprising green barley leaves and labeled as useful for preventing or alleviating viral respiratory or gastrointestinal infections.
[32] A composition characterized by containing barley green leaves and labeled as useful for enhancing intestinal barrier function.
[33] A composition characterized by containing barley green leaves and labeled as being useful for suppressing the growth or growth of pathogens.
[34] A composition characterized by containing barley green leaves and labeling that it is useful for inhibiting the growth of spoilage product-producing bacteria.
[35] A composition characterized by containing barley green leaves and labeled as being useful for inhibiting the growth of indole-producing bacteria.
[36] Contains young barley leaves, "proliferates short-chain fatty acid-producing bacteria in the (large) intestine", "helps grow short-chain fatty acid-producing bacteria in the (large) intestine", " Helps the growth of short-chain fatty acid-producing bacteria", "Proliferates butyric acid bacteria in the intestine", "Helps the growth of butyric acid bacteria in the intestine", "Helps the growth of butyric acid bacteria in the intestine", "In (large) intestine "Proliferates butyric acid bacteria", "Helps in the growth of butyric acid bacteria in the (large) intestine", "Helps the growth of butyric acid bacteria in the (large) intestine", "Proliferates acetic acid bacteria in the (large) intestine", " (Large) Helps the growth of acetic acid bacteria in the intestine”, “(Large) Helps the growth of acetic acid bacteria in the intestine”, “Improves the intestinal environment by short-chain fatty acid-producing bacteria”, “Intestinal improvement by short-chain fatty acid-producing bacteria” Helps improve the internal environment", "Helps improve the intestinal environment by short-chain fatty acid-producing bacteria", "Maintains normal immune function", "Helps maintain normal immune function", "Normal immune function "helps maintain normal mucosal immune function", "helps maintain normal mucosal immune function", "helps maintain normal mucosal immune function", "maintains normal oral immune function"","helps maintain normal oral immune function", "helps maintain normal oral immune function", "maintains normal oral mucosal immune function", "helps maintain normal oral mucosal immune function" , "helps maintain normal oral mucosal immune function", "enhancement of intestinal barrier function", "helps enhance intestinal barrier function", "helps enhance intestinal barrier function", "maintains intestinal barrier function", "Helps maintain intestinal barrier function", "Helps maintain intestinal barrier function", "Enhancement of intestinal barrier function", "Helps enhance intestinal barrier function", "Helps enhance intestinal barrier function" , "maintenance of intestinal barrier function", "helps maintain intestinal barrier function", "helps maintain intestinal barrier function", "enhancement of body barrier function", "helps enhance body barrier function" , ``Helps strengthen the body's barrier function'', ``Maintains the body's barrier function'', ``Helps maintain the body's barrier function'', ``Helps maintain the body's barrier function'', ``Respiratory infections "prevents or alleviates respiratory infections", "helps prevent or alleviate respiratory infections", "helps prevent or alleviate respiratory infections", "prevents or alleviates gastrointestinal infections", "prevents or alleviates gastrointestinal infections""helpsalleviate","helps prevent or alleviate gastrointestinal infections", "prevents or alleviates viral infections", "helps prevent or alleviates viral infections", "helps prevent or alleviate viral infections", ""preventing or alleviating pathogen infection", "helping to prevent or alleviating pathogen infection", "helping to prevent or alleviating pathogen infection", "inhibiting the growth or growth of pathogens", "helping to inhibit the growth or growth of pathogens" , ``helps control the growth or development of pathogens,'' ``suppresses the growth of spoilage product-producing bacteria,'' ``helps suppress the growth of spoilage product-producing bacteria,'' and ``helps suppress the growth of spoilage product-producing bacteria.'' A composition labeled with one or more functional indications selected from

According to the present invention, intestinal butyric acid bacteria and acetic acid bacteria can be effectively propagated, and respiratory infections such as viral respiratory infections and gastrointestinal infections such as viral gastrointestinal infections can be prevented or alleviated. , enhancement of intestinal barrier function, and inhibition of proliferation or growth of pathogens. Moreover, according to the present invention, the growth of indole-producing bacteria can be effectively suppressed, leading to a decrease in the production of putrefaction products in the intestine.

The agent of the present invention is characterized by containing barley green leaves.
The agent of the present invention effectively proliferates short-chain fatty acid-producing bacteria such as intestinal butyric acid-producing bacteria (hereinafter also referred to as "butyric acid bacteria") and acetic acid-producing bacteria (hereinafter also referred to as "acetic acid bacteria"). It is possible to prevent or alleviate respiratory infections such as viral respiratory infections and gastrointestinal infections such as viral gastrointestinal infections, and intestinal barrier function by daily and continuous oral intake. enhancement, and inhibition of proliferation or development of pathogens.
In the present invention, the growth of butyric bacteria in the intestine is preferably promotion of the growth of butyric bacteria in the large intestine lumen, and the growth of intestinal acetic acid bacteria is promotion of the growth of butyric bacteria in the large intestine lumen. is preferred.

The prevention or alleviation of respiratory infections in the present invention means that the symptoms of respiratory infections are improved due to the promotion of growth of short-chain fatty acid-producing bacteria in the intestine, or the symptoms do not appear or appear. It is a concept that includes very light things. Respiratory infections include colds, upper respiratory tract inflammation, bronchitis and lower respiratory tract inflammation such as pneumonia, as well as associated nasal discharge, nasal congestion, sore throat, cough, joint pain, abdominal pain, general fever, These include malaise, chills, diarrhea, nausea, and vomiting.
Respiratory infections include viral and bacterial infections, and viral infections include the above-mentioned various symptoms caused by viral infection. Known causative viruses include coronavirus, influenza virus, respiratory syncytial virus, adenovirus, norovirus, and the like. Pneumonia caused by Streptococcus pneumoniae is known as a bacterial pneumonia.

The prevention or alleviation of gastrointestinal infections in the present invention means that the symptoms of gastrointestinal infections are improved due to the promotion of growth of short-chain fatty acid-producing bacteria in the intestine, or the symptoms do not appear or appear. It is a concept that includes very light things. Examples of gastrointestinal infections include gastroenteritis, and symptoms include gastrointestinal disorders such as abdominal pain, diarrhea, and vomiting, fever, and the like. Salmonella, Staphylococcus, Vibrio parahaemolyticus, Shigella, pathogenic Escherichia coli, Campylobacter, Clostridium perfringens, Bacillus cereus, Norovirus (SRSV), and Rotavirus are known to cause intestinal infections. Coronaviruses are also known to cause gastrointestinal symptoms such as diarrhea.

The enhancement of the intestinal barrier function in the present invention refers to enhancement of the function of eliminating pathogenic bacteria and pathogenic viruses in the intestinal tract due to promotion of proliferation of short-chain fatty acid-producing bacteria in the intestine. As an example of strengthening the intestinal barrier function, for example, butyric acid produced by butyric acid bacteria supplies energy to colon cells, promotes metabolism, maintains normal colon functions such as the colon epithelial mucosa, and produces butyric acid. Functions include suppressing the growth of pathogenic bacteria, enhancing tight junctions with butyric acid produced by butyric acid bacteria, and contributing to the maintenance of intestinal barrier function by promoting differentiation of regulatory T cells. In addition, the acetic acid produced by acetic acid bacteria also has the function of preventing infection by Escherichia coli and the like.

The agent for suppressing the proliferation or growth of pathogens in the present invention includes suppressing the proliferation or growth of pathogens by promoting the proliferation of intestinal butyric acid bacteria and acetic acid bacteria. As pathogens in the respiratory tract, viral ones include the above-mentioned various symptoms caused by viral infection. Known causative viruses include coronavirus, influenza virus, respiratory syncytial virus, and adenovirus. Bacterial ones include Streptococcus pneumoniae. In digestive organs, salmonella, staphylococci, vibrio parahaemolyticus, shigella, pathogenic Escherichia coli, campylobacter, Clostridium perfringens, Bacillus cereus, norovirus (SRSV), rotavirus, coronavirus, and the like.

Decayed products are said to be the cause of foul odors of feces and are known as indicators of deterioration of the intestinal environment. Examples of putrefaction products include indole and skatole, and indole is preferred. Anaerotruncus genus and Escherichia coli are known as indole-producing bacteria.

(Short-chain fatty acid-producing bacteria)
Short-chain fatty acid-producing bacteria refer to bacteria that produce short-chain fatty acids such as butyric acid and acetic acid in the intestine. In the present invention, short-chain fatty acids do not include lactic acid. Among short-chain fatty acid-producing bacteria, butyric acid bacteria are bacteria that produce butyric acid. Specifically, bacteria of the genus Coprococcus, bacteria of the genus Marvinbryantia, bacteria of the genus Anaerostipes, bacteria of the genus Roseburia, bacteria of the genus Faecalibacterium, etc. is mentioned. Among short-chain fatty acid-producing bacteria, acetic acid bacteria include bacteria belonging to the genus Paraprevotella.
The short-chain fatty acid-producing bacterium to be propagated is preferably butyric acid bacterium or acetic acid bacterium. , is preferable because it is expected to be highly effective in enhancing the intestinal barrier function. In the case of butyric acid bacteria, it is confirmed that the butyric acid bacteria to be propagated include at least one selected from bacteria of the genus Coprococcus, bacteria of the genus Anaerostipes, bacteria of the genus Roseburia, and bacteria of the genus Faecalibacterium. It is preferable because it has a high growth-promoting effect, and it is particularly preferable to contain at least one selected from bacteria belonging to the genus Roseburia and bacteria belonging to the genus Faecalibacterium. In addition, including at least one selected from bacteria of the genus Coprococcus, bacteria of the genus Roseburia and bacteria of the genus Faecalibacterium prevents or alleviates changes in the intestinal flora caused by virus infection such as the new coronavirus, It is also preferable from the viewpoint of improving symptoms in the gastrointestinal tract and preventing deterioration of symptoms.

(barley green leaves)
This embodiment uses barley green leaves as an active ingredient. Barley (Hordeum vulgare L.) is native to Central Asia and is an annual or perennial herb belonging to the Poaceae family. Barley is rich in barley β-glucan, which is a water-soluble dietary fiber, and insoluble dietary fiber. Barley varieties used for the barley green leaves used in the agent of the present invention are not particularly limited as long as they are commonly available, and barley green leaves of any variety such as two-rowed barley and six-rowed barley may be used. Moreover, the stem may be included together with the green leaves.

The green leaves may be harvested at any harvest time, and are not particularly limited. Specifically, green leaves are generally harvested from barley with a height of 10 cm or more, preferably about 10 to 90 cm, particularly preferably about 20 to 80 cm, and especially about 30 to 70 cm, although this varies depending on the variety. are preferred, but not limited to these.

The green leaves are preferably pulverized immediately after harvesting. If it takes a long time to pulverize, it is preferable to store by a storage means commonly used by those skilled in the art, such as low-temperature storage, in order to prevent deterioration of green leaves.

As barley green leaves used in the present invention, various processed products obtained from barley green leaves can be used. For example, barley green leaf powder may be used, or a fermented product of barley green leaves may be used, but from the viewpoint of particularly excellent effects of the present invention, it is particularly preferable to use barley green leaf powder. Barley green leaf powder means a product obtained by processing barley green leaves into a dry powder. Barley green leaf powder includes, for example, green leaf pulverized into dry powder (green leaf pulverized powder), green leaf juice squeezed into dry powder (green leaf juice powder), and green leaf extract dried powder. (extract powder of green leaves) and the like, but are not limited to these. As the barley green leaf powder of the present invention, it is particularly preferable to use pulverized powder of barley green leaves from the viewpoint that the effect of the present invention is particularly excellent.

As the pulverized powder of barley green leaves, those subjected to various treatments in addition to the pulverization treatment may be used. Such treatments include, but are not limited to, drying, blanching, sterilization, shredding, and the like.

For example, the green leaves can be dry powdered by combining the drying treatment and the pulverizing treatment. The drying treatment and the pulverizing treatment may be carried out simultaneously, or either one may be carried out first, but it is preferable to carry out the pulverizing treatment after the drying treatment. When the green leaves are dried and pulverized, one or a combination of two or more treatments selected from blanching treatment, sterilization treatment, and the like may be carried out, if necessary. In addition, the number of times of pulverizing treatment is not particularly limited, and the treatment may be performed once or twice or more, such as performing coarse pulverizing treatment followed by fine pulverizing treatment for more finely pulverizing.

The blanching treatment is a treatment for keeping the green color of green leaves vivid, and examples of the blanching treatment include hot water treatment and steaming treatment.

The hot water treatment includes, for example, a method of treating green leaves with hot water of 70 to 100° C., preferably 80 to 100° C. for 60 to 240 seconds, preferably 90 to 180 seconds. Further, in the hot water treatment, it is preferable to use a carbonate such as magnesium carbonate or a hydrogen carbonate such as sodium hydrogen carbonate. By dissolving the hydrogen carbonate salt in the hot water, the green color of the green leaves can be made more vivid. can be done.

The steaming treatment is preferably an intermittent steaming treatment in which a treatment of steaming green leaves with steam and a treatment of cooling are repeated under normal pressure or increased pressure. In the intermittent steaming treatment, the steaming treatment is performed for, for example, 20 to 40 seconds, preferably 30 seconds. The cooling treatment after the steaming treatment is preferably performed immediately, and the method is not particularly limited, but immersion in cold water, refrigeration, cooling with cold air, evaporative cooling with hot air, and evaporative cooling with a combination of hot and cold air. etc. are used. Among these, evaporative cooling in which warm air and cold air are combined is preferable. Such cooling treatment is carried out so that the product temperature of green leaves is preferably 60° C. or lower, more preferably 50° C. or lower, and still more preferably 40° C. or lower. In order to produce a green leaf powder rich in nutrients such as vitamins, minerals and chlorophyll, it is preferable to repeat the intermittent steaming treatment 2 to 5 times.

The sterilization treatment is not particularly limited as long as it is a sterilization treatment commonly known to those skilled in the art. For example, it is a treatment that physically or chemically kills microorganisms using temperature, pressure, electromagnetic waves, chemicals, etc. can be done.

When blanching is performed in addition to drying and pulverization, blanching is preferably performed before drying. Moreover, when sterilization treatment is performed in addition to the drying treatment and the pulverization treatment, the sterilization treatment is preferably performed after the drying treatment or before or after the pulverization treatment.

Although the drying treatment is not particularly limited, for example, a treatment to dry the green leaves so that the water content of the green leaves is 10% by mass or less, preferably 5% by mass or less. The drying treatment can be performed by any method known to those skilled in the art, such as hot air drying, high-pressure steam drying, and electromagnetic wave drying. Drying by heating can be carried out, for example, at 40° C. to 140° C., preferably 80° C. to 130° C., at a temperature and for a time that does not cause discoloration of the green leaves. The drying treatment may be a freeze-drying treatment, but from the viewpoint of particularly excellent effects of the present invention, a drying treatment by heating is preferable.

As the squeezed powder of barley green leaves, for example, one obtained by concentrating the squeezed green leaf juice at a low temperature to concentrate the solid content, and freeze-drying or spray-drying the concentrate may be used.

In order to enhance the effect of short-chain fatty acid-producing bacteria growth and the effect of inhibiting the growth of spoilage product-producing bacteria, when barley green leaf powder is used as barley green leaves, it is particularly preferable to have any of the following configurations.

The barley green leaf powder used in the present invention preferably has a median diameter of 5 μm or more and 50 μm or less, more preferably 8 μm or more and 30 μm or less.

The median diameter means the particle size that is cumulative 50% of the particle size distribution of the powder. It is the cumulative 50% (×50) particle size of the particle size distribution measured using LMS-300 or LMS-350 manufactured by Co., Ltd.

In addition, the barley green leaves used in the present invention preferably contain 10% by mass or more of dietary fiber, more preferably 20% by mass or more, more preferably 30% by mass, so that the effects of the present invention can be further enjoyed. % or more is more preferable. The upper limit may be, for example, 80% by mass. Dietary fiber here is the total amount of insoluble dietary fiber and water-soluble dietary fiber.
The amount of dietary fiber is measured by the Prosky method.

In addition, the barley green leaves used in the present invention preferably contain 5% by mass or more, more preferably 10% by mass or more, of insoluble dietary fiber from the viewpoint of being able to enjoy the effects of the present invention more. It is more preferable that the content is not less than mass %. The upper limit may be, for example, 70% by mass.
The amount of insoluble dietary fiber is measured by the modified Prosky method.

In order to make the amount of dietary fiber and the amount of insoluble dietary fiber within the above range, barley green leaf powder may be prepared by pulverizing barley green leaves without squeezing or extracting in the method for producing barley green leaves.

(Agent of the present invention)
The agent of the present invention is, for example, a drug (including quasi-drugs), a food for specified health use, a food with nutrient function claims, a food with functional claims, etc. It can be used as a health food or the like.

The agent for promoting the growth of short-chain fatty acid-producing bacteria in the intestine of the present invention contains barley green leaves, and is used to promote the growth of short-chain fatty acid-producing bacteria in the intestine, prevent or alleviate (ameliorate) gastrointestinal infections, and reduce respiratory infections. Especially if the product can be distinguished from other products in that it is used for prevention or mitigation (improvement), enhancement of intestinal barrier function, inhibition of proliferation or development of pathogens, and inhibition of proliferation of putrefaction-producing bacteria. Without limitation, for example, a product labeling the function of proliferating butyric acid bacteria or acetic acid bacteria in the intestine on any of the main body, packaging, instructions, and advertising materials (advertising media) of the product according to the present invention Included within the scope of the present invention. In addition, even general foods that are manufactured and sold with indications of uses are included in the scope of the present invention. For example, a functional claim that uses barley green leaves or ingredients derived from barley green leaves (dietary fiber, etc.) as functionally related ingredients based on scientific evidence of functionality, such as papers showing the promotion of the growth of butyric acid bacteria or acetic acid bacteria in the intestine. The scope of the present invention also includes foods with functional claims, which are food products and have notification labeling of the effects caused by the proliferation of butyric acid bacteria or acetic acid bacteria in the intestines and the proliferation of butyric acid bacteria or acetic acid bacteria. A food with functional claims that uses barley green leaves or ingredients derived from barley green leaves (dietary fiber, etc.) as functionally related ingredients, based on scientific evidence such as papers showing the promotion of the growth of butyric acid bacteria or acetic acid bacteria in the intestines. There are also functionally labeled foods with notification claims for prevention or mitigation (improvement) of respiratory infections and digestive infections, enhancement of intestinal barrier function, suppression of the growth or growth of pathogens, and suppression of the growth of spoilage product-producing bacteria. Included within the scope of the present invention. In addition, for example, it is a food with functional claims that uses barley green leaves or ingredients derived from barley green leaves as ingredients involved in functionality, based on the scientific basis of functionality, such as papers showing the growth of butyric acid bacteria, and maintains immune function and / Alternatively, food with functional claims, in which functionality related to improvement is notified and labeled, is also included in the scope of the present invention.

Specifically, in the so-called health food, "proliferate short-chain fatty acid-producing bacteria in the (large) intestine", "useful for the growth of short-chain fatty acid-producing bacteria in the (large) intestine", "(large) intestine "helps the growth of short-chain fatty acid-producing bacteria in the intestine", "proliferates butyric acid bacteria in the intestine", "helps the growth of butyric acid bacteria in the intestine", "helps the growth of butyric acid bacteria in the intestine", "(large) intestine "Proliferate butyric acid bacteria in the (large) intestine", "Help the growth of butyric acid bacteria in the (large) intestine", "Help the growth of butyric acid bacteria in the (large) intestine", "Proliferate acetic acid bacteria in the (large) intestine", “(Large) Helps the growth of acetic acid bacteria in the intestine”, “(Large) Helps the growth of acetic acid bacteria in the intestine”, “Improves the intestinal environment by short-chain fatty acid-producing bacteria”, “By short-chain fatty acid-producing bacteria Helps improve the intestinal environment", "Helps improve the intestinal environment by short-chain fatty acid-producing bacteria", "Maintains normal immune function", "Helps maintain normal immune function", "Normal immunity Helps maintain function", "Maintains normal mucosal immune function", "Helps maintain normal mucosal immune function", "Helps maintain normal mucosal immune function", "Maintains normal oral immune function" "helps maintain normal oral immune function", "helps maintain normal oral immune function", "maintains normal oral mucosal immune function", "helps maintain normal oral mucosal immune function" , ``Helps maintain normal oral mucosal immune function'', ``Enhancement of intestinal barrier function'', ``Helps enhance intestinal barrier function'', ``Helps enhance intestinal barrier function'', ``Maintains intestinal barrier function'' , "Helps maintain intestinal barrier function", "Helps maintain intestinal barrier function", "Enhancement of intestinal barrier function", "Helps enhance intestinal barrier function", "Helps enhance intestinal barrier function" ", "Maintenance of intestinal barrier function", "Helps maintain intestinal barrier function", "Helps maintain intestinal barrier function", "Enhancement of body barrier function", "Enhancement of body barrier function" Helps", "Helps strengthen the body's barrier function", "Maintains the body's barrier function", "Helps maintain the body's barrier function", "Helps maintain the body's barrier function", "Respiratory infections" "preventing or alleviating respiratory infections", "helping prevent or alleviate respiratory infections", "helping prevent or alleviate respiratory infections", "preventing or alleviating gastrointestinal infections", "preventing gastrointestinal infections" "helps prevent or alleviate gastrointestinal infections"; "helps prevent or alleviate viral infections"; "helps prevent or alleviate viral infections"; "helps prevent or alleviate viral infections"; "preventing or mitigating pathogen infection", "helping to prevent or mitigating pathogen infection", "helping prevent or mitigating pathogen infection", "inhibiting the growth or development of pathogens", "inhibiting the growth or development of pathogens" "useful", "helps suppress the growth or development of pathogens", "suppresses the growth of spoilage product-producing bacteria", "helps suppress the growth of spoilage product-producing bacteria", "helps suppress the growth of spoilage product-producing bacteria", etc. can be exemplified.

Forms of the agent of the present invention include, for example, tablets, capsules, powders, granules, liquids, granules, rods, plates, blocks, solids, rounds, pastes, creams, caplets, Gel-like, chewable tablet-like, stick-like and the like can be mentioned. It may be in the form of ice, jelly, cookie, cake, chocolate, PET bottle drink, and the like. Among these, preferred are tablets, capsules, powders, granules, rounds, and chewable tablets, and particularly preferred are powders and granules.

When the agent of the present invention is in the form of a tablet, a round tablet, or a chewable tablet, it is preferable to add one or more of excipients, lubricants, and fluidizing agents. This enhances the moldability and improves the storage stability of the produced agent. In particular, storage stability can be further enhanced by using excipients and lubricants.

The content of barley green leaves in the agent of the present invention may be appropriately contained within the range in which the effect is exhibited. For example, the agent of the present invention can contain 0.01 to 100% by mass of barley green leaves, preferably 0.1 to 100% by mass, and 1 to 100% by mass in terms of dry mass. is more preferable.

The content of the barley green leaf-derived dietary fiber in the agent of the present invention may be appropriately contained within a range in which the effect is exhibited. For example, the agent of the present invention can contain barley green leaf-derived dietary fiber in an amount of 0.01 to 80% by mass, preferably 0.1 to 75% by mass, and 1 to 70% by mass in terms of dry mass. % is more preferable.

The intake of barley green leaves in the present invention is not particularly limited, but the intake of barley green leaves is 0.25 g per day for an adult in order to more effectively enjoy the effect of promoting the growth of short-chain fatty acid-producing bacteria. It is preferable to ingest 0.5 g or more, more preferably 1.0 g or more, and even more preferably 1.0 g or more. The upper limit is, for example, 30 g, preferably 20 g, more preferably 10 g.

In the present invention, there is no particular limitation on the amount of dietary fiber derived from green barley leaves. It is preferable to ingest 125 g or more, more preferably 0.25 g or more, and even more preferably 0.5 g or more. The upper limit is, for example, 15 g, preferably 10 g, more preferably 5 g.

The agent of the present invention may be appropriately designed so that the daily intake of barley green leaves or barley green leaf-derived dietary fiber is the above-mentioned intake, and the above-mentioned intake may be ingested at one time. Alternatively, the intake amount may be divided into a plurality of times and ingested. That is, for example, it can be contained in one container or divided into a plurality of containers of 2 to 4 for one day.

The agent of the present invention is preferably applied to mammals such as humans, and particularly preferably to human subjects. This is because when applied to humans, the agent of the present invention particularly effectively promotes the growth of butyric acid-producing butyric bacteria such as Roseburia, Faecalibacterium, Coprococcus, and Anaerostipes in the human intestine. In addition, acetic acid bacteria such as Paraprevotella can be effectively propagated. Based on these facts, the present invention prevents the growth and decrease of short-chain fatty acid-producing bacteria in the intestine, and prevents digestive and respiratory infections due to the increase in butyric acid and acetic acid in the intestine caused by them. It may contribute to alleviation, enhancement of intestinal barrier function, and inhibition of pathogen proliferation or development. In addition, the agent of the present invention can effectively suppress the growth of an indole-producing bacterium, Anaerotruncus, in the intestines of mammals such as humans, leading to a decrease in the production of putrefaction products in the intestines.

The agent of the present invention can be produced by a known method by adding other ingredients than barley green leaves, if necessary.

EXAMPLES The present invention will be described in more detail below with reference to examples. However, the scope of the invention is not limited to such examples. Hereinafter, unless otherwise specified, "%" means % by mass, and "part" means part by mass.

[Production of barley green leaf powder]
As a raw material, the above-ground parts (leaves and stems) of barley harvested at a height of about 30 cm were used. This was washed with water to remove adhering mud, etc., and cut into pieces of about 5 to 10 cm in size for pretreatment. The pretreated stems and leaves were blanched only once in hot water at 90-100° C. for 90-120 seconds and then cooled in cold water. Subsequently, the resulting stems and leaves were dried with hot air at 80° C. to 130° C. in a dryer for 20 minutes to 180 minutes until the water content was 5% by mass or less. The dried stems and leaves were coarsely pulverized to a size of about 1 mm. The obtained barley stems and leaves are finely pulverized using a jet mill pulverizer while adjusting the supply conditions and discharge pressure within the above ranges to produce barley green leaf powder (pulverized powder) with a moisture content of 5% by mass or less. bottom.

(dietary fiber content)
Analyzed by the Prosky method (enzyme-weight method) described in the food labeling standard appendix (analytical method of nutrients, etc.).

(clinical trial)
Study design: Placebo-controlled, randomized, double-blind, parallel group comparison method Subjects: Healthy adult men and women (55 subjects for analysis (12 men, 43 women), 20 to 65 years old)
Test method: Subjects were divided into two groups and given either the test food of Example 1 or the control food of Comparative Example 1 for 4 weeks. rate was measured.
Subjects considered unsuitable for this study, such as regular users of antiflatulents and laxatives (including laxatives), and those who took antibiotics within two weeks of the examination, were excluded from the study. During the test period, the intake of foods containing live bacteria such as lactic acid bacteria, bifidobacteria, and natto bacteria, foods enriched with oligosaccharides and dietary fiber, health foods that are said to improve constipation, and foods containing large amounts of sugar alcohols should be avoided. I got it.
As the test food of Example 1, a powdered drink prepared by mixing maltose with the barley green leaf powder (dietary fiber content: 47.1% by mass, median diameter: about 20 µm) and granulating the mixture was used. As a control food of Comparative Example 1, a powdered drink prepared without barley green leaf powder and using maltose with a coloring agent and a flavoring agent so as to be indistinguishable from the test food in appearance was used. Dietary fiber derived from barley green leaves contained in the test food was calculated to be 0.7 g per recommended daily intake.
Ingestion method: Each subject dissolved the test food in an appropriate amount of water or hot water and ingested the recommended daily intake every day.
The recovered feces were stored frozen until DNA extraction. It was then pulverized under refrigerated conditions. DNA was extracted from the pulverized specimen using QuickGene-810 system and QuickGene DNA tissue kit (KURABO).
The following was followed according to "16S Metagenomic Sequencing Library Preparation" provided by Illumina Inc.
PCR (first round) was performed using the obtained bacterial DNA as a template. The PCR regions were V3 and V4 of 16S rDNA, and the primers and PCR conditions referred to the protocol above. After PCR, the success or failure was confirmed by electrophoresis. Samples for which PCR amplification was confirmed were purified using NucleoFast 96 (TaKaRa).
PCR (second round) was performed according to the above protocol. The total volume of PCR products was 40 μL. The primers and PCR conditions referred to the protocol above. Using the entire amount of the PCR product, the PCR product was purified using the SequalPrep Normalization Plate Kit (Life Technologies).
Collect 10 μL of each PCR product per plate (960 μL/plate), mix well in a 1.5 mL microtube, divide into 2 equal portions (480 μL/tube), and add AMPure XP beads solution to each tube. (BECKMAN COULTER) (900 µL) was added and mixed well. After standing still for 2 minutes, the DNA-bound beads were adsorbed using a magnetic stand. After discarding the supernatant, the plate was washed twice with 80% by mass ethanol, and then DNA was eluted with 50 μL/plate of Tris buffer. Final DNA concentration confirmation was performed using KAPA Library Quantification Kits (Nippon Genetics).
For samples prepared to 4 nM, 1/3 volume of 0.4N NaOH aqueous solution was used for denaturation at room temperature for 5 minutes, and gene sequences were analyzed using MiSeq Reagent Kit v3 600 Cycle (Illumina) and Miseq. made an acquisition.
The obtained genetic information was analyzed using Qiime (Quantitative Insights Into Microbial Ecology) under Linux (registered trademark) environment. First, arrays acquired in paired ends by Fast Length Adjustment of Short reads (FLASH) (http://www.cbcb.umd.edu/software/flash) were concatenated under the condition of a maximum mismatch ratio of 0.4. Subsequently, the quality check of the concatenated sequences was performed using split_libraries_fastq.py (http://qiime.org/scripts/split_libraries.html). After that, USEARCH (http://www.drive5.com/usearch/) was run to perform sequence clustering and strain identification. The homology was set at 97% or higher. Greengenes database 13_8 (http://qiime.org/home_static/dataFiles.html) was used as a strain identification database.
The above analysis results were expressed as bacterial occupancy (%) at the genus level. Table 1 shows the results.

As shown in Table 1, the test food group of Example 1 compared with the control food group of Comparative Example 1 in the change values from before ingestion in Roseburia, Faecalibacterium, Anaerostipes, Coprococcus, and Paraprevotella, which are butyric bacteria. showed a high price. In addition, the test food group of Example 1 showed lower values than the control food group of Comparative Example 1 for Anaerotruncus, which is an indole-producing bacterium.

The agent of the present invention can effectively proliferate butyric bacteria such as Roseburia, Faecalibacterium and Coprococcus, and acetic acid bacteria such as Paraprevotella in the intestines of mammals such as humans, and can be used for respiratory or digestive tract infections such as viral respiratory or digestive tract infections. It can contribute to prevention or alleviation of infectious diseases, enhancement of intestinal barrier function, and suppression of proliferation or growth of pathogens. In addition, the agent of the present invention can effectively suppress the growth of an indole-producing bacterium, Anaerotruncus, in the intestines of mammals such as humans, leading to a decrease in the production of putrefaction products in the intestines.

Claims (5)

An agent for promoting the growth of short-chain fatty acid-producing bacteria in the intestine, characterized by containing barley green leaves. An agent for preventing or alleviating digestive or respiratory infections, characterized by containing barley green leaves. An intestinal barrier function enhancer comprising barley green leaves. A pathogen growth or development inhibitor characterized by containing barley green leaves. A growth inhibitor for spoilage product-producing bacteria, characterized by containing barley green leaves.