WO2016153247A1 - Souche de clostridium butyricum présentant une amélioration immunitaire et activités antivirales, et utilisation correspondante - Google Patents

Souche de clostridium butyricum présentant une amélioration immunitaire et activités antivirales, et utilisation correspondante Download PDF

Info

Publication number
WO2016153247A1
WO2016153247A1 PCT/KR2016/002839 KR2016002839W WO2016153247A1 WO 2016153247 A1 WO2016153247 A1 WO 2016153247A1 KR 2016002839 W KR2016002839 W KR 2016002839W WO 2016153247 A1 WO2016153247 A1 WO 2016153247A1
Authority
WO
WIPO (PCT)
Prior art keywords
strain
virus
cells
composition
antiviral
Prior art date
Application number
PCT/KR2016/002839
Other languages
English (en)
Korean (ko)
Inventor
장영효
백자영
신예슬
Original Assignee
한국생명공학연구원
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 한국생명공학연구원 filed Critical 한국생명공학연구원
Priority to CN201680003213.7A priority Critical patent/CN107075460B/zh
Publication of WO2016153247A1 publication Critical patent/WO2016153247A1/fr

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • C12N1/205—Bacterial isolates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
    • C12R2001/145—Clostridium
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/10—Animal feeding-stuffs obtained by microbiological or biochemical processes
    • A23K10/16—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/742—Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/40—Preparation of oxygen-containing organic compounds containing a carboxyl group including Peroxycarboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/40—Preparation of oxygen-containing organic compounds containing a carboxyl group including Peroxycarboxylic acids
    • C12P7/54—Acetic acid
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/32—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the digestive tract
    • A23V2200/3204—Probiotics, living bacteria to be ingested for action in the digestive tract

Definitions

  • the present invention relates to a strain of Clostridium butyricum having an immune enhancing and antiviral activity and its use, and more particularly to a Clostridium butyricum strain having the immune enhancing and antiviral activity, the strain or Butyric acid comprising the step of culturing the strain and the composition for immune enhancement and antiviral, probiotic composition, antimicrobial composition, butyric acid or acetic acid production containing the culture thereof as an active ingredient Or to a method of producing acetic acid.
  • Immunity is largely divided into innate immunity, which has been born since birth, and acquired immunity, which is obtained by adapting to life after being acquired.
  • Innate immunity also known as 'natural immunity', is characterized by a nonspecific response to antigen.
  • Innate immune systems include skin, mucus, acidic gastric acid, complement and antimicrobial peptides present in the blood, and Pattern Recognition Receptors containing TLRs (Toll like receptors) to block antigen invasion
  • the cells include macrophages (macrophage) and polymorpho nuclear leukocytes (polymorpho nuclear leukocytes) that are responsible for phagocytosis, and K cells that can kill infected cells. In fact, most pathogen infections are initially defended by this innate immunity.
  • Innate immunity basically distinguishes between self and non-magnetic. In other words, it recognizes self and pathogens, and the elements that are recognized as nonmagnetic devices have unique molecular biochemical characteristics. This is called Pathogen-Associated Molecular Pattern (PAMP), and the receptor that recognizes it is PRR (Pattern Recognition Receptor). It is called. PRRs known to date can be classified into four types: toll like receptor (TLR), RIG-I-like helicase (RLH), nod-like receptor (NLR), and C-type lectin receptor (CLR). . Each PRR differs depending on the specificity of the recognized PAMP and plays a starting role in the activation mechanism of the innate immune system.
  • the most important research area in the innate defense immune system as a defense against viral infection is the innate immunity induced by interferon, and the activation of such interferon-mediated immunity is a fundamental prevention against various viral infectious agents. It can be a way. Therefore, studies on the interferon activation mechanism and the development of immunomodulators capable of inducing interferon are active.
  • immune factors inflammatory cytokines
  • inducing an appropriate level of inflammatory response may also be a prophylactic and treatment method for various infectious disease pathogens, and research on the development of immunopotentiators capable of inducing this is necessary.
  • Virus refers to a toxic substance in Latin and refers to a group of infectious pathogenic particles passing through a bacterial filter paper (0.22 ⁇ m). Viruses may be classified as bacteriophage, plant viruses, or animal viruses according to host cell types, and may be classified as DNA viruses or RNA viruses according to nucleic acid types. Recently, various viral diseases such as swine flu, AI and foot-and-mouth disease cause social problems, and concerns about effective measures for viral diseases are raising social attention.
  • Vaccination is the best way to prevent viral disease at present. Nevertheless, the disease caused by RNA virus has become an important issue due to the effectiveness of vaccines due to the generation of many virus serotypes (subtypes). Therefore, the development and dissemination of virus prevention inhibitors that can supplement the problems of vaccines.
  • the discovery and development of prophylactic agents that enhance the immunity of individuals by stimulating the innate immune system in vivo can be an important agent development method.
  • As a method of stimulating the innate immune system in vivo to increase an individual's immunity foods having an immunomodulatory action may be consumed.
  • Probiotics are commercially available as such functional food materials. Lactic acid bacteria, lactic acid bacteria, Bacillus bacteria, yeast bacteria, fungi, etc.
  • Probiotics are distributed in the intestines of humans and animals, have the effect of inhibiting the growth of harmful microorganisms in the intestine, treating abnormal fermentation, lowering blood cholesterol, enhancing immune function, and also have anti-cancer effects. Lactic acid bacteria-containing fermented dairy products and formals have been commercialized and widely consumed or edible so that humans can consume these probiotics to promote health. Recently, studies on the inhibition of viral infection by lactic acid bacteria have been reported.
  • lactic acid bacteria are representative microorganisms of the fermentation industry, and most studies on lactic acid bacteria have been mainly carried out by lactic acid bacteria having acid resistance, bile acid resistance and harmful microbial inhibitory activity.
  • Herpes simplex virus is the cause of painful skin or mucosal lesions that appear in the form of blisters filled with clear fluid.
  • Herpes simplex virus (HSV) type 1 (HSV-1) mainly infects the mouth, face and eyes.
  • Herpes simplex virus (HSV) type 2 (HSV-2) mainly infects the genitals and buttocks.
  • HSV Herpes simplex virus
  • HSV-1 and type 2 serotype can cause infection at all sites.
  • Primary infection with herpes simplex virus (HSV) generally causes mild fever lesions at the site of infection. The duration of treatment ranges from 8 to 12 days on average, during which the virus migrates to the ganglion where it lingers.
  • a latent virus can be reactivated by a variety of causes, including physical or emotional stress, cold, fever, reduced immune function, or an unknown cause. When activated, this causes a secondary infection.
  • VSV Bullous stomatitis virus
  • RNA virus a negative stranded RNA virus that infects most mammalian cells and expresses up to 60% of the viral proteins of the infected cells.
  • VSV infects pigs, cows and horses and causes vesicular disease around the mouth and feet.
  • human infection by VSV has been reported, VSV does not cause serious symptoms in humans.
  • Influenza viruses belong to the Orthomyxoviridae and have eight negative sense RNA fragments of PB2, PB1, PA, HA, NP, NA, M and NS.
  • the two proteins hemagglutinin (abbreviated as “HA”) and neuraminidase (abbreviated as "NA”) that make up the envelope protein are important immunogens for inducing immune antibodies. They are characterized by modification through antigenic / antigenic shift and drift. Such flu virus changes can also avoid immunity against other influenza viruses in the same subspecies. In general, immunity induced by influenza virus is lost in a short period of time, and for viruses that are expected to be epidemic every season. Induce new immunity
  • Newcastle disease is a lethal, highly contagious livestock epidemic in poultry, with a 100% mortality rate when infected with unvaccinated chickens. If not properly vaccinated, respiratory and digestive symptoms and laying rates in laying hens It is a deadly disease that causes economic damage from degradation. Every year, announcing advisories are issued, but the number of occurrences continues to increase and occurs nationwide. The main symptoms of Newcastle disease begin to slumber, show respiratory symptoms such as runny nose and cough, and die from green diarrhea.
  • the vaccine is not properly administered, laying hens or breeders with low antibody titers may have lower or lower egg production rates, and even if they are vaccinated, neurological symptoms of paralysis of legs and neck may occur in chickens with high antibody titers due to incorrect timing or methods of vaccination. It may appear.
  • Korean Patent Publication No. 2010-0044472 discloses 'Crotritium Butyricum IDC 9207 white rice fermented product that inhibits intestinal harmful bacteria and enhances immunity', and in Korean Patent Publication No. 2013-0028279
  • the present invention was derived by the above-described needs, and in the present invention, two strains of Clostridium butyricum were isolated from feces of adults and infants, and the two strains were composed of a variety of RNA viruses and It was confirmed that the antiviral activity is excellent against the DNA virus. In addition, it was confirmed that the antimicrobial activity against harmful bacteria, acid and bile resistance, antibiotic resistance and intestinal adhesiveness can be very useful for antiviral as well as probiotic or antibacterial. In addition, the two strains produced butyric acid (butyric acid) and acetic acid (acetic acid), thereby confirming that it can also be used for butyric acid or acetic acid production, the present invention was completed.
  • the present invention provides a Clostridium butyricum strain having immune enhancement and antiviral activity.
  • the present invention provides a composition for immune enhancement and antiviral containing the strain or its culture as an active ingredient.
  • the present invention also provides a probiotic composition containing the strain or its culture as an active ingredient.
  • the present invention also provides an antimicrobial composition containing the strain or its culture as an active ingredient.
  • the present invention also provides a composition for producing butyric acid or acetic acid containing the strain or its culture as an active ingredient.
  • the present invention also provides a method for producing butyric acid or acetic acid comprising culturing the strain.
  • a novel Clostridium butyricum strain excellent in immunity and antiviral activity can be obtained, and when using the strain of the present invention and its culture, an antiviral composition, a probiotic composition, and an antimicrobial composition It can be usefully used in related industries for the production of butyric acid or acetic acid.
  • Figure 1 shows the 16S rRNA gene sequence of Clostridium butyricum Fb5-3 strain isolated in the present invention.
  • Figure 2 shows the 16S rRNA gene sequence of Clostridium butyricum S-45-5 strain isolated in the present invention.
  • Figure 3 is a result of analysis of butyric acid and organic acid of Clostridium butyricum Fb5-3 strain isolated in the present invention.
  • Figure 4 is a result of analyzing the acid and organic acids Clostridium butyricum S-45-5 strain isolated in the present invention.
  • FIG. 5 shows the results of analysis of antivirality of S-45-5 strain of the present invention against Vesicular stomatitis virus (VSV) (1.0 MOI) using Raw264.7 cells, which are mouse macrophage lines.
  • VSV Vesicular stomatitis virus
  • Figure 6 shows the results of analyzing the antivirality of the S-45-5 strain of the present invention against influenza virus (Influenza virus, PR8) using Raw264.7 cells, a mouse macrophage line.
  • Figure 7 shows the results of the antiviral analysis of the S-45-5 strain of the present invention against bullous stomatitis virus (VSV) (0.01 MOI) using HEK293T cells, human embryonic kidney cells.
  • VSV bullous stomatitis virus
  • FIG. 8 shows the results of analysis of the antivirality of the S-45-5 strain of the present invention against Herpes simplex virus (HSV) (3.0 MOI) using HEK293T cells, which are human embryonic kidney cells.
  • HSV Herpes simplex virus
  • NDV Newcastle disease virus
  • FIG. 10 shows the results of analysis of antivirality of the S-45-5 strain of the present invention against Herpes simplex virus (HSV) (3.0 MOI) using Raw264.7 cells, which are mouse macrophage lines.
  • HSV Herpes simplex virus
  • Figure 11 is a result of verifying the induction of pro-inflammatory cytokine (Inter-inflammatory cytokine & Interferon) of the S-45-5 strain of the present invention in Raw264.7 cells and HEK293T cells.
  • pro-inflammatory cytokine Inter-inflammatory cytokine & Interferon
  • FIG. 13 shows the results of activating antiviral related signal transduction molecules of S-45-5 strain in mouse macrophage line.
  • Figure 14 shows the results of influenza virus infection inhibition experiments of S-45-5 strain in mice.
  • Figure 15 shows the cytokine and IgA secretion induction experiment of the S-45-5 strain in mice. (DPT is Day Post-Infection)
  • Figure 16 shows the results of the analysis of the antiviral Fb5-3 strain of the present invention against bullous stomatitis virus (VSV) (1.0 MOI) using Raw264.7 cells.
  • VSV bullous stomatitis virus
  • FIG. 17 shows Fb5-3 of the present invention for influenza virus (PR8) (1.0 MOI). Antivirality of Strains Using Raw264.7 Cells The result of the analysis.
  • VSV bullous stomatitis virus
  • FIG. 21 shows the results of analysis of the antivirality of the Fb5-3 strain of the present invention against herpes simplex virus (HSV) (3.0 MOI) using HEK293T cells.
  • HSV herpes simplex virus
  • the present invention provides a Clostridium butyricum strain having immune enhancement and antiviral activity.
  • the Clostridium butyricum strain has antibacterial, acid and bile resistance, but may be a strain producing butyric acid (butyric acid) and acetic acid (acetic acid), This is not restrictive.
  • strains were isolated from feces of adults and infants, and among them, strains having excellent antiviral activity against viruses were isolated and identified as Clostridium butyricum strains.
  • the Clostridium butyricum strain may be Clostridium butyricum Fb5-3 strain (Accession No. KCTC12753BP) or Clostridium butyricum S-45-5 strain (Accession No. KCTC12754BP). It was deposited on February 03.
  • the present invention provides a composition for immune enhancement and antiviral containing the strain or its culture as an active ingredient.
  • the immune enhancing and antiviral composition may be used as a pharmaceutical composition or nutraceutical composition for immune enhancing and antiviral.
  • composition when it is a pharmaceutical composition for immune enhancing and antiviral, it may include pharmaceutically acceptable carriers, excipients or diluents, for example fillers, extenders, binders, wetting agents, disintegrants, surfactants, lubricants, Sweeteners, fragrances, preservatives and the like.
  • pharmaceutically acceptable carriers for example fillers, extenders, binders, wetting agents, disintegrants, surfactants, lubricants, Sweeteners, fragrances, preservatives and the like.
  • Representative examples of pharmaceutically acceptable carriers, excipients or diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, maltitol, starch, gelatin, glycerin, acacia rubber, alginate, calcium phosphate, calcium carbonate, calcium Silicates, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil, propylene glycol, polyethylene glycol, vegetable oil, injectable Ester, utopsol, macrogol, tween 61, cacao butter, lauridge, etc.
  • composition for innate immunity enhancement and antiviral of the present invention may be in the form selected from the group consisting of tablets, pills, powders, granules, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories and injections.
  • the method of formulating the pharmaceutical composition may be carried out according to conventional methods known in the art, and is not particularly limited.
  • antiviral is meant the ability to reduce, prevent, inhibit or eliminate the growth or survival of the virus at any concentration.
  • the virus is one selected from orthomixoviridae, Rhabdoviridae, Paramixoviridae and Herpesviridae. It may be more than one virus.
  • Orthomixoviridae is an Influenza virus
  • Rhabdoviridae is a Vesicular stomatitis virus
  • Paramixoviridae is a Newcastle disease virus.
  • Newcastle disease virus Herpesviridae may be a herpes simplex virus, but is not limited thereto.
  • the present invention also provides a probiotic composition containing the strain or its culture as an active ingredient.
  • Clostridium butyricum Fb5-3 strain, Clostridium butyricum S-45-5 strain or culture medium thereof of the present invention is excellent in intestinal cell adhesion, acid resistance and bile resistance, and less risk of antibiotic resistance transfer
  • all of the above conditions to be provided as probiotics are significantly satisfied, and thus may be usefully used as probiotic compositions.
  • composition of the present invention may be prepared according to a conventional probiotic composition preparation method, and generally, may be in lyophilized or encapsulated form or in a culture suspension or in a dry powder form.
  • the carrier may be used by selecting one or two or more from diluents, lubricants, binders, disintegrants, sweeteners, stabilizers, and preservatives, and one or two or more of the fragrances, vitamins, and antioxidants. Can be used.
  • the carrier and the additive may be used in all pharmaceutically acceptable, and specifically, as a diluent, lactose monohydrate, trehalose, corn starch, soybean oil.
  • a diluent lactose monohydrate, trehalose, corn starch, soybean oil.
  • Microcrystalline cellulose or mannitol (D-mannitorl) is preferable, and magnesium stearate or talc is preferable as a lubricant, and polyvinylpyrrolidone (PVP: polyvinyipyrolidone) or It is preferable to select from hydroxypropyl cellulose (HPC: hydroxypropyl cellulose).
  • the disintegrant may be selected from among carboxymethylcellulose calcium (Ca-CMC), sodium starch glycolate, polyacrylin potassium or cross-linked polyvinylpyrrolidone.
  • the sweetening agent is selected from sucrose, fructose, sorbitol or aspartame
  • the stabilizer is carboxymethylcellulose sodium (Na-CMC), beta-cyclodextrin ( ⁇ -cyclodextrin) or white lead. (white bee's wax) or xanthan gum, and preservatives include methyl p-hydroxy benzoate (methhlparaben), propyl p-hydroxybenzoate (propylparaben), or potassium sorbate ( potassium sorbate).
  • strain cultures obtained by inoculating the Clostridium butyricum Fb5-3 strain and Clostridium butyricum S-45-5 strains were further inoculated with the microorganisms having probiotic activity.
  • Water may be administered to the animal as a probiotic having probiotic activity or may be administered to the animal together with a food, medicine, animal drug or lactic acid bacterium and is preferably used as a feed additive or supplementary feed for livestock.
  • the rich nutrients and useful physiologically active substances contained in colostrum during feeding can prevent the increase of pig growth rate and diarrhea of weaning piglets.
  • the present invention also provides an antimicrobial composition containing the strain or its culture as an active ingredient.
  • antimicrobial is meant the ability to reduce, prevent, inhibit or eliminate the growth or survival of bacteria at any concentration.
  • the antimicrobial activity is Enterobacter sp., Pseudomonas sp., Vibrio sp., Enterobacter sp. Fu earthy Te Solarium in (Fusobacterium sp.) May be antimicrobial for one or more selected from, preferably Enterobacter claw Asia (Enterobacter cloacea), Pseudomonas Erotic based labor (Pseudomonas aeroginosa), Vibrio para H.
  • Morley Tea Caicos (Vibrio parahaemolyticus) , Enterobacter aerogenes and Fusobacterium varium ( fusobacterium varium ) may be antimicrobial to at least one selected from, but is not limited thereto.
  • the composition may be in the form of food, food additives, feed or feed additives
  • the food may be dairy products (milk, soy milk, processed milk), fermented milk (liquid yogurt, staple yogurt) ), Drink, meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, gum, ice cream, soups, beverages, alcoholic beverages and vitamin complexes, but is not limited thereto. .
  • the food of the present invention may include a functional food.
  • the functional food of the present invention may further contain various auxiliary ingredients as necessary in addition to the active ingredient.
  • vitamins such as vitamin A, vitamin B1, vitamin B2, vitamin B3, vitamin B6, vitamin B12, folic acid, vitamin C, vitamin D3, vitamin E, copper, calcium, Minerals such as iron, magnesium, potassium, zinc, or lactic acid bacteria, and the like.
  • the health beverage may include various flavors or natural carbohydrates, and the like as an additional ingredient, as in a general beverage.
  • Flavoring agents include natural sweeteners such as taumartin and stevia extract, and synthetic sweeteners such as saccharin and aspartame.
  • natural carbohydrate 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.
  • the strain or its culture obtained in the step of culturing the strain of the present invention may be added as it is, or used with other food or food ingredients, and may be appropriately used according to a conventional method.
  • the mixed amount of the active ingredient can be suitably determined depending on the purpose of use (prevention, health or therapeutic treatment).
  • the feed additive of the present invention is to be added to the basic feed at a predetermined ratio.
  • the basic feed may be made of corn, soybean meal, whey, fish meal, molasses, salt, vitamin premix and mineral premix.
  • Vitamin premixes may consist of vitamin A, vitamin D, vitamin E, riboprabin and niacin
  • mineral premixes may consist of manganese, iron, zinc, calcium, copper, cobalt and selenium.
  • the feed is a livestock feed, but may include broiler feed, pig feed or cattle feed, but is not limited thereto.
  • the present invention also provides a composition for producing butyric acid or acetic acid containing the strain or its culture as an active ingredient.
  • the present invention also provides a method for producing butyric acid or acetic acid comprising culturing the strain.
  • the method of culturing the strain of the present invention may be cultured according to methods commonly used in the art, and is not limited by any particular method.
  • forward primer 27F (5'-agagtttgatccctcag-3 ': SEQ ID NO: 3) and reverse primer 1492R (5'-ggttaccttgttacgactt-3': SEQ ID NO: 4) for 16S rDNA amplification of colony samples of each isolate strain Using the first cycle of 2 minutes at 95 ° C, 30 cycles of 20 seconds at 95 ° C, 40 seconds at 50 ° C, 1 minute 30 seconds at 72 ° C, the last cycle of 5 minutes at 72 ° C and 10 minutes at 4 ° C PCR (Polymerase chain reaction) was performed. PCR products were primarily confirmed the size of the amplified gene (electrophoresis) through electrophoresis, and then commissioned the sequencing analysis to Biofact.
  • Butyric and organic acid metabolites were analyzed using gas chromatography (GC). Lactic acid bacteria Fb5-3 and S-45-5 were used as samples as culture supernatants incubated for 48 hours at 37 ° C. in PYG liquid medium. Ethanol, acetic acid, butanol and butyric acid were used as standards for analysis. The lactobacillus culture supernatant and standard were filtered with a 0.22 ⁇ m filter and mixed with an equivalent amount of 10% (v / v) phosphoric acid to mount a GC-FID equipped with an HP-INNOWax column (60 m ⁇ 250 ⁇ m ⁇ 0.25 ⁇ m, Agilent Technologies). 1 ⁇ l was injected.
  • HP-INNOWax column 60 m ⁇ 250 ⁇ m ⁇ 0.25 ⁇ m, Agilent Technologies
  • Helium was used as the carrier gas at a flow rate of 1 ml / min.
  • the oven temperature was programmed to increase from 50 ° C. to 170 ° C. at a rate of 10 ° C.
  • the injector and detector temperatures were set at 250 ° C.
  • Antiviral efficacy experiments were performed on lactobacilli using GFP-VSV (vesicular stomatitis virus) expressing fluorescence while proliferating with Raw264.7 cells, a mouse macrophage line. Cytotoxicity experiments were performed on Raw264.7 cells of lactic acid bacteria before antiviral efficacy experiments. As a result, cell death could not be observed with lactic acid bacteria having 5 ⁇ 10 7 bacteria or less.
  • an antiviral efficacy experiment was conducted according to the number of lactic acid bacteria, and some lactic acid bacteria that inhibit the growth of GFP-VSV in 1 ⁇ 10 3 lactic acid bacteria were identified. Antiviral efficacy experiments were performed for 125 strains of lactic acid bacteria with a bacterial count of 1 ⁇ 10 3 .
  • RNA viruses Vesicular stomatitis virus, Influenza virus, Newcastle disease virus
  • DNA virus Herpes simplex virus
  • Raw264.7 cells which are mouse macrophage lines
  • HEK293T cells human embryonic kidney cells (human embryonic kidney cells)
  • Raw264.7 cells were 8 ⁇ 10 5 cells / well
  • HEK293T cells were 3 ⁇ 10 5). cells / well).
  • Cell seeding was carried out on 12-well TC plates and lactic acid bacteria were treated with 1 ⁇ 10 3 water in DMEM to which 1% FBS was added.
  • VSV-gfp MOI: 1.0
  • PR8-gfp MOI: 1.0
  • NDV-gfp MOI: 1.0
  • HSV-gfp MOI: 3.0
  • the cell viability measurement experiment was performed as follows.
  • Raw 264.7 cells which are mouse macrophage lines
  • HEK293T cells which are human embryonic kidney cells (human embryonic kidney cells)
  • lactic acid bacteria were treated with 1 ⁇ 10 3 water in DMEM with 1% FBS.
  • Negative controls treated only DMEM with 1% FBS and positive controls treated with mouse or human IFN-B (500 units / ml).
  • VSV-gfp (MOI: 1.0 or 0.01), PR8-gfp (MOI: 1.0), NDV-gfp (MOI: 1.0), and HSV-gfp (MOI: 3.0) were inoculated. Two hours after inoculation, the inoculum was removed, washed three times with PBS, and replaced with DMEM with 10% FBS. After 12 and 24 hours, apoptosis was confirmed by staining with 0.4% tryptophan blue.
  • Raw264.7 cells which are mouse macrophage lines
  • HEK293T cells which are human embryonic kidney cells (human embryonic kidney cells)
  • lactic acid bacteria were treated with 1 ⁇ 10 3 water in DMEM with 1% FBS.
  • Negative control was treated only with DMEM added 1% FBS
  • positive control was treated with LPS (lipopolysaccharide) powder (100ng / ml).
  • the supernatants of 12 hours and 24 hours were measured for IFN- ⁇ , TNF- ⁇ and IL-6 by ELISA.
  • Raw264.7 cells a mouse macrophage line, were grown and used for experiments (Raw264.7 cells, 8 ⁇ 10 5 cells). After inoculating cells in 6-well TC plates, lactic acid bacteria were treated with 1 ⁇ 10 3 water in DMEM to which 1% FBS was added. Negative controls treated only DMEM with 1% FBS. After treatment, cells were collected at 12 hours and mRNA values of IFN- ⁇ and IFN-related genes were measured using real-time qPCR.
  • the secretion of interferon or inflammatory cytokine is an important mechanism of innate immunity that responds to viruses that enter the body. Activation is important.
  • lactic acid bacteria induced secretion of cytokines including interferon of immune cells and epithelial cells, and interferon and IFN-associated gene levels also increased. Therefore, in the present invention, the degree of activation of intracellular signaling molecules was confirmed using specific antibodies.
  • Raw264.7 cells, a mouse macrophage line were grown and used for experiments (Raw264.7 cells, 8 ⁇ 10 5 cells). After inoculating cells in 6-well TC plates, lactic acid bacteria were treated with 1 ⁇ 10 3 water in DMEM to which 1% FBS was added.
  • Negative control was treated only with DMEM added 1% FBS, positive control was treated with LPS (lipopolysaccharide) powder (100ng / ml). After the treatment, cells were collected at 0, 8, 12, and 24 hours, and then subjected to antibody and Western blot for each protein to confirm the protein in the phosphorylation form (phosphorylation form) that is the active form of the proteins involved in signaling.
  • LPS lipopolysaccharide
  • In vivo anti-influenza efficacy test (Lhallenge test) test by oral administration of lactic acid bacteria was carried out in the following manner.
  • Six-week-old Female Balb / c mice were used, PBS was administered to the negative control group, and lactic acid bacteria (1 ⁇ 10 3 ) of the S-45-5 strain to the experimental group were orally administered daily for 21 days, and the IFN- to the positive control group.
  • ⁇ was administered nasal 12 hours before viral infection. After pretreatment, each group was infected with influenza (H3N2 or H5N2) with 5LD 50 . Body weight changes and mortality were measured for 13 days.
  • mice Six-week old female Balb / c mice were used for the experiment. Mice were orally administered PBS or S-45-5 strains (1 ⁇ 10 3 ) daily for 10 or 21 days. At 10 and 21 days after influenza virus (H1N1) was infected nasal, serum, BAL fluid and small intestinal fluid were collected at 12, 24 and 36 hours, respectively. The secretion amount of IL-6, IFN- ⁇ , and IgA was measured by ELISA.
  • H1N1 influenza virus
  • RNA viruses Vesicular stomatitis virus, Influenza virus, Newcastle disease virus
  • DNA virus Herpes simplex virus
  • Raw264.7 cells which are mouse macrophage lines
  • HEK293T cells human embryonic kidney cells (human embryonic kidney cells)
  • lactic acid bacteria were treated with 1 ⁇ 10 3 water in DMEM with 1% FBS.
  • VSV-gfp MOI: 1.0
  • PR8-gfp MOI: 1.0
  • NDV-gfp MOI: 1.0
  • HSV-gfp MOI: 3.0
  • VSV-gfp (MOI: 1.0 or 0.01), PR8-gfp (MOI: 1.0), NDV-gfp (MOI: 1.0), and HSV-gfp (MOI: 3.0) were inoculated. Two hours after inoculation, the inoculum was removed, washed three times with PBS, and replaced with DMEM with 10% FBS. After 12 and 24 hours, apoptosis was confirmed by staining with 0.4% tryptophan blue.
  • LPS lipopolysaccharide
  • the lactate strains were inoculated in RCM liquid medium adjusted to pH 1.0-6.0 with HCl for 2 hours, and then the survival rate was measured using the absorbance (OD 600) after incubation for 48 hours at 37 ° C.
  • Bile resistance was measured by adding Bacto oxgall (Difco) to RCM plate medium at 0.3, 1.0, and 3.0% (w / v) concentrations, respectively.
  • Harmful bacteria are mainly related to intestinal diseases.E. Coli KCTC 2441, Klebsiella pneumoniae KCTC 2208, Shigella flexneri KCTC 22192, distributed by KCTC (Microbial Resource Center) Enterobacter claw Asia KCTC 1685, Pseudomonas difficulties based labor (Pseudomonas aeroginosa) KCTC 2004, Vibrio para H.
  • the diameter of the inhibitory ring was measured using a paper disk (8 mm, Yoyo Roshi Kaisha, Japan).
  • the concentration of the indicator strain incubated for about 24 hours was adjusted to 10 6-7 CFU / ml, dried on Mueller-Hinton agar medium, and 100 ⁇ l of the culture supernatant of the isolated strain was inoculated into a sterile disk and cultured for 48 hours.
  • Supernatants were prepared by adjusting the liquid culture to pH 4 and pH 6 and removing the cells with a membrane (0.22 ⁇ L pore size, Sartorius, France).
  • the control group compared the antimicrobial activity by using the same amount of the RCM liquid medium without inoculation.
  • Antibiotics include kanamycin (30 ⁇ g / disc), penicillin (10 ⁇ g), cepharosine (30 ⁇ g), clindamycin (2 ⁇ g), tetracycline (30 ⁇ g), gentamicin (10 ⁇ g), streptomycin (10 ⁇ g)
  • kanamycin (30 ⁇ g / disc)
  • penicillin (10 ⁇ g)
  • cepharosine (30 ⁇ g)
  • tetracycline (30 ⁇ g)
  • gentamicin (10 ⁇ g) gentamicin (10 ⁇ g)
  • streptomycin (10 ⁇ g) A total of nine antibiotics were used, ampicillin (10 ⁇ g) and bencomycin (30 ⁇ g).
  • Antibiotic testing was carried out in Muller-Hinton medium to separate the strain to 10 6-7 CFU / ml, and then inoculated antibiotic disk on the medium. After 48 hours of incubation at 37 °C the diameter (mm, diameter) of the inhibitor
  • Lactobacillus and Bifidobacterium bacteria were selected for lactic acid bacteria growth promotion test and growth effects were analyzed. Isolation strains were Lactobacillus plantarum K3108, Lactobacillus reuteri K3564, Lactobacillus salivarius K3600, Lactobacillus rhamnosus parac. casei (Lactobacillus paracasei subsp. paracasei) K3510 , Lactobacillus four K subspecies four K (Lactobacillus sakei subsp. sakei) K3603 , Bifidobacterium ronggeom subspecies ronggeom (Bifidobacterium longum subsp.
  • Bifidobacterium category press ratum ( Bifidobacterium catenulatum ) K3221, Bifidobacterium longum subsp. Infantis K3249, Bifidobacterium bifidum K3202 were used.
  • the culture of lactic acid bacteria and lactic acid bacteria were mixed and cultured 1: 1 in MRS liquid medium to analyze CFU / ml of lactic acid bacteria.
  • Naksan bacteria 10 7 to 10 9 were infected with the cell line (5.0x10 5 ) for 2 hours and then real-time qPCR was performed. The number of bacteria was measured by substituting the CT values of each sample into the standard curve.
  • Isolated strains were amplified 16S rRNA gene by PCR for identification, and determined a partial base sequence of 1,400bp.
  • the homology of the determined nucleotide sequences using NCBI's BLAST analysis program showed that Fb5-3 (SEQ ID NO: 1) in adults and S-45-5 (SEQ ID NO: 2) in newborns showed Clostridium butyricum ( Clostridium butyricum ) showed homology (FIGS. 1 and 2).
  • Fb5-3 produced the most butyric acid at 60%, and secondly, it produced the acetic acid 32%.
  • Antiviral efficacy test was performed on lactobacillus using GFP-VSV (vesicular stomatitis virus) expressing fluorescence while proliferating with Raw264.7 cells, a mouse macrophage line. Cytotoxicity experiments were performed on Raw264.7 cells of lactic acid bacteria before antiviral efficacy experiments. As a result, cell death could not be observed with lactic acid bacteria having 5 ⁇ 10 7 bacteria or less.
  • an antiviral efficacy test was performed according to the number of lactic acid bacteria, and some lactic acid bacteria that inhibit the growth of GFP-VSV in 1 ⁇ 10 3 lactic acid bacteria were identified.
  • Antiviral efficacy experiments were performed for 125 strains of lactic acid bacteria with a bacterial count of 1 ⁇ 10 3 .
  • the antiviral efficacy test of 125 strains of lactic acid bacteria showed that the antiviral efficacy of S-45-5 and Fb5-3 strains was the largest among 125 strains (data not shown).
  • RNA virus Vesicular stomatitis virus, Influenza virus and Newcastle disease virus RNA virus and Herpes simplex virus
  • S-45-5 the extent of virus proliferation was confirmed by expression of GFP in immune cells and epithelial cells.
  • proliferation of not only RNA virus but also DNA virus was significantly reduced in cells treated with lactic acid bacteria as in cells pretreated with interferon- ⁇ (see values indicated by Viral Titer or Viral Replication in FIGS. 5 to 10).
  • apoptosis caused by virus proliferation was also reduced, and as a result, antiviral efficacy by lactic acid bacteria was demonstrated (FIGS. 5 to 10).
  • lactic acid bacteria showed strong induction of innate immune factors cytokines and interferon- ⁇ from Raw264.7 cells and HEK293T cells.
  • Interferon- ⁇ is a cytokine secreted in response to foreign substances such as viruses and cancer cells, and is a substance that induces an immune response by causing intracellular anticancer and antiviral actions.
  • TNF-a is an important mediator of immune and inflammatory responses. It activates macrophage lines and proliferates B-cells.
  • IL-6 activates B-cells to increase antibody production, which is an important cytokine that promotes antigen-specific immune responses. to be. Therefore, it can be seen that the immune activity is increased due to the lactic acid bacteria, and the antiviral effect is shown (FIG. 11).
  • the phosphorylation of IRF3, TBK1, and STAT1 molecules related to activation of the interferon signaling pathway was confirmed over time in cells treated with lactic acid bacteria, such as L26-treated TLR4 ligand LPS.
  • Activation of the NF-kB signaling pathway involved in the secretion of cytokines associated with was confirmed by phosphorylation of p65, ERK, p38 and the like (FIG. 13).
  • Raw 264.7 cells treated with TLR4 ligand LPS and Lactobacillus treated Raw 264.7 cells compared to Raw 264.7 cells from control, treated with LPS and lactic acid bacteria and phosphorylation of IRF3, TBK1, STAT1 molecules and p65, ERK, p38 from 8 hours It was confirmed that phosphorylation, such as the activation of interferon signaling pathways and secretion activation of cytokines associated with inflammatory effects.
  • Serum, bronchoalveolar lavage fluid (BALF), and intestinal IFN- ⁇ and the inflammatory cytokine IL-6 were increased in mice orally administered with lactic acid bacteria, and secreted IgA was induced.
  • oral administration of lactic acid bacteria promoted the secretion of several immune factors in the blood, digestive and respiratory systems, and it was analyzed that lactic acid bacteria showed excellent efficacy in systemic immunity enhancement (FIG. 15).
  • lactic acid bacteria showed strong induction of innate immune factor cytokine from Raw264.7 cells, which are immune cells.
  • TNF- ⁇ is an important mediator of immune and inflammatory responses. It activates macrophage lines and proliferates B-cells.
  • IL-6 activates B-cells to increase antibody production, which is an important cytokine that promotes antigen-specific immune responses. to be. Therefore, it can be said that immune action is increased due to lactic acid bacteria (FIG. 22).
  • Acid resistance resulted in survival of both lactic acid bacteria at 60% at pH 2 and 90% at pH 3. Survival rate of 60% or higher at pH 2 shows significant acid resistance (Table 1). As a result of bile resistance, both lactic acid bacteria have high resistance to bile acids because they have enough resistance to grow in a medium containing 3% bile acid (FIG. 23).
  • the culture supernatant (pH 6) of the pH-controlled isolates did not show antimicrobial activity against pathogens (Table 2).
  • the mechanism by which these pathogenic bacteria are suppressed is thought to be related to several factors, such as butyric acid produced, pH lowering, and the production of antimicrobial substances.
  • a Inhibition zones (mm, diameter); -0 mm; w +, 1 mm or less; +, 1mm or more

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Mycology (AREA)
  • Biomedical Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Virology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Molecular Biology (AREA)
  • Polymers & Plastics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Food Science & Technology (AREA)
  • Physiology (AREA)
  • Animal Husbandry (AREA)
  • Nutrition Science (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)

Abstract

La présente invention concerne une souche de Clostridium butyricum présentant une amélioration immunitaire et des activités antivirales ; une amélioration immunitaire et une composition antivirale, une composition probiotique, une composition antibactérienne et une composition de production d'acide butyrique ou d'acide acétique, dans laquelle toutes les compositions contiennent, en tant qu'ingrédient actif, la souche ou une solution de culture de celle-ci ; et un procédé de production d'acide butyrique ou d'acide acétique, comprenant une étape de culture de la souche.
PCT/KR2016/002839 2015-03-26 2016-03-22 Souche de clostridium butyricum présentant une amélioration immunitaire et activités antivirales, et utilisation correspondante WO2016153247A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201680003213.7A CN107075460B (zh) 2015-03-26 2016-03-22 具有增强免疫及抗病毒活性的丁酸梭菌菌株及其用途

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2015-0042407 2015-03-26
KR1020150042407A KR101773059B1 (ko) 2015-03-26 2015-03-26 면역 증진 및 항바이러스 활성을 가지는 클로스트리디움 부티리쿰 균주 및 이의 용도

Publications (1)

Publication Number Publication Date
WO2016153247A1 true WO2016153247A1 (fr) 2016-09-29

Family

ID=56978890

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2016/002839 WO2016153247A1 (fr) 2015-03-26 2016-03-22 Souche de clostridium butyricum présentant une amélioration immunitaire et activités antivirales, et utilisation correspondante

Country Status (3)

Country Link
KR (1) KR101773059B1 (fr)
CN (1) CN107075460B (fr)
WO (1) WO2016153247A1 (fr)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9938558B2 (en) 2015-06-25 2018-04-10 Ascus Biosciences, Inc. Methods, apparatuses, and systems for analyzing microorganism strains from complex heterogeneous communities, predicting and identifying functional relationships and interactions thereof, and selecting and synthesizing microbial ensembles based thereon
US9993507B2 (en) 2016-01-07 2018-06-12 Ascus Biosciences, Inc. Methods of improving milk production and compositional characteristics
WO2018204792A2 (fr) 2017-05-05 2018-11-08 White Dog Labs, Inc. Produits protéiques unicellulaires et procédé intégré de production d'éthanol et de protéine unicellulaire
US10844419B2 (en) 2015-06-25 2020-11-24 Native Microbials, Inc. Methods, apparatuses, and systems for analyzing microorganism strains from complex heterogeneous communities, predicting and identifying functional relationships and interactions thereof, and selecting and synthesizing microbial ensembles based thereon
US10851399B2 (en) 2015-06-25 2020-12-01 Native Microbials, Inc. Methods, apparatuses, and systems for microorganism strain analysis of complex heterogeneous communities, predicting and identifying functional relationships and interactions thereof, and selecting and synthesizing microbial ensembles based thereon
KR102249897B1 (ko) * 2019-12-13 2021-05-10 옥민 부티르산 생산능, 유해세균에 대한 항균 활성, 혈전분해 활성, 리폭시게나아제 억제 활성 및 지질과산화물 생성 억제 활성을 가지는 클로스트리디움 부티리쿰 obl_1 균주 및 이의 용도
US11044924B2 (en) 2017-04-28 2021-06-29 Native Microbials, Inc. Methods for supporting grain intensive and or energy intensive diets in ruminants by administration of a synthetic bioensemble of microbes or purified strains therefor
WO2021234650A1 (fr) * 2020-05-21 2021-11-25 Superbrewed Food, Inc. Procédé de traitement ou de prévention d'une infection
CN116998635A (zh) * 2023-08-28 2023-11-07 威海优乐生物科技有限公司 一种南美白对虾养殖用饲料添加剂及其制备方法和应用
US11891647B2 (en) 2016-12-28 2024-02-06 Native Microbials, Inc. Methods, apparatuses, and systems for analyzing complete microorganism strains in complex heterogeneous communities, determining functional relationships and interactions thereof, and identifying and synthesizing bioreactive modificators based thereon
EP4306120A4 (fr) * 2021-03-11 2024-04-17 Miyarisan Pharmaceutical Co Ltd Promoteur de production d'interférons
US12018313B2 (en) 2017-12-28 2024-06-25 Native Microbials, Inc. Methods, apparatuses, and systems for microorganism strain analysis of complex heterogeneous communities with tracer analytics, determination of functional relationships and interactions thereof, and synthesis of microbial ensembles

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106591195B (zh) * 2016-12-29 2019-10-08 中国科学院水生生物研究所 一种适用于水产动物的微生物免疫增强剂及其应用
CN108478603B (zh) * 2018-04-03 2020-09-04 潍坊华英生物科技有限公司 一种灭活丁酸梭菌注射剂
CN108342345A (zh) * 2018-04-27 2018-07-31 江南大学 一种唾液乳杆菌特异性培养基及其应用
KR20190127156A (ko) * 2018-05-03 2019-11-13 씨제이제일제당 (주) 항바이러스 및 면역조절 효능을 가지는 락토바실러스 플란타럼 cjlp17 및 이를 포함하는 조성물
CN113308396B (zh) * 2021-05-18 2023-03-21 上海市公共卫生临床中心 一种植物乳杆菌及在制备新冠疫苗免疫增强剂中的应用
KR102587892B1 (ko) 2021-07-21 2023-10-12 주식회사 에치와이 홍삼을 영양원으로 이용하여 균주의 특성이 강화되고 면역 기능이 증진된 락토바실러스 파라카제이 hy7017 균주 및 이의 용도
CN115704002B (zh) * 2021-08-11 2024-04-26 北京科为博生物科技有限公司 一种丁酸梭菌cc02001及其应用

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10194980A (ja) * 1996-11-15 1998-07-28 Nippon Kayaku Co Ltd 水産養殖動物のウイルス感染防除方法、ウイルス感染防除剤及び酪酸菌死菌体の使用
JP2010095504A (ja) * 2008-10-17 2010-04-30 Ace Bio Product Kk 微生物を活用した口内炎及び帯状疱疹剤の発明
KR20110124976A (ko) * 2010-05-12 2011-11-18 일동제약주식회사 장내 유해세균 억제능과 면역 증강작용을 하는 클로스트리디움 부티리쿰 아이디씨씨 9207 백미 발효물
KR20140114524A (ko) * 2013-03-15 2014-09-29 단국대학교 천안캠퍼스 산학협력단 신규한 부틸산 생산 균주

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012093859A2 (fr) * 2011-01-04 2012-07-12 한국생명공학연구원 Composition antifongique comprenant un composé peptidique polycyclique et son procédé de production
KR101335454B1 (ko) * 2011-11-29 2013-12-02 (주) 피엘바이오 신규한 락토바실러스 속 균주 및 이의 생균제 용도

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10194980A (ja) * 1996-11-15 1998-07-28 Nippon Kayaku Co Ltd 水産養殖動物のウイルス感染防除方法、ウイルス感染防除剤及び酪酸菌死菌体の使用
JP2010095504A (ja) * 2008-10-17 2010-04-30 Ace Bio Product Kk 微生物を活用した口内炎及び帯状疱疹剤の発明
KR20110124976A (ko) * 2010-05-12 2011-11-18 일동제약주식회사 장내 유해세균 억제능과 면역 증강작용을 하는 클로스트리디움 부티리쿰 아이디씨씨 9207 백미 발효물
KR20140114524A (ko) * 2013-03-15 2014-09-29 단국대학교 천안캠퍼스 산학협력단 신규한 부틸산 생산 균주

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
XIANYAN, SHI ET AL.: "An Observation on the Efficacy of Clostridium Butyricum Powder in Treatment of Virus Diarrhea in Infants", JOURNAL OF MICROECOLOGY, vol. 21, no. 4, 2009, pages 343 - 344 *

Cited By (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10844419B2 (en) 2015-06-25 2020-11-24 Native Microbials, Inc. Methods, apparatuses, and systems for analyzing microorganism strains from complex heterogeneous communities, predicting and identifying functional relationships and interactions thereof, and selecting and synthesizing microbial ensembles based thereon
US9938558B2 (en) 2015-06-25 2018-04-10 Ascus Biosciences, Inc. Methods, apparatuses, and systems for analyzing microorganism strains from complex heterogeneous communities, predicting and identifying functional relationships and interactions thereof, and selecting and synthesizing microbial ensembles based thereon
US10851399B2 (en) 2015-06-25 2020-12-01 Native Microbials, Inc. Methods, apparatuses, and systems for microorganism strain analysis of complex heterogeneous communities, predicting and identifying functional relationships and interactions thereof, and selecting and synthesizing microbial ensembles based thereon
US10966437B2 (en) 2016-01-07 2021-04-06 Native Microbials, Inc. Microbial compositions and methods of use for improving milk production
US11291219B2 (en) 2016-01-07 2022-04-05 Native Microbials, Inc. Microbial compositions and methods of use for improving milk production
US10448658B2 (en) 2016-01-07 2019-10-22 Ascus Biosciences, Inc. Cow food and methods of husbandry for increased milk production
US10448657B2 (en) 2016-01-07 2019-10-22 Ascus Biosciences, Inc. Cow food and methods of husbandry for increased milk production
US10645952B2 (en) 2016-01-07 2020-05-12 Ascus Biosciences, Inc. Microbial compositions and methods of use for improving milk production
US10701955B2 (en) 2016-01-07 2020-07-07 Ascus Biosciences, Inc. Ruminant compositions
US10293006B2 (en) 2016-01-07 2019-05-21 Ascus Biosciences, Inc. Microbial compositions for improving milk production in ruminants
US11910809B2 (en) 2016-01-07 2024-02-27 Native Microbials, Inc. Microbial compositions and methods of use for improving milk production
US11910808B2 (en) 2016-01-07 2024-02-27 Native Microbials, Inc. Ruminant compositions
US9993507B2 (en) 2016-01-07 2018-06-12 Ascus Biosciences, Inc. Methods of improving milk production and compositional characteristics
US10398154B2 (en) 2016-01-07 2019-09-03 Ascus Biosciences, Inc. Microbial compositions and methods of use for improving milk production
US11891647B2 (en) 2016-12-28 2024-02-06 Native Microbials, Inc. Methods, apparatuses, and systems for analyzing complete microorganism strains in complex heterogeneous communities, determining functional relationships and interactions thereof, and identifying and synthesizing bioreactive modificators based thereon
US11044924B2 (en) 2017-04-28 2021-06-29 Native Microbials, Inc. Methods for supporting grain intensive and or energy intensive diets in ruminants by administration of a synthetic bioensemble of microbes or purified strains therefor
US11871767B2 (en) 2017-04-28 2024-01-16 Native Microbials, Inc. Microbial compositions and methods for ruminant health and performance
EP3619315A4 (fr) * 2017-05-05 2021-01-27 White Dog Labs, Inc. Produits protéiques unicellulaires et procédé intégré de production d'éthanol et de protéine unicellulaire
WO2018204792A2 (fr) 2017-05-05 2018-11-08 White Dog Labs, Inc. Produits protéiques unicellulaires et procédé intégré de production d'éthanol et de protéine unicellulaire
US12018313B2 (en) 2017-12-28 2024-06-25 Native Microbials, Inc. Methods, apparatuses, and systems for microorganism strain analysis of complex heterogeneous communities with tracer analytics, determination of functional relationships and interactions thereof, and synthesis of microbial ensembles
KR102249897B1 (ko) * 2019-12-13 2021-05-10 옥민 부티르산 생산능, 유해세균에 대한 항균 활성, 혈전분해 활성, 리폭시게나아제 억제 활성 및 지질과산화물 생성 억제 활성을 가지는 클로스트리디움 부티리쿰 obl_1 균주 및 이의 용도
WO2021234650A1 (fr) * 2020-05-21 2021-11-25 Superbrewed Food, Inc. Procédé de traitement ou de prévention d'une infection
EP4306120A4 (fr) * 2021-03-11 2024-04-17 Miyarisan Pharmaceutical Co Ltd Promoteur de production d'interférons
CN116998635A (zh) * 2023-08-28 2023-11-07 威海优乐生物科技有限公司 一种南美白对虾养殖用饲料添加剂及其制备方法和应用

Also Published As

Publication number Publication date
CN107075460A (zh) 2017-08-18
KR20160115202A (ko) 2016-10-06
CN107075460B (zh) 2020-12-25
KR101773059B1 (ko) 2017-08-31

Similar Documents

Publication Publication Date Title
WO2016153247A1 (fr) Souche de clostridium butyricum présentant une amélioration immunitaire et activités antivirales, et utilisation correspondante
KR101772870B1 (ko) 프로바이오틱 활성을 갖는 신규 락토바실러스 플란타럼 및 이의 용도
WO2011007922A1 (fr) Nouveau lactobacillus plantarum et composition en contenant
WO2010064777A1 (fr) Nouveau lactobacillus plantarum et composition le contenant
WO2011052996A2 (fr) Nouveau lactobacillus plantarum et composition le comprenant
KR101235561B1 (ko) 항바이러스 및 항균 활성을 갖는 락토바실러스 플란타룸 ｃｌｐ-1 균주 및 이를 포함하는 생균제
WO2019212299A1 (fr) Lactobacillus plantarum cjlp17 présentant une efficacité antivirale et immunomodulatrice et composition comprenant celle-ci
WO2020116733A1 (fr) Nouvelle souche atg-f4 de lactobacillus reuteri possédant une fonction d'amélioration de la sécrétion de dopamine et composition pharmaceutique la comprenant pour la prévention ou le traitement de la psychopathie
WO2015160166A1 (fr) Nouveau bactériophage et composition antibactérienne le comprenant
WO2016064000A1 (fr) Probio 090 à base de lactobacillus plantarum présentant des activités bactériennes antivirales et antipathogènes et produit à base de celui-ci
WO2020013669A1 (fr) Souche de lactobacillus plantarum cjlp475 ayant un effet antiviral et une efficacité immunorégulatrice et composition la comprenant
WO2020197188A1 (fr) Bactéries lactiques de kimchi lactobacillus sakei ayant une efficacité pour le soulagement de l'arthrite
KR20160046826A (ko) 유아의 과도한 울음용 프로바이오틱
US20220370519A1 (en) Probiotics for use in the prevention or treatment of illness and/or symptoms associated with coronaviruses
KR20180011490A (ko) 프로바이오틱 활성을 갖는 신규 락토바실러스 퍼멘텀 및 이의 용도
WO2012141540A2 (fr) Nouvelle souche isolée de lactobacillus fermentum ayant une activité inhibitrice d'infection virale
KR20180075463A (ko) 프로바이오틱 활성을 갖는 신규 락토바실러스 퍼멘텀 및 이의 용도
CN110997898A (zh) 包括植物乳杆菌cjlp475菌株和植物乳杆菌cjlp17菌株的组合物及其用途
WO2017196140A2 (fr) Additif alimentaire pour animaux d'aquaculture comprenant la souche bfe920 de lactococcus lactis induisant des lymphocytes t immunomodulateurs
KR101772875B1 (ko) 프로바이오틱 활성을 갖는 신규 락토바실러스 플란타럼 및 이의 용도
KR102175115B1 (ko) 락토바실러스 플란타럼 cjlp475 균주 및 락토바실러스 플란타럼 cjlp243 균주를 포함하는 조성물 및 이의 용도
WO2016064214A1 (fr) Composition contenant un extrait de curcuma zedoaria et son utilisation
KR102327753B1 (ko) 면역 증진, 항바이러스 및 항균 활성을 가지는 유산균 YH-Lpro-37 및 이의 용도
WO2023058801A1 (fr) Composition pour soulager, prévenir ou traiter un trouble intestinal, comprenant une souche de lactobacillus acidophilus kbl402 ou kbl409
WO2022039514A1 (fr) Composition pour le traitement de maladies cérébrales comprenant lactobacillus sakei ou des vésicules extracellulaires dérivées de celui-ci en tant que principe actif

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 16769065

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 16769065

Country of ref document: EP

Kind code of ref document: A1