WO2020171256A1 - Souche de lactobacillus ayant un effet inhibiteur de croissance sur un clostridium difficile - Google Patents

Souche de lactobacillus ayant un effet inhibiteur de croissance sur un clostridium difficile Download PDF

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WO2020171256A1
WO2020171256A1 PCT/KR2019/002115 KR2019002115W WO2020171256A1 WO 2020171256 A1 WO2020171256 A1 WO 2020171256A1 KR 2019002115 W KR2019002115 W KR 2019002115W WO 2020171256 A1 WO2020171256 A1 WO 2020171256A1
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cdi
strain
clostridium difficile
lactobacillus plantarum
kctc
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PCT/KR2019/002115
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Korean (ko)
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고광표
유현주
유준선
이길재
김성호
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서울대학교산학협력단
주식회사 고바이오랩
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Priority to PCT/KR2019/002115 priority Critical patent/WO2020171256A1/fr
Publication of WO2020171256A1 publication Critical patent/WO2020171256A1/fr

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    • 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
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • 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
    • 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
    • C12R2001/225—Lactobacillus
    • C12R2001/25—Lactobacillus plantarum

Definitions

  • the present invention relates to a CDI (Clostridium difficile infection) treatment pharmaceutical composition
  • a CDI (Clostridium difficile infection) treatment pharmaceutical composition comprising the Lactobacillus plantarum strain or a culture thereof having a Clostridium difficile growth inhibitory effect, and a culture thereof.
  • CDI Clostridium difficile infection
  • AAD antibiotics-associated diarrhea
  • C. difficile shows relatively high resistance to disinfectant treatment such as alcohol, and it is difficult to properly manage and remove because it can build spores that can survive in extreme environments for several years or more.
  • disinfectant treatment such as alcohol
  • the number of CDI patients per year is around 500,000, and the death toll is 14,000 a year, a serious disease.
  • recurrence is frequent even after treatment.
  • recurrence patients are classified as a major disease because it is difficult to see great efficacy even with general antibiotic treatment.
  • CDI treatment is antibiotic prescription, which is known to show relatively low treatment success rate and high recurrence rate.
  • Metronidazole and vancomycin both have a limited treatment success rate at the time of primary treatment and show a recurrence rate of 20 to 30%, the treatment success rate at the first recurrence is 70%, and at more recurrences it decreases to 35%, but due to highly toxic strains. Inadequate for use in refractory severe CDIs and recurrent CDIs.
  • Fidaxomicin inhibits the synthesis of C.
  • FMT fecal microbiota transplantation
  • Useful microorganisms isolated in the intestine can cause changes in the intestinal ecosystem and interaction with the immune system, and as a result, maintain space and resource competition with C. difficile.
  • these When these are treated, it has been reported that they actually show the same level of therapeutic effect as metronidazole or vancomycin, and that the recurrence rate is also significantly lower (Ollech et al., 2016. Best Practice & Research Clinical Gastroenterology). Therefore, the process of securing and mass-producing functional beneficial strains that can make a big contribution to the prevention/treatment of CDI can be seen as having very important significance as a method that can supplement/replace chemical antibiotic therapy in the future.
  • Intestinal microbes play a role of protecting the intestinal epithelium from pathogens such as C. difficile, and when an imbalance of intestinal microbes is caused by certain causes such as antibiotics (dysbiosis), the pathogen penetrates the intestinal wall and prevents disease. cause.
  • IL-25 produced by intestinal microbes increased the tight junction of the intestinal wall to prevent CDI (Buonomo et al., 2016. Cell Reports). It has also been reported that there is a high correlation with the degree of diversity of (Milani et al., 2016. Scientific Reports).
  • An object of the present invention is to provide a Lactobacillus plantarum (Lactobacillus plantarum) KBL396 (KCTC 13278 BP) strain, characterized in that it has a Clostridium difficile growth inhibitory effect.
  • Another object of the present invention is to provide a pharmaceutical composition for the treatment of Clostridium difficile infection (CDI), comprising a Lactobacillus plantarum KBL396 (KCTC 13278 BP) strain or a culture therefor. .
  • CDI Clostridium difficile infection
  • KCTC 13278 BP Lactobacillus plantarum KBL396
  • Another object of the present invention is to provide a functional food for alleviation or improvement of Clostridium difficile infection (CDI), characterized in that it comprises a Lactobacillus plantarum KBL396 (KCTC 13278 BP) strain or a culture therefor. Is to do.
  • CDI Clostridium difficile infection
  • the present invention provides a Lactobacillus plantarum KBL396 (KCTC 13278 BP) strain, characterized in that it has a Clostridium difficile growth inhibitory effect.
  • Clostridium difficile may be bile acid independent.
  • the present invention provides a pharmaceutical composition for treating or preventing CDI (Clostridium difficile infection), characterized in that it comprises a Lactobacillus plantarum KBL396 (KCTC 13278 BP) strain or a culture therefor.
  • CDI Clotridium difficile infection
  • the present invention provides a health functional food for alleviating or improving Clostridium difficile infection (CDI), characterized in that it comprises a Lactobacillus plantarum KBL396 (KCTC 13278 BP) strain or a culture therefor.
  • CDI Clostridium difficile infection
  • the Clostridium difficile infection may be a recurrent CDI.
  • Clostridium difficile infection may be caused by an intestinal microbial imbalance.
  • the present invention provides a method for preventing, improving or treating CDI by administering an effective amount of Lactobacillus plantarum KBL396 (KCTC 13278 BP) strain to an individual in need thereof.
  • KCTC 13278 BP Lactobacillus plantarum KBL396
  • the present invention provides the use of the Lactobacillus plantarum KBL396 (KCTC 13278 BP) strain to inhibit the growth of Clostridium difficile in an individual.
  • the present invention provides the use of the Lactobacillus plantarum KBL396 (KCTC 13278 BP) strain for the manufacture of a pharmaceutical formulation for preventing, improving or treating CDI.
  • the present invention relates to a strain of Lactobacillus plantarum KBL396 (KCTC 13278 BP) characterized by having a Clostridium difficile growth inhibitory effect, and is effective in CDI treatment and symptom improvement, In particular, it is very effective in treating recurrent CDI and improving symptoms.
  • KCTC 13278 BP Lactobacillus plantarum KBL396
  • Figure 2 is a result of the inhibitory effect of Lactobacillus plantarum (Lactobacillus plantarum) KBL396 (KCTC 13278 BP) strain (LP) on C. difficile growth experiments.
  • Lactobacillus plantarum Lactobacillus plantarum
  • KBL396 KCTC 13278 BP
  • LP strain
  • Figure 4 is a result of the weight loss prevention effect experiment by the Lactobacillus plantarum (Lactobacillus plantarum) KBL396 (KCTC 13278 BP) strain in the C.difficile infection prevention model.
  • Figure 5 is a result of the survival rate increase experiment by Lactobacillus plantarum (Lactobacillus plantarum) KBL396 (KCTC 13278 BP) strain in the C.difficile infection prevention model.
  • FIG. 6 is a profile analysis result of bile acid, DCA and LCA in feces before/after C. difficile infection
  • FIG. 6A is a result of DCA content in feces 24 hours after C. difficile infection
  • FIG. 6B is C. Results of LCA content in feces 24 hours after difficile infection).
  • microbiom metabolic pathway analysis is a functional microbiom analysis (microbiom metabolic pathway analysis) between the LP administration group and the infection control experimental results.
  • Fig. 10 is a result of analysis of genes related to the biosynthetic pathway of secondary bile acids among fecal microvims of the LP administration group and the infection control.
  • 11 is an experimental result of correlation between the amount of bile acids in feces and functional microbial analysis.
  • Fig. 12 is a result of experimentation of changes in bile acid composition according to LP culture (in vitro).
  • FIG. 13 is an experimental result of the conversion effect of TCA and TDCA according to LP culture (in vitro) (FIG. 13A is an experimental result for Cholic acid, and FIG. 13B is an experimental result for Deoxycholic acid).
  • Figure 15 is a result of the weight recovery effect test caused by LP administration in the C. difficile infection recurrence prevention model.
  • the present invention provides a Lactobacillus plantarum (Lactobacillus plantarum) KBL396 (KCTC 13278 BP) strain, characterized in that it has a Clostridium difficile (C.difficile) growth inhibitory effect.
  • Lactobacillus plantarum KBL396 (KCTC 13278 BP) strain was isolated from feces provided by healthy adult volunteers. Since the strain is an absolute anaerobic strain, the separation process was performed under an anaerobic system.
  • Clostridium difficile (C.difficile) is a gram-positive bacterium, an anaerobic bacterium, is a relatively large bacterium with a length of 2-17 ⁇ m, has a structure such as flagella or projections, and is a bacterium living in human intestine. Clostridium difficile is likely to occur even after administration of antibiotics such as Clindamycin, Lincomycin, Amoxicillin, Cephalotin, and Cefazoline. After the destruction of the normal intestinal flora due to antibiotics, colonization may occur due to toxic C. difficile.
  • Clostridium difficile produces toxin A (enterotoxin) with a molecular weight of about 310,000 and toxin B (cytotoxin) with a molecular weight of about 270,000.
  • Toxin A first injures the intestinal epithelial cells and then invades the intestinal membrane at the site of toxin B stage and exerts a poison effect.
  • the growth inhibitory effect on the Clostridium difficile strain can be confirmed through an inhibition assay, but is not limited thereto.
  • C.difficile may be due to inhibition of spore germination, but is not limited thereto.
  • Lactobacillus plantarum KBL396 (KCTC 13278 BP) strain is a deposited strain and was deposited with the Biological Resource Center on May 29, 2017, and the accession number is KCTC 13278 BP.
  • Clostridium difficile may be bile acid independent.
  • the present invention provides a pharmaceutical composition for the treatment or prevention of Clostridium difficile infection (CDI), characterized in that it comprises a Lactobacillus plantarum KBL396 (KCTC 13278 BP) strain or a culture therefor.
  • CDI Clostridium difficile infection
  • CDI may be caused by spore-forming bacteria, and specifically, may be caused by a Clostridium difficile strain. CDI can also be accompanied by diarrhea, high temperatures, and unusual pain.
  • the CDI may occur in patients whose bile secretion is not normally performed in the liver.
  • the CDI may be a type of antibiotic-associated diarrhea.
  • CDI may have occurred in patients receiving broad spectrum antibiotics (especially clindamycin) that alter the ecological balance of the intestinal flora.
  • the CDI may be mild CDI, severe CDI, complex CDI, or recurrent CDI, and more preferably, may be recurrent CDI.
  • the severity of the CDI can be determined based on age, whether a systemic antitussive agent is used, the number of white blood cells, albumin, and serum creatine.
  • the number of leukocytes may be less than 15,000 cells/ml, and the serum creatine may be less than 1.5 times premorbid level
  • the number of white blood cells is 15,000 cells/ml or more, and serum creatine is 1.5 times premorbid level. It may be abnormal, and complex (complicated CDI) may involve hypotension, shock, rainy season, megacolon, and recurrent CDI may mean recurrence within 8 weeks after successful treatment for CDI.
  • the pharmaceutical composition according to the present invention can be administered to mammals including humans by various routes.
  • the mode of administration may be any method commonly used, for example, may be administered by oral, dermal, intravenous, intramuscular, subcutaneous, and the like, preferably orally.
  • the pharmaceutical compositions of the present invention are each parenterally in the form of oral dosage forms such as powders, granules, tablets, capsules, ointments, suspensions, emulsions, syrups, aerosols, or transdermal preparations, suppositories, and sterile injectable solutions according to conventional methods. It can be formulated and used as an old formulation.
  • the pharmaceutical composition of the present invention may further contain adjuvants such as a pharmaceutically suitable and physiologically acceptable carrier, excipient, and diluent.
  • Carriers, excipients and diluents that may be included in the pharmaceutical composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium. Silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oils.
  • diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants can be used.
  • the pharmaceutical composition of the present invention may be administered alone, but generally, a pharmaceutical composition selected in consideration of the mode of administration and standard pharmaceutical practice. It can be administered in admixture with a carrier.
  • the composition containing the Clostridium syndense strain of the present invention is in the form of a tablet containing starch or lactose, alone or in the form of a capsule containing an excipient, or contains a chemical agent to taste or color It can be administered orally, intraorally, or sublingually in the form of an elixir or suspension.
  • the dosage of the pharmaceutical composition containing the strain of Lactobacillus plantarum KBL396 (KCTC 13278 BP) of the present invention may vary depending on the patient's age, weight, sex, dosage form, health condition, and degree of disease. Alternatively, according to the judgment of the pharmacist, it may be dividedly administered once or several times a day at regular time intervals.
  • the daily dosage may be 0.1 to 500 mg/kg, preferably 0.5 to 300 mg/kg, based on the content of the active ingredient.
  • the above dosage is an example of an average case, and the dosage may be high or low depending on individual differences.
  • the daily dosage of the composition containing the mixed extract of the present invention is less than the above dosage, a significant effect cannot be obtained, and if it exceeds that, it is not only uneconomical, but also outside the range of the normal dosage, there is a concern that undesirable side effects may occur. It may occur, so it is better to set it within the above range.
  • Another example of the present invention is a health functional food for alleviating or improving Clostridium difficile infection (CDI), characterized in that it comprises a Lactobacillus plantarum KBL396 (KCTC 13278 BP) strain or a culture therefor. to provide.
  • CDI Clostridium difficile infection
  • the health functional food may be various beverages, fermented milk, food additives, and the like.
  • the content of the Clostridium syndense strain as an active ingredient contained in the health functional food is not particularly limited appropriately depending on the form of the food, the desired use, etc., and may be added in an amount of 0.01 to 15% by weight of the total food ,
  • the healthy beverage composition may be added in an amount of 0.02 to 10 g, preferably 0.3 to 1 g, based on 100 ml.
  • natural carbohydrates examples include monosaccharides such as disaccharides such as glucose and fructose, such as maltose, sucrose, and the like, and polysaccharides such as dextrin, cyclodextrin, and the like. Sugar and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • sweetitol a sugar alcohol
  • erythritol erythritol.
  • natural flavoring agents tacmatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.)
  • synthetic flavoring agents sacharin, aspartame, etc.
  • the ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.
  • the health functional food of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring agents and enhancers (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid, and It may contain salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonates used in carbonated beverages, and the like.
  • the health functional food of the present invention may contain flesh for the manufacture of natural fruit juice and fruit juice beverage and vegetable beverage. These components may be used independently or in combination. The proportion of these additives is not so important, but is generally selected from 0 to about 20 parts by weight per 100 parts by weight of the health functional food of the present invention.
  • Lactobacillus plantarum (Lactobacillus plantarum) KBL396 (KCTC 13278 BP) using the Clostridium difficile growth inhibitory effect of the strain Lactobacillus plantarum (Lactobacillus plantarum) KBL396 ( KCTC 13278 BP) provides a method of inhibiting or enhancing CDI (Clostridium difficile infection) inhibition or curative ability of an individual, comprising administering a strain to an individual in need thereof, and a method of preventing, improving, or treating CDI.
  • CDI Clostridium difficile infection
  • Lactobacillus plantarum KBL396 (KCTC 13278 BP) strain for inhibiting the growth of Clostridium difficile.
  • Use of the Lactobacillus plantarum KBL396 (KCTC 13278 BP) strain for enhancing the CDI inhibitory or healing ability of an individual, and Lactobacillus plantarum KBL396 (Lactobacillus plantarum) for the prevention, improvement or treatment of CDI ( KCTC 13278 BP) strain is provided.
  • The'individual' refers to an animal that is expected to exhibit an effect according to the Lactobacillus plantarum KBL396 (KCTC 13278 BP) strain by administering a composition containing the strain or strain according to the present invention as an active ingredient
  • the animals include, for example, dogs, monkeys, goats, pigs, mice, and the like, and are preferably humans.
  • The'prevention' refers to any action of inhibiting or delaying the progress of CDI by administration of a composition comprising the strain or strain according to the present invention as an active ingredient.
  • The'treatment' or'improvement' refers to any action in which symptoms of CDI are improved or beneficially changed by administration of a composition comprising the strain or strain according to the present invention as an active ingredient.
  • The'administration' means providing a pharmaceutical composition comprising a predetermined strain or strain according to the present invention as an active ingredient to an individual by any suitable method.
  • the research team intensively isolated candidate strains from feces provided by more than 40 healthy adult volunteers. For the comparison of efficacy, several commercial strains and 12 strains of a total of 5 species were cultured to conduct C. difficile inhibition experiments. Particularly, considering that most of the candidate strains are obligate anaerobes, all processes were performed under the anaerobic system of Go Bio Lab.
  • the strains used for the C. difficile inhibitory effect comparison experiment were C. difficile KCTC 5009 strain and C. difficile ATCC43255 strain, and the growth inhibitory effect on the strain was compared. After diluting the OD of the C.
  • Lactobacillus plantarum (Lactobacillus plantarum) KBL396 (KCTC 13278 BP) strain could be selected as a strain excellent in growth inhibition against C. difficile KCTC 5009 strain and C. difficile ATCC43255 strain.
  • the Lactobacillus plantarum KBL396 (KCTC 13278 BP) strain showed superior growth inhibitory ability of C. difficile strains compared to other strains, Bacteroides caccae strain, Bacteroides ovatus strain, Faecalibacterium prausnitzi, and Roseburia intestinalis strain (Figure 1) Reference).
  • Lactobacillus Plantarum (Lactobacillus plantarum ) KBL396 ( KCTC 13278 BP)( Lp ) Strain of C. difficile Inhibitory effect on growth
  • the inhibitory ability of C. difficile was confirmed using the supernatant obtained after culturing each isolated strain for 24 hours. Considering that the metabolism of bile affects spore germination and growth of C. difficile, the same experiment was conducted by adding bile of an appropriate concentration to the C. difficile culture medium so that candidate strains can metabolize bile. Observed.
  • the concentration of bile acids in the small intestine of a living body was 0.2 to 2.0% (wt/vol) (Kristoffersen et al., 2007. Journal of Bacteriology). By adjusting the concentration of bile acids from 0 to 2.0% (wt/vol.), the inhibitory effect of C.
  • the test strain was inoculated into a liquid medium containing bile acids at concentrations of 0, 0.5, 1%, and 2%, cultured at 37°C for 24 hours, and then the supernatant was used. I did. After diluting the OD of the C. difficile strain cultured in the liquid medium for 4 hours to 0.3 and re-inoculating the liquid medium at a concentration of 2%, the CD culture solution and the prepared test strain supernatant were mixed at a ratio of 1:1 at 37°C. Incubated for 24 hours, OD was measured to evaluate the CD growth rate.
  • LP has both a bile acid concentration-dependent inhibitory effect and an independent CD inhibitory effect.
  • C57BL/6 mice that were negatively administered antibiotics for 3 days to disturb intestinal microbial strains were orally administered the candidate strain for 2 days, followed by intraperitoneal administration of clindamycin and infection with C. difficile, resulting in CDI symptoms of the candidate strain ( Body weight change) and the efficacy on survival were measured every day for 3 weeks (see Fig. 3).
  • the survival rate also showed an effect of significantly increasing the survival rate in the case of the resulting LP compared to the control group (see FIG. 5).
  • microbial analysis was performed that significantly changed between the LP administration group and the infection control group, and for this purpose, bacterial DNA was extracted from feces obtained on the 7th day of the animal experiment (24 hours after C. difficile infection) using the Qiagen FastStool DNA isolation kit. Then, PCR (polymerized chain reaction) was performed using primers corresponding to the V4-V5 region of the bacterial 16S rRNA gene. The amplified 16S rRNA gene profile was NGS sequenced using Illumina Miseq, followed by OTU analysis and taxon analysis using the Qiime 1.8 pipeline.

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Abstract

La présente invention concerne une souche de Lactobacillus plantarum KBL396 (KCTC 13278 BP) caractérisée en ce qu'elle présente un effet inhibiteur de croissance sur un Clostridium difficile.
PCT/KR2019/002115 2019-02-21 2019-02-21 Souche de lactobacillus ayant un effet inhibiteur de croissance sur un clostridium difficile WO2020171256A1 (fr)

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Cited By (1)

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EP3747988A4 (fr) * 2018-02-02 2021-11-03 Kobiolabs, Inc. Souche de lactobacillus plantarum kbl396 et son utilisation

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WO2015149818A1 (fr) * 2014-04-03 2015-10-08 Oü Tervisliku Piima Biotehnoloogiate Arenduskeskus (Bio-Competence Centre Of Healthy Dairy Products) Souche inducia dsm 21379 de lactobacillus plantarum utilisée comme agent hypocholestérolémique et agent antimicrobien dirigé contre clostridium difficile

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Cited By (2)

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Publication number Priority date Publication date Assignee Title
EP3747988A4 (fr) * 2018-02-02 2021-11-03 Kobiolabs, Inc. Souche de lactobacillus plantarum kbl396 et son utilisation
US11602552B2 (en) 2018-02-02 2023-03-14 Kobiolabs, Inc. Lactobacillus plantarum KBL396 strain and use thereof

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