NOVEL BIFIDOBACTERIUM BIFIDUM HEM972 STRAIN AND COMPOSITION FOR IMPROVING INTESTINAL ENVIRONMENT COMPRISING THE SAME OR A CULTURE THEREOF

Abstract

The present application relates to Bifidobacterium bifidum HEM972 strain (KCTC14144BP), a composition for improving intestinal environment containing the same, and a composition for treating or preventing intestinal diseases. Bifidobacterium bifidum HEM972 strain (KCTC14144BP) according to an embodiment of the present application can improve intestinal environment and treat or prevent intestinal diseases by promoting production of beneficial short-chain fatty acids such as butyric acid and propionic acid and suppressing production of harmful short-chain fatty acids such as isobutyric acid, and can be applied to pharmaceutical compositions, food compositions, health functional food compositions, feed compositions, etc.

Description

[Technical field]

[0001] The present application relates to Bifidobacterium bifidum HEM972 strain (KCTC14144BP), a composition for improving intestinal environment containing the same, and a composition for treating or preventing intestinal diseases. [Background technology]

[0002] Modern people have undesirable dietary habits and unhealthy lifestyles, such as a diet centered on meat, a diet centered on instant and processed foods, excessive intake of spicy foods, and hasty changes in food and drink intake patterns due to busy living environments. As we age, harmful bacteria become more prevalent than beneficial bacteria, causing an imbalance in intestinal bacteria and greatly affecting intestinal health, which can lead to indigestion, constipation, and colon cancer. Therefore, various methods, such as exercise therapy and intake of health functional foods, are being researched to prevent and improve such diseases.

[0003] The intestinal microbiota is a microbial flora, which refers to a community of microorganisms in the environment. The intestinal microbiota is known to play an important role in maintaining homeostasis of the host, such as the human immune system and metabolic substances. The intestinal microbiota exchanges chemical signals with the host, and the expression of immune cells, production of neurotransmitters, and short chain fatty acids (SCFAs) by the intestinal microbiota have a significant impact on the host's system. In particular, probiotics / prebiotics can balance the host's imbalanced intestinal microbiota, and the resulting metabolic products of healthy intestinal microbiota can promote the health of the host.

[0004] As a result of research on compositions for improving intestinal environment, there are compositions containing an aqueous extract of red yeast rice as an active ingredient (Korea Patent Registration No. 10-1850308) and a composition containing an ethanol extract of ginseng as an active ingredient (Korea Patent Registration No. 10-1826673), but there is still a need for research and development on compositions that show excellent effects in improving intestinal environment and treating intestinal diseases.

[0005] Therefore, the inventors made intensive efforts to develop an excellent composition capable of improving the intestinal environment and treating or preventing intestinal diseases, and as a result, they developed a novel strain having the ability to promote the production of beneficial short-chain fatty acids and inhibit the production of harmful short-chain fatty acids, thereby completing the present invention. Summary of the Invention [Problem to be solved by the invention]

[0006] The present application aims to provide Bifidobacterium bifidum HEM972 strain (KCTC14144BP), a composition for improving intestinal environment and a composition for treating or preventing intestinal diseases, each containing the strain.

[0007] However, the problems to be solved by the present application are not limited to those mentioned above, and other problems not mentioned will be clearly understood by those of ordinary skill in the art from the following description. [Means for solving the problem]

[0008] A first aspect of the present application provides Bifidobacterium bifidum strain HEM972 (KCTC14144BP).

[0009] A second aspect of the present application provides a food composition for improving intestinal environment, which comprises Bifidobacterium bifidum HEM972 strain (KCTC14144BP) or a culture thereof as an active ingredient.

[0010] A third aspect of the present application provides a pharmaceutical composition for treating or preventing an intestinal disease, comprising Bifidobacterium bifidum HEM972 strain (KCTC14144BP) or a culture thereof as an active ingredient. Effect of the Invention

[0011] Bifidobacterium bifidum HEM972 strain (KCTC14144BP) according to an embodiment of the present application can improve intestinal environment and treat or prevent intestinal diseases by promoting production of beneficial short-chain fatty acids such as butyric acid and propionic acid and suppressing production of harmful short-chain fatty acids such as isobutyric acid, and thus the strain can be applied to pharmaceutical compositions, food compositions, health functional food compositions, feed compositions, and the like. [Brief description of the drawings]

[0012] [Figure 1] FIG. 1 is a schematic diagram showing a method for measuring the short-chain fatty acid production-promoting and -reducing ability of novel bacterial strains. [Diagram 2] FIG. 1 shows the results of confirming the ability of novel bacterial strains to promote butyric acid production. [Diagram 3] FIG. 1 shows the results of confirming the ability of novel strains to promote propionic acid production. [Figure 4] FIG. 1 shows the results of confirming the ability of novel strains to reduce isobutyric acid production. [Diagram 5] FIG. 1 shows the results that the novel strain does not produce short-chain fatty acids by itself. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0013] Hereinafter, the present application will be described in detail with reference to the accompanying drawings so that those skilled in the art can easily carry out the present application. However, the present application may be embodied in various different forms and is not limited to the embodiments described herein. In the drawings, in order to clearly explain the present application, parts that are not related to the description are omitted, and similar parts are designated by similar reference numerals throughout the specification.

[0014] Throughout this specification, when a member is said to be "on" another member, this includes not only when the member is in contact with the other member, but also when there is another member between the two members.

[0015] Throughout the specification of this application, when a part "comprises" a certain component, this means that it may further include other components, not excluding other components, unless otherwise specified. The terms "about," "substantially," and the like, which are used throughout the specification of this application, are used to mean a numerical value or close to a numerical value when manufacturing and material tolerances inherent in the referred meaning are presented, and are used to prevent unscrupulous infringers from unfairly taking advantage of the disclosure in which precise or absolute numerical values ​​are recited to aid in the understanding of this application. The terms "step of" or "step of" which are used throughout the specification of this application do not mean "step for".

[0016] Throughout the specification of this application, the term "combinations thereof" contained in a Markush form phrase means a mixture or combination of one or more selected from the group of elements set forth in the Markush form phrase, and is meant to include one or more selected from the group of elements.

[0017] Throughout the specification of this application, the statement "A and / or B" means "A or B, or A and B."

[0018] Hereinafter, embodiments and examples of the present application will be described in detail with reference to the accompanying drawings, but the present application is not limited to the embodiments and examples and drawings.

[0019] A first aspect of the present application provides Bifidobacterium bifidum strain HEM972 (KCTC14144BP).

[0020] In one embodiment of the present application, the strain may promote the production of beneficial short-chain fatty acids, specifically, may increase the proportion of beneficial short-chain fatty acids in the total short-chain fatty acid content.

[0021] In one embodiment of the present application, the bacterial strain may promote the production of butyric acid, specifically, the bacterial strain may promote the production of butyric acid in the intestinal environment or intestinal flora.

[0022] The term "butyrate" as used throughout the specification of this application is a beneficial metabolite produced by carbohydrate fermentation by intestinal microorganisms and used as an energy source for colon cells. It also plays a role in suppressing inflammation in the colon and promoting the function of tight junctions in colon cells, thereby making the colon healthier and regulating the immune system. It is also known to inhibit colon cancer by affecting cell death and to have preventive effects against various intestinal diseases.

[0023] Therefore, it can be seen that the Bifidobacterium bifidum HEM972 strain of the present application increases the proportion of butyric acid among short-chain fatty acids in the intestine by promoting the production of butyric acid in the intestinal environment or intestinal flora, thereby exhibiting the effects of suppressing colon inflammation, regulating colon immunity, and suppressing colon cancer.

[0024] In one embodiment of the present application, the strain may promote the production of propionic acid, specifically, the strain may promote the production of propionic acid in the intestinal environment or intestinal flora.

[0025] The term "propionate" or "propionic acid" as used throughout this specification is a normal metabolic product produced by carbohydrate fermentation by intestinal microorganisms and is known to be beneficial for intestinal health, such as exerting anti-inflammatory and anti-cancer effects, inhibiting fat production, and helping with colon cell surface and irritable bowel syndrome.

[0026] Therefore, it can be seen that the Bifidobacterium bifidum HEM972 strain of the present application increases the proportion of propionic acid in intestinal short-chain fatty acids by promoting the production of propionic acid in the intestinal environment or intestinal flora, thereby exhibiting anti-inflammatory effects, anti-cancer effects, lipogenesis inhibitory effects, colon cell surface improving effects, and therapeutic or preventive effects for irritable bowel syndrome.

[0027] In one embodiment of the present application, the strain may reduce the production of harmful short-chain fatty acids, specifically, may reduce the proportion of harmful short-chain fatty acids in the total short-chain fatty acid content.

[0028] In one embodiment of the present application, the strain may reduce the production of one or more selected from the group consisting of isobutyric acid and isovaleric acid.

[0029] In one embodiment of the present application, the strain may have reduced production of isobutyric acid.

[0030] The term "isobutyrate" or "isobutyric acid" as used throughout the specification of this application is a harmful metabolite produced by abnormal fermentation of intestinal microorganisms, and is known to be closely related to poor intestinal health because it is found in higher concentrations in patients with various intestinal diseases, specifically, irritable bowel syndrome, ulcerative colitis, colon cancer, celiac disease, Crohn's disease, Low Anterior Resection Syndrome (LARS), and Leaky Gut Syndrome.

[0031] Therefore, it can be seen that the Bifidobacterium bifidum HEM972 strain of the present application reduces the proportion of isobutyric acid in intestinal short-chain fatty acids by suppressing the production of isobutyric acid in the intestinal environment or intestinal flora, thereby exhibiting therapeutic or preventive effects against various intestinal diseases.

[0032] In one embodiment of the present application, the bacterial strain may be one that is unable to produce short-chain fatty acids by itself, and specifically, the bacterial strain may promote the production of beneficial short-chain fatty acids in the intestinal environment, intestinal substances and / or intestinal flora, etc.

[0033] In one embodiment of the present application, the strain may improve the intestinal environment or treat or prevent an intestinal disease. Specifically, the strain may be included in various compositions such as a pharmaceutical composition, a food composition, a health functional food composition, a feed composition, etc. for improving the intestinal environment or treating an intestinal disease.

[0034] A second aspect of the present application provides a food composition for improving intestinal environment, comprising Bifidobacterium bifidum HEM972 strain (KCTC14144BP) or a culture thereof as an active ingredient. The contents overlapping with those of the first aspect also apply to the food composition of the second aspect.

[0035] The term "improvement" as used throughout the specification of this application means any action that improves or favorably changes the intestinal environment by administration of the composition.

[0036] The term "improving intestinal environment" used throughout the specification of this application means favorably changing the composition of intestinal microorganisms and metabolites of the microorganisms, improving the intestinal flora, and improving intestinal function and intestinal health, and means that by improving the intestinal environment, beneficial bacteria and beneficial bacteria metabolites in the intestine are increased, which can show effects such as vitamin synthesis, promotion of digestion and absorption, infection prevention, and immunity enhancement, and harmful bacteria and harmful bacteria metabolites are decreased, which can reduce intestinal putrefaction, bacterial toxins, and carcinogens. In addition, by improving the intestinal environment, intestinal-related diseases such as diarrhea, constipation, and enteritis, as well as cancer, obesity, diabetes, and brain-related diseases can be prevented or treated.

[0037] In one embodiment of the present application, the improvement of the intestinal environment may be one or more selected from the group consisting of an increase in microbial diversity of the intestinal flora, an improvement of the intestinal flora, an increase in beneficial intestinal bacteria, an improvement and promotion of intestinal health, a reduction in endotoxins and hydrogen sulfide derived from intestinal microorganisms, an increase in beneficial metabolites derived from the intestinal flora, an increase in beneficial short-chain fatty acids, a reduction in harmful short-chain fatty acids, an increase in the types and number of beneficial bacteria, and a reduction in the types and number of harmful bacteria, but is not limited thereto.

[0038] In one embodiment of the present application, the composition may be a composition for improving intestinal flora, a composition for promoting beneficial intestinal bacteria, or a composition for improving intestinal health.

[0039] In one embodiment of the present application, the composition may promote the production of beneficial short chain fatty acids, specifically, butyric acid and / or propionic acid.

[0040] In one embodiment of the present application, the composition may inhibit the production of harmful short chain fatty acids, specifically, may inhibit the production of isobutyric acid and / or isovaleric acid, and more specifically, may inhibit the production of isobutyric acid.

[0041] In one embodiment of the present application, the composition may promote the production of beneficial short-chain fatty acids in the intestinal environment, intestinal substances and / or intestinal flora.

[0042] In one embodiment of the present application, the composition may treat or prevent an intestinal disorder.

[0043] In one embodiment of the present application, the composition may contain Bifidobacterium bifidum HEM972 strain, live cells thereof, killed cells thereof, a culture medium thereof, a lysate thereof and / or an extract thereof.

[0044] The term "killed bacteria" used throughout the specification of this application is the opposite concept of live bacteria, and refers to live bacteria and metabolic products obtained by fermentation in a form in which the bacteria cannot grow by heat treatment or the like. The killed bacteria may contain cytoplasm, cell wall, antibacterial active substances such as bacteriocin, polysaccharides, organic acids, etc. Products using the killed bacteria have higher stability than live bacteria products, especially excellent heat resistance, high stability against external environments, easier storage than existing live bacteria products, and a longer shelf life. In addition, since regulations on the use of antibiotics are tightening, they can be used as an alternative, and since there are only a few companies that have fully entered the production of killed bacteria products, they have high marketability and growth potential.

[0045] The term "culture medium" as used throughout the specification of this application means a product obtained by culturing the strain of the present application in a publicly known liquid medium or solid medium, and may be used interchangeably with "culture."

[0046] The term "food" as used throughout this specification includes all foods in the ordinary sense, such as meats, sausages, bread, chocolates, candies, snacks, confectionery, pizza, ramen and other noodles, gums, dairy products including ice cream, various soups, beverages, teas, energy drinks, alcoholic beverages, vitamin complexes, health functional foods and health foods.

[0047] The term "health functional food" as used throughout the specification of this application means food manufactured and processed using raw materials and ingredients that have functional properties beneficial to the human body in accordance with Law No. 6727 on Health Functional Foods, where "functional" means obtaining beneficial effects for health purposes such as regulating nutrients and physiological effects on the structure and function of the human body.

[0048] The food of the present application can be produced by a method commonly used in the art, and may be produced by adding raw materials and ingredients commonly added in the art. The dosage form of the food may also be produced without any restrictions as long as it is a dosage form recognized as a food. The food composition of the present invention may be produced in various dosage forms, and unlike general medicines, it uses food as a raw material, so it has the advantage of being free of side effects that may occur when taking medicines for a long period of time, and is highly portable, so the food of the present invention can be taken as an adjuvant to enhance the effect of improving the intestinal environment.

[0049] The term "health food" refers to food that has a more active effect on maintaining or improving health than general foods, and "health supplement food" refers to food for the purpose of supplementing health. In some cases, the terms "health functional food," "health food," and "health supplement" may be used interchangeably. Specifically, the term "health functional food" refers to food in which the Bifidobacterium bifidum HEM972 strain of the present application is added to food materials such as beverages, teas, spices, gums, and confectioneries, or is encapsulated, powdered, or prepared into a suspension, etc., and which brings about a specific health effect when ingested. However, unlike general medicines, the health functional food is made from food as a raw material, and therefore has the advantage of being free of side effects that may occur when medicines are taken for a long period of time.

[0050] The food composition of the present application can be taken on a daily basis, and is therefore expected to be highly effective in improving the intestinal environment, making it highly useful.

[0051] The food composition may further contain a physiologically acceptable carrier, but the type of carrier is not particularly limited, and any carrier commonly used in the art can be used.

[0052] The food composition may also contain additional ingredients that are commonly used in food compositions and can improve smell, taste, vision, etc. For example, the food composition may contain vitamins A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, panthotenic acid, etc. Minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn), copper (Cu), and chromium (Cr) may also be contained. Amino acids such as lysine, tryptophan, cysteine, and valine may also be contained.

[0053] In addition, the food composition may contain food additives such as preservatives (potassium sorbate, sodium benzoate, salicylic acid, sodium dehydroacetate, etc.), bactericides (bleaching powder, highly bleached powder, sodium hypochlorite, etc.), antioxidants (butyl hydroxyanisole (BHA), butyl hydroxytoluene (BHT), etc.), colorants (tar dyes, etc.), colorants (sodium nitrite, sodium nitrite, etc.), bleaching agents (sodium sulfite), seasonings (MSG monosodium glutamate, etc.), sweeteners (dulcin, cyclamate, saccharin, sodium, etc.), flavors (vanillin, lactones, etc.), leavening agents (alum, potassium hydrogen D-tartrate, etc.), strengthening agents, emulsifiers, thickeners (thickening agents), coating agents, gum base agents, foam inhibitors, solvents, and improvers. The additives may be selected according to the type of food and used in an appropriate amount.

[0054] The Bifidobacterium bifidum HEM972 strain of the present application may be added as it is, or may be used together with other foods or food ingredients, or may be used appropriately by a conventional method. The amount of the active ingredient to be mixed may be determined appropriately depending on the purpose of use (prevention, health, or therapeutic treatment). In general, when producing a food or beverage, the food composition of the present invention may be added to the food or beverage in an amount of 50 parts by weight or less, specifically, 20 parts by weight or less. However, when taking the food or beverage for a long period of time for health and hygiene purposes, the content may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount greater than the above range.

[0055] An example of the food composition of the present application may be a health drink composition, which may contain various flavorings or natural carbohydrates as additional ingredients, as in ordinary drinks. The above-mentioned natural carbohydrates may be monosaccharides such as glucose and fructose; disaccharides such as maltose and sucrose; polysaccharides such as dextrin and cyclodextrin; and sugar alcohols such as xylitol, sorbitol, and erythritol. The sweetener may be a natural sweetener such as thaumatin or stevia extract; or a synthetic sweetener such as saccharin or aspartame. The proportion of the natural carbohydrates may generally be about 0.01 to 0.04 g, specifically about 0.02 to 0.03 g, per 100 mL of the health drink composition of the present invention.

[0056] In addition to the above, the health drink composition may contain various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid, salts of pectic acid, alginic acid, salts of alginic acid, organic acids, protective colloid thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohol, or carbonation agents. In addition, fruit pulp for producing natural fruit juice, fruit juice beverage, or vegetable beverage may be contained. Such ingredients may be used independently or in mixture. The proportion of such additives is not particularly important, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the health drink composition of the present invention.

[0057] The food composition of the present application may contain the Bifidobacterium bifidum HEM972 strain of the present application in various weight percentages, so long as it exhibits the effect of improving the intestinal environment. Specifically, the food composition may contain the Bifidobacterium bifidum HEM972 strain of the present application in an amount of 0.00001 to 100 weight % or 0.01 to 80 weight % of the total weight of the food composition, but is not limited thereto.

[0058] In one embodiment of the present application, the food composition may be a functional health food composition.

[0059] A third aspect of the present application provides a pharmaceutical composition for treating or preventing intestinal diseases, comprising Bifidobacterium bifidum HEM972 strain (KCTC14144BP) or a culture thereof as an active ingredient. The contents overlapping with the first and second aspects also apply to the pharmaceutical composition of the third aspect.

[0060] In one embodiment of the present application, the composition may contain Bifidobacterium bifidum HEM972 strain, live cells thereof, killed cells thereof, a culture medium thereof, a lysate thereof and / or an extract thereof.

[0061] The term "intestinal disease" as used throughout the specification of this application means any disease that is or may be caused by a deterioration of the intestinal environment, an imbalance of intestinal bacteria (intestinal flora), deterioration of intestinal health, intestinal damage, etc., and may include intestinal damage, stomach disease, digestive tract disease, digestive tract damage, etc.

[0062] In one embodiment of the present application, the intestinal disease may be one or more selected from the group consisting of inflammatory bowel disease, irritable bowel syndrome (IBS), ulcerative colitis (UC), colorectal cancer, celiac disease, Crohn's disease, low anterior resection syndrome (LARS), and leaky gut syndrome, but is not limited thereto as long as it is a disease caused by intestinal abnormality.

[0063] The term "treatment" as used throughout the specification of this application means any action of ameliorating or improving the symptoms of an intestinal disease by administering a pharmaceutical composition containing the Bifidobacterium bifidum HEM972 strain of the present application as an active ingredient to an individual suffering from an intestinal disease.

[0064] In one embodiment of the present application, the composition may promote the production of beneficial short chain fatty acids, specifically, butyric acid and / or propionic acid.

[0065] In one embodiment of the present application, the composition may inhibit the production of harmful short chain fatty acids, specifically, may inhibit the production of isobutyric acid and / or isovaleric acid, and more specifically, may inhibit the production of isobutyric acid.

[0066] In one embodiment of the present application, the composition may promote the production of beneficial short-chain fatty acids in the intestinal environment, intestinal substances and / or intestinal flora.

[0067] In one embodiment of the present application, the composition may improve the intestinal environment.

[0068] In one embodiment of the present application, the pharmaceutical composition may be formulated and used in the form of an oral dosage form such as powder, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, topical preparations, suppositories, or sterile injection solutions by conventional methods, but is not limited thereto.

[0069] In one embodiment of the present application, when the pharmaceutical composition is formulated, it may be prepared using a diluent or excipient, such as a commonly used filler, extender, binder, wetting agent, disintegrant, or surfactant, but is not limited thereto.

[0070] In one embodiment of the present application, solid formulations for oral administration include tablets, pills, powders, granules, capsules, etc., and such solid formulations may be prepared by mixing killed cells of the strain with at least one or more excipients, such as starch, calcium carbonate, sucrose, lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc may be used, but are not limited thereto.

[0071] In one embodiment of the present application, liquid preparations for oral administration include suspensions, liquid preparations for internal use, emulsions, syrups, etc., and may contain various excipients such as wetting agents, sweeteners, flavoring agents, preservatives, etc. in addition to water and liquid paraffin, which are commonly used diluents, but are not limited thereto.

[0072] In one embodiment of the present application, the formulation for parenteral administration may include, but is not limited to, a sterile aqueous solution, a non-aqueous solvent, a suspension, an emulsion, a lyophilized preparation, and a suppository. For example, the non-aqueous solvent or suspension may include, but is not limited to, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, etc. For example, the suppository may include, but is not limited to, witepsol, macrogol, Tween 61, cacao butter, laurin butter, glycerogelatin, etc.

[0073] The pharmaceutical composition according to an embodiment of the present application may be a drug composition or a quasi-drug composition.

[0074] The term "quasi-drug" as used throughout the specification of this application means an article used for the purpose of diagnosing, curing, ameliorating, mitigating, treating, or preventing a disease in humans or animals, which has a milder effect than a drug. For example, according to the Pharmaceutical Affairs Law, quasi-drugs exclude articles used for medicinal purposes, and include products used to treat or prevent diseases in humans and animals, and products that have a mild effect on the human body or that do not have a direct effect.

[0075] The quasi-drug composition of the present application may be prepared in a dosage form selected from the group consisting of body cleansers, disinfectants, cleaners, kitchen cleaners, cleaning cleaners, toothpaste, mouthwashes, wet tissues, detergents, soaps, hand washes, hair cleaners, hair softeners, humidifier fillers, masks, ointments, and filter fillers, but is not limited thereto.

[0076] In one embodiment of the present application, the pharmaceutical composition may be administered in a pharmaceutical effective amount, and the term "pharmaceutical effective amount" as used herein means an amount sufficient to treat or prevent a disease with a reasonable benefit / risk ratio applicable to medical treatment or prevention, and the level of the effective dose may be determined based on factors including the severity of the disease, the activity of the drug, the age, weight, health, sex, drug sensitivity of the patient, the administration time, administration route and excretion rate of the composition of the present invention used, the duration of treatment, drugs used in combination with or simultaneously with the composition of the present invention used, and other factors well known in the medical field. The pharmaceutical composition of the present application may be administered alone or in combination with a known component that is known to have a therapeutic effect against a known intestinal disease. Taking all of the above factors into consideration, it is important to administer an amount that provides maximum effect with minimum amount without side effects.

[0077] In one embodiment of the present application, the dosage of the pharmaceutical composition may be determined by a person skilled in the art in consideration of the purpose of use, the severity of the disease, the age, weight, sex, medical history, or the type of substance used as an active ingredient of the patient. For example, the pharmaceutical composition of the present application may be administered at about 0.1 ng to about 1,000 mg / kg, preferably 1 ng to about 100 mg / kg per adult, and the administration frequency of the composition of the present application is not particularly limited, but may be once a day or may be administered in divided doses several times. The dosage or administration frequency does not limit the scope of the present application in any aspect.

[0078] A fourth aspect of the present application provides a method for treating an intestinal disease, comprising administering a pharma- ceutical composition of the present application in a pharma- ceutical effective amount to an individual suffering from the intestinal disease. The contents overlapping with the first to third aspects also apply to the treatment method of the fourth aspect.

[0079] The term "individual" as used throughout this specification may include, without limitation, mammals, including mice, livestock, humans, farmed fish, etc., that are affected or at risk of developing enteric disease.

[0080] In one embodiment of the present application, the individual may be a non-human.

[0081] In one embodiment of the present application, the pharmaceutical composition may be administered in a single or multiple doses in a pharma- ceutical effective amount, and may be formulated and administered in the form of a liquid, powder, aerosol, injection, drip (Ringer's), capsule, pill, tablet, suppository, or patch.

[0082] The pharmaceutical composition for preventing or treating intestinal diseases of the present application may be administered via any common route as long as it can reach the target tissue.

[0083] The pharmaceutical composition of the present application may be administered via routes such as intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, transdermal patch administration, oral administration, intranasal administration, intrapulmonary administration, and intrarectal administration, depending on the purpose, but is not limited thereto. However, when administered orally, it may be administered in an unformulated form, and since the Bifidobacterium bifidum HEM972 strain may be denatured or decomposed by gastric acid, the oral composition may be administered in a form formulated so that the active agent is coated or protected from degradation in the stomach, or in the form of an oral patch, into the oral cavity. In addition, the composition may be administered by any device that can transport the active agent to the target cells. EXAMPLES

[0084] The present invention will be described in more detail with reference to the following examples. However, the following examples are merely illustrative to aid in understanding the present application, and the contents of the present application are not limited to the following examples.

[0085] Example 1: Confirmation of the ability of Bifidobacterium bifidum HEM972 to promote the production and reduction of short-chain fatty acids In order to confirm the ability of the novel strain of the present application, Bifidobacterium bifidum HEM972 (depositary: Korea Biological Resource Center, accession number: KCTC14144BP, date of accession: February 21, 2020), to promote the production and reduction of short-chain fatty acids, the following experiment was performed.

[0086] Example 1-1: In vitro culture for analyzing the amount of short-chain fatty acids produced In order to confirm the amount of short-chain fatty acids produced by the strain of the present invention under in vitro conditions, the strain was cultured as follows.

[0087] First, an intestinal environment-simulating medium having the following composition was prepared, and then the medium was placed in an anaerobic chamber (Whitley A95 anaerobic workstation) for 24 hours to replace the medium in an anaerobic state.

[0088] -Intestinal environment-like medium: NaCl 60mM, NaHCO340mM, KCl 10mM, Hemin 5×10 -5 g / L, mucin 0.5%(w / v), L-cysteine ​​HCl 0.05%(w / v)

[0089] In each well of a 96-well plate, the experimental group (HEM972, PB_B) contained 5 × 10 7 30 μl of the strain corresponding to the CFU / ml concentration, 180 μl of intestinal environment-simulating medium, and 15 mg of human fecal sample were dispensed, and 210 μl of intestinal environment-simulating medium and 15 mg of human fecal sample were dispensed into the wells of the control group (NC, negative control) that was not treated with bacteria. In addition, PB_B uses a Bifidobacterium strain of the same genus, which is a probiotic that has already been commonly used, in order to be used as a reference, and the strain HEM972 in the experimental group means Bifidobacterium bifidum HEM972.

[0090] The 96-well plates containing the experimental and control groups were then cultured for 18 hours in an anaerobic chamber (Whitley A95 anaerobic workstation) with stirring using a stirrer (DLAB mx-m), and after culturing, the plates were centrifuged at 3800 rpm for 10 minutes, and 100 μl of the supernatant from each well was transferred to a 96-well cell culture plate. Next, 100 μl of GC extraction solution for metabolite extraction [GC extraction solution composition: DW 10 ml, NaCl 3.3 g, phosphoric acid 50 μl, 2-ethyl butyric acid 0.5 μl] and 50 μl of DW and 50 μl of the supernatant from the 96-well cell culture plate were dispensed into 96 GC (Gas Chromatography) vials, and the microbial metabolites acetic acid, propionic acid, butyric acid, and isobutyric acid were analyzed using gas chromatography (Gas Chromatography) analysis (Figure 1).

[0091] Example 1-2: Confirmation of butyrate production promoting ability The change in the proportion of butyric acid due to the treatment with the novel strain was confirmed using the gas chromatography analysis method performed in Example 1-1 above. Specifically, the proportion of butyric acid may be confirmed as the proportion of butyric acid relative to the total amount of normal short chain fatty acids present in one sample, including acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and isovaleric acid.

[0092] In Figure 2, "Total SCFA" refers to the total amount of acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and isovaleric acid, "Butyrate" refers to the amount of butyric acid, and "Butyrate / Total SCFA" is the amount of butyric acid divided by "Total SCFA," which represents the proportion of butyric acid. In order to easily confirm the increase or decrease in butyric acid in each experimental group, which is treated with bacteria, compared to the control group (NC) that was not treated with any bacteria, the Butyrate / Total SCFA value of NC is expressed as 100%, and the Butyrate / Total SCFA of each experimental group (TG) is expressed as the TG / NC value, which is obtained by dividing it by NC. In addition, to compare the butyrate / total SCFA values ​​of each experimental group and the control group (NC), statistical significance was confirmed for NC and HEM972 using one-way ANOVA (post-hoc test: Fisher's LSD) and is indicated in the bar graphs with * (P-value<0.05), ** (P-value<0.01), and *** (P-value<0.001). To compare the butyrate / total SCFA values ​​of HEM972 and the reference strain PB_B, statistical significance was confirmed using one-way ANOVA (post-hoc test: Fisher's LSD) and is indicated with # (P-value<0.05), ## (P-value<0.01), and ### (P-value<0.001).

[0093] As a result of checking the increase or decrease in butyric acid, it was confirmed that the proportion of butyric acid increased statistically significantly when treated with the HEM972 strain compared to the control group and PB_B (FIG. 2).

[0094] Based on the above results, it is evident that the HEM972 strain of the present application has the function of promoting the production of butyric acid in the intestinal environment (intestinal flora).

[0095] Example 1-3: Confirmation of propionic acid production promoting ability The gas chromatography analysis method performed in Example 1-1 was used to confirm the change in the proportion of propionic acid due to the treatment with the novel strain. Specifically, the proportion of propionic acid may be confirmed as the proportion of propionic acid relative to the total amount of normal short chain fatty acids present in one sample, including acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and isovaleric acid.

[0096] In Figure 3, "Total SCFA" means the total amount of acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and isovaleric acid, "Propionate" means the amount of propionic acid, and "Propionate / Total SCFA" is the amount of propionic acid divided by "Total SCFA", which indicates the proportion of propionic acid. In order to easily confirm the increase or decrease in propionic acid in each experimental group, which is a case where bacteria were treated, compared to a control group (NC) that was not treated with any bacteria, the Propionate / Total SCFA value of NC was expressed as 100%, and the Propionate / Total SCFA of the experimental group (TG) was expressed as the TG / NC value, which was obtained by dividing the Propionate / Total SCFA by NC. In addition, to compare the propionate / total SCFA values ​​of each experimental group and the control group (NC), statistical significance was confirmed for NC and HEM972 using one-way ANOVA (post-hoc test: Fisher's LSD), and is indicated in the bar graphs with * (P-value<0.05), ** (P-value<0.01), and *** (P-value<0.001). To compare the propionate / total SCFA values ​​of HEM972 and the reference strain PB_B, statistical significance was confirmed using one-way ANOVA (post-hoc test: Fisher's LSD), and is indicated with # (P-value<0.05), ## (P-value<0.01), and ### (P-value<0.001).

[0097] As a result of checking the increase or decrease in the propionic acid, it was confirmed that the proportion of propionic acid increased statistically significantly when the HEM972 strain was treated compared to the control group and PB_B (FIG. 3).

[0098] Based on the above results, it is evident that the HEM972 strain of the present application has the function of promoting the production of propionic acid in the intestinal environment (intestinal flora).

[0099] Example 1-4: Confirmation of ability to reduce isobutyrate production Using the gas chromatography analysis method performed in Example 1-1 above, the change in the proportion of isobutyric acid due to the treatment with the new strain was confirmed.

[0100] "Isobutyrate" in Figure 4 refers to the amount of isobutyric acid. In order to easily confirm the increase or decrease in isobutyric acid in each experimental group, which is when bacteria were treated compared to the control group (NC) where no bacteria were treated, the isobutyrate value for NC is expressed as 100%, and the isobutyrate value for each experimental group (TG) is expressed as TG / NC value, which is calculated by dividing the isobutyrate value by NC. In addition, to compare the isobutyrate values ​​of HEM972 and the control group (NC), statistical significance was confirmed by one-way ANOVA (post-hoc test: Fisher's LSD) for NC and the experimental group, respectively, and is indicated in the bar graphs with * (P-value<0.05), ** (P-value<0.01), and *** (P-value<0.001). To compare the isobutyrate values ​​of HEM972 and the reference strain PB_B, statistical significance was confirmed by one-way ANOVA (post-hoc test: Fisher's LSD) and is indicated with # (P-value<0.05), ## (P-value<0.01), and ### (P-value<0.001).

[0101] As a result of checking the increase or decrease in the isobutyric acid, it was confirmed that the amount of isobutyric acid was statistically significantly decreased when the HEM972 strain was treated compared to the control group and PB_B (FIG. 4).

[0102] Based on the above results, it is evident that the HEM972 strain of the present application has the function of suppressing the production of isobutyric acid in the intestinal environment (intestinal flora).

[0103] Example 2: Confirmation of whether Bifidobacterium bifidum HEM972 can synthesize short-chain fatty acids by itself In the above Example 1, it was confirmed that the novel strain of the present invention, Bifidobacterium bifidum HEM972, increases the ratio of butyric acid and propionic acid and inhibits the production of isobutyric acid. However, the above experiment did not clearly show whether the strain itself produces butyric acid and propionic acid or whether the strain promotes the production of the short-chain fatty acids in the intestinal environment. In order to clarify this, the following experiment was performed.

[0104] First, an intestinal environment-simulating medium having the following composition was prepared, and then the medium was placed in an anaerobic chamber (Whitley A95 anaerobic workstation) for 24 hours to replace the medium in an anaerobic state.

[0105] -Intestinal environment-like medium: NaCl 60mM, NaHCO340mM, KCl 10mM, Hemin 5×10 -5 g / L, mucin 0.5%(w / v), L-cysteine ​​HCl 0.05%(w / v)

[0106] Next, in a 96-well plate, treatment group A (HEM972) was treated with 5 × 10 7 30 μl of the strain corresponding to the CFU / ml concentration and 195 μl of the intestinal environment-simulating medium were dispensed. 7 30 μl of the bacterial strain (corresponding to the CFU / ml concentration), 180 μl of intestinal environment-simulating medium, and 15 mg of human fecal sample were dispensed. In addition, 225 μl of intestinal environment-simulating medium was dispensed into the negative control (NC) wells, which were not treated with the bacterial strain.

[0107] Next, the 96-well plate into which the experimental group was dispensed was cultured for 18 hours in an anaerobic chamber (Whitley A95 anaerobic workstation) while stirring using a stirrer (DLAB mx-m), and after culturing, it was centrifuged at 3800 rpm for 10 minutes, and 100 μl of the supernatant from each well was transferred to a 96-well cell culture plate. Next, 100 μl of GC extraction solution for metabolite extraction [GC extraction solution composition: DW 10 ml, NaCl 3.3 g, phosphoric acid 50 μl, 2-ethyl butyric acid 0.5 μl] and 50 μl of DW and 50 μl of the supernatant from the 96-well cell culture plate were dispensed into 96 GC (Gas Chromatography) vials, and the production amounts of microbial metabolites, acetic acid, propionic acid, butyric acid, isobutyric acid, and 2-ethyl butyric acid as an internal standard for GC, were analyzed using gas chromatography analysis.

[0108] As a result of the above analysis, it was confirmed that in the case of experimental group A, in which only the HEM972 strain was treated and no fecal samples were treated, but in the case of experimental group B, in which both the strain and the fecal samples were treated, butyric acid and propionic acid were produced (Figure 5).

[0109] Based on the above experimental results, it is found that the HEM972 strain of the present application does not have the ability to produce butyric acid and propionic acid by itself, but has the function of stimulating and regulating the intestinal flora (fecal sample) to promote the production of butyric acid and propionic acid.

[0110] The above description of the present application is for illustrative purposes only, and a person having ordinary skill in the art to which the present application pertains should understand that the present application can be easily modified into other specific forms without changing the technical idea or essential features of the present application. Therefore, it should be understood that the above-described embodiments are illustrative in all respects and are not limiting. For example, each component described as a single type may be implemented in a distributed form, and similarly, each component described as a distributed type may be implemented in a combined form.

[0111] The scope of the present application is indicated by the claims set forth below rather than by the above detailed description, and all modifications and variations derived from the meaning and scope of the claims, as well as their equivalent concepts, should be construed as being included within the scope of the present application.

[0112] [Accession number] Depository institution name: Korea Institute of Bioscience and Biotechnology Accession number: KCTC14144BP Date of acceptance: 20200221

[0113] JPEG2025513918000002.jpg241170

Claims

1. Bifidobacterium bifidum HEM972 strain (KCTC14144BP).

2. 2. The strain of claim 1, wherein the strain promotes the production of one or more selected from the group consisting of butyric acid and propionic acid.

3. 2. The strain of claim 1, wherein the strain reduces production of isobutyric acid.

4. The strain of claim 1, wherein the strain is unable to produce short chain fatty acids by itself.

5. A food composition for improving intestinal environment, comprising Bifidobacterium bifidum HEM972 strain (KCTC14144BP) or a culture thereof as an active ingredient.

6. A pharmaceutical composition for treating or preventing intestinal diseases, comprising Bifidobacterium bifidum HEM972 strain (KCTC14144BP) or a culture thereof as an active ingredient.

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