JP2023106282A - Pharmaceutical composition for preventing Vibrio sepsis - Google Patents

Abstract

To provide a pharmaceutical composition for preventing vibrio sepsis.SOLUTION: A pharmaceutical composition contains Bacteroides vulgatus strain, a crushed product of the strain, or a culture supernatant of the strain as an active ingredient.SELECTED DRAWING: None

Description

There is an application for the application of Article 30, Paragraph 2 of the Patent Act. https://doi. org/10.1186/s40168-021-01095-w Posted on July 20, 2021

TECHNICAL FIELD The present invention relates to a pharmaceutical composition for preventing sepsis, and more particularly to a pharmaceutical composition for preventing Vibrio sepsis.

Foodborne pathogens undergo many stresses through the host's gastrointestinal tract (GI) during the course of infection. They must survive in varying conditions of pH, oxygen, osmolarity and nutrients while also overcoming the barriers between antimicrobial agents and host epithelial structures generated by the host's immune system (Takiishi T, et al., Tissue Barriers. 5: e1373208.2017). Therefore, for a successful infection, pathogens must perform chemotaxis-based motility, penetration of the intestinal mucus layer, attachment to epithelial surfaces, colonization processes and the production and/or secretion of virulence factors at the site of infection. A process is required.
In the case of the pathogen Vibrio vulnificus, there have been many reports on various virulence factors. In addition to the well-known lipopolysaccharides and capsular polysaccharides, immunogenic lipoprotein A (IlpA), hemolysin/cytolysin (VvhA), metalloprotease M (VvpM), phosphoripa se A2 (PlpA), multifunctional , autoprocessing repeats-in-toxins (MARTX) exhibit diverse activities that cause immunogenicity, cytotoxicity and cell death through necrosis or cell death (Jones MK, et al., Disease and pathogenesis. Infect Immun. 77: 1723-33.2009). The production of such virulence factors is tightly regulated by sensing extracellular signals derived from the host or bacteria and expressing them under appropriate conditions. Iron ions, an autoinducer (AI-2) and a cyclic dipeptide (cyclo-Phe-Pro [cFP]) were obtained from V.I. vulnificus as the major signal factor associated with such a definition. Until now, V.I. Most studies on vulnificus virulence have focused on bacterial effects on model animals at the cellular, tissue or organ level.

However, the V.I. It can be said that research on interactions with gut commensals during the infection process of vulnificus is still an unexplored field.
Disclosure of the Invention The present invention is intended to solve various problems including the above-mentioned problems, and is a method for preventing Vibrio sepsis using Bacteroides vulgatus, which effectively reduces the pathogenicity of Vibrio septicemia. The object is to provide a pharmaceutical composition. However, such issues are exemplary and are not intended to limit the scope of the invention.

According to one aspect of the present invention, there is provided a pharmaceutical composition for preventing Vibrio sepsis infection, which contains as an active ingredient a Bacteroides vulgarus strain, a homogenate of the strain, or a culture supernatant of the strain.
According to another aspect of the present invention, there is provided a method for preventing Vibrio septicemia infection, which comprises administering the pharmaceutical composition for preventing Vibrio septicemia infection to an individual.
According to another aspect of the present invention, there is provided a feed additive for preventing Vibrio sepsis infection containing a Bacteroides vulgaratus strain as an active ingredient.
According to another aspect of the present invention, there is provided a health functional food for preventing Vibrio septicemia infection, which contains, as active ingredients, a Bacteroides vulgarus strain, a crushed product of the strain, or a culture supernatant of the strain.

The pharmaceutical composition for preventing Vibrio sepsis of the present invention, which is prepared as described above, effectively reduces the pathogenicity of Vibrio septicemia, and thus can be utilized in the development of therapeutic agents for Vibrio septicemia. In addition, the problem of antibiotic-resistant bacteria due to misuse of antibiotics, the problem of residual antibiotics in food, and the problems of a wide host range can be resolved. Of course, such effects do not limit the scope of the present invention.

B. in vivo in mice. Fig. 10 is a graph showing the results of confirming the establishment of a mouse model with varying amounts of vulgatus. B. Fig. 10 is a graph showing the results of analysis of changes in lethality of Vibrio septicemia in vulgatus-depleted mice. B. of the present invention. At the time of boosting administration of V. vulgatus, V. vulgatus Fig. 10 is a graph showing the results of analysis of changes in mouse lethality due to vulnificus.

Definition of terms:
The term "Vibrio" as used herein, of which 34 species are known so far, is a Gram-negative bacterium, whose cell shape is rod-shaped, curved, and single-stranded. Or, there is a feature that several pieces are connected to form a spiral. At one end of the body, one or more flagella protrude, which are used to actively swim and move. Vibrio is widely distributed in the wild in the sea, and is often found in freshwater and soil. Among Vibrio, there are many species that show pathogenicity in humans and fish and shellfish, and typical pathogenic species include Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus. (V. vulnificus), Vibrio alginolyticus.
As used herein, the term "Vibrio vulnificus sepsis" is an acute disease that appears when Vibrio-contaminated seafood is eaten raw or infected through skin wounds, and is a marine-dwelling disease. It means sepsis caused by infection with Vibrio vulnificus, a bacterium that causes pneumonia.
As used herein, the term "Bacteroides vulgatus" means a flora of commensal microorganisms that are resistant to infection treatment. In the present invention, experimental mice to which Bacteroides vulgarus was administered against Vibrio sepsis infection showed higher infection resistance than control group mice.

According to one aspect of the present invention, there is provided a pharmaceutical composition for preventing Vibrio sepsis infection, which contains as an active ingredient a Bacteroides vulgarus strain, a homogenate of the strain, or a culture supernatant of the strain.
According to another aspect of the present invention, there is provided a method for preventing Vibrio septicemia infection, which comprises administering the pharmaceutical composition for preventing Vibrio septicemia infection to an individual.
In the preventive method, the individual is a mammal, the mammal is of the order Primate, Carnivora, Proboscis, Artiodactyla, Perissodactyla or Rodenta, including humans, dogs Carnivora, including lions, tigers, and cats; Rodents, including house mice, hamsters, mice, and guinea pigs; Lagomorphs, including rabbits and pikas; Perissodactyla, including horses, donkeys, rhinos, and tapirs; , Artiodactyla, which includes deer, goats, sheep, and antelope, and Proboscis, which includes elephants.
According to another aspect of the present invention, there is provided a feed additive for preventing Vibrio sepsis infection containing a Bacteroides vulgaratus strain as an active ingredient.

According to another aspect of the present invention, there is provided a health functional food for preventing Vibrio septicemia infection, which contains, as active ingredients, a Bacteroides vulgarus strain, a crushed product of the strain, or a culture supernatant of the strain.
The health functional food is selected from the group consisting of foods, beverages, gums, teas and vitamin complexes, capsules, tablets, powders, granules, liquid phases, rounds, flakes, pastes, syrups, gels, jelly or It is characterized by being a bar-shaped preparation, and various dosage forms suitable for health functional foods, such as hot water, drink, powder, pill, capsule, tablet (coated tablet, sugar-coated tablet, sublingual tablet) etc.), and a dosage form such as jelly is used.
The method for preventing infectious diseases caused by Vibrio bacteria of the present invention is carried out by directly administering the pharmaceutical composition of the present invention to an individual, or by mixing it with an individual's feed or drinking water and feeding it. In the method for preventing infectious diseases caused by Vibrio bacteria of the present invention, the administration route is administered through various oral or parenteral routes as long as the target tissue can be reached. It is administered in the usual manner, such as intravenously, intraperitoneally, intramuscularly, intraarterially, transdermally, intranasally, by inhalation, and the like.

It will be apparent to those skilled in the art that suitable total daily usage of the pharmaceutical compositions administered in the methods of the present invention can be determined within the scope of sound medical judgment. A specific therapeutically effective amount for a particular individual depends on the type and degree of response to be achieved, patient's age, weight, general health condition, sex and diet, administration time, administration route and secretion rate of the composition, treatment. It may be desirable to apply them differently over time, depending on a variety of factors, including drugs used with or concurrently with the specific composition, and analogous factors well known in the pharmaceutical arts.
In one embodiment of the present invention, the Vibrio disease is Vibrio sepsis and Vibrio fish infection, preferably Vibrio sepsis.
The pharmaceutical composition of the present invention is formulated for oral or parenteral administration by mixing with pharmaceutically acceptable carriers, excipients, additives and the like. Examples of pharmaceutically acceptable carriers or excipients are lactose, magnesium stearate, starch, talc, gelatin, agar, pectin, gum arabic, olive oil, sesame oil, cocoa butter, ethylene glycol, and others commonly used. including. Examples of solid compositions for oral administration include tablets, pills, capsules, powders, granules and the like. In such solid compositions, the active ingredient, the plant extract, is combined with at least one inert diluent such as lactose, mannitol, glucose, hydroxypropylcellulose, microcrystalline cellulose, starch, polyvinylpyrrolidone, aluminometasilicate. mixed with magnesium. Solid compositions may be prepared by conventional methods with additives other than inert diluents, e.g. lubricants such as magnesium stearate, disintegrants such as calcium cellulose glycolate, solubilizers such as glutamic acid or aspartic acid. can contain Tablets or pills are optionally coated with a film of substances such as sucrose, gelatin, hydroxypropylmethylcellulose phthalate, and optionally two or more layers. Liquid compositions for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, elixirs and the like, and commonly used inert diluents such as purified water, May include ethanol and the like. In addition to inert diluents, the compositions may contain adjuvants such as wetting agents, suspending agents, sweetening agents, flavoring agents, fragrances, preservatives and the like.

Injections for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions and emulsions. Aqueous solutions and suspensions include, for example, water for injection and physiological saline for injection. Non-aqueous solutions and suspensions include, for example, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, alcohols such as ethanol, polysorbate 80, and the like. Such compositions may also contain adjuvants such as preservatives, wetting agents, emulsifying agents, dispersing agents, stabilizing agents (eg lactose), solubilizing agents (eg glutamic acid, aspartic acid). These are sterilized by conventional sterilization methods such as, for example, filter sterilization using microfiltration membranes, heat sterilization such as autoclave sterilization, or compounding with sterilizing agents. Injections are either liquid preparations or freeze-dried preparations that can be dissolved before use. As excipients for freeze-drying, for example, sugar alcohols and sugars such as mannitol and glucose can be used.

The pharmaceutical compositions of the present invention are administered by oral or parenteral methods. Preferred parenteral administration methods include administration by injection (administration by subcutaneous injection, intravenous injection, intramuscular injection, intraperitoneal injection, etc.), transdermal administration, transmucosal administration (transrectal administration, etc.), transpulmonary administration, and the like. be. Of course, oral administration methods are also used.
The dosage of the active ingredient of the pharmaceutical composition of the present invention can be determined according to the severity of the disease, age of the patient, etc., but is generally in the range of 0.005 μg/kg to 100 mg/kg. , desirably in the range of 0.02 μg/kg to 5 mg/kg. However, the dosage of the pharmaceutical composition of the present invention is determined in light of various related factors such as the route of administration, age, sex, weight of the patient, and severity of the patient. No aspect should be understood to limit the scope of the invention.
The pharmaceutical compositions of this invention are administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat disease at a reasonable benefit/risk ratio applicable to medical treatment, and effective dosage levels are those of atlantoaxial disease. It can be determined by factors including type, severity, drug activity, drug sensitivity, administration time, administration route and excretion rate, treatment duration, concurrent drugs, and other factors well known in the medical field. Pharmaceutical compositions according to the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents, either sequentially or concurrently with conventional therapeutic agents, in single or multiple doses. It is important to administer the amount that achieves the maximum effect in the least amount without side effects considering all of the above factors, which can be readily determined by one of ordinary skill in the art. Specifically, the effective amount of the pharmaceutical composition of the present invention includes age, sex, condition, body weight, absorption rate, inactivity rate and excretion rate of the active ingredient in the body, type of disease, and concomitant drugs. Generally, 1-500 mg/kg body weight can be administered daily or every other day, or in 1-3 divided doses per day, depending on the patient. However, since the dosage may be increased or decreased depending on administration route, sex, body weight, age, etc., the above dosage does not limit the scope of the present invention in any way.

The intestinal tract of mammals is home to vast amounts of normal microorganisms, consisting of hundreds to thousands of species of bacteria, mainly belonging to the phylum Bacteroidetes, Firmicutes, Actinobacteria and Proteobacteria. Interactions between pathogens and intestinal commensals have been reported in diverse pathogens in model systems. Antagonistic effects of intestinal commensals on pathogen entry are achieved through limiting resources available to pathogens, competitive elimination of pathogens in mucosal colonies, inhibitory effects of commensal antimicrobial compounds or appendages, and stimulation of host defense systems. (Martens, E.C. et al., Nat. Rev. Microbiol. 16:457-70.2018). Thus, host animals that experienced changes in gut microbial community composition and abundance appeared to have altered susceptibility to plant-borne pathogens. Increased virulence in host animals has been reported in Salmonella enterica Typhimurium, Listeria monocytogenes, V. cholerae and pathogenic Escherichia coli infections (Ferreira, RB et al., PLoS One. 6:e20338.2011). Also, some pathogens have demonstrated the ability to affect gut microbes by direct killing with the type VI secretion system or bacteriocins. Thus, the pathogens interact with the host through timely generated virulence factors, overcoming potential defense mechanisms derived directly or indirectly from the intestinal microbiota.

Currently, some antibiotics are used to treat diseases caused by Vibrio sp., but they are not very effective and are not suitable due to the recent problem of antibiotic resistance. , the development of new antibiotics is required. On the other hand, pathogenic microorganisms survive or proliferate in the host through the production of various virulence factors that are toxic to the host, and the various virulence factors are collectively expressed during the pathogenic process, We have developed the regulatory mechanisms that enable us to act. The regulatory mechanisms of such virulence factors are very sophisticated, and the production of virulence factors can be suppressed by inhibiting the regulatory mechanisms. Through this, the virulence of pathogenic microorganisms is weakened, and the virulence of microorganisms can be easily inhibited by the host's immune response. Inhibition of virulence factor generation mechanism does not artificially inhibit the growth of microorganisms, so the possibility of inducing antibiotic resistance is very low. , has attracted attention among experts. From this point of view, research into inhibiting the activity of Vibrio bacteria that have invaded from the outside using useful commensal microorganisms existing in the intestine is attracting interest. Thus, the present inventors observed the effect of the intestinal symbiotic bacteria Bacteroides vulgatas on the pathogenicity-inhibiting effect of the food poisoning bacterium Vibrio vulnificus. Conventionally, there have been studies on compositions for treating bacterial infectious diseases using Bacteroides vulgateus, which has an antibacterial activity against enteropathogenic bacteria such as Vibrio cholerae, but during the infection process, there is Little research has been done on interactions.

Vibrio vulnificus, a food-borne pathogen, meets the normal flora of the intestinal environment before causing fatal sepsis and gastroenteritis, overcoming the barrier derived from intestinal commensals for infection. Must. In the present invention, the effect of Vibrio vulnificus on gut microbial community structure in mice was investigated. V. Analysis of the microbial community in faecal samples from mice killed by vulnificus infection showed a decrease in the abundance of Bacteroidetes, in particular bacteria belonging to the species Bacteroides vulgatas, one of the leading intestinal commensals. was expressed. Pseudohypophytes are known to be an important phylum in the gut, of which Bacteroides vulgatus, which accounts for the majority, reduces LPS expression in intestinal commensal bacteria or by pathogenic bacteria. It is known to play an important role in maintaining host immunity, such as alleviating inflammatory reactions (Yoshida et al., Circulation. 138:2486-2498.2018).
In conclusion, the present inventors found that when laboratory mice were infected with Vibrio septicemia, Bacteroides vulgatus decreased in the intestine of said mice, which was due to the excretion of Vibrio septicemia out of the cells. cFP (cyclo-Phe-Pro) induces cell death in Bacteroides vulgarus through interaction with ObgE, a protein of Bacteroides vulgarus (Kim et al., Microbiome. 9 (1) : 161.2021). In addition, the present invention was completed by confirming that the mortality rate of mice infected with Vibrio septicemia was effectively reduced as a result of additionally administering Bacteroides vulgarus to mice. Therefore, the pharmaceutical composition of the present invention can be used to solve the resistance problem of existing antibiotics and to develop therapeutic agents for preventing and treating vibriosepticemia.
Hereinafter, the present invention will be described in more detail through examples. The present invention, however, should not be construed as limited to the embodiments disclosed below, but rather may be embodied in many different forms, and the following embodiments will provide a complete disclosure of the invention and the It is provided to fully inform the trader of the scope of the invention.

experimental method
Strain Culture The bacterial species and strains used in this experiment were V. vulnificus MO6-24/O, B. vulgatus JK001 was used. First, the V.I. B. vulnificus was cultured in Luria-Bertani (LB) medium with 2.5% sodium chloride at 30°C. vulgatus was cultured in a reinforced clostridial medium (RCM) medium at 37° C. in an anaerobic environment. Information regarding the bacterial strains used in the present invention is summarized in Table 1 below.

Experimental Animals Animal experiments were performed using 4-week-old female ICR mice (CrljOri: CD1 [ICR], OrientBio, Korea). Mice were maintained at 23° C. and 50% humidity under a 12/12 hour light-dark cycle condition and fed water and food ad libitum (LabDiet 5L79, OrientBio, Republic of Korea). After acclimating to the laboratory conditions for 2 days, mice were treated to the specific conditions for each experiment. During the entire experimental process, mice were carried out according to the institutional guidelines and legal requirements of Sogang University, Republic of Korea (Permit No. IACUCSGU2015_03 and IACUCSGU2019_01).

Quantitative RT-PCR
After injecting PBS and cFP into rats, rat fecal samples were collected from 6 hours to 24 hours, and total bacterial DNA was obtained from the collected fecal samples. 2.5 ng of DNA extracted from each sample was added to B. vulgatus 16s rDNA-specific primer (Wang et al., Appl Environ Microbiol. 62(4):1242-1247.1996) and a bacterial universal 16s rDNA primer (Ziesemer et al., Sci Rep. 5:16498.2015). ) was used to perform qRT-PCR. Each CT value obtained from the qRT-PCR was normalized using the 2 ^-ΔΔCT method. Nucleic acid sequence information of the primers used in the present invention is summarized in Table 2 below.

Isolation of mouse visceral microbes To obtain pure cultures of bacteria in mouse viscera, fecal samples collected from 7-week-old female ICR mice were resuspended in PBS. After that, it was briefly centrifuged to remove fecal debris, the supernatant was collected, and the diluted suspension was plated on GAM (Gifu Anaerobic medium; BD Difco), RCM or MRS agar plates and plated anaerobic at 37°C. The cells were cultured for 24-48 hours under sexual conditions. Bacterial colonies were treated to amplify the 16S rDNA fragment using 27F (SEQ ID NO:5) and 1492R (SEQ ID NO:6) primers and the purified PCR products were 785F (SEQ ID NO:3) and 907R (SEQ ID NO:3). No. 4) DNA sequencing analysis was performed using primers (Macrozen, Korea). The strain is B. It showed more than 97% identity with the relevant region of vulgatus 16S rDNA and was named MGM001 (see Table 1). The DNA sequence of the 16S rRNA has been deposited in GenBank under the accession number MT764994.
Mouse lethality test
To analyze the lethality of experimental mice to Vibrio septicemia by cFP administration, we administered cFP (110 μg/g mouse weight) to 4-week-old female ICR mice that were starved for 12 hours. Twelve hours after dosing, each mouse was injected intraperitoneally with iron dextran (30 μg/g mouse weight) at 8.5% [w/vol. ] of sodium bicarbonate (50 μl) was injected intragastrically. Then, various numbers of bacteria (10 ⁴ to 10 ⁸ ) of Vibrio septicemia were injected into the stomach to infect the mice, and the 24-hour survival rate was investigated. Also, B. To investigate mouse lethality to Vibrio septicemia upon administration of vulgatus, 4-week-old female ICR mice starved for 24 h were injected intraperitoneally with iron dextran (30 μg/g rat weight), resulting in 8.5% [w / vol. ] of sodium bicarbonate (50 μl) was injected intragastrically. After that, V.I. vulnificus and/or B. vulgatus was injected intragastrically for infection. At this time, the injected V.I. vulnificus is LBS and B. vulnificus. vulgatus were harvested by growing in RCM to OD ₅₉₅ =1, resuspended in PBS and assayed for 24 hour mouse survival.

Example 1: B.I. V. vulgatus through changes in abundance. Mouse mortality due to V. vulnificus of the present invention. Introduction of B. vulnificus in fecal samples. Vulgatus levels are reduced, said reduced composition being associated with V. vulgatus levels. It was postulated to be mediated by cFP secreted by vulnificus infection. Therefore, in mouse fecal samples B. The effect of exogenous addition of cFP on C. vulgatus abundance was investigated. Fecal samples were collected from 4-week-old female mice orally administered cFP at a concentration of 110 μg cFP per gram of mouse. Total DNA extracted from each stool sample was isolated from B. q-PCR was performed using a primer set specific to the 16S rDNA of vulgatus (Bv-F and Bv-R) or a universal primer set to the eubacterial 16S rDNA (785F and 907R). B. Relative abundance of vulgatus 16S rDNA was normalized by the abundance of total 16S rDNA derived from PCR using universal primer sets. As a result, the median 2-[CT (B. vulgatus)-CT (total bacteria)] estimate was 0.00 in the PBS-treated control group (n=20 mice) and cFP-treated mice (n=20 mice), respectively. 1369 (±0.0748) and 0.0619 (±0.0766) (Fig. 1). Therefore, B. Levels of vulgatus appeared to be reduced approximately 2.2-fold in cFP-injected mice (P=0.006, two-sided Student's t-test).

Example 2: B.I. V. vulgatus through changes in abundance. Mouse lethality by B. vulnificus We found that reduced levels of B. vulnificus Mice containing V. vulgatus It was investigated whether other susceptibility to infection by S. vulnificus was exhibited. Mice were orally administered cFP and infected with various doses of 10 ⁴ to 10 ⁸ cells (n=7 mice per treatment) (open symbols) 12 h after cFP administration. The same experiment was performed using control group mice (7 mice per treatment) injected with DMSO cells without cFP (closed symbols). As a result, V.I. When infected with the highest dose of C. vulnificus (ie, 10 ⁸ cells), mice died prematurely within 24 hours in both conditions equally well (FIG. 2). Similarly, the lowest capacity V.V. Mice infected with C. vulnificus (ie, 10 ⁴ cells) showed a similar survival pattern regardless of exogenous supplementation of cFP. However, the number of mice that died was higher than that of V.C. after pre-administration of cFP. It was more abundant in the cFP-treated mouse set infected with 10 ⁵ -10 ⁷ cells of C. vulnificus. V. In the case of 10 ⁶ cell infection with C. vulnificus, the difference in survival was significant with a P-value of 0.001 (log-rank test). The above results suggest that mice in which Bacteroides vulgataus was reduced by cFP administration also had an increased mortality rate due to infection with Vibrio septicemia.

Example 3: Investigation of Vibrio septicemia mouse mortality by addition of Bacteroides vulgarus The present inventors demonstrate that the observed increase in Vibrio septicemia mouse mortality is due to the reduction of Bacteroides vulgarus. In order to do so, we increased the intake of Bacteroides vulgaratus to laboratory animals and investigated the mortality rate of mice caused by Vibrio septicemia. Therefore, different ratios (1:20, 1:50) of Bacteroides vulgatus were administered to mice infected with Vibrio septicemia under the same conditions as above. As a result, it was observed that the lethality rate of Vibrio septicemia to rats decreased as the number of added Bacteroides vulgarus increased (Fig. 3). The above results show that in order for Vibrio septicemia to successfully show lethality in mice, it is necessary to reduce the intestinal commensal bacterium Bacteroides vulgarus through the cFP excreted by Vibrio. • Experimentally demonstrated that additional doses of vulgatas reduced the lethality of Vibrio septicemia to mice.
In conclusion, the results show that as the intestinal commensal bacterium, Bacteroides vulgatus, is decreased by cFP secreted by Vibrio septicemia, the mortality rate of experimental mice increases, but the Bacteroides vulgatus is further administered to mice. In this case, the fatality rate due to Vibrio septicemia was reduced, suggesting that the Bacteroides vulgarus can be utilized as a composition for preventing Vibrio septicemia infection.
Although the present invention has been described with reference to the foregoing embodiments, it should be understood that these are merely exemplary and that a person skilled in the art will be able to make various modifications and other equivalent embodiments. You can understand. Therefore, the true technical protection scope of the present invention should be determined by the technical ideas of the claims.

Claims (5)

A pharmaceutical composition for preventing Vibrio septicemia infection, comprising a Bacteroides vulgarus strain, a homogenate of said strain, or a culture supernatant of said strain as an active ingredient. 2. The pharmaceutical composition of claim 1, wherein said Vibrio sepsis is induced by Vibrio vulnificus. A method for preventing Vibrio sepsis infection, comprising administering the pharmaceutical composition of claim 1 or 2 to an individual. A feed additive for preventing Vibrio septicemia infection, comprising a Bacteroides vulgarus strain, a crushed product of the strain, or a culture supernatant of the strain as an active ingredient. A health functional food for preventing Vibrio septicemia infection, comprising a Bacteroides vulgarus strain, a crushed product of the strain, or a culture supernatant of the strain as an active ingredient.

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