Novel strain and vesicles derived therefrom, and Anti-inflammatory and antibacterial uses thereof
Patent Information
- Application Number
- PCT/KR2024/003778
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-08-08
- Filing Date
- 2024-03-26
- Publication Date
- 2025-02-13
Smart Images

Figure KR2024003778_13022025_PF_FP_ABST
Abstract
Description
Novel strains and endoplasmic reticulum derived therefrom and their anti-inflammatory and antibacterial uses
[0001] The present invention relates to novel microorganisms, their lysates, cultures, extracts of cultures, endoplasmic reticulum and their anti-inflammatory and / or antibacterial uses.
[0002] The microbiome refers to the microorganisms and their entire genetic information existing in a specific environment. It refers to the collection of genomes, the entire genetic information of a single organism. Therefore, the human microbiome refers to the microorganisms that inhabit both inside and outside the human body, along with their entire genetic information.
[0003] The human body coexists with numerous microorganisms, and the gut, in particular, is home to the largest number of microorganisms, providing an optimal environment for them to consume nutrients and form systematic communities. Gut microbes provide nutrients that the host's own enzymes alone cannot produce, and they are deeply connected to the host's metabolism and immune system. Furthermore, they have been linked to the development of various diseases, including irritable bowel syndrome, obesity, atopy, depression, rheumatoid arthritis, autism spectrum disorder, and dementia.
[0004] Recently, Western eating habits and indiscriminate use of antibiotics have led to an imbalance in the gut microbiota, worsening gut health. Furthermore, research on gut microbiota and various diseases has highlighted the importance of gut microbiota and raised interest in it.
[0005] Meanwhile, endoplasmic reticulum (ER) is a nano-sized substance, approximately 20 to 200 nm in size, produced and secreted by cells and capable of free movement between cells. Furthermore, ER contains membrane lipids, membrane proteins, DNA, and RNA, and these genetic materials act as complexes to transmit toxic factors between cells and play roles in regulating inflammation and immune responses. From unicellular to multicellular organisms, intercellular information exchange is an essential process for life. Recently, ER has been recognized as a mediator of intercellular information exchange, leading to the development of methods to utilize ER as a drug delivery system.
[0006] Accordingly, there is a need to develop substances for improving, preventing, or treating diseases using novel microorganisms derived from the human intestine and endoplasmic reticulum derived therefrom.
[0007] One aspect provides a strain of Blautia hominis belonging to the genus Blautiasp., deposited under accession number KCTC 15293BP, a strain of Prevotella copri belonging to the genus Prevotellasp., deposited under KCTC 15272BP, or a strain of Limosilactobacillus mucosae belonging to the genus Limosilactobacillus sp., deposited under KCTC 15273BP.
[0008] Another aspect is to provide a vesicle derived from the strain, a lysate of the strain, or a culture medium of the strain.
[0009] Another aspect provides a composition having antibacterial or anti-inflammatory activity comprising, as an active ingredient, a Blautia hominis strain, a Prevotella copri strain, or a Rimosyl Lactobacillus mucoceae strain; an endoplasmic reticulum derived from the strain; a lysate of the strain; a culture medium of the strain; or a mixture thereof.
[0010] Another aspect provides a pharmaceutical composition for preventing or treating an inflammatory disease, comprising as an active ingredient a Blautia hominis strain, a Prevotella copri strain, or a Rimosyl Lactobacillus mucoce strain; an endoplasmic reticulum derived from the strain; a lysate of the strain; a culture medium of the strain; or a mixture thereof.
[0011] Another aspect provides a health functional food for preventing or improving inflammatory diseases, comprising as an active ingredient a Blautia hominis strain, a Prevotella copri strain, or a Rimosyl Lactobacillus mucoce strain; an endoplasmic reticulum derived from the strain; a lysate of the strain; a culture medium of the strain; or a mixture thereof.
[0012] Another aspect provides a health functional food for improving intestinal health, comprising as an active ingredient a Blautia hominis strain, a Prevotella copri strain, or a Rimosyl Lactobacillus mucoce strain; an endoplasmic reticulum derived from the strain; a lysate of the strain; a culture medium of the strain; or a mixture thereof.
[0013] Another aspect provides a pharmaceutical composition for preventing or treating bacterial infection, comprising as an active ingredient a strain of Blautia hominis, a strain of Prevotella copri or a strain of Rimosyl Lactobacillus mucocei; an endoplasmic reticulum derived from the strain; a lysate of the strain; a culture medium of the strain; or a mixture thereof.
[0014] Another aspect provides a health functional food for preventing or improving bacterial infection, comprising as an active ingredient a Blautia hominis strain, a Prevotella copri strain, or a Rimosyl Lactobacillus mucoce strain; an endoplasmic reticulum derived from the strain; a lysate of the strain; a culture medium of the strain; or a mixture thereof.
[0015] Another aspect provides a method for preventing or treating an inflammatory disease, comprising administering to a subject in need thereof a strain of Blautia hominis, a strain of Prevotella copri, or a strain of Rimosyl Lactobacillus mucocei; an endoplasmic reticulum derived from the strain; a lysate of the strain; a culture of the strain; or a mixture thereof.
[0016] Another aspect provides a method for preventing or treating bacterial infection, which comprises administering to a subject in need thereof a strain of Blautia hominis, a strain of Prevotella copri, or a strain of Rimosyl Lactobacillus mucoce; an endoplasmic reticulum derived from said strain; a lysate of said strain; a culture of said strain; or a mixture thereof.
[0017] Another aspect provides a use for preparing a composition for preventing or treating an inflammatory disease, comprising a Blautia hominis strain, a Prevotella copri strain, or a Rimosyl Lactobacillus mucoce strain; an endoplasmic reticulum derived from said strain; a lysate of said strain; a culture of said strain; or a mixture thereof.
[0018] Another aspect provides a use for preparing a composition for preventing or treating bacterial infection, comprising a Blautia hominis strain, a Prevotella copri strain, or a Rimosyl Lactobacillus mucoce strain; an endoplasmic reticulum derived from said strain; a lysate of said strain; a culture of said strain; or a mixture thereof.
[0019] One aspect provides a strain of Blautia hominis belonging to the genus Blautia, a strain of Prevotella copri belonging to the genus Prevotellasp, or a strain of Limosilactobacillus mucosae belonging to the genus Limosilactobacillus sp.
[0020] The above Blautia hominis strain may be a strain deposited under accession number KCTC 15293BP. The above Prevotella copri strain may be a strain deposited under accession number KCTC 15272BP. The above Rimosyl Lactobacillus mucoceae strain may be a strain deposited under accession number KCTC 15273BP.
[0021] The above Blautia hominis strain may be a strain comprising 16S rRNA of sequence number 1. The above Prevotella copri strain may be a strain comprising 16S rRNA of sequence number 2. The above Rimosyl Lactobacillus mucoceae strain may be a strain comprising 16S rRNA of sequence number 3.
[0022] The above strain may have anti-inflammatory and / or antibacterial activity.
[0023] The strain may inhibit the production of nitric oxide in inflamed cells, inhibit the expression of inflammatory cytokines (e.g., TNF-α or IL-6), or inhibit the growth of bacteria (e.g., C. difficile). Furthermore, the strain may decrease inflammatory factors induced by C. difficile, such as proinflammatory cytokines (e.g., TNF or CCL2), or increase anti-inflammatory cytokines (e.g., IL-10).
[0024]
[0025] Another aspect provides a vesicle derived from the strain, a lysate of the strain, a culture medium, an extract of the culture medium, or a mixture thereof.
[0026] The strains are as described above.
[0027] The term “vesicle” as used herein refers to a particle secreted from a cell and released into the extracellular space, and may include many different species such as exosomes, ectosomes, microvesicles, microparticles, and exosome-like vesicles. Extracellular vesicles can reflect the state of the secreting source cell (donor cell), exhibit various biological activities depending on which cell they are secreted from, and play an important role in cell-to-cell interactions by transferring genetic material and proteins between cells. In addition, cell-derived substances including the vesicles can cause diseases or stimulate immune cells to fight diseases, and have the effect of helping humans break down and absorb substances that cannot be digested through the metabolic process of microorganisms. The above endoplasmic reticulum is a membrane-structured endoplasmic reticulum, which is divided into an inside and an outside, and contains plasma membrane lipids, plasma membrane proteins, nucleic acids, and cytoplasmic components of the cell, and may be smaller than the original cell.
[0028] In one specific example, the endoplasmic reticulum may be isolated from a cell lysate of a culture of a Blautia hominis strain, a Prevotella copri strain, or a Rimosyl Lactobacillus mucoce strain.
[0029] In one specific example, the extracellular vesicles may have a diameter of 10 nm to 400 nm. For example, the diameter may be 10 nm to 400 nm, 10 nm to 350 nm, 10 nm to 300 nm, or 10 nm to 250 nm.
[0030] In this specification, the term “culture medium” may be used interchangeably with “culture supernatant”, “conditioned medium” or “conditioned medium”, and may mean the entire medium including the strain, its metabolites, extra nutrients, etc., obtained by culturing the strain for a certain period of time in a medium capable of supplying nutrients so that Blautia hominis, Prevotella copri or Rimosyl Lactobacillus mucosae can grow and survive in vitro. In addition, the culture medium may mean a culture medium obtained by removing the bacterial cells from the bacterial culture obtained by culturing the strain. Meanwhile, the liquid from the culture medium from which the bacterial cells have been removed is also called a “supernatant”, and may be obtained by allowing the culture medium to stand still for a certain period of time and taking only the liquid in the upper layer excluding the portion that has settled to the lower layer, removing the bacterial cells through filtration, or centrifuging the culture medium to remove the sediment at the lower layer and taking only the liquid in the upper layer. The above "bacteria" refers to the strain of the present invention itself, and includes the strain itself selected by isolating from a skin sample or the like, or the strain isolated from the culture medium by culturing the strain. The bacteria can be obtained by centrifuging the culture medium and taking the portion that has settled to the lower layer, or by allowing the bacteria to settle to the lower layer of the culture medium by gravity and then removing the upper liquid after leaving it still for a certain period of time.
[0031] The above culture solution may include the culture solution itself, a concentrate thereof, or a lyophilized product obtained by culturing the strain, or a culture supernatant obtained by removing the strain from the culture solution, a concentrate thereof, or a lyophilized product thereof.
[0032] The above culture solution may be obtained by culturing Blautia hominis, Prevotella copri, or Rimosyl Lactobacillus mucosa in an appropriate medium (e.g., R2A medium or TSA medium) at a temperature of more than 10°C or less than 40°C for a certain period of time, for example, 4 to 50 hours.
[0033] In one specific example, the culture supernatant of the strain can be obtained by a step of removing the strain by centrifuging or filtering the strain culture.
[0034] In another specific example, the concentrate can be obtained by concentrating the strain culture itself, or the supernatant obtained after filtering the culture using centrifugation or a filter.
[0035] The culture medium and culture conditions for culturing the above-mentioned Blautia hominis, Prevotella copri, or Rimosyl Lactobacillus mucoceae can be appropriately selected or modified and used by a person of ordinary skill in the art.
[0036] In this specification, the term “disruption solution” may mean a product obtained by disrupting the cell wall of the strain itself by chemical or physical force.
[0037] The term "culture solution extract" in this specification means an extract obtained from the culture solution or a concentrate thereof, and may include an extract, a diluted or concentrated extract, a dried product obtained by drying the extract, or a controlled or purified product thereof, or a fraction obtained by fractionating the same.
[0038]
[0039] Another aspect provides a use for improving, preventing or treating a disease using a strain of Blautia hominis, a strain of Prevotella copri, or a strain of Rimosyl Lactobacillus mucoce, an endoplasmic reticulum derived from the strain, a lysate, a culture medium or an extract of the culture medium of the strain.
[0040] The term "treatment" herein may refer to the healing of inflammation or bacterial infection, etc., in a shorter period of time compared to natural healing. Such treatment may include the improvement and / or alleviation of the inflammation or bacterial infection. Furthermore, such treatment may refer to the healing and / or recovery of symptoms resulting from the inflammation or bacterial infection.
[0041] As used herein, the term "prevention" refers to a method of partially or completely delaying or preventing the onset or recurrence of a disease, disorder, or its associated symptoms, preventing the acquisition or reacquisition of a disease or disorder, or reducing the risk of acquiring a disease or disorder. For example, the term "prevention" refers to any action that inhibits or delays the development of inflammation or bacterial infection by administering a composition according to the present invention.
[0042] Uses of the above strain may include preventing, ameliorating, or treating inflammatory diseases (anti-inflammatory activity), preventing, ameliorating, or treating bacterial infections (antibacterial activity), or preventing or improving intestinal health.
[0043] The above inflammatory diseases may include inflammation of the digestive system (gastrointestinal tract, etc.), inflammation of the eye, inflammation of the mouth, inflammation of the respiratory system including the lungs, inflammation of the skin, inflammation of the cardiovascular system, inflammation of the brain, inflammation of the ear, etc.
[0044] More specifically, the inflammatory disease includes inflammatory bowel diseases (IBD); irritable bowel syndrome; Behcet's disease; enteritis, Crohn's disease; ulcerative colitis; vasculitis; mucositis; stomatitis; peri-implantitis; periodontitis; pulpitis; gingivitis; pneumonia; dermatitis; atopic dermatitis; contact dermatitis; CREST syndrome; dermatitis herpetiformis; dermatomyositis; systemic scleroderma; erythema nodosum; Henoch-Schonlein purpura; Hidradenitis suppurativa; Lichen planus; Majeed syndrome; Schnitzler syndrome; psoriasis; eczema; acne; mouth ulcers; uveitis; pharyngitis; tonsillitis; otitis media (otitis); psoriatic arthritis; synovitis; meningitis; encephalitis; Bickerstaff's encephalitis; encephalomyelitis; spondylitis; osteomyelitis;It may be any one selected from the group consisting of Guillain-Barre syndrome; myelitis; neuromyelitis optica; cystitis; acute inflammation at the site of infection or injury; nephritis; and glomerulonephritis.;
[0045] The inflammatory disease may be an inflammatory disease of the intestine, such as inflammatory bowel diseases (IBD); irritable bowel syndrome; enteritis; Crohn's disease; or ulcerative colitis.
[0046] Additionally, the improvement in intestinal health may be due to help in the proliferation of beneficial bacteria and suppression of harmful bacteria in the intestines, help intestinal health by regulating immunity, or help in smooth bowel movements.
[0047] The term "antimicrobial agent" as used herein refers to a substance capable of (i) inhibiting, reducing, or preventing the growth of bacteria; (ii) inhibiting or reducing the ability of bacteria to cause an infection in a subject; or (iii) inhibiting or reducing the ability of bacteria to multiply or remain infectious in an environment.
[0048] Examples of the above bacterial infections may include infections caused by gram-positive or gram-negative bacteria. Specifically, the bacterial infection may include an infection caused by bacteria belonging to the genus Clostridioides, Helicobacter, Escherichia, Salmonella, Staphylococcus, Streptococcus, Haemophilus, Klebsiella, Moraxella, Enterobacter, Proteus, Serratia, Pseudomonas, Acinetobacter, Citrobacter, Stenotrophomonas, Bacteroides, Prevotella, and Fusobacterium. More specifically, the bacterial infection may include Clostridioides difficile infection (CDI), or Clostridioides difficile-associated disease (CDAD), for example, Clostridioides difficile-associated diarrhea.
[0049] The composition is present in an amount of 0.00001 wt% to 80 wt%, for example, 0.00001 wt% to 60 wt%, 0.00001 wt% to 40 wt%, 0.00001 wt% to 30 wt%, 0.00001 wt% to 20 wt%, 0.00001 wt% to 10 wt%, 0.00001 wt% to 5 wt%, 0.05 wt% to 60 wt%, 0.05 wt% to 40 wt%, 0.05 wt% to 30 wt%, 0.05 wt% to 20 wt%, 0.05 wt% to 10 wt%, 0.05 wt% to 5 wt%, 0.1 wt% to 60 wt%, 0.1 wt% to 40 wt%, 0.1 It may include from 0.1 wt% to 30 wt%, from 0.1 wt% to 20 wt%, from 0.1 wt% to 10 wt%, or from 0.1 wt% to 5 wt% of the strain, its lysate, its culture, or its extract of the culture.
[0050] The term "including as an active ingredient" means that the strain of the present specification, the vesicles derived from the strain, the lysate of the strain, the culture medium, or the extract of the culture medium thereof are added to an extent capable of exhibiting the above-mentioned effect, and includes the formulation in various forms by adding various components as auxiliary components for drug delivery and stabilization, etc.
[0051]
[0052] In another embodiment, the composition may be a pharmaceutical composition.
[0053] The types of pharmaceutically active ingredients that can be delivered into a subject include anticancer agents, contrast agents (dyes), hormones, antihormones, vitamins, calcium agents, mineral agents, sugar agents, organic acid agents, protein amino acid agents, detoxifiers, enzyme agents, metabolic agents, diabetes agents, tissue revitalizing agents, chlorophyll agents, pigment agents, tumor agents, tumor treatment agents, radiopharmaceuticals, tissue cell diagnostic agents, tissue cell treatment agents, antibiotic agents, antiviral agents, combination antibiotic agents, chemotherapeutic agents, vaccines, toxins, toxoids, antitoxins, leptospira serum, blood products, biological agents, analgesics, immunogenic molecules, antihistamines, allergy agents, nonspecific immunogenic agents, anesthetics, stimulants, psychotropic agents, low molecular weight compounds, nucleic acids, aptamers, antisense nucleic acids, oligonucleotides, peptides, siRNAs, and microRNAs.
[0054] The pharmaceutical composition may additionally comprise a pharmaceutically acceptable diluent or carrier. The diluent may be lactose, corn starch, soybean oil, microcrystalline cellulose, or mannitol, and the lubricant may be magnesium stearate, talc, or a combination thereof. The carrier may be an excipient, a disintegrant, a binder, a glidant, or a combination thereof. The excipient may be microcrystalline cellulose, lactose, low-substituted hydroxycellulose, or a combination thereof. The disintegrant may be calcium carboxymethylcellulose, sodium starch glycolate, calcium dihydrogen phosphate anhydrous, or a combination thereof. The binder may be polyvinylpyrrolidone, low-substituted hydroxypropylcellulose, hydroxypropylcellulose, or a combination thereof. The lubricant may be magnesium stearate, silicon dioxide, talc, or a combination thereof.
[0055] When formulating the above pharmaceutical composition, it is prepared using diluents or excipients such as fillers, bulking agents, binders, wetting agents, disintegrating agents, and surfactants that are commonly used. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Suppository bases may include Witepsol, macrogol, Tween 61, cacao butter, liurin butter, and glycerogelatin.
[0056] The pharmaceutical composition may contain carbohydrates such as glucose, sucrose or dextran, antioxidants such as ascorbic acid or glutathione, chelating agents, low-molecular-weight proteins or other stabilizers to increase stability or absorbability.
[0057] The pharmaceutical composition may be formulated as an oral or parenteral dosage form. The oral dosage form may be a granule, powder, liquid, tablet, capsule, dry syrup, or a combination thereof. The parenteral dosage form may be an injection.
[0058]
[0059] The above composition may be a health functional food composition.
[0060] The above health functional food composition can be used alone or in combination with other foods or food ingredients, and can be used appropriately according to a conventional method. The amount of the active ingredient mixed can be appropriately determined depending on the purpose of use (prevention, health, or therapeutic treatment). Generally, when manufacturing a food or beverage, the composition of the present specification can be added in an amount of 15 parts by weight or less based on the raw material. There is no particular limitation on the type of the health functional food. Among the types of health functional foods, the beverage composition can contain various flavoring agents or natural carbohydrates as additional ingredients, like conventional beverages. The natural carbohydrates include 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. As a sweetener, a natural sweetener such as thaumatin and stevia extract, or a synthetic sweetener such as saccharin and aspartame can be used. The health food composition may also contain nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, or combinations thereof. The health functional food composition may also contain fruit pulp for the production of natural fruit juice, fruit juice drinks, vegetable drinks, or combinations thereof.
[0061]
[0062] The above composition may be a cosmetic composition.
[0063] The above cosmetic composition may have, for example, a cosmetic formulation of a softening toner, a nourishing toner, a massage cream, a nourishing cream, an essence, a pack, a gel, an ampoule, or a skin adhesive type.
[0064] The ingredients included in the above cosmetic composition may include ingredients commonly used in cosmetic compositions in addition to the composition as an active ingredient, and may include, for example, conventional auxiliary agents and carriers such as stabilizers, solubilizers, vitamins, pigments, and fragrances.
[0065]
[0066] Additionally, the composition may be a composition for external use on the skin.
[0067] In the present specification, the external skin preparation may be a cream, gel, ointment, skin emulsifier, skin suspension, transdermal delivery patch, drug-containing bandage, lotion, or a combination thereof. The external skin preparation may be appropriately mixed with ingredients commonly used in external skin preparations such as cosmetics or pharmaceuticals, such as aqueous ingredients, oily ingredients, powder ingredients, alcohols, moisturizers, thickeners, UV absorbers, whitening agents, preservatives, antioxidants, surfactants, fragrances, colorants, various skin nutrients, or combinations thereof, as needed. The above skin external preparation may also appropriately contain metal sequestrants such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, and gluconic acid; caffeine, tannin, bellapamil, licorice extract, glabridin, hot water extract of the fruit of Calin; various herbal medicines; tocopheryl acetate, glycyrrhizic acid, tranexamic acid and derivatives or salts thereof; and sugars such as vitamin C, magnesium ascorbic acid phosphate, ascorbic acid glucoside, arbutin, kojic acid, glucose, fructose, and trehalose.
[0068]
[0069] Another aspect provides a method of preventing, improving, or treating a condition of a subject comprising the step of treating or administering to a subject in need thereof an effective amount of the above composition.
[0070] In addition, another aspect provides a use for preparing the above composition for use in preventing, improving, or treating the above-mentioned disease.
[0071] The condition of the above entity may be an inflammatory condition or a bacterial infection condition.
[0072] Administration may be by any method known in the art. Administration may be administered directly to the subject by any means, including intravenous, intramuscular, oral, transdermal, mucosal, intranasal, intratracheal, or subcutaneous administration. Administration may be systemic or local.
[0073] The subject may be a mammal, such as a human, cow, horse, pig, dog, sheep, goat, or cat. The subject may be an individual in need of an improvement in a condition associated with inflammation or a condition associated with a bacterial infection.
[0074] The above administration is 0.00001 mg to 1,000 mg of the composition according to one specific example per subject per day, for example, 0.00001 mg to 500 mg, 0.00001 mg to 100 mg, 0.00001 mg to 50 mg, 0.00001 mg to 25 mg, 1 mg to 1,000 mg, 1 mg to 500 mg, 1 mg to 100 mg, 1 mg to 50 mg, 1 mg to 25 mg, 5 mg to 1,000 mg, 5 mg to 500 mg, 5 mg to 100 mg, 5 mg to 50 mg, 5 mg to 25 mg, 10 mg to 1,000 mg, 10 mg to 500 mg, 10 mg to 100 mg, 10 mg to 50 mg, Or it may be administered 10 mg to 25 mg. However, the dosage may be prescribed in various ways depending on factors such as the formulation method, administration method, patient's age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and response sensitivity, and a person skilled in the art can appropriately adjust the dosage by considering these factors. The frequency of administration can be once a day or twice or more within the range of clinically acceptable side effects, and the administration site can be administered in one or more sites, and the total number of administration days can be administered daily or at intervals of 2 to 5 days, from 1 day to 30 days for a single treatment. If necessary, the same treatment can be repeated after an appropriate period. For animals other than humans, the same dosage as for humans per kg can be administered, or the above dosage can be converted into an amount based on the volume ratio (e.g., average value) of the organs (heart, etc.) of the target animal and humans.
[0075] According to the novel strain and the endoplasmic reticulum derived therefrom, it has the effect that it can be usefully used in the prevention, improvement, or treatment of inflammatory conditions or bacterial infections.
[0076] Figure 1 is a graph showing the amount of nitric oxide produced according to cell treatment of the endoplasmic reticulum of a strain according to one specific example; N: negative control, P: untreated control, EV: endoplasmic reticulum of Example 2.
[0077] Figure 2 is a graph showing the protein expression levels of pro-inflammatory cytokines (TNF and CCL2) and anti-inflammatory cytokines (IL-10) in the cell processing of the endoplasmic reticulum of a strain according to one specific example; N: negative control, P: untreated control, EV: endoplasmic reticulum of Example 2.
[0078] Figure 3 is a graph showing the culture rate according to co-culture of a strain and C. difficile according to one specific example; C. difficile: Clostridioides difficile, BBH043: Example 1 strain, Type: Blautia hominis standard strain.
[0079] Figure 4 is a graph showing the culture rate of C. difficile in the endoplasmic reticulum of a strain according to one specific example; C. difficile: Clostridioides difficile, BBH043: endoplasmic reticulum of the strain of Example 1, Type: endoplasmic reticulum of the standard strain of Blautia hominis.
[0080] Figure 5 is a graph showing the cytotoxicity results of the endoplasmic reticulum of a strain according to one specific example; N: negative control, P: untreated control, EV: endoplasmic reticulum of Example 2.
[0081] Figure 6 is a graph showing the cytotoxicity results when the endoplasmic reticulum of a strain according to one specific example and Clostridioides difficile toxin B were treated together; C. difficiletoxin B: Clostridioides difficile toxin B, BBH043: endoplasmic reticulum of the strain of Example 1, Type strain: endoplasmic reticulum of the standard strain of Blautia hominis.
[0082] FIG. 7 is a graph showing the activity of the endoplasmic reticulum of a strain according to one specific example to reduce inflammation induced by Clostridioides difficile; C. difficiletoxin B: Clostridioides difficile toxin B, BBH043: endoplasmic reticulum of the strain of Example 1, Type strain: endoplasmic reticulum of the standard strain of Blautia hominis.
[0083] Figure 8 is a graph showing the amount of nitric oxide produced according to cell treatment of the endoplasmic reticulum of a strain according to one specific example; N: negative control, P: untreated control, EV: endoplasmic reticulum of Example 2.
[0084] Figure 9 is a graph showing the protein expression levels of proinflammatory cytokines (TNF, IL-6, and CCL2) in the cell processing of the endoplasmic reticulum of a strain according to one specific example; N: negative control, P: untreated control, EV: endoplasmic reticulum of Example 2.
[0085] Figure 10 is a graph showing the culture rate according to co-culture of a strain and C. difficile according to one specific example; C. difficile: Clostridioides difficile, BBH044: Example 1 strain, Type: Prevotella copri standard strain.
[0086] Figure 11 is a graph showing the culture rate of C. difficile in the endoplasmic reticulum of a strain according to one specific example; C. difficile: Clostridioides difficile, BBH044: endoplasmic reticulum of the strain of Example 1, Type: endoplasmic reticulum of the standard strain Prevotella copri.
[0087] Figure 12 is a graph showing the cytotoxicity results of the endoplasmic reticulum of a strain according to one specific example; N: negative control, P: untreated control, EV: endoplasmic reticulum of Example 2.
[0088] Figure 13 is a graph showing the cytotoxicity results when the endoplasmic reticulum of a strain according to one specific example and Clostridioides difficile toxin B were treated together; C. difficiletoxin B: Clostridioides difficile toxin B, BBH044: endoplasmic reticulum of the strain of Example 1, Type strain: endoplasmic reticulum of the standard strain of Prevotella copri.
[0089] Figure 14 is a graph showing the activity of reducing inflammation induced by Clostridioides difficile of the endoplasmic reticulum of a strain according to one specific example; C. difficiletoxin B: Clostridioides difficile toxin B, BBH044: endoplasmic reticulum of the strain of Example 1, Type strain: endoplasmic reticulum of the standard strain of Prevotella copri
[0090] Figure 15 is a graph showing the amount of nitric oxide produced according to cell treatment of the endoplasmic reticulum of a strain according to one specific example; N: negative control, P: untreated control, EV: endoplasmic reticulum of Example 2.
[0091] Figure 16 is a graph showing the protein expression levels of proinflammatory cytokines (TNF, IL-6, and CCL2) and anti-inflammatory cytokines (IL-10) in cell processing of the endoplasmic reticulum of a strain according to one specific example; N: negative control, P: untreated control, EV: endoplasmic reticulum of Example 2.
[0092] Figure 17 is a graph showing the culture rate according to co-culture of a strain and C. difficile according to one specific example; C. difficile: Clostridioides difficile, BBH045: Example 1 strain, Type: Rimosyl Lactobacillus mucoceus standard strain.
[0093] Figure 18 is a graph showing the culture rate of C. difficile in the endoplasmic reticulum of a strain according to one specific example; C. difficile: Clostridioides difficile, BBH045: endoplasmic reticulum of the strain of Example 1, Type: endoplasmic reticulum of the standard strain of Rimosyl Lactobacillus mucosa.
[0094] Figure 19 is a graph showing the cytotoxicity results of the endoplasmic reticulum of a strain according to one specific example; N: negative control, P: untreated control, EV: endoplasmic reticulum of Example 2.
[0095] FIG. 20 is a graph showing the cytotoxicity results when the endoplasmic reticulum of a strain according to one specific example and Clostridioides difficile toxin B were treated together; C. difficiletoxin B: Clostridioides difficile toxin B, BBH045: endoplasmic reticulum of the strain of Example 1, Type strain: endoplasmic reticulum of the standard strain of Rimosyl Lactobacillus mucosa.
[0096] FIG. 21 is a graph showing the activity of reducing inflammation induced by Clostridioides difficile of the endoplasmic reticulum of a strain according to one specific example; C. difficiletoxin B: Clostridioides difficile toxin B, BBH045: endoplasmic reticulum of the strain of Example 1, Type strain: endoplasmic reticulum of the standard strain of Lactobacillus mucosa.
[0097] The following examples are provided for more detailed description. However, these examples are provided solely to illustrate one or more specific examples, and the scope of the present invention is not limited to these examples.
[0098]
[0099] Example 1. Isolation and identification of strains
[0100] To isolate and identify strains from the feces of healthy people, the following procedures were performed.
[0101] First, 1 g of feces collected from a healthy person and 10 ml of 1 x PBS (phosphate buffer saline) were mixed and vortexed to suspend the feces. Then, the feces were filtered through a cell strainer to remove undigested food and small particles. The filtered feces suspension was serially diluted and placed in a 10 MRS plate. -6 ~10-8 Spreading was performed and the bacteria were selected after culturing at 37℃ for more than 3 days. PCR amplification was performed on the colonies after culture was completed, and the base sequence of the 16S rRNA region determined among the isolated cultured microbial colonies was compared and analyzed with other registered strains using the BLAST program provided on the National Center for Biotechnology Information (NCBI) website.
[0102] As a result of comparative analysis, Blautia hominis BBH043 with 98.74% homology was isolated. The selected Blautia hominis BBH043 strain was deposited at the Korea Center for Biological Resources on January 16, 2023, and was assigned the accession number KCTC 15293BP. The Blautia hominis BBH043 strain has the 16S rRNA sequence of sequence number 1 (complementary DNA).
[0103] As a result of comparative analysis, Prevotella copriBBH044 with 98.61% homology was isolated. The selected Prevotella copriBBH044 strain was deposited with the Korea Center for Biological Resources on January 6, 2023, and was assigned the accession number KCTC 15272BP. The Prevotella copriBBH044 strain has the 16S rRNA sequence of sequence number 2 (complementary DNA).
[0104] As a result of comparative analysis, Limosilactobacillus mucosaeBBH045 with 99.67% homology was isolated. The selected Limosilactobacillus mucosaeBBH045 strain was deposited at the Korea Biological Resource Center on January 6, 2023, and was assigned the accession number KCTC 15273BP. The Limosilactobacillus mucosaeBBH045 strain has a 16S rRNA sequence of sequence number 3 (complementary DNA).
[0105]
[0106] Example 2. Isolation of endoplasmic reticulum
[0107] In the above example, the endoplasmic reticulum of the isolated strain was isolated.
[0108] Specifically, to prepare vesicles, the isolated strain was cultured in MRS broth at 30°C under aerobic conditions for 2 days. The culture was then centrifuged at 5000 xg for 20 minutes to remove bacterial debris. Subsequently, the culture was filtered through a 0.45 μm filter and then again through a 0.22 μm filter, and then a centrifuge tube (Amicon® Ultra-15 Centrifugal Filter Unit) was used to concentrate substances weighing 100 kDa or more, and the vesicles of the isolated strain were isolated.
[0109]
[0110] Experimental Example 1. Anti-inflammatory activity analysis
[0111] The anti-inflammatory activity of the endoplasmic reticulum of the strain isolated in Example 2 above was analyzed.
[0112] First, to evaluate the anti-inflammatory activity, the decrease in nitric oxide (NO) production was measured. Mouse macrophage Raw264.7 cells were cultured in DMEM (Dulbecco's Modified Eagle Medium) containing 10% fetal bovine serum (FBS), 1% antibiotics (100 U / mL penicillin and 100 μg / mL streptomycin) at 5% CO 2 Cultured at 37°C in the presence of 10% CO. Afterwards, the Raw 264.7 cells were seeded in a 48-well plate at a density of 6 × 10 4 300 μL was dispensed at a concentration of 10 cells / well and cultured in a CO2 incubator at 37°C for 24 hours. The well supernatant was discarded, and the medium containing 10 μg / ml lipopolysaccharide (LPS) to induce inflammation was dispensed, and the culture was further performed for 4 hours. The supernatant containing LPS was discarded, and the vesicles were divided into 1 × 10 3 1 X 105 The cells were treated by adding them to the medium at a concentration of 100 particles / ml and then cultured at 37°C for 16 hours. Afterwards, 50 μL of the well supernatant and 50 μL of Griess reagent were mixed and reacted at room temperature for 10 minutes. The amount of nitric oxide produced was measured by measuring the absorbance at 540 nm using a plate reader, and the results are shown in Figures 1, 8, and 15 for each strain, respectively.
[0113]
[0114] FIG. 1, FIG. 8 and FIG. 15 are graphs showing the amount of nitric oxide produced according to cell treatment of the endoplasmic reticulum of a strain according to one specific example; N: negative control, P: untreated control, EV: endoplasmic reticulum of Example 2.
[0115]
[0116] As shown in FIGS. 1, 8, and 15, it was found that the endoplasmic reticulum of the strain according to one specific example significantly reduced the NO production of inflammation-induced cells compared to the untreated control group.
[0117]
[0118] Next, the proinflammatory cytokine inhibitory activity and anti-inflammatory cytokine promoting activity of the endoplasmic reticulum of the strain were measured. Specifically, 1 X 10 of the endoplasmic reticulum was injected into Raw264.7 cells treated with LPS using the same method as above. 3 1 X 10 8 particles / ml and then cultured at 37°C for 16 hours. Thereafter, the protein expression of the pro-inflammatory cytokines TNF, CCL2, and IL-6 of the cells and the protein expression of the anti-inflammatory cytokine IL-10 were measured by absorbance at 450 nm using an ELISA kit (BD bioscience, USA) according to the manufacturer's instructions, and the results are shown in Figs. 2, 9, and 16 for each strain, respectively.
[0119]
[0120] FIG. 2, FIG. 9 and FIG. 16 are graphs showing the protein expression levels of proinflammatory cytokines (TNF, CCL2, IL-6) and anti-inflammatory cytokines (IL-10) in cell processing of the endoplasmic reticulum of a strain according to one specific example; N: negative control, P: untreated control, EV: endoplasmic reticulum of Example 2.
[0121]
[0122] As shown in Fig. 2, it was found that the endoplasmic reticulum of the strain according to one specific example significantly reduced pro-inflammatory cytokines compared to the untreated control group and significantly increased anti-inflammatory cytokines compared to the untreated control group.
[0123] As shown in Fig. 9, it was found that the endoplasmic reticulum of the strain according to one specific example significantly reduced proinflammatory cytokines compared to the untreated control group.
[0124] As shown in Fig. 16, it was found that the endoplasmic reticulum of the strain according to one specific example significantly reduced pro-inflammatory cytokines compared to the untreated control group and significantly increased anti-inflammatory cytokines compared to the untreated control group.
[0125]
[0126] The above results imply that the strain according to one specific example can be useful for preventing, improving, or treating inflammatory diseases, particularly inflammatory bowel disease or irritable bowel syndrome.
[0127]
[0128] Experimental Example 2. Antibacterial Activity Analysis
[0129] The antibacterial activity of the strain isolated in Example 1 above was analyzed.
[0130] Specifically, in order to analyze the antibacterial activity of the strain of Example 1 against Clostridioides difficile, the C. difficile strain was pre-cultured in BHI broth and the strain of Example 1 in MRS broth, and then inoculated into BHI broth at a ratio of 1%. The C. difficile strain was anaerobically cultured at 37°C for 24 hours, and the strain of Example 1 was aerobically cultured at 30°C for 24 hours. The cultured strain of Example 1 was centrifuged at 5000 xg for 20 minutes to separate the pellet and the supernatant, and the pellet was washed twice with PBS and resuspended, and then each was adjusted to an OD of 0.5. C. difficile and the strain of Example 1 were inoculated into 30 ml of BHI broth at the same ratio, and then C. The culture rate of Clostridioides difficile was measured using the colony forming unit calculation method. In order to compare the antibacterial activity with the strains of Example 1, the Blautia hominis standard strain (KCTC15618), Prevotella copri standard strain (DSM18205), and Rimosyl Lactobacillus mucoce standard strain (KCTC21011) were also analyzed for antibacterial activity against Clostridioides difficile using the same method as above. The results of the analysis are shown for each strain in Figs. 3, 10, and 17.
[0131]
[0132] In addition, in order to analyze the antibacterial activity of the endoplasmic reticulum of the strain of the above example against C. difficile, the endoplasmic reticulum was isolated by the method of Example 2. After culturing C. difficile in BHI broth for 48 hours and adjusting the OD to 0.5, the endoplasmic reticulum of the strain of the above example was inoculated with C. difficile at a ratio of 10%, and then cultured under anaerobic conditions for 1 day. Thereafter, the culture rate of C. difficile was measured spectrophotometrically. The results of the analysis are shown in FIG. 4, FIG. 11, and FIG. 18 for each strain, respectively.
[0133]
[0134] Figure 3 is a graph showing the culture rate according to co-culture of a strain and C. difficile according to one specific example; C. difficile: Clostridioides difficile, BBH043: Example 1 strain, Type: Blautia hominis standard strain.
[0135] Figure 10 is a graph showing the culture rate according to co-culture of a strain and C. difficile according to one specific example; C. difficile: Clostridioides difficile, BBH044: Example 1 strain, Type: Prevotella copri standard strain.
[0136] Figure 17 is a graph showing the culture rate according to co-culture of a strain and C. difficile according to one specific example; C. difficile: Clostridioides difficile, BBH045: Example 1 strain, Type: Rimosyl Lactobacillus mucoceus standard strain.
[0137]
[0138] Figure 4 is a graph showing the culture rate of C. difficile in the endoplasmic reticulum of a strain according to one specific example; C. difficile: Clostridioides difficile, BBH043: endoplasmic reticulum of the strain of Example 1, Type: endoplasmic reticulum of the standard strain of Blautia hominis.
[0139] Figure 11 is a graph showing the culture rate of C. difficile in the endoplasmic reticulum of a strain according to one specific example; C. difficile: Clostridioides difficile, BBH044: endoplasmic reticulum of the strain of Example 1, Type: endoplasmic reticulum of the standard strain Prevotella copri.
[0140] Figure 18 is a graph showing the culture rate of C. difficile in the endoplasmic reticulum of a strain according to one specific example; C. difficile: Clostridioides difficile, BBH045: endoplasmic reticulum of the strain of Example 1, Type: endoplasmic reticulum of the standard strain of Rimosyl Lactobacillus mucosa.
[0141]
[0142]
[0143] As shown in Fig. 3, the strain according to one specific example was found to significantly reduce the growth rate of C. difficile to around 29%. In contrast, the standard strain of Blautia hominis showed a growth rate of C. difficile of approximately 194%.
[0144] As shown in Fig. 10, it was found that the strain according to one specific example significantly reduced the growth rate of C. difficile to 6.9%. In contrast, in the case of the standard strain of Prevotella copri, C. difficile showed a growth rate of approximately 120%.
[0145] As shown in Fig. 17, it was found that the strain according to one specific example and the standard strain of Limosyl Lactobacillus mucosa completely inhibited the growth rate of C. difficile to 0%.
[0146]
[0147] As shown in Fig. 4, the endoplasmic reticulum of the strain according to one specific example was found to significantly reduce the growth rate of C. difficile to around 32%. In contrast, the endoplasmic reticulum of the standard strain of Blautia hominis was found to reduce the growth rate of C. difficile to around 76%.
[0148] As shown in Fig. 11, the endoplasmic reticulum of the strain according to one specific example exhibited an antibacterial effect against C. difficile at a level of about 72% of that of the endoplasmic reticulum of the standard strain of Prevotella copri.
[0149] As shown in Fig. 18, the endoplasmic reticulum of the strain according to one specific example reduced the growth rate of C. difficile to 35%, and in the case of the endoplasmic reticulum of the standard strain of Rimosyl Lactobacillus mucosa, it was found that the growth rate of C. difficile was reduced to 39%.
[0150]
[0151] The above results indicate that the strain according to one embodiment and / or the vesicles derived therefrom have antibacterial activity against bacteria, for example, Gram-negative bacteria, and that the activity is higher than that of a standard strain. In particular, these results indicate that the strain according to one embodiment and / or the vesicles derived therefrom can be usefully used for the prevention, improvement, or treatment of Clostridioides difficile infection (CDI) or irritable bowel syndrome caused thereby.
[0152]
[0153] Experimental Example 3. Cytotoxicity Test
[0154] For the cytotoxicity test of the endoplasmic reticulum of the strain isolated in Example 2 above, a Cell viability assay kit (WST-8, Biomax, Korea) was used.
[0155] Specifically, Raw264.7 cells were seeded at 6 × 10 in 48-well plates. 4 300 μL was dispensed at a concentration of 10 cells / well and cultured in a CO2 incubator at 37°C for 24 hours. The well supernatant was discarded, and the medium containing 10 μg / ml lipopolysaccharide (LPS) to induce inflammation was dispensed, and the culture was further performed for 4 hours. The supernatant containing LPS was discarded, and the vesicles were divided into 1 × 10 3 1 X 10 8 The cells were treated by adding them to the medium at a concentration of 10 particles / ml and then incubated at 37°C for 16 hours. Afterwards, the supernatant was removed, and 300 μl of the medium containing 10% WST-8 solution was treated to each well and reacted for 4 hours. After 4 hours, the concentration of water-soluble formazan produced by succinate dehydrogenase present in the mitochondria of living cells was measured by measuring the absorbance at 450 nm to determine the cell viability, and the results are shown in Figs. 5, 12, and 19 for each strain, respectively.
[0156]
[0157] FIG. 5, FIG. 12 and FIG. 19 are graphs showing the cytotoxicity results of the endoplasmic reticulum of a strain according to one specific example; N: negative control, P: untreated control, EV: endoplasmic reticulum of Example 2.
[0158]
[0159] As shown in FIG. 5, FIG. 12 and FIG. 19, the endoplasmic reticulum of the strain according to one specific example is 1 X 10 3 1 X 10 8 It was found that no cytotoxicity was observed at a concentration of particles / ml.
[0160]
[0161] Experimental Example 4. Analysis of the activity to reduce inflammation induced by Clostridioides difficile toxin B.
[0162] The effect of reducing pro-inflammatory cytokines and increasing anti-inflammatory cytokines induced by Clostridioides difficile toxin B in the endoplasmic reticulum of the strain isolated in Example 1 was confirmed.
[0163] First, mouse macrophage Raw264.7 cells were treated with Clostridioides difficile toxin B (C. difficiletoxin B) at an amount of 10 ng / ml in the same manner as in Experimental Example 1, and then cultured at 37°C for 4 hours. Afterwards, 1 X 10 of the endoplasmic reticulum of the Blautia hominis standard strain (KCTC15618) and the Blautia hominis strain of Example 1, the endoplasmic reticulum of the Prevotella copri standard strain (DSM18205) and the Prevotella copri strain of Example 1, or the endoplasmic reticulum of the Rimosyl Lactobacillus mucoce standard strain (KCTC21011) and the Rimosyl Lactobacillus mucoce strain of Example 1 were added to each well. 3 1 X 10 8 After treatment at a concentration of particles / ml, the cells were cultured at 37°C for 16 hours, and the cell viability was measured using the same method as in Experimental Example 3, and the results are shown in Figs. 6, 13, and 20.
[0164] In addition, the relative concentrations of pro-inflammatory cytokines TNF and CCL2 and anti-inflammatory cytokine IL-10 in the cells were measured by absorbance at 450 nm using an ELISA kit (BD bioscience, USA) according to the manufacturer's instructions, and the results are shown in Figs. 7, 14, and 21.
[0165]
[0166] Figure 6 is a graph showing the cytotoxicity results when the endoplasmic reticulum of a strain according to one specific example and Clostridioides difficile toxin B were treated together; C. difficiletoxin B: Clostridioides difficile toxin B, BBH043: endoplasmic reticulum of the strain of Example 1, Type strain: endoplasmic reticulum of the standard strain of Blautia hominis.
[0167] Figure 13 is a graph showing the cytotoxicity results when the endoplasmic reticulum of a strain according to one specific example and Clostridioides difficile toxin B were treated together; C. difficiletoxin B: Clostridioides difficile toxin B, BBH044: endoplasmic reticulum of the strain of Example 1, Type strain: endoplasmic reticulum of the standard strain of Prevotella copri.
[0168] FIG. 20 is a graph showing the cytotoxicity results when the endoplasmic reticulum of a strain according to one specific example and Clostridioides difficile toxin B were treated together; C. difficiletoxin B: Clostridioides difficile toxin B, BBH045: endoplasmic reticulum of the strain of Example 1, Type strain: endoplasmic reticulum of the standard strain of Rimosyl Lactobacillus mucosa.
[0169]
[0170] FIG. 7 is a graph showing the activity of the endoplasmic reticulum of a strain according to one specific example to reduce inflammation induced by Clostridioides difficile; C. difficiletoxin B: Clostridioides difficile toxin B, BBH043: endoplasmic reticulum of the strain of Example 1, Type strain: endoplasmic reticulum of the standard strain of Blautia hominis.
[0171] FIG. 14 is a graph showing the activity of the endoplasmic reticulum of a strain according to one specific example to reduce inflammation induced by Clostridioides difficile; C. difficiletoxin B: Clostridioides difficile toxin B, BBH044: endoplasmic reticulum of the strain of Example 1, Type strain: endoplasmic reticulum of the standard strain of Prevotella copri.
[0172] FIG. 21 is a graph showing the activity of reducing inflammation induced by Clostridioides difficile of the endoplasmic reticulum of a strain according to one specific example; C. difficiletoxin B: Clostridioides difficile toxin B, BBH045: endoplasmic reticulum of the strain of Example 1, Type strain: endoplasmic reticulum of the standard strain of Lactobacillus mucosa.
[0173]
[0174] As shown in FIG. 6, FIG. 13 and FIG. 20, no cytotoxicity was observed in the endoplasmic reticulum of both the strain according to one specific example and the standard strain.
[0175]
[0176] In addition, as shown in FIG. 7, FIG. 14, and FIG. 21, it was found that the endoplasmic reticulum of the strain according to one specific example significantly reduced the pro-inflammatory cytokines TNF and CCL2 increased by Clostridioides difficile toxin B compared to the standard strain, and significantly increased the anti-inflammatory cytokine IL-10 compared to the standard strain.
[0177]
[0178] These results indicate that the strain and / or the vesicles derived therefrom according to one specific example have significant anti-inflammatory activity compared to the standard strain, and thus can be usefully used for the prevention, improvement, or treatment of Clostridioides difficile infection (CDI) or irritable bowel syndrome caused thereby.
[0179]
[0180] [Accession number]
[0181] Name of depositor: Korea Biological Resource Center (overseas)
[0182] Accession number: KCTC 15293BP
[0183] Date of acceptance: 20230116
[0184]
[0185]
[0186] [Accession number]
[0187] Name of depositor: Korea Biological Resource Center (overseas)
[0188] Accession number: KCTC 15272BP
[0189] Date of acceptance: 20230106
[0190]
[0191]
[0192] [Accession number]
[0193] Name of depositor: Korea Biological Resource Center (overseas)
[0194] Accession number: KCTC 15273BP
[0195] Date of acceptance: 20230106
[0196]
Claims
1. A strain of Blautia hominis belonging to the genus Blautia, deposited under the accession number KCTC 15293BP; a strain of Prevotella copri belonging to the genus Prevotella sp., deposited under the accession number KCTC 15272BP; or a strain of Limosilactobacillus mucosae belonging to the genus Limosilactobacillus sp., deposited under the accession number KCTC 15273BP.
2. In claim 1, the strain comprises 16S rRNA of sequence number 1, sequence number 2, or sequence number 3.
3. Endoplasmic reticulum derived from the strain of claim 1.
4. A fragment of the strain of claim 1.
5. Culture medium of the strain of claim 1.
6. A composition having antibacterial or anti-inflammatory activity, comprising as an active ingredient a Blautia hominis strain, a Prevotella copri strain, or a Rimosyl Lactobacillus mucoceae strain; an endoplasmic reticulum derived from any one of the above strains; a lysate of any one of the above strains; a culture medium of any one of the above strains; or a mixture thereof.
7. A composition according to claim 6, wherein the composition has an activity of inhibiting the production of inflammatory cytokines.
8. A pharmaceutical composition for preventing or treating an inflammatory disease, comprising as an active ingredient a Blautia hominis strain, a Prevotella copri strain, or a Rimosyl Lactobacillus mucoce strain; an endoplasmic reticulum derived from any one of the above strains; a lysate of any one of the above strains; a culture medium of any one of the above strains; or a mixture thereof.
9. A pharmaceutical composition according to claim 8, wherein the inflammatory disease is an inflammatory disease of the digestive system.
10. In claim 8, the inflammatory disease is a pharmaceutical composition for preventing or treating inflammatory bowel diseases (IBD); irritable bowel syndrome; enteritis, Crohn's disease; or ulcerative colitis.
11. A health functional food for preventing or improving inflammatory diseases, comprising as an active ingredient a Blautia hominis strain, a Prevotella copri strain, or a Rimosyl Lactobacillus mucoce strain; an endoplasmic reticulum derived from any one of the above strains; a lysate of any one of the above strains; a culture medium of any one of the above strains; or a mixture thereof.
12. A health functional food for preventing or improving intestinal health, comprising as an active ingredient a Blautia hominis strain, a Prevotella copri strain, or a Rimosyl Lactobacillus mucoce strain; an endoplasmic reticulum derived from any one of the above strains; a lysate of any one of the above strains; a culture medium of any one of the above strains; or a mixture thereof.
13. A pharmaceutical composition for preventing or treating bacterial infection, comprising as an active ingredient a Blautia hominis strain, a Prevotella copri strain, or a Rimosyl Lactobacillus mucoce strain; an endoplasmic reticulum derived from any one of the above strains; a lysate of any one of the above strains; a culture medium of any one of the above strains; or a mixture thereof.
14. A pharmaceutical composition according to claim 11, wherein the bacterial infection is Clostridioides difficile infection (CDI).
15. A health functional food for preventing or improving bacterial infection, comprising as an active ingredient a Blautia hominis strain, a Prevotella copri strain, or a Rimosyl Lactobacillus mucoce strain; an endoplasmic reticulum derived from any one of the above strains; a lysate of any one of the above strains; a culture solution of any one of the above strains; or a mixture thereof.
16. A method for preventing or treating an inflammatory disease, comprising administering to a subject in need thereof a Blautia hominis strain, a Prevotella copri strain, or a Rimosyl Lactobacillus mucoce strain; an endoplasmic reticulum derived from any one of the above strains; a lysate of any one of the above strains; a culture medium of any one of the above strains; or a mixture thereof.
17. A method for preventing or treating bacterial infection, comprising administering to a subject in need thereof a strain of Blautia hominis, a strain of Prevotella copri, or a strain of Rimosyl Lactobacillus mucoce; an endoplasmic reticulum derived from any one of the above strains; a lysate of any one of the above strains; a culture of any one of the above strains; or a mixture thereof.
18. Use of a Blautia hominis strain, a Prevotella copri strain, or a Rimosyl Lactobacillus mucoce strain; an endoplasmic reticulum derived from any one of the above strains; a lysate of any one of the above strains; a culture medium of any one of the above strains; or a mixture thereof for the preparation of a composition for the prevention or treatment of an inflammatory disease.
19. Use of a Blautia hominis strain, a Prevotella copri strain, or a Rimosyl Lactobacillus mucoce strain; an endoplasmic reticulum derived from any one of the above strains; a lysate of any one of the above strains; a culture medium of any one of the above strains; or a mixture thereof for use in the manufacture of a composition for preventing or treating bacterial infection.
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