Novel lactobacillus plantarum strains and uses thereof

Abstract

The present invention relates to a new strain of Lactobacillus plantarum (Lactobacillus plantarum), and the new strain of Lactobacillus plantarum (Lactobacillus plantarum). Furthermore, the present invention relates to a composition for preventing, ameliorating or treating infertility or hypofertility, the composition comprising a Lactobacillus plantarum strain. The Lactobacillus plantarum strain of the present invention reduces the expression of a specific gene in cells constituting the placenta to help implantation of an embryo, increases the number of immune cells in the uterus, and increases the implantation rate of the embryo reduced by immune imbalance. Therefore, the Lactobacillus plantarum strain of the present invention can be effectively used as a composition for preventing, ameliorating or treating infertility or hypofertility.

Description

Technical Field

[0001] The present invention relates to a novel Lactobacillus plantarum strain and a composition for preventing, improving or treating infertility or subfertility comprising the Lactobacillus plantarum strain. Background Art

[0002] Infertility or subfertility refers to a situation where healthy married men and women of childbearing age have not become pregnant after one year despite having normal sexual intercourse without any contraception. Currently, the number of patients with unexplained infertility or subfertility is gradually increasing, and the number of patients in Korea has increased by more than 3.7 times in the past 10 years. However, even after undergoing in vitro fertilization, which is a representative treatment for infertility or subfertility, about 5% of patients have difficulty becoming pregnant due to repeated implantation failure.

[0003] Therefore, people are actively conducting research to reveal the cause of infertility or low fertility and develop drugs for the treatment thereof. In this regard, published studies have shown that repeated implantation failure is caused by immune factors (Jason M Franasiak et al., Fertil Steril, June 2017, 107 (6): 1279-1283). The results of the study show that the microbiome in the uterus and vagina is an important environmental factor for pregnancy, and the advantage that Lactobacillus spp. may contribute to conception and pregnancy maintenance has attracted people's attention (Alex Farr et al., PLoS One, December 11, 2015, 10 (12): e0144181). In addition, the Lactin-V drug based on Lactobacillus crispatus is currently undergoing clinical trials and is known to be effective in preventing recurrent bacterial vaginosis and improving the success rate of in vitro fertilization (Craig R Cohen et al., N Engl J Med, May 14, 2020, 382(20): 1906-1915).

[0004] However, a therapy for treating infertility or subfertility from an immunological perspective, or a drug for treating infertility or subfertility using microbiome immunity has not yet been developed. In the field to which the present invention belongs, there is still a great need for such treatments. Summary of the invention

[0005] The inventors conducted various studies on strains that can treat infertility or subfertility caused by immune factors and microbiome imbalance. As a result, they discovered a new Lactobacillus plantarum strain and preserved it. Experiments proved that the strain regulates the expression of genes that help implantation, increases the number of immune cells in the uterus and improves the embryo implantation rate, thereby completing the present invention.

[0006] The invention provides a new Lactobacillus plantarum strain.

[0007] As used herein, the term "Lactobacillus plantarum" refers to a strain deposited by the applicant at the Korea Collection of Type Cultures (KCTC) of the Korea Research Institute of Life Science and Biotechnology (KRIBB) on August 24, 2021, with a deposit number of KCTC 14678BP. In the present invention, "Lactobacillus plantarum" can be used interchangeably with "Lactobacillus plantarum strain" or "strain". The strain is interpreted as including the strain itself, the culture of the strain, the lysate of the strain, the extract of the strain, and the cytoplasmic component obtained by lysing the strain.

[0008] The term "culture" refers to the strain itself, a strain extract obtained by culturing the strain for a certain period of time on a medium supplemented with nutrients, a metabolite of the strain, or a whole medium containing additional nutrients. The term "culture" also includes a culture medium from which the strain is removed after culturing the strain. In addition, the culture includes a concentrate of the whole culture medium or the culture medium and a dried product of the concentrate. Specifically, those skilled in the art can easily select a culture medium according to the purpose in the culture medium for microbial cultivation.

[0009] In the present invention, the plant lactobacillus strain can be used to prevent or treat infertility or subfertility. In addition, the strain can reduce the expression or activity of T cell immunoglobulin and mucin domain-containing protein 3 (TIM3), increase the number of immune cells in the uterus, or increase embryo implantation rate.

[0010] Specifically, "TIM3" refers to the "T cell immunoglobulin and mucin domain-containing protein 3" gene. Among the cells that make up the embryo, the cells that are directly involved in implantation are trophoblast cells. Trophoblast cells surround the blastocyst in the embryo and interact directly with endometrial cells. When the expression of TIMP3 in trophoblast cells is reduced, the invasion of the endometrial layer increases, resulting in successful implantation. Therefore, the plantarum Lactobacillus strain of the present invention that can reduce the expression of TIM3 in trophoblast cells can help implantation.

[0011] In addition, the immune cells in the uterus can be lymphocytes and / or NK (Natural Killer) cells. It is known that when the immune cells such as lymphocytes and NK cells present in the uterus are sufficient in number, it helps embryo implantation. Therefore, the plant lactobacillus strain of the present invention that can increase the number of immune cells can help implantation.

[0012] In addition, the strain of the present invention can increase the implantation rate which is reduced by immune imbalance to a normal level.

[0013] Another aspect of the present invention provides a pharmaceutical composition for preventing or treating infertility or subfertility, the pharmaceutical composition comprising at least one selected from a Lactobacillus plantarum strain preserved under the accession number KCTC 14678BP, a culture of the strain, a fermentation product of the strain, a lysate of the strain, an extract of the strain, and a cytoplasmic component obtained by lysing the strain.

[0014] In the pharmaceutical composition according to the present invention, unless particularly mentioned, each term is the same as described for the Lactobacillus plantarum strain.

[0015] Pharmaceutical composition of the present invention comprises plant lactobacillus strain as active ingredient. In addition, as mentioned above, plant lactobacillus strain is interpreted as comprising strain itself, culture of strain, fermentation product of strain, lysate of strain, extract of strain and cytoplasmic component obtained by cracking strain, therefore pharmaceutical composition of the present invention comprises plant lactobacillus strain, culture of strain, strain lysate, strain extract or cytoplasmic component obtained by cracking strain.

[0016] As used herein, the terms "infertility" and "subfertility" refer to a condition in which pregnancy is difficult or impossible within one year despite normal sexual activity without contraception. Infertility or subfertility may be female infertility or female subfertility.

[0017] Furthermore, infertility or subfertility may be due to one or more causes selected from immune abnormalities, diminished ovarian reserve, ovulatory disorders, implantation failure, fallopian tube damage, fallopian tube obstruction, paratubal adhesions, infection, immune diseases, and endometriosis.

[0018] The pharmaceutical composition of the present invention comprises an effective amount of the strain, and can be administered to a subject in need of preventing or treating infertility or subfertility.

[0019] As used herein, the term "administering" refers to physically introducing a composition into a subject using any of the methods and delivery systems known to those skilled in the art. Routes of administration include, for example, oral, intravaginal, intravenous, intramuscular, subcutaneous, intraperitoneal, spinal or other parenteral routes, such as by injection or infusion, but are not limited thereto. Administration may be performed, for example, once, multiple times, or over one or more extended time periods.

[0020] Pharmaceutical composition of the present invention can only comprise plant lactobacillus strain, or can also comprise acceptable carrier, excipient or diluent that are generally used to prepare pharmaceutical composition.Carrier, excipient or diluent that can comprise in composition comprise for example lactose, glucose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum arabic, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talcum, magnesium stearate and mineral oil, but be not limited to this.These can be used alone, also can two or more are used in combination. In addition, if necessary, the pharmaceutical composition may also contain other acceptable additives, such as antioxidants, buffers and / or antibacterial agents, and may further contain dispersants, surfactants, binders, lubricants, etc. to be formulated into powders, granules, tablets, liquids, capsules, suspensions, emulsions, syrups, emulsions, lotions, gels, ointments, aerosols, powder sprays, emulsions, suppositories, pills, etc.

[0021] As an embodiment of the above dosage form, the pharmaceutical composition of the present invention can be a dosage form for intravaginal administration. Specific examples of the dosage form for intravaginal administration can be one or more selected from tablets, liquids, emulsions, lotions, gels, ointments, powder sprays, suppositories and pills, but are not limited thereto.

[0022] As used herein, the term "subject" includes humans or any non-human animals. Non-human animals can be, for example, vertebrates such as primates, dogs, cows, horses, pigs, rodents such as mice, rats, guinea pigs, etc. The term "subject" can be used interchangeably with "individual" or "patient" herein.

[0023] The effective amount can be a "therapeutically effective amount" or a "prophylactic effective amount". As used herein, the term "therapeutically effective amount" refers to any amount that can reduce the severity of the disease, increase the frequency and duration of the disease asymptomatic period, or prevent damage or injury caused by the pain of the disease when the drug or therapeutic agent is used alone or in combination with other therapeutic agents. As used herein, the term "prophylactic effective amount" refers to any amount that inhibits the occurrence or recurrence of infertility or subfertility in a subject. The level of the effective amount can be determined based on factors including severity, age, sex, drug activity, drug sensitivity, administration time, administration route, excretion rate, treatment period, concurrently used drugs, and other factors known in the medical field.

[0024] In addition, the administration of the pharmaceutical composition may vary according to the age, sex and weight of the subject. Specifically, according to the symptoms of the subject, 0.1 mg / kg to 100 mg / kg of the composition of the present invention may be administered once a day to several times or every few days to several months. In addition, the dosage may be increased or decreased according to the route of administration, severity of the disease, sex, weight, age, etc.

[0025] The pharmaceutical composition may be administered in combination with other therapeutic agents. In this case, the pharmaceutical composition of the present invention and other therapeutic agents may be administered simultaneously, sequentially or separately. Other therapeutic agents may be drugs that have the effect of preventing, treating or improving infertility or subfertility, such as compounds, proteins or hormones, but are not limited thereto. For example, the hormone may be progesterone.

[0026] In addition, pharmaceutical composition according to the present invention can be formulated into and use simultaneously, successively or respectively with other therapeutic agents.For example, bacterial strain and other therapeutic agents can be used as a preparation to use simultaneously, or can be used as independent preparation to use simultaneously, successively or respectively.For using simultaneously, successively or respectively, bacterial strain and other therapeutic agents included in pharmaceutical composition of the present invention can be prepared respectively in each container, or can be prepared together in the same container.In addition, the effective amount, application time, application interval, administration route, treatment period etc. of bacterial strain and other therapeutic agents included in the present composition can be identical or different from each other.

[0027] Another aspect of the present invention provides a use for preventing or treating infertility or subfertility by using at least one of a Lactobacillus plantarum strain deposited with the accession number KCTC 14678BP, a culture of the strain, a fermentation product of the strain, a lysate of the strain, an extract of the strain, and a cytoplasmic component obtained by lysing the strain.

[0028] In the preventive or therapeutic use according to the present invention, each term has the same meaning as described above with respect to the strain or pharmaceutical composition, unless otherwise specifically stated.

[0029] Another aspect of the present invention provides a method for preventing or treating infertility or subfertility. The method comprises administering to a subject in need thereof at least one selected from a Lactobacillus plantarum strain deposited with the accession number KCTC 14678BP, a culture of the strain, a fermentation product of the strain, a lysate of the strain, an extract of the strain, or a cytoplasmic fraction obtained by lysing the strain.

[0030] In the method of prevention or treatment according to the present invention, each term has the same meaning as described in the above-mentioned strain or pharmaceutical composition, unless otherwise specifically stated.

[0031] In the prevention or treatment method according to the present invention, the Lactobacillus plantarum strain deposited under the accession number KCTC 14678BP can be administered to the subject simultaneously, sequentially or separately with other therapeutic agents.

[0032] "Simultaneous" application refers to the one-time application of plant lactobacillus strains and other therapeutic agents in a preparation form, or the one-time application of plant lactobacillus strains and other therapeutic agents in a separate preparation form, wherein the administration routes of plant lactobacillus strains and other therapeutic agents can be different from each other. "Sequentially" application refers to the relatively continuous application of plant lactobacillus strains and other therapeutic agents, so that the application interval is minimized. "Separately" application refers to the application of plant lactobacillus strains and other therapeutic agents at predetermined time intervals. The application method of plant lactobacillus strains and other therapeutic agents can be appropriately selected by a doctor or an expert in the field according to the therapeutic effect or side effects of the experimenter.

[0033] Another aspect of the present invention provides a food composition for preventing or improving infertility or subfertility, the food composition comprising at least one selected from a Lactobacillus plantarum strain preserved under the accession number KCTC 14678BP, a culture of the strain, a fermentation product of the strain, a lysate of the strain, an extract of the strain, and a cytoplasmic component obtained by lysing the strain.

[0034] In the food composition according to the present invention, each term has the same meaning as described in the above-mentioned strain or pharmaceutical composition, unless otherwise specifically stated.

[0035] The food may be a health functional food. As used herein, the term "health functional food" refers to a food manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc. using raw materials or ingredients having functions useful to the human body. "Functional" or "functionality" herein refers to obtaining an effect useful for health purposes, such as regulating nutrients or physiological effects on the structure and function of the human body.

[0036] The type of food is not limited. For example, the type of food may be commercialized or formulated into yogurt, dairy products, meat, sausage, bread, chocolate, candy, snacks, sweets, pizza, ramen, noodles, chewing gum, dairy products including ice cream, soup, beverages, tea, drinks, alcoholic beverages, or vitamin complexes, and includes all foods in the conventional sense.

[0037] Food composition according to the present invention can be manufactured by methods commonly used in this area, and can be manufactured by adding raw materials and components usually added in this area.Different from conventional medicines, the advantage of this food is that there is no side effect that long-term medication may produce and highly portable.Therefore, food composition of the present invention can be used as a supplement for strengthening prevention or improving infertility or low fertility effect.

[0038] The effective amount of the plant lactobacillus strain included in the food composition according to the present invention can be appropriately determined according to the purpose of use, such as prevention, improvement or therapeutic treatment. Usually, the plant lactobacillus strain, the culture of the strain, the fermentation product of the strain, the lysate of the strain, the extract of the strain or the cytoplasmic component obtained by lysing the strain can be included in the food composition with 0.001 weight percent (wt%) to 20 weight percents, 0.001 weight percent to 15 weight percents or 0.001 weight percent to 10 weight percents. In the case of health drink, with 100mL as a benchmark, 0.01 to 2g can be included, specifically 0.02g to 2g, more specifically 0.3g to 1g of the amount of the plant lactobacillus strain, the culture of the strain, the fermentation product of the strain, the lysate of the strain, the extract of the strain or the cytoplasmic component obtained by lysing the strain. However, for the situation of long-term intake for health and sanitation purposes or health control, the amount lower than the above-mentioned scope can be used. In the process of preparing food composition, the plant lactobacillus strain added to the food composition can be appropriately increased or reduced as needed.

[0039] The food composition may be in any dosage form such as pills, tablets, granules, powders, capsules, liquids and solutions.

[0040] Food compositions can contain various sweeteners or natural carbohydrates as additional ingredients like conventional foods. Natural carbohydrates can be, for example, 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. Sweeteners can be, for example, natural sweeteners such as thaumatin and stevia extract, or synthetic sweeteners such as saccharin and aspartame.

[0041] Furthermore, when the food composition is a beverage composition, there is no limitation on the liquid component if it contains a specified ratio of the Lactobacillus plantarum strain as an active ingredient. Like conventional beverages, the beverage composition may contain various flavorings or natural carbohydrates as additional ingredients.

[0042] The plant lactobacillus strain of the present invention reduces the expression of specific genes in cells constituting the placenta to help the implantation of the embryo, increases the number of immune cells in the uterus, and improves the implantation rate of the embryo that is reduced by immune imbalance. Therefore, it can be effectively used as a composition for preventing, improving or treating infertility or subfertility. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] Figure 1 : is a graph showing the effect of the Lactobacillus plantarum strain according to the present invention on reducing the expression level of the TIM3 gene. * indicates P<0.05, ** indicates P<0.01, and *** indicates P<0.001.

[0044] Figure 2 Schematic diagram of an experiment conducted to confirm the effect of the Lactobacillus plantarum strain according to the present invention on improving the success rate of embryo implantation.

[0045] Figure 3 This is a diagram showing the effect of the Lactobacillus plantarum strain according to the present invention on increasing uterine immune cells. A refers to the total number of lymphocytes, and B refers to the number of uterine NK cells. DETAILED DESCRIPTION

[0046] Hereinafter, the present invention will be described in more detail by way of examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited thereto.

[0047] Example 1, TIM3 expression inhibition effect

[0048] When the endometrium is thicker and embryo implantation occurs, the lower the expression of tissue inhibitor of metalloproteinases (TIMP3) in the trophoblast, the more favorable it is for implantation (Jia-Yu Zhu et al., Rev Obstet Gynecol, 2012; 5(3-4): e137-43). Therefore, if the plant lactobacillus strain deposited by the applicant at the Korea Institute of Life Science and Biotechnology with the deposit number KCTC 14678BP on August 24, 2021 reduces the expression of the TIMP3 gene in the trophoblast HTR-8 / SVneo cell line, it proves that the strain is a strain that can improve the implantation rate and pregnancy rate.

[0049] Specifically, one day before the experiment, HTR-8 cells were plated at 4 × 10 5Cells / mL were inoculated in 12-well plates. The next day, after confirming that the confluence was 70%-80% and the layer was evenly formed under a microscope, it was washed with PBS and replaced with 0.8 mL of serum-free medium. Thereafter, the strain suspension was treated so that the multiplicity of infection (MOI) relative to the number of cells was 50 or 100. As a positive control, leukemia inhibitory factor (LIF) expressed in endometrial cells was used, which is an important factor for pregnancy and implantation (Pankaj Suman et al., Fertil Steril, February 2013; 99(2): 533-42), and it was treated so that the final concentration was 50 ng / mL. After 4 hours of LIF treatment, RNA was extracted, the 18S gene and TIMP3 gene were amplified by cDNA synthesis, and the expression level of each gene was calculated relative to the 18S rRNA expression level.

[0050] Therefore, if Figure 1 As shown, when treated with LIF in the positive control group, the TIMP3 gene expression level was confirmed to be significantly reduced compared to the untreated control group. In addition, when the strain was treated with 50 or 100 MOI relative to the cell number, the TIMP3 gene expression level was confirmed to be reduced in a dose-dependent manner, which showed a significant effect of about 2 times higher than that of the positive control group treated with LIF.

[0051] From the above results, it can be seen that the Lactobacillus plantarum strain of the present invention can reduce the expression level of the TIM3 gene, thereby facilitating the embryo implantation process, thereby preventing or treating infertility or subfertility.

[0052] Example 2: Effect of increasing implantation success rate

[0053] In order to confirm whether the Lactobacillus plantarum strain of the present invention deposited under the accession number KCTC 14678BP can prevent repeated implantation failure due to immune reasons and microbiome imbalance, the implantation rate was evaluated after the Lactobacillus plantarum strain was applied to a mouse model of LPS-induced implantation failure. Implantation failure was induced by administering LPS, which is known to cause immune imbalance (Sarah Moustafa et al., Am J Reprod Immunol, February 2019; 81(2): e13082).

[0054] Specifically, the control group and experimental group were set up as follows:

[0055] - Control group: normal mice not treated with strain or LPS

[0056] - Negative control group (LPS-treated group): mice treated with LPS to induce implantation failure

[0057] - Experimental group (LPS and strain treatment group): mice treated with LPS to induce implantation failure while being treated with Lactobacillus plantarum strains

[0058] Eight female balb / c mice were randomly divided into each group and the drugs were administered vaginally in the morning for 10 days (-10d to 0d). The control group was administered with PBS, the negative control group was administered with PBS, and the experimental group was administered with 1×10 8 CFU of the strain. Based on the first day of strain treatment (-10d) as the benchmark, 10μg LPS dissolved in PBS was administered intravaginally to the negative control group and the experimental group on the afternoon of the 5th day (-5d). Then, on the afternoon of the 10th day (0d), mating was performed for 3 days at a male-female ratio of 2:1. Based on the first day of mating (0d) as the benchmark, an autopsy was performed on the 10th day (10d) to confirm whether implantation was successful. The schematic diagram of this experiment is shown in the figure below. Figure 2 shown.

[0059] Table 1

[0060]

[0061] As a result, as shown in Table 1, the implantation success rate of the control group was 87.5%, but the implantation success rate of the negative control group processed by LPS was 25%, showing a decrease of about 62.5% compared with the control group. On the other hand, although it was confirmed that the LPS treatment was carried out, the experimental group of the treated bacterial strain showed an implantation success rate of 87.5%, which was at the same level as the control group. As can be seen from the above results, plant lactobacillus strain of the present invention has the effect of improving the embryo implantation rate reduced by immune imbalance, and therefore can be effectively used to prevent or treat infertility or low fertility.

[0062] Example 3 Effect of increasing the number of uterine immune cells

[0063] It is well known that enough immune cells present in the uterus contribute to the implantation of the embryo. In particular, lymphocytes and NK cells (uterine NK; uNK) in the uterus play an important role in the maturation of decidual NK cells, and decidual NK cells are essential for the implantation process. In the absence of uNK, even if the embryo implants, it may fall off later (Dorothy K Sojka et al., Front Immunol, May 1, 2019; 10:960; Nabila Jabrane-Ferrat et al., Immunology, April 2014; 141 (4): 490-497). Therefore, it was evaluated how the plant lactobacillus strain of the present invention, which was preserved with the accession number KCTC 14678BP, affects uNK and related immunity in the uterus.

[0064] Specifically, the strain was administered to a mouse model in which implantation failure was induced by the method of Example 2. The control group and the experimental group were set up as follows:

[0065] - Control group: normal mice not treated with strain or LPS

[0066] - Negative control group (LPS-treated group): mice treated with LPS to induce implantation failure

[0067] - Experimental group (LPS and strain treatment group): mice treated with LPS to induce implantation failure while being treated with Lactobacillus plantarum strains

[0068] After the treatment of each substance was completed, the uterine tissue of the mouse was extracted and minced, and the tissue was separated using separation buffer, and immune cells were separated using FBS. The separated immune cells (1×10 6 Cells / mL) were transferred to a 1.5 mL tube and attached to Fc block. NK cell antibodies (CD45+, CD3-, CD335+, CD49b+) were attached to immune cells. The number of total lymphocytes and uNK cells was analyzed by flow cytometry.

[0069] Therefore, if Figure 3 As shown in A in Figure 1, it was confirmed that the negative control group treated with LPS showed a significant decrease in the total number of lymphocytes compared to the control group. On the other hand, in the case of the experimental group treated with LPS and the strain, it was confirmed that the total number of lymphocytes decreased by LPS increased and recovered to a level similar to that of the control group.

[0070] In addition, if Figure 3 As shown in B, the negative control group treated with LPS was confirmed to show a significant decrease in the number of uNKs compared to the control group. On the other hand, in the case of the experimental group treated with LPS and the strain, the number of uNKs reduced by LPS was confirmed to increase and return to a level similar to the control group.

[0071] From the above results, it can be seen that the Lactobacillus plantarum strain of the present invention has the effect of increasing the number of immune cells in the uterus that contribute to implantation, and therefore, can be effectively used to prevent or treat infertility or subfertility.

[0072] [Accession Number]

[0073] Depository: Korea Institute of Biotechnology

[0074] Accession number: KCTC 14678BP

[0075] Collection date: 20210824

[0076]

Claims

1. A Lactobacillus plantarum strain, deposited with the accession number of KCTC 14678BP.

2. The plant lactobacillus strain according to claim 1, in, The strain is used for preventing or treating infertility or subfertility.

3. The plant lactobacillus strain according to claim 1, in, The strain reduces the expression or activity of T cell immunoglobulin and mucin domain-containing protein 3 (TIM3), increases the number of immune cells in the uterus, or increases the implantation rate of embryos.

4. A pharmaceutical composition for preventing or treating infertility or subfertility, in, The pharmaceutical composition comprises at least one selected from the group consisting of a Lactobacillus plantarum strain deposited with the accession number of KCTC 14678BP, a culture of the strain, a fermentation product of the strain, a lysate of the strain, an extract of the strain, and a cytoplasmic component obtained by lysing the strain.

5. The pharmaceutical composition according to claim 4, in, The infertility or subfertility is female infertility or female subfertility.

6. The pharmaceutical composition according to claim 4, in, The infertility or the subfertility is caused by at least one selected from the group consisting of immune abnormality, decreased ovarian reserve, ovulation disorder, implantation failure, fallopian tube damage, fallopian tube obstruction, paratubal adhesions, infection, immune disease and endometriosis.

7. The pharmaceutical composition according to claim 4, in, The pharmaceutical composition is administered via the intravaginal route.

8. The pharmaceutical composition according to claim 4, in, The pharmaceutical composition is formulated into tablets, liquids, creams, lotions, gels, ointments, powder sprays, suppositories or pills.

9. The pharmaceutical composition according to claim 4, in, The pharmaceutical composition is administered in combination with a progestin.

10. A food composition for preventing or improving infertility or subfertility, the food composition comprising at least one selected from the group consisting of a Lactobacillus plantarum strain deposited with accession number KCTC 14678BP, a culture of the strain, a fermentation product of the strain, a lysate of the strain, an extract of the strain, and a cytoplasmic component obtained by cracking the strain.

11. The food composition according to claim 10, in, The infertility or subfertility is female infertility or female subfertility.

12. The food composition according to claim 10, in, The infertility or subfertility is caused by at least one selected from the group consisting of immune abnormalities, decreased ovarian reserve, ovulation disorders, implantation failure, fallopian tube damage, fallopian tube obstruction, paratubal adhesions, infection, immune diseases and endometriosis.

13. The food composition according to claim 10, in, The food composition is ingested in combination with a progesterone.

14. A use for preventing or treating infertility or subfertility of at least one selected from the group consisting of a Lactobacillus plantarum strain deposited with the accession number KCTC 14678BP, a culture of the strain, a fermentation product of the strain, a lysate of the strain, an extract of the strain, and a cytoplasmic component obtained by lysing the strain.

15. A method for preventing or treating infertility or subfertility, in, The method comprises administering to a subject in need thereof at least one selected from the group consisting of a Lactobacillus plantarum strain deposited with the deposit number KCTC 14678BP, a culture of the strain, a fermentation product of the strain, a lysate of the strain, an extract of the strain, and a cytoplasmic fraction obtained by lysing the strain.

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