Novel Lactobacillus plantarum strains and their uses

Abstract

The present invention relates to a novel Lactobacillus plantarum strain. The present invention also relates to a composition for preventing, improving or treating infertility or difficulty in pregnancy, which contains the Lactobacillus plantarum strain. The Lactobacillus plantarum strain of the present invention reduces the expression of a specific gene in cells constituting the placenta to aid in embryo implantation, or increases the number of immune cells in the uterus, and also increases the rate of embryo implantation, which is reduced due to immune imbalance. Therefore, it can be usefully used as a composition for preventing, improving or treating infertility or difficulty in pregnancy.

Description

Technical Field

[0001] The present invention relates to a novel Lactobacillus plantarum strain. The present invention also relates to a composition for preventing, improving or treating infertility or subfertility, which contains a Lactobacillus plantarum strain.

Background Art

[0002] Infertility or subfertility refers to a state in which healthy men and women of childbearing age are married and have no contraception, and after one year has passed without pregnancy even though they have normal sexual life. Currently, the number of patients with unexplained infertility or subfertility is gradually increasing, and in the past 10 years, the number of patients has increased by about 3.7 times or more only in South Korea. However, even after in vitro fertilization, which is a typical infertility or subfertility treatment, about 5% still experience repeated implantation failure and have difficulty in getting pregnant.

[0003] Therefore, research to identify the causes of infertility or subfertility and the development of drugs for treating it are being actively conducted. In connection with this, research results have been published that repeated implantation failure is caused by immunological factors (Jason M Franasiak et al., Fertil Steril. 2017 Jun, 107(6):1279-1283), and the uterine and vaginal microbiomes are important environmental factors for pregnancy, and research results showing that Lactobacillus spp. are beneficial for pregnancy and maintenance have attracted attention (Alex Farr et al., PLoS One. 2015 Dec 11, 10(12):e0144181). In addition, the Lactobacillus crispatus-based Lactin-V drug is currently in clinical development and is known to be effective in preventing repeated bacterial vaginitis and improving the success rate of in vitro babies (Craig R Cohen et al., N Engl J Med. 2020 May 14, 382(20):1906-1915).

[0004] However, therapies that treat infertility or fertility from an immunological perspective, or pharmaceuticals that treat these conditions by applying the microbiome immunologically, have yet to be developed, and the need for such therapies remains very strong in the field to which this invention belongs. [Prior art documents] [Non-patent literature]

[0005] [Non-Patent Document 1] Jason M Franasiak et al., Fertil Steril.2017 Jun, 107(6):1279-1283 [Non-Patent Document 2] Alex Farr et al., PLoS One.2015 Dec 11, 10(12):e0144181 [Non-Patent Document 3] Craig R Cohen et al., N Engl J Med.2020 May 14, 382(20):1906-1915 [Overview of the Initiative] [Problems that the invention aims to solve]

[0006] The inventors of this invention have conducted various studies on bacterial strains that can treat infertility or fertility caused by immunological factors and microbiota imbalances, and as a result have discovered and deposited a novel Lactobacillus plantarum strain. Furthermore, the inventors have completed this invention by experimentally demonstrating that the said strain regulates the expression of genes that aid implantation, increases the number of uterine immune cells, and increases the embryo implantation rate. [Means for solving the problem]

[0007] This invention provides a novel strain of Lactobacillus plantarum.

[0008] As used herein, the term "Lactobacillus plantarum" refers to the strain deposited by the applicant with the Korea Institute of Biotechnology on August 24, 2021, under accession number KCTC 14678BP. In this specification, "Lactobacillus plantarum," "Lactobacillus plantarum strain," or "strain" may be used interchangeably, and the said strain is analyzed to include the strain itself, cultures of the strain, lysates of the strain, extracts of the strain, and cytoplasmic fractions obtained by lysing the strain.

[0009] The term "culture" refers to the entire culture medium containing the bacterial strain itself, an extract of the strain, metabolites of the strain, or excess nutrients, obtained by culturing the bacterial strain in a nutrient-supplied medium for a certain period of time, and also includes the culture solution from which the bacterial strain has been removed after culturing the strain. Furthermore, the culture may include a concentrate of the entire culture medium or culture solution, and a dried version of the concentrate. Specifically, the culture of the present invention can use a culture medium that can be easily selected by an ordinary technician according to the purpose among the culture media used for microbial culture.

[0010] In the present invention, the Lactobacillus plantarum strain may be used for the prevention or treatment of infertility or fertility. The strain may also reduce the expression or activity of TIM3 (T cell immunoglobulin and mucin domain-containing protein 3), increase the number of intrauterine immune cells, or increase the embryo implantation rate.

[0011] 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 directly involved in implantation are trophoblasts. Trophoblasts surround the blastocyst in the embryo and directly interact with endometrial cells. If TIMP3 expression is reduced in trophoblasts, invasion into the endometrial layer increases, leading to successful implantation. Therefore, the Lactobacillus plantarum strain of the present invention, which can reduce the expression of TIM3 in trophoblasts, can be helpful in implantation.

[0012] Furthermore, the intrauterine immune cells may be lymphocytes and / or NK cells. Immune cells such as lymphocytes and NK cells present in the uterus are known to be helpful for embryo implantation when they are present in sufficient numbers. Therefore, the Lactobacillus plantarum strain of the present invention, which can increase the number of such immune cells, can be helpful for implantation.

[0013] Furthermore, the bacterial strain of the present invention can increase the implantation rate, which has been reduced due to immune imbalance, to a normal level.

[0014] Another embodiment of the present invention provides a pharmaceutical composition for the prevention or treatment of infertility or fertility, comprising one or more selected from the group consisting of a Lactobacillus plantarum strain deposited under accession number KCTC 14678BP, a culture of the strain, a ferment of the strain, a lysate of the strain, an extract of the strain, and a cytoplasmic fraction obtained by lysing the strain.

[0015] In the pharmaceutical compositions according to the present invention, unless otherwise specified, each term has the same meaning as described in the Lactobacillus plantarum strain.

[0016] The pharmaceutical composition of the present invention contains the Lactobacillus plantarum strain as an active ingredient. Furthermore, as described above, the Lactobacillus plantarum strain is analyzed to include the Lactobacillus plantarum strain itself, a culture of the strain, a fermented product of the strain, a lysate of the strain, an extract of the strain, and a cytoplasmic fraction obtained by lysing the strain. Therefore, the pharmaceutical composition of the present invention contains the Lactobacillus plantarum strain, a culture of the strain, a lysate of the strain, an extract of the strain, or a cytoplasmic fraction obtained by lysing the strain.

[0017] As used herein, the terms "infertility" and "difficulty conceiving" mean the inability or difficulty of conceiving within one year despite normal, unprotected sexual intercourse. Such infertility or difficulty conceiving may refer to female infertility or difficulty conceiving.

[0018] Furthermore, the infertility or refusal to conceive may be due to one or more causes selected from the group consisting of immunologic aberration, decreased ovarian reserve, ovulatory disorder, implantation failure, tubal injury, tubal blockage, paratubal adhesions, infection, immunologic illness, and endometriosis.

[0019] The pharmaceutical composition of the present invention contains the aforementioned bacterial strain in an effective amount and can be administered to subjects requiring the prevention or treatment of infertility or fertility.

[0020] As used herein, the term "administer" means physically introducing a composition into a subject using any of a variety of methods and delivery systems known to one of ordinary skill in the relevant art. The administration can be carried out, for example, by oral administration, or by vaginal, intravenous, intramuscular, subcutaneous, intraperitoneal, spinal or other parenteral administration, such as by injection or infusion, but is not limited thereto. The number of administrations can be carried out, for example, once, multiple times, and over one or more extended periods.

[0021] In addition, the pharmaceutical composition of the present invention can contain the Lactobacillus plantarum strain alone, or can further contain a suitable carrier, excipient or diluent normally used in the production of pharmaceutical compositions. Specifically, the carriers, excipients and diluents that can be included in the pharmaceutical composition can be, for example, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginic acid, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate and mineral oil, but are not limited thereto. These can be used alone or in combination of two or more. In addition, the pharmaceutical composition can further contain other conventional additives, such as antioxidants, buffers and / or bacteriostatic agents, if necessary, and can additionally contain dispersants, surfactants, binders, lubricants, etc., and can be formulated into acid agents, granules, tablets, liquids, capsules, suspensions, emulsions, syrups, creams, lotions, gels, ointments, aerosols, powder sprays, creams, suppositories, pills, etc.

[0022] As an example of the dosage form, the pharmaceutical composition of the present invention can be a vaginal administration dosage form, and specific examples of the vaginal administration dosage form can be one or more selected from the group consisting of purified products, liquids, creams, lotions, gels, ointments, powder sprays, suppositories and pills, but are not limited thereto.

[0023] As used herein, the term "subject" includes humans or any non-human animal, and the non-human animal may be a vertebrate, such as a primate, dog, cow, horse, pig, rodent, such as a mouse, rat, guinea pig, etc. As used herein, the "subject" is used interchangeably with "individual" and "patient".

[0024] Also, the effective amount may be a "therapeutically effective amount" or a "preventive effective amount". The term "therapeutically effective amount" means any amount that can indicate a decrease in the severity of a disease symptom, an increase in the frequency and duration of the period without the disease symptom, or the prevention of damage or impairment due to disease pain when a drug or therapeutic agent is used alone or in combination with other therapeutic agents. The term "preventive effective amount" means any amount that suppresses the occurrence or recurrence of infertility or subfertility in a subject. The level of the effective amount can be determined by factors such as the severity, age, sex, drug activity, sensitivity to the drug, administration time, administration route and excretion rate of the subject, treatment period, factors including drugs used simultaneously, and other factors well known in the pharmaceutical field.

[0025] Also, the pharmaceutical composition can vary depending on the age, sex, and weight of the subject. Specifically, the composition of the present invention can be administered at 0.1 - 100 mg / kg once daily to several times a day or at intervals of several days to several months depending on the symptoms of the subject. Also, the dosage can be increased or decreased depending on factors such as the administration route, severity of the disease, sex, weight, age, etc.

[0026] Also, the pharmaceutical composition can be administered in combination with other therapeutic agents. In this case, the pharmaceutical composition of the present invention and other therapeutic agents can be administered simultaneously, sequentially, or individually. The other therapeutic agents may be drugs such as compounds, proteins, and hormone preparations having preventive, therapeutic, and improvement effects on infertility or subfertility, but are not limited thereto. For example, the hormone preparation may be progesterone.

[0027] Furthermore, the pharmaceutical composition can be formulated to be administered simultaneously, sequentially, or individually with other therapeutic agents. For example, the bacterial strain and other therapeutic agents can be administered simultaneously in a single formulation, or simultaneously, sequentially, or individually in separate formulations. To administer simultaneously, sequentially, or individually, the bacterial strain and other therapeutic agents contained in the pharmaceutical composition of the present invention can be formulated separately in different containers, or they can be formulated together in the same container. In addition, the bacterial strain and other therapeutic agents contained in the pharmaceutical composition of the present invention may be the same or different in terms of pharmaceutically effective amount, administration time, administration interval, administration route, treatment period, etc.

[0028] Another embodiment of the present invention provides one or more uses for the prevention or treatment of infertility or fertility selected from the group consisting of the Lactobacillus plantarum strain deposited under accession number KCTC 14678BP, cultures of the strain, ferments of the strain, lysates of the strain, extracts of the strain, and cytoplasmic fractions obtained by lysing the strain.

[0029] In the preventive or therapeutic applications of the present invention, each term has the same meaning as described in the descriptions of the bacterial strain or pharmaceutical composition, unless otherwise specified.

[0030] Another embodiment of the present invention provides a method for preventing or treating infertility or infertility, comprising the step of administering to a subject requiring prevention or treatment of infertility or infertility one or more selected from the group consisting of a Lactobacillus plantarum strain deposited under accession number KCTC 14678BP, a culture of the strain, a ferment of the strain, a lysate of the strain, an extract of the strain, and a cytoplasmic fraction obtained by lysing the strain.

[0031] In the preventive or therapeutic methods according to the present invention, each term has the same meaning as described in the descriptions of the bacterial strain or pharmaceutical composition, unless otherwise specified.

[0032] Furthermore, in the method for preventing or treating infertility or fertility according to the present invention, the Lactobacillus plantarum strain deposited under accession number KCTC 14678BP can be administered to the subject simultaneously with other therapeutic agents, sequentially, or individually.

[0033] The term "simultaneous" administration means administering the Lactobacillus plantarum strain and other therapeutic agents of the present invention at once in a single formulation, or administering the Lactobacillus plantarum strain and other therapeutic agents at once in separate formulations, in which case the administration routes for the Lactobacillus plantarum strain and the other therapeutic agents may be different. The term "sequential" administration means administering the Lactobacillus plantarum strain and other therapeutic agents relatively continuously, accepting the minimum possible time consumed between administrations. The term "individual" administration means administering the Lactobacillus plantarum strain and other therapeutic agents at regular time intervals. The method of administering the Lactobacillus plantarum strain and other therapeutic agents can be appropriately selected by physicians or specialists in the industry, taking into consideration the therapeutic efficacy, side effects, etc. of the target organism.

[0034] Another embodiment of the present invention provides a food composition for the prevention or improvement of infertility or fertility, comprising one or more selected from the group consisting of a Lactobacillus plantarum strain deposited under accession number KCTC 14678BP, a culture of the strain, a fermented product of the strain, a crushed product of the strain, an extract of the strain, and a cytoplasmic fraction obtained by crushing the strain.

[0035] In the food composition according to the present invention, unless otherwise specified, each term has the same meaning as described in the description of the bacterial strain or pharmaceutical composition.

[0036] The aforementioned food may be a health-functional food. The term "health-functional food" means a food manufactured and processed in forms such as refined, capsules, powders, granules, liquids, and pellets using raw materials or ingredients that have functional properties useful to the human body. Here, "functional" means that the food modulates nutrients to the structure and function of the human body or obtains effects useful for health purposes, such as physiological effects.

[0037] The types of food mentioned above are not particularly limited. Specific examples include yogurt, dairy products, meats, sausages, bread, chocolate, candies, snacks, sweets, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages, tea, energy drinks, alcoholic beverages, vitamin complexes, and all other foods in the ordinary sense.

[0038] The food composition according to the present invention can be manufactured by methods commonly used in the industry, and during such manufacturing, raw materials and components commonly added in the industry can be added. Furthermore, unlike general pharmaceuticals, using food as a raw material has the advantage of not having side effects that may occur with long-term use of pharmaceuticals, and is highly portable. Therefore, the food composition according to the present invention can be used as an adjunct to enhance or improve the preventive or corrective effects of infertility or difficulty conceiving.

[0039] The effective amount of Lactobacillus plantarum strain contained in the food composition of the present invention can be appropriately determined depending on the intended use (prevention, improvement, or therapeutic treatment). Generally, during food production, the Lactobacillus plantarum strain, culture of the strain, fermented product of the strain, crushed product of the strain, extract of the strain, or cytoplasmic fraction obtained by crushing the strain can be included in the food composition in amounts of 0.001 to 20% by weight, 0.001 to 15% by weight, or 0.001 to 10% by weight. In the case of health beverages, the amount can be 0.01 to 2 g, specifically 0.02 to 2 g, or more specifically 0.3 to 1 g, based on 100 mL. However, for long-term intake for health and hygiene purposes, or for health regulation purposes, amounts below the above ranges can also be used. The content of Lactobacillus plantarum strain added to the food composition during the manufacturing process of the food composition of the present invention can be appropriately adjusted as needed.

[0040] The food composition may be in any dosage form selected from the group consisting of pills, purified material, granules, powder, capsules, and liquid solutions.

[0041] Furthermore, the food composition may contain various flavorings or natural carbohydrates as additional ingredients, as is the case with ordinary foods. Examples of natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As sweeteners, natural sweeteners such as thaumatin and stevia extract, or synthetic sweeteners such as saccharin and aspartame, may be used.

[0042] Furthermore, if the food composition is a beverage composition, there are no special restrictions on the liquid components other than containing the Lactobacillus plantarum strain of the present invention in the indicated proportion as an essential component. Like ordinary beverages, it can contain various flavorings or natural carbohydrates as additional components. [Effects of the Invention]

[0043] The Lactobacillus plantarum strain of the present invention has the effect of reducing the expression of specific genes in placental cells, increasing the number of uterine immune cells, and increasing the embryo implantation rate which has been reduced by immune imbalance, in order to aid in embryo implantation. Therefore, it can be usefully utilized as a composition for the prevention, improvement, or treatment of infertility or fertility. [Brief explanation of the drawing]

[0044] [Figure 1] This graph shows the effect of the present invention on reducing the TIM3 gene expression level of Lactobacillus plantarum strains. In this case, * means P<0.05, ** means P<0.01, and *** means P<0.001. [Figure 2] This is a schematic diagram of an experiment conducted to confirm the effect of the Lactobacillus plantarum strain according to the present invention on increasing the success rate of embryo implantation. [Figure 3] This graph shows the effect of the Lactobacillus plantarum strain according to the present invention on increasing uterine immune cells, where A represents the number of total lymphocytes and B represents the number of uterine NK cells. [Modes for carrying out the invention]

[0045] The present invention will be explained in more detail below through the examples. These examples are provided to illustrate the present invention more concretely, and the scope of the present invention is not limited by these examples.

[0046] Example 1. TIM3 expression suppression effect In conditions where the uterine lining is thickened and embryo implantation is possible, a decrease in the expression of TIMP3 (tissue inhibitors of metalloproteinase) in trophoblast cells is advantageous for implantation (Jia-Yu Zhu et al., Rev Obstet Gynecol. 2012;5(3-4):e137-43). Therefore, the present applicant aims to demonstrate that the Lactobacillus plantarum strain deposited with the Korea Institute of Biotechnology on August 24, 2021, under accession number KCTC 14678BP, is a strain that can increase implantation and pregnancy rates by reducing the expression of the TIMP3 gene in the HTR-8 / SVneo cell line, which is a trophoblast cell.

[0047] Specifically, place 4 x 10 HTR-8 cells in a 12-well plate the day before the experiment. 5 Siding was performed at a cell / mL concentration. The following day, after confirming under a microscope that the confluency was 70-80% and that the layer was uniformly formed, the culture was washed with PBS and replaced with 0.8 mL of serum-free medium. Thereafter, the bacterial strain suspension was treated to achieve a cell number ratio of 50 or 100 MOI (multiplicity of infection). As a positive control group, leukemia inhibitory factor (LIF), expressed in endometrial cells, was used as an important factor for pregnancy and implantation (Pankaj Suman et al., Fertil Steril. 2013 Feb;99(2):533-42), and treated to a final concentration of 50 ng / mL. Four hours after LIF treatment, RNA was extracted, and the 18S gene and TIMP3 gene were amplified through the cDNA synthesis process, and the expression levels of each gene were calculated relative to the 18S rRNA expression level.

[0048] As a result, as can be seen in Figure 1, it was confirmed that when the positive control group LIF was treated, the expression level of the TIMP3 gene was significantly reduced compared to the control group that was not treated. Furthermore, when the aforementioned bacterial strain was treated with 50 or 100 MOI relative to the number of cells, it was confirmed that the expression level of the TIMP3 gene decreased in a concentration-dependent manner, and this was found to have a more than twice as significant effect as treating the positive control group LIF.

[0049] Through the results described above, it can be seen that the Lactobacillus plantarum strain of the present invention can reduce the expression level of the TIM3 gene, thereby aiding in the embryo implantation process and exhibiting effects that prevent or treat infertility or fertility.

[0050] Example 2. Effect of increasing implantation success rate To determine whether the Lactobacillus plantarum strain deposited under accession number KCTC 14678BP can prevent recurrent implantation failures due to immunological causes and microbiota imbalance, we investigated whether the implantation rate increased after administering the Lactobacillus plantarum strain to a mouse model with induced implantation failure (LPS-induced implantation failure). Implantation failure was induced by administering LPS, which is known to induce immune imbalance (Sarah Moustafa et al., Am J Reprod Immunol. 2019 Feb;81(2):e13082).

[0051] Specifically, the control group and experimental group were defined as follows. -Control group: Normal mice that have not been treated with bacterial strain or LPS. - Negative control group (LPS-treated group): Mice treated with LPS to induce implantation failure. - Experimental group (LPS and strain treatment group): Mice that were treated with LPS during the Lactobacillus plantarum strain treatment process to induce implantation failure.

[0052] After randomly isolating 8 female balb / c mice from each group, 1 × 10⁻¹⁶ mice were dissolved in PBS for the control group, PBS for the negative control group, and PBS for the experimental group. 8 The aforementioned strain of CFU was administered vaginally in the morning for 10 days (-10d to 0d). To induce implantation failure, 10 μg of LPS dissolved in PBS was administered vaginally to the negative control group and the experimental group in the afternoon of the 5th day (-5d), based on the day the strain treatment began (-10d). Subsequently, mating was carried out for 3 days in a 2:1 ratio of females to males starting in the afternoon of the 10th day (0d). Dissection was carried out on the 10th day (10d), based on the day mating began (0d), to check the degree of implantation. A schematic diagram of this experiment is shown in Figure 2.

[0053] [Table 1]

[0054] As a result, as can be seen in Table 1 above, the implantation success rate in the control group was 87.5%, while the implantation success rate in the negative control group treated with LPS was 25%, confirming a decrease of approximately 62.5% compared to the control group. On the other hand, in the experimental group administered with the aforementioned strain, despite LPS treatment, the implantation success rate was confirmed to be 87.5%, the same as the control group. Through these results, it can be seen that the Lactobacillus plantarum strain of the present invention has the effect of increasing the implantation rate of embryos reduced by immune imbalance, and therefore can be usefully used to prevent or treat infertility or fertility.

[0055] Example 3. Effect of increasing the number of uterine immune cells A sufficient number of immune cells present in the uterus are known to aid in embryo implantation. In particular, uterine lymphocytes and NK cells (uNK) play a crucial role in the maturation of decidual NK cells, which are essential for implantation. Without uNK, even if the embryo implants, it may subsequently drop off (Dorothy K Sojka et al., Front Immunol. 2019 May 1;10:960; Nabila Jabrane-Ferrat et al., Immunology. 2014 Apr;141(4):490-497). Therefore, we investigated the effects of the Lactobacillus plantarum strain deposited under accession number KCTC 14678BP on uterine uNK and related immunity.

[0056] Specifically, the bacterial strain was administered to a mouse model in which implantation failure was induced using the method described in Example 2. The control group and experimental group were set up as follows. -Control group: Normal mice that have not been treated with bacterial strain or LPS. - Negative control group (LPS-treated group): Mice treated with LPS to induce implantation failure. - Experimental group (LPS and strain treatment group): Mice that were treated with LPS during the Lactobacillus plantarum strain treatment process to induce implantation failure.

[0057] After administration of each substance, mouse uterine tissue was excised and chopped, the tissue was separated using a separation buffer, and immune cells were isolated using FBS. The isolated immune cells (1 × 10⁶) 6 After transferring the cells ( / mL) to a 1.5 mL tube, an Fc block was applied, and the NK cell antibody (CD45) was applied to the immune cells. + CD3 - CD335 + CD49b + The following steps were taken: ) was applied, and the number of total lymphocytes and uNK cells was analyzed using a flow cytometer.

[0058] As a result, as can be seen in Figure 3A, we confirmed that the number of total lymphocytes in the negative control group treated with LPS was significantly reduced compared to the control group. On the other hand, in the experimental groups treated with LPS and the aforementioned bacterial strain, we confirmed that the number of total lymphocytes, which had been reduced by LPS, increased and recovered to a level similar to that of the control group.

[0059] Furthermore, as can be seen in Figure 3B, we confirmed that the number of uNK cells in the negative control group treated with LPS decreased significantly compared to the control group. On the other hand, in the experimental groups treated with LPS and the aforementioned bacterial strain, we confirmed that the number of uNK cells, which had decreased due to LPS, increased and recovered to a level similar to that of the control group.

[0060] Through the results described above, it can be seen that the Lactobacillus plantarum strain of the present invention can increase the number of intrauterine immune cells that are useful for implantation, and therefore can be usefully used to prevent or treat infertility or fertility.

[0061] [Accession Number] Depositor's name: Korea Institute of Biotechnology Accession number: KCTC14678BP Entrustment date: August 24, 2021 JPEG0007849913000002.jpg240165JPEG0007849913000003.jpg248162

Claims

1. A strain of Lactobacillus plantarum deposited under accession number KCTC 14678BP.

2. The strain according to claim 1, wherein the strain is used for the prevention or treatment of infertility or fertility.

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

4. A pharmaceutical composition for the prevention or treatment of infertility or fertility, comprising one or more selected from the group consisting of a Lactobacillus plantarum strain deposited under accession number KCTC 14678BP and a culture of the said strain.

5. The pharmaceutical composition according to claim 4, wherein the infertility or difficulty in conception is female infertility or difficulty in conception.

6. The pharmaceutical composition according to claim 4, wherein the infertility or refusal to conceive is due to one or more causes selected from the group consisting of immunological abnormalities, decreased ovarian reserve, ovulation disorder, implantation failure, tubal injury, tubal blockage, paratubal adhesions, infection, immunological illness, and endometriosis.

7. The pharmaceutical composition according to claim 4, wherein the pharmaceutical composition is administered via the vaginal route.

8. The pharmaceutical composition according to claim 4, wherein the pharmaceutical composition is put into dosage form as a tablet, liquid, cream, lotion, gel, ointment, powder spray, suppository or pill.

9. The pharmaceutical composition according to claim 4, wherein the pharmaceutical composition is administered in combination with progesterone.

10. A food composition for the prevention or improvement of infertility or fertility, comprising one or more selected from the group consisting of a Lactobacillus plantarum strain deposited under accession number KCTC 14678BP and a culture of the said strain.

11. The food composition according to claim 10, wherein the infertility or difficulty in conception refers to female infertility or difficulty in conception.

12. The food composition according to claim 10, wherein the infertility or difficulty in conception is due to one or more causes selected from the group consisting of immunological abnormalities, decreased ovarian reserve, ovulation disorder, implantation failure, tubal injury, tubal blockage, paratubal adhesions, infection, immunological illness, and endometriosis.

13. The food composition according to claim 10, wherein the food composition is taken in combination with progesterone administration.

14. One or more methods of use selected from the group consisting of a Lactobacillus plantarum strain deposited under accession number KCTC 14678BP and a culture of the said strain, for the manufacture of a composition for the prevention, improvement, or treatment of infertility or fertility.

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