Composition for preventing or treating sarcopenia containing Lactobacillus gasseri

The use of Lactobacillus gasseri BNR17 in a composition addresses the lack of effective treatments for sarcopenia by improving muscle mass, function, strength, and endurance, effectively countering the negative effects of stress, obesity, aging, and disease on muscle health.

JP2025518437APending Publication Date: 2025-06-17ACEBIOME INC
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Patent Information

Application Number
JP2024549756
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Priority Date
2023-02-09
Filing Date
2023-06-22
Publication Date
2025-06-17

AI Technical Summary

Technical Problem

There is currently no effective treatment for sarcopenia, a condition characterized by the loss of muscle mass, strength, and function, which can be exacerbated by stress, obesity, aging, and certain diseases.

Method used

A composition containing Lactobacillus gasseri BNR17 is used to prevent or treat sarcopenia, improve muscle mass and function, and enhance muscle strength and endurance.

Benefits of technology

Lactobacillus gasseri BNR17 effectively suppresses the decrease in muscle function and mass by inhibiting the decrease of MyHC and MyoD and the increase of MuRF1, MAFbx, and FOXO3, thereby improving muscle endurance, strength, and overall quality of life.

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Abstract

The present invention relates to a composition for preventing or treating sarcopenia containing Lactobacillus gasseri, and specifically, to a composition for preventing, treating or improving sarcopenia, reduction of muscle mass and muscle function, and reduction of muscle strength and muscle endurance caused by causes such as stress, obesity, aging, drugs, tumors, etc., containing Lactobacillus gasseri BNR17.
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Description

Technical Field

[0001] The present invention relates to a composition for preventing or treating sarcopenia containing Lactobacillus gasseri, and specifically, to a composition for preventing, treating, or improving sarcopenia, reduction of muscle mass and muscle function, and reduction of muscle strength and muscle endurance associated with stress, obesity, aging, drugs, tumors, etc., containing Lactobacillus gasseri BNR17.

[0002]

Background Art

[0003] Lactic acid bacteria are Gram-positive bacteria that mainly produce lactic acid as a result of fermentation, and are also called good bacteria. They include bacteria of the family Lactobacillaceae in the order Lactobacillales and are distributed in fermented foods such as yogurt and kimchi, the intestine, and milk.

[0004] Lactic acid bacteria are known as bacteria that are beneficial to human health, such as preventing the growth of harmful bacteria in the intestine and regulating immunity within the normal range. Examples of prior art utilizing lactic acid bacteria include Korean Patent Publication No. 10-2013-0002545 (novel lactic acid bacteria and a composition for preventing and treating diabetes containing the same), Korean Patent Publication No. 10-2018-0087662 (a pharmaceutical composition for treating colorectal diseases containing a lactic acid bacteria-derived protein and cystatin), and the like.

[0005] Lactobacillus gasseri is one of the lactic acid bacteria species belonging to the genus Lactobacillus. Lactobacillus gasseri is known for its efficacy against rheumatoid arthritis (Korean Patent Publication No. 10-2021-0043797), antifungal activity (Korean Registered Patent Publication No. 10-2063554), etc., but there is a need for more research on various physiological effects.

[0006] Lactobacillus gasseri BNR17 is a strain belonging to the Lactobacillus gasseri species isolated from the breast milk of Koreans.

[0007] On the one hand, sarcopenia refers to a disease in which muscle mass, muscle strength, and muscle function all decrease due to various causes. The causes of sarcopenia vary from person to person, but common causes include insufficient intake of protein containing essential amino acids, insufficient exercise, aging, hormonal changes, side effects of taking drugs, etc. In addition, sarcopenia occurs secondarily not only in diseases that occur in the muscle itself but also in acute diseases such as cancer, diabetes, chronic diseases of the heart, lungs, and kidneys, hormonal diseases, degenerative diseases such as spinal stenosis, and infectious diseases.

[0008] The symptoms of sarcopenia include muscle weakness, a feeling of weakness, and fatigue. Although muscle mass and muscle strength naturally decrease with aging, sarcopenia causes excessive reduction in muscle mass and muscle strength even considering age, gender, etc., and a decrease in physical function increases the health risks and mortality rate. Patients with sarcopenia have reduced muscle strength and muscle endurance, are prone to osteoporosis, falls, and fractures, and an increase in the risk of diabetes and cardiovascular diseases due to a decrease in basal metabolic rate.

[0009] Sarcopenia is diagnosed by measuring muscle mass, muscle strength, and muscle function. For measuring muscle mass from the human body, methods such as dual energy X-ray absorptiometry, bioimpedance measurement, CT, and MRI are used. Muscle strength is measured by leg muscle strength or grip strength, and muscle function is measured by walking speed measurement, 400-meter walking test, 6-minute walking test, etc.

[0010] There is still no treatment method for sarcopenia, and it only delays the occurrence of sarcopenia by taking protein centered on essential amino acids, strength training, and aerobic exercise.

[0011] Therefore, there is an increasing need for a method that can develop a method for suppressing sarcopenia that is safe and effective for the human body and can prevent, improve, or treat sarcopenia caused by various causes, thereby promoting health and improving the quality of life.

[0012] Under such a technical background, the inventors of the present application have confirmed that Lactobacillus gasseri BNR17 exhibits useful effects for the prevention or treatment of sarcopenia, and have thus completed the present invention.

[0013]

[0014]

Summary of the Invention

[0015] An object of the present invention is to provide a composition for preventing or treating sarcopenia containing Lactobacillus gasseri. Another object of the present invention is to provide a method for preventing or treating sarcopenia including administering Lactobacillus gasseri. Another object of the present invention is to provide a use of a composition containing Lactobacillus gasseri for preventing or treating sarcopenia.

[0016] Another object of the present invention is to provide a composition for improving the reduction of muscle mass and muscle function containing Lactobacillus gasseri. Another object of the present invention is to provide an improvement in the reduction of muscle mass and muscle function including administering Lactobacillus gasseri. Another object of the present invention is to provide a use of a composition containing Lactobacillus gasseri for improving the reduction of muscle mass and muscle function.

[0017] Another object of the present invention is to provide a composition for improving muscle strength and muscle endurance containing Lactobacillus gasseri. Another object of the present invention is to provide an improvement in muscle strength and muscle endurance including administering Lactobacillus gasseri. Another object of the present invention is to provide a use of a composition containing Lactobacillus gasseri for improving muscle strength and muscle endurance.

[0018] Another object of the present invention is to provide an anti-cancer adjuvant containing Lactobacillus gasseri.

[0019] To achieve the above object, the present invention relates to a pharmaceutical composition for preventing or treating sarcopenia, comprising Lactobacillus gasseri BNR17 having accession number KCTC 10902BP or a culture thereof. The present invention also relates to a method for preventing or treating sarcopenia, comprising the step of administering Lactobacillus gasseri BNR17 having accession number KCTC 10902BP or a culture thereof. The present invention further relates to the use of Lactobacillus gasseri BNR17 having accession number KCTC 10902BP or a culture thereof for the manufacture of a pharmaceutical composition for preventing or treating sarcopenia.

[0020] The present invention relates to a food composition for improving the reduction of muscle mass and muscle function, comprising Lactobacillus gasseri BNR17 having accession number KCTC 10902BP or a culture thereof. The present invention also relates to a method for improving the reduction of muscle mass and muscle function, comprising the step of administering a food composition comprising Lactobacillus gasseri BNR17 having accession number KCTC 10902BP or a culture thereof. The present invention further relates to the use of Lactobacillus gasseri BNR17 having accession number KCTC 10902BP or a culture thereof for the manufacture of a food composition for improving the reduction of muscle mass and muscle function.

[0021]

[0022] The present invention relates to a composition for improving muscle strength and muscle endurance, comprising Lactobacillus gasseri BNR17 having an accession number of KCTC 10902BP or a culture thereof. The present invention also relates to a method for improving muscle strength and muscle endurance, comprising the step of administering a composition comprising Lactobacillus gasseri BNR17 having an accession number of KCTC 10902BP or a culture thereof. The present invention further relates to the use of Lactobacillus gasseri BNR17 having an accession number of KCTC 10902BP or a culture thereof for the production of a composition for improving muscle strength and muscle endurance.

[0023] The present invention relates to an anticancer adjuvant comprising Lactobacillus gasseri BNR17 having an accession number of KCTC 10902BP or a culture thereof.

[0024]

Brief Description of the Drawings

[0025]

Figure 1-4

[0026]

Figure 5-10

[0027]

Figure 11-22

[0028]

Figure 23-31

[0029]

Figure 32-39

[0030]

Figure 40-43

[0031]

Figure 44-46

[0032]

[0033]

Mode for Carrying Out the Invention

[0034] Unless otherwise specified, all technical and scientific terms used in this specification have the same meaning as commonly understood by a person skilled in the art to which the present invention pertains. Generally, the nomenclature used in this specification and the experimental methods described below are well known and commonly used in the technical field.

[0035] In a specific embodiment according to the present invention, it was confirmed that Lactobacillus gasseri BNR17 with the accession number KCTC 10902BP or its culture can be used for the prevention or treatment of sarcopenia, improvement of the decrease in muscle mass and muscle function, and improvement of muscle strength and muscle endurance, and can be used as an anticancer adjuvant.

[0036] In one aspect, the present invention relates to a composition for preventing or treating sarcopenia, comprising Lactobacillus gasseri BNR17 with accession number KCTC 10902BP or a culture thereof.

[0037] In another aspect, the present invention relates to a food composition for improving the reduction of muscle mass and muscle function, comprising Lactobacillus gasseri BNR17 with accession number KCTC 10902BP or a culture thereof.

[0038] In still another aspect, the present invention relates to a composition for improving muscle strength and muscle endurance, comprising Lactobacillus gasseri BNR17 with accession number KCTC 10902BP or a culture thereof.

[0039] In yet another aspect, the present invention relates to an anticancer adjuvant, comprising Lactobacillus gasseri BNR17 with accession number KCTC 10902BP or a culture thereof.

[0040] The strain according to the present invention was deposited with the Korea Research Institute of Bioscience and Biotechnology on February 1, 2006 under the accession number KCTC 10902BP.

[0041] Lactobacillus gasseri BNR17 with accession number KCTC 10902BP or a culture thereof can exhibit the following effects:

[0042] Suppression of the decrease in MyoD (Myoblast determination protein-1);

[0043] Suppression of the decrease in MyHC (Myosin heavy chain);

[0044] Suppression of the increase in MuRF1 (muscle RING-finger protein-1);

[0045] Inhibition of the increase in MAFbx (muscle atrophy F-box, also known as atrogin-1);

[0046] Inhibition of the increase in FOXO3 (Forkhead Box O3); and

[0047] Inhibition of the increase in GDF-15 (growth differentiation factor 15).

[0048] In connection with the culture of the strain, "culture" can mean something cultured in a culture medium or culture solution containing the strain. The culture may or may not contain the strain. The culture may have a liquid or solid dosage form, but is not limited thereto.

[0049] Various forms of the culture may be included, such as a concentrated solution, a dried product, or an extract of the culture.

[0050] The extract can be extracted using water, an organic solvent, etc. For example, it can be extracted using water, a lower alcohol having 1 to 4 carbon atoms, hexane, chloroform, ethyl acetate, or a mixed solvent thereof.

[0051] "Prevention" means all acts of suppressing or delaying the onset of the disease by administration of the composition according to the present invention. "Treatment or improvement" means all acts in which the symptoms of the disease improve or are beneficially changed.

[0052] The decrease in muscle strength and muscle endurance may be due to one or more causes selected from the group consisting of sarcopenia, muscle loss, muscle weakness, hypotonus, muscular atrophy, and myasthenia.

[0053] More specifically, the decrease in muscle strength and muscle endurance may be due to one or more causes selected from the group consisting of sarcopenia, muscle loss, muscle weakness, hypotonus, muscular atrophy, myasthenia, ankylosing spondylitis, amyotrophic lateral sclerosis, cachexia, Charcot-Marie-Tooth disease, muscle regression, muscle degeneration, and muscular regression atrophy.

[0054] In the present invention, sarcopenia refers to the reduction of muscle mass in the body, and is a disease that means the reduction of muscle tissue due to a disease of the muscle itself or the reduction of muscle tissue due to damage to the nerve that controls the muscle.

[0055] The above sarcopenia may be caused by a tumor or drug treatment. Specifically, the drug may be an anticancer agent. Muscle function reduction such as muscle mass loss, muscle loss, muscle strength reduction, and muscle endurance reduction may occur due to a tumor or drug treatment. The present invention has a preventive, ameliorative, and therapeutic use for sarcopenia or the prevention, amelioration, or treatment of the reduction of muscle mass and muscle function in that the preventive, ameliorative, and therapeutic effects on such a reduction of muscle function were confirmed in the examples.

[0056] The composition may further improve symptoms selected from the group consisting of increased fatigue, weight loss, and decreased appetite.

[0057] The composition for preventing or treating sarcopenia of the present invention may be used alone or in combination or appropriate combination with other pharmaceutically active compounds.

[0058] The composition of the present invention may further contain a pharmaceutically acceptable carrier.

[0059] The composition of the present invention may be manufactured as a pharmaceutical dosage form using methods well known in the art so as to provide rapid, sustained, or delayed release of the active ingredient after administration to a mammal. In the manufacture of the dosage form, it is preferable to mix or dilute the active ingredient with a carrier or enclose it in a carrier in the form of a container.

[0060] Therefore, the composition of the present invention can be formulated and used in the form of an oral dosage form such as a powder, granule, tablet, capsule, suspension, emulsion, syrup, aerosol, etc., an external preparation, a suppository, and a sterile injection solution by a conventional method, and may further contain appropriate carriers, excipients, and diluents generally used in the manufacture of the composition.

[0061] For example, carriers that may be included in the composition of the present invention include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and mineral oil. When formulating, it is generally prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants that are commonly used.

[0062] Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. Such solid preparations are prepared by mixing at least one or more excipients, such as starch, calcium carbonate, sucrose or lactose, gelatin, etc., with the above-mentioned compounds. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used.

[0063] Liquid preparations for oral use include suspensions, solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients, such as wetting agents, sweeteners, flavoring agents, preservatives, etc., may be included.

[0064] Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, and suppositories. For non-aqueous solvents and suspensions, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used. For suppository bases, witepsol, macrogol, tween 61, cocoa butter, laurin fat, glycerogelatin, etc. may be used.

[0065] The concentration of the active ingredient contained in the composition can be determined in consideration of the treatment purpose, the patient's condition, the required period, etc., and is not limited to a specific range of concentrations. The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. In the present invention, "a pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment. The effective dosage level may be determined by factors including the type and severity of the patient's disease, the activity of the drug, the sensitivity to the drug, the administration time, the administration route and excretion ratio, the treatment period, the drugs used concomitantly, and other factors well known in the medical field.

[0066] The pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and can be administered sequentially or simultaneously with conventional therapeutic agents. And it may be administered singly or multiply. Considering all of the above factors, it is important to administer an amount that does not induce side effects and can obtain the maximum effect with the minimum amount, which can be easily determined by those skilled in the art.

[0067] The term "administration" used in the present invention means introducing the pharmaceutical composition of the present invention into a patient by any appropriate method, and the administration route of the composition of the present invention may be administered by various oral or parenteral routes as long as the target tissue can be reached.

[0068] The administration method of the pharmaceutical composition according to the present invention is not particularly limited, and may follow the methods commonly used in the technical field. As a non-limiting example of the administration method, the composition can be administered by an oral administration or parenteral administration method. The pharmaceutical composition according to the present invention may be prepared in various dosage forms depending on the intended administration method.

[0069] The administration frequency of the composition of the present invention is not particularly limited, but it may be administered once a day or divided into several doses for administration.

[0070] The general daily dosage of the composition according to the present invention is 2.5×10 4 ~2.5×10 12 cfu / da and may be administered, and more specifically, 2.5×10 6~2.5×10 10 It may be administered so as to be 10 cfu / day, and may be administered once or in several divided doses.

[0071] The term "individual" used in the present invention can mean all animals including humans in whom a disease has developed or is likely to develop. The animals may be mammals such as cows, horses, sheep, pigs, goats, camels, serows, dogs, cats, etc. that require treatment for symptoms similar to those of humans, but are not limited thereto.

[0072] Specifically, the prophylactic or therapeutic method of the present invention may include the step of administering the composition to an individual in whom a disease has developed or is at risk of developing, in a pharmaceutically effective amount.

[0073] The food composition may be for improving exercise performance ability.

[0074] Since the food composition of the present invention can be ingested daily, a prophylactic or ameliorating effect on the target disease can be expected, and it is very useful.

[0075] The term "amelioration" in the present invention means all acts in which a disease is improved or beneficially changed by administration of the composition of the present invention.

[0076] The food composition of the present invention includes forms such as pills, powders, granules, infusions, tablets, capsules or liquids, and foods to which the composition of the present invention can be added include, for example, various foods, such as beverages, gums, teas, vitamin complexes, health supplements, etc.

[0077] Other components are not particularly limited as long as they do not contain, as an essential component that may be included in the food composition of the present invention, a composition having prophylactic and therapeutic activity against the target disease containing the active substance or its active ingredient, or a physiologically acceptable salt thereof, and may contain various crude drug extracts, food adjuvants or natural carbohydrates, etc. as additional components like ordinary foods.

[0078] The food may be a health functional food. A health functional food refers to a food with high medical and healthcare effects that is processed so that its biological regulatory function can be efficiently manifested in addition to nutrient supply. A health functional food may be manufactured in various forms such as tablets, capsules, powders, granules, liquids, pills, etc. in order to obtain useful effects for disease prevention or improvement.

[0079] The health functional food composition may be manufactured as a food, particularly a functional food. The functional food of the present invention contains components generally added during food production, and may include, for example, proteins, carbohydrates, fats, nutrients, and seasonings. For example, when manufactured as a drink, in addition to the active ingredient, natural carbohydrates or flavoring agents may be included as additional ingredients. The natural carbohydrates are preferably monosaccharides (e.g., glucose, fructose, etc.), disaccharides (e.g., maltose, sucrose, etc.), oligosaccharides, polysaccharides (e.g., dextrin, cyclodextrin, etc.), or sugar alcohols (e.g., xylitol, sorbitol, erythritol, etc.). As the flavoring agent, natural flavoring agents (e.g., thaumatin, stevia extract, etc.) and synthetic flavoring agents (e.g., saccharin, aspartame, etc.) can be used.

[0080] There is no particular limitation on the type of the health functional food. There are dairy products, drinking water, tea drinks, alcoholic beverages, vitamin complexes, etc., and any health food with its ordinary meaning may be included.

[0081] In addition, it may further contain various nutritional agents, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc.

[0082] The present invention relates to an anti-cancer adjuvant containing Lactobacillus gasseri BNR17 with accession number KCTC 10902BP or a culture thereof. The present invention can be administered simultaneously or sequentially with an anti-cancer agent as an anti-cancer adjuvant in that it has been confirmed that Lactobacillus gasseri BNR17 has a preventive or therapeutic effect on sarcopenia caused by drug treatment such as tumors or anti-cancer agents.

[0083] The anti-cancer agent may be one or more anti-cancer agents selected from the group consisting of cisplatin, doxorubicin, irinotecan, paclitaxel, daunorubicin, docetaxel, and 5-fluorouracil.

[0084] In the present invention, the "anti-cancer adjuvant" means an adjuvant that shows an effect of improving the side effects of an anti-cancer agent during anti-cancer treatment. The side effects of the anti-cancer agent may include sarcopenia, reduction in muscle mass and muscle function, reduction in muscle strength and muscle endurance, fatigue, weight loss, and loss of appetite.

[0085] In addition to containing Lactobacillus gasseri BNR17 as an active ingredient, the anti-cancer adjuvant may further contain one or more active ingredients showing the same or similar functions. The anti-cancer adjuvant can be administered orally or parenterally during clinical administration. When administered parenterally, it may be administered by intraperitoneal injection, rectal injection, subcutaneous injection, intravenous injection, intramuscular injection, intrauterine epidural injection, intracerebrovascular injection, or intrathoracic injection, and can be used in the form of a general pharmaceutical preparation.

[0086] The anti-cancer adjuvant can be used alone or in combination with methods using surgery, radiotherapy, hormone therapy, chemotherapy, and biological response modifiers.

[0087] The daily dose of the anti-cancer adjuvant is 2.5×10 4 ~2.5×10 12It may be administered so as to be 2.5×10 6 ~2.5×10 10 cfu / day, and it is preferably administered once or multiple times a day. However, the range varies depending on factors such as the patient's weight, age, gender, health status, diet, administration time, administration method, excretion rate, and severity of the disease. The anti-cancer adjuvant of the present invention may be administered in various parenteral dosage forms during actual clinical administration. When formulating, it is generally prepared using diluents or excipients such as fillers, bulking agents, binders, wetting agents, disintegrants, and surfactants. Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. As the non-aqueous solvent and suspension solvent, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used. As the base of the suppository, witepsol, macrogol, tween 61, cocoa butter, laurin fat, glycerogelatin, etc. may be used.

[0088]

[0089] Another aspect of the present invention provides a method for suppressing the decrease in muscle mass and muscle function associated with sarcopenia, a method for suppressing the decrease in muscle strength and muscle endurance, a method for suppressing the decrease in myosin and MyoD (Myoblast determination protein 1), and a method for suppressing the increase in GDF-15 (Growth differentiation factor-15) using Lactobacillus gasseri BNR17.

[0090] Myosin is in charge of the muscle contraction function through its interaction with actin. MyoD (Myoblast determination protein 1) is a transcription factor that plays a central role in increasing muscle mass and its expression is activated by exercise (Rudnicki et al., Cell 75(7):1351-1359, 1993). The decrease in these proteins that control muscle function and muscle mass is triggered by stress, obesity, aging, drug use, tumorigenesis, etc., which is the most direct cause of sarcopenia.

[0091] MuRF1 (Muscle Ring finger 1) and MAFbx (muscle atrophy F-box) are muscle-specific ubiquitin E3 ligases and play a central role in the ubiquitin-dependent proteolysis of actin, myosin, and MyoD (Polge et al., FASEB J25:3790-3802, 2011; Lokireddy et al., Am J Physiol Cell Physiol 303:C512-C529, 2012). Also, the expression of MuRF1 and MAFbx in muscle is regulated by the FOXO3 (forkhead box O3) transcription factor (Bodine et al., Am J Physiol Endocrinol Metab 307:E469-E484, 2014).

[0092] GDF-15 (Growth differentiation factor-15) is known as an indicator of tissue damage that increases when various tissues including the lung, kidney, and liver are damaged. Tissue damage in the human body causes a decrease in muscle function (Zimmers et al., Shock 23:543-548, 2005). In particular, since GDF-15 is associated with sarcopenia caused by tumors, it has been reported that sarcopenia caused by tumors can be treated by suppressing GDF-15 by methods such as monoclonal antibodies (Wu et al., Annals of Oncology 31:S245-S259, 2020).

[0093]

[0094] Hereinafter, the present invention will be described in more detail using examples. These examples are merely for more specifically explaining the present invention, and it is obvious to those with ordinary knowledge in the relevant technical field that the scope of the present invention is not limited by these examples.

[0095]

[0096] Example 1: Comparative experiment on the efficacy of suppressing sarcopenia by stress hormones of various Lactobacillus

[0097] Lactobacillus casei (LC: accession number KCTC 3109 T ), Lactobacillus paragasseri (LP: accession number KCTC 3510 T ), Lactobacillus ruteri (LR: accession number KCTC 3594 T ), and Lactobacillus gasseri (LG: accession number KCTC 10902BP) of the genus Lactobacillus were isolated from fermented foods, human feces, human milk, etc., and cultured in MRS medium for 16 hours.

[0098] The experimental animals were 4-week-old female Balb / c mice (18 - 20 g), supplied by Central Laboratory Animal Inc., and after being adapted in the experimental animal breeding facility for 1 week, they were used in the experiment. During the experimental period, solid feed and water were freely available, and the temperature (22 ± 2 °C), relative humidity (60 ± 5%), and light-dark cycle of the breeding room were maintained at a 12-hour cycle.

[0099] The mice were divided into a control group and a glucocorticoid (stress hormone) treatment group, and the glucocorticoid treatment group was further divided into a vehicle administration group and a Lactobacillus administration group. The control group was intraperitoneally injected with 200 μl of saline each time, and the glucocorticoid treatment group was intraperitoneally injected with 30 mg / kg of glucocorticoid once a day.

[0100] At the same time, among the glucocorticoid-treated groups, distilled water was administered to the Vehicle group, and LC, LP, LR, LG, and LRG (a 1:1 mixture of LR and LG) as various Lactobacillus strains were administered to the Lactobacillus administration group at a dose of 10 8 cfu / mouse (converted to the human dose, it is 2.5×10 10 cfu / human) orally for 3 weeks (2.5×10 10 cfu / human = 10 8 cfu / 20g×60,000g / 12, mouse standard body weight 20g, human standard body weight 60kg, dose equivalent factor of human-to-mouse 12).

[0101] After the administration was completed, the muscle endurance of the mice was measured using a treadmill device (Columbus Instrument, USA). Muscle endurance was measured by the maximum exercise time and maximum exercise distance until the mice became tired and could no longer run. The lean body mass of each mouse was measured using an InAlyzer (Medikors, Korea) device by the dual energy X-ray absorptiometry method. After the experiment, the mice were sacrificed and the weights of the gastrocnemius muscle and quadriceps femoris muscle were measured.

[0102]

[0103] Example 2: Comparison of the inhibitory effects of various Lactobacillus strains on sarcopenia caused by stress hormones

[0104] As a result of measuring the muscle endurance of mice using a treadmill device, the running time and distance of the solvent-administered group in the glucocorticoid group were significantly lower than those in the control group. Among the various Lactobacillus-administered groups, it was confirmed that the muscle endurance was significantly restored in the Lactobacillus gasseri (LG)-administered group (Figs. 1 and 2). In addition, it was confirmed that the weight of the gastrocnemius muscle was significantly increased in the Lactobacillus gasseri-administered group (Fig. 3). The lean body mass measured by the dual-energy X-ray absorptiometry method was significantly decreased in the solvent-administered group of the glucocorticoid group compared to the control group, but it was confirmed that it was significantly increased in the Lactobacillus gasseri-administered group (Fig. 4).

[0105] Among various Lactobacillus microorganisms, Lactobacillus gasseri showed a significant sarcopenia inhibitory effect, so the subsequent experiments were conducted using Lactobacillus gasseri.

[0106]

[0107] Example 3: Comparative experiment on the sarcopenia inhibitory efficacy of various Lactobacillus gasseri strains against stress hormones

[0108] Various Lactobacillus gasseri strains, namely, H65 (Lactobacillus gasseri H65: accession number KCCM 80404), H30 (Lactobacillus gasseri H30: accession number KCCM 80403), RM2, FF557 (Lactobacillus gasseri FF557, accession number KCCM 80406), and BNR17, were cultured in MRS medium for 16 hours.

[0109]

[0110] The experimental animals were 4-week-old female Balb / c mice (18 - 20 g), supplied by Central Laboratory Animal Inc., and after being acclimated for one week in the experimental animal breeding facility, they were used in the experiment. During the experimental period, solid feed and water were provided ad libitum, and the temperature (22 ± 2°C), relative humidity (60 ± 5%), and 12-hour light-dark cycle of the breeding room were maintained.

[0111] The mice were divided into a control group and a glucocorticoid (stress hormone) treatment group. The glucocorticoid treatment group was further divided into a vehicle administration group and a Lactobacillus administration group. The control group was intraperitoneally injected with 200 μl of saline each time, and the glucocorticoid treatment group was intraperitoneally injected with 30 mg / kg of glucocorticoid once a day.

[0112] At the same time, among the glucocorticoid treatment group, the vehicle administration group was orally administered distilled water, and the Lactobacillus administration group was orally administered various Lactobacillus gasseri strains, namely ABH2, ABH7, ABF7, ABF3, and BNR17, at a dose of 10 8 cfu / mouse (converted to human dose: 2.5×10 10 cfu / human) for 16 days (2.5×10 10 cfu / human = 10 8 cfu / 20 g × 60,000 g / 12, mouse standard weight 20 g, human standard weight 60 kg, human-to-mouse dose equivalence coefficient 12).

[0113] The body weight changes during the administration period and the final body weight were measured. The muscle endurance of the mice was measured using a treadmill device (Columbus Instrument, USA). Muscle endurance was quantified by the maximum exercise time and maximum exercise distance until the mice became exhausted and could no longer run. The muscle strength of the forelimbs was measured using a grip strength meter (Bioseb, France). After the experiment, the mice were sacrificed, and the weights of the gastrocnemius muscle and quadriceps femoris muscle were measured.

[0114]

[0115] Example 4: Comparison of the inhibitory effects of various Lactobacillus gasseri strains on sarcopenia caused by stress hormones

[0116] The body weight of the mice decreased due to the administration of glucocorticoid. Among various Lactobacillus gasseri strains, only the BNR17 administration group had less weight loss compared to the glucocorticoid administration group, and other strains showed similar or greater weight loss (Figure 5). The final body weight significantly decreased in the glucocorticoid administration group compared to the control group, and only the BNR17 administration group significantly inhibited the weight loss caused by glucocorticoid (Figure 6). The weight of the quadriceps significantly decreased in the glucocorticoid administration group compared to the control group, and only the BNR17 administration group significantly inhibited the weight loss of the quadriceps caused by glucocorticoid (Figure 7). As a result of measuring the muscle strength of the mice with a grip strength meter, the muscle strength significantly decreased in the glucocorticoid administration group compared to the control group, and only the BNR17 administration group significantly inhibited the decrease in muscle strength caused by glucocorticoid (Figure 8).

[0117] As a result of measuring the muscle endurance of the mice with a treadmill device, the solvent administration group of the glucocorticoid group had significantly lower treadmill running time and distance compared to the control group. Among various Lactobacillus gasseri strains, it was confirmed that the muscle endurance significantly recovered in the BNR17 administration group (Figures 9 and 10).

[0118] Among various Lactobacillus gasseri strains, Lactobacillus gasseri BNR17 showed a significant sarcopenia inhibitory effect. Therefore, the subsequent experiments were conducted using Lactobacillus gasseri BNR17.

[0119]

[0120] Example 5: Experiment on the inhibitory efficacy and mechanism of sarcopenia caused by stress hormones

[0121] The Lactobacillus gasseri BNR17 strain was cultured in MRS medium for 16 hours.

[0122] Next, the experimental animals were 4-week-old female Balb / c mice (18 - 20 g), supplied by Central Laboratory Animal Inc., and after being acclimated in the experimental animal breeding facility for one week, they were used in the experiment. During the experimental period, solid feed and water were freely available, and the temperature (22 ± 2 °C), relative humidity (60 ± 5%), and 12-hour light-dark cycle in the breeding room were maintained.

[0123] The mice were divided into a control group and a glucocorticoid (stress hormone) group, and the glucocorticoid group was further divided into a vehicle administration group and a Lactobacillus gasseri administration group. The control group was intraperitoneally injected with 200 μl of saline each time, and the glucocorticoid group was intraperitoneally injected with 30 mg / kg of glucocorticoid once a day.

[0124] At the same time, among the glucocorticoid group, the vehicle administration group was orally administered distilled water, and the Lactobacillus gasseri administration group was orally administered Lactobacillus gasseri at a dose of 10 7 ~10 8 cfu / mouse (converted to human dose, 2.5×10 9 ~2.5×10 10 cfu / human) for 14 days.

[0125] After the administration, the muscle endurance of the mice was measured using a treadmill device (Columbus Instrument, USA). Muscle endurance was quantified by the maximum exercise time and maximum exercise distance until the mice became tired and could no longer run. Also, the forelimb muscle strength of the mice was measured using a grip strength tester (Bioseb, France). The fat-free mass (Len body mass) of the whole body and the gastrocnemius part of the hindlimbs of each mouse was measured using a dual-energy X-ray absorption measurement method with an InAlyzer (Medikors, South Korea) device.

[0126] After the experiment, the mice were sacrificed, and the weights of the quadriceps femoris and gastrocnemius muscles were measured. Proteins were extracted from the quadriceps femoris of each mouse, and the levels of myosin heavy chain (MyHC), MyoD (Myoblast determination protein 1), MuRF1, MAFbx, FOXO3, and β-actin (control protein) were measured by Western blotting. Quantitative analysis was performed using ImageJ software (NIH, Bethesda, MD, USA) by comparing with β-actin (control protein).

[0127]

[0128] Example 6: Confirmation of the inhibitory effect and mechanism of Lactobacillus gasseri BNR17 on sarcopenia by stress hormones

[0129] As a result of measuring the muscle endurance of mice using a treadmill device, the solvent administration group of the glucocorticoid (stress hormone) group had significantly lower treadmill running time and distance compared to the control group. However, it was confirmed that the muscle endurance was significantly restored in the Lactobacillus gasseri BNR17 administration group (Figs. 11 and 12). The grip strength of the mice was significantly decreased in the solvent administration group of the glucocorticoid group compared to the control group, but it was confirmed that the muscle strength was significantly restored in the Lactobacillus gasseri BNR17 administration group (Fig. 13). It was confirmed that the weights of the gastrocnemius and quadriceps femoris muscles were significantly increased in the Lactobacillus gasseri BNR17 administration group (Figs. 14 and 15). The lean body mass of the whole body and the lean body mass of the hindlimbs measured by dual-energy X-ray absorptiometry were significantly decreased in the solvent administration group of the glucocorticoid group compared to the control group, but it was confirmed that they were significantly increased in the Lactobacillus gasseri BNR17 administration group (Figs. 16 and 17).

[0130] Muscle contraction is achieved by the interaction between myosin and actin. As a result of extracting proteins from the quadriceps femoris muscle and examining the level of myosin heavy chain (MyHC), which plays a central role in muscle contraction, it was confirmed that the level of MyHC decreased in the solvent administration group of the glucocorticoid group compared to the control group, but the level of MyHC was significantly increased in the Lactobacillus gasseri BNR17 administration group compared to the solvent administration group of the glucocorticoid group (Figure 18).

[0131] MyoD (Myoblast determination protein 1) is a transcription factor that plays a central role in increasing muscle mass and whose expression is activated by exercise (Rudnicki et al., Cell 75(7):1351-1359, 1993). As a result of extracting proteins from the quadriceps femoris muscle and examining the level of MyoD, it was confirmed that the level of MyoD decreased in the solvent administration group of the glucocorticoid group compared to the control group, but the level of MyoD was significantly increased in the Lactobacillus gasseri BNR17 administration group compared to the solvent administration group of the glucocorticoid group (Figure 19).

[0132] The increase in the levels of MyHC, which plays a central role in muscle contraction, and MyoD, which plays a central role in increasing muscle mass, suggests a direct mechanism of action for the increase in muscle endurance, muscle strength, and muscle mass by Lactobacillus gasseri BNR17.

[0133] The levels of MuRF1 and MAFbx, which cause ubiquitin-dependent proteolysis of MyHC and MyoD, increased in the solvent administration group of the glucocorticoid group compared to the control group, but it was confirmed that their levels were significantly decreased in the Lactobacillus gasseri BNR17 administration group compared to the solvent administration group of the glucocorticoid group (Figures 20 and 21).

[0134] The level of the transcription factor FOXO3 that causes the transcription of MuRF1 and MAFbx also increased in the solvent administration group of the glucocorticoid group compared to the control group, but it was confirmed that it significantly decreased in the Lactobacillus gasseri BNR17 administration group compared to the solvent administration group of the glucocorticoid group (Figure 22).

[0135]

[0136] Example 7: Experiment on the efficacy of drugs in suppressing sarcopenia

[0137] The experimental animals were 4-week-old female Balb / c mice (18 - 20 g), supplied by Central Laboratory Animal Inc., and after being acclimatized in the experimental animal breeding facility for 1 week, they were used in the experiment. During the experimental period, solid feed and water were freely available, and the temperature (22 ± 2 °C), relative humidity (60 ± 5%), and 12-hour light-dark cycle of the breeding room were maintained.

[0138] Cisplatin was used to produce sarcopenia model mice with drugs. The drugs used in anticancer chemotherapy containing cisplatin cause sarcopenia as a major side effect, which leads to a decrease in the cure rate and quality of life (Davis MP et al., Annals of Palliative Medicine, 8(1):86 - 101, 2019).

[0139] The mice were divided into a control group and a cisplatin group, and the cisplatin group was further divided into a vehicle administration group and a Lactobacillus gasseri administration group. The control group was intraperitoneally injected with 200 μl of saline, and the cisplatin group was intraperitoneally injected with 3 mg / kg of cisplatin 4 times at 2-day intervals.

[0140] At the same time, among the cisplatin group, the vehicle administration group was orally administered with distilled water, and the Lactobacillus gasseri administration group was orally administered with Lactobacillus gasseri at a dose of 10 4 ~10 7 cfu / mouse (converted to human dose, 2.5 × 10 6 ~2.5 × 10 9 cfu / human) for 9 days.

[0141] After the administration, the muscle endurance of the mice was measured using a treadmill device (Columbus Instrument, USA). Muscle endurance was quantified by the maximum exercise time and maximum exercise distance until the mice became tired and could no longer run. Also, the forelimb muscle strength of the mice was measured using a grip strength testing device (Bioseb, France).

[0142] After the experiment, the mice were sacrificed, blood was collected from the heart, and then serum was separated by centrifugation. Proteins were extracted from the quadriceps femoris of each mouse, and the levels of myosin heavy chain (MyHC), MyoD (Myoblast determination protein 1), and β-actin (control protein) were observed by Western blotting and quantitatively analyzed using ImageJ software (NIH, Bethesda, MD, USA) relative to β-actin (control protein). GDF-15 in muscle and serum was quantified by ELISA method.

[0143]

[0144] Example 8: Confirmation of the effect of Lactobacillus gasseri BNR17 on sarcopenia by drugs

[0145] As a result of measuring the muscle endurance of the mice using a treadmill device, the solvent administration group of the cisplatin group showed a significant decrease in treadmill running time and distance compared to the control group. However, an excellent muscle endurance recovery effect was confirmed in the Lactobacillus gasseri BNR17 administration group (Figs. 23 and 24). It was confirmed that the grip strength of the mice in the solvent administration group of the cisplatin group was significantly decreased compared to the control group, but was significantly recovered in the Lactobacillus gasseri BNR17 administration group (Fig. 25). It was confirmed that the weights of the gastrocnemius and quadriceps femoris were significantly increased in the Lactobacillus gasseri BNR17 administration group (Figs. 26 and 27).

[0146] Muscle contraction is achieved by the interaction between myosin and actin. Protein was extracted from the quadriceps femoris muscle, and the level of myosin heavy chain (MyHC), which plays a central role in muscle contraction, was examined. As a result, the level of MyHC decreased in the vehicle-administered group of the cisplatin group compared with the control group, but was significantly increased in the Lactobacillus gasseri BNR17-administered group compared with the vehicle-administered group of the cisplatin group (Figure 28).

[0147] MyoD (Myoblast determination protein 1) is a transcription factor that plays a central role in increasing muscle mass and is activated by exercise (Rudnicki et al., Cell 75(7):1351-1359, 1993). Protein was extracted from the quadriceps femoris muscle, and the level of MyoD was examined. As a result, the level of MyoD decreased in the vehicle-administered group of the cisplatin group compared with the control group, but was significantly increased in the Lactobacillus gasseri BNR17-administered group compared with the vehicle-administered group of the cisplatin group (Figure 29).

[0148] The increase in the levels of MyHC, which plays a central role in muscle contraction, and MyoD, which plays a central role in increasing muscle mass, suggests a direct mechanism of action for the increase in muscle endurance, muscle strength, and muscle weight by Lactobacillus gasseri.

[0149] As a result of quantifying GDF-15 in muscle, the level of GDF-15 in muscle was significantly increased in the vehicle-administered group of the cisplatin group compared with the control group, but was significantly decreased in the Lactobacillus gasseri-administered group (Figure 30). The results of quantifying GDF-15 in serum showed the same pattern as the level of GDF-15 in muscle (Figure 31).

[0150]

[0151] Example 9: Experiment on the efficacy of suppressing sarcopenia by tumors

[0152] The experimental animals were 4-week-old female Balb / c mice (18 - 20 g), supplied by Central Laboratory Animal Inc., and after being acclimated in the experimental animal breeding facility for one week, they were used in the experiment. During the experimental period, solid feed and water were freely available, and the temperature (22 ± 2 °C), relative humidity (60 ± 5 %), and 12-hour light-dark cycle in the breeding room were maintained.

[0153] The mice were divided into a control group and a tumor group. The tumor group was further divided into a vehicle administration group and a Lactobacillus gasseri administration group. The control group was subcutaneously injected with 200 μl of saline, and the tumor group was subcutaneously injected with 6 10

[0154] cells / mouse of C26 colon carcinoma cells.

[0155] After 14 days when the tumors were clearly formed, the vehicle administration group was orally administered distilled water once a day for 7 days, and the control drug administration group was orally administered 160 mg / kg of Megestrol acetate (MA), the most commonly used drug for weight loss in cancer patients, once a day for 7 days (mouse dose calculation: 160 mg / kg = 800 mg / 60 kg × 12, human daily dose 800 mg, human standard weight 60 kg, human-to-mouse dose equivalence coefficient 12). 5 ~10 7 cfu / mouse of Lactobacillus gasseri BNR17 was orally administered for 7 days.

[0156] After the administration, the muscle endurance of the mice was measured using a treadmill device (Columbus Instrument, USA), and the muscle strength of the mice was measured using a grip strength tester (Bioseb, France).

[0157] After the experiment, the mice were sacrificed, blood was collected from the heart, and then serum was separated by centrifugation. Proteins were extracted from the quadriceps femoris of each mouse, and the levels of myosin heavy chain (MyHC), MyoD (Myoblast determination protein 1), and β-actin (control protein) were observed by Western blotting and quantitatively analyzed using ImageJ software (NIH, Bethesda, MD, USA) in comparison with β-actin (control protein). GDF-15 in muscle and serum was quantified by ELISA method.

[0158]

[0159] Example 10: Confirmation of the effect of Lactobacillus gasseri BNR17 on sarcopenia caused by tumors

[0160] As a result of measuring the muscle endurance of mice with a treadmill device, the running time and distance on the treadmill in the solvent-administered group of the tumor group were significantly reduced compared to the control group. However, it was confirmed that the muscle endurance significantly increased in the Lactobacillus gasseri BNR17-administered group (Figures 32 and 33). The muscle strength of the mice was significantly decreased in the solvent-administered group of the tumor group compared to the control group, but it was confirmed that the muscle strength was significantly restored in the Lactobacillus gasseri BNR17-administered group (Figure 34).

[0161] Next, as a result of measuring and comparing the weight of the quadriceps femoris, the weight of the quadriceps femoris was significantly decreased in the solvent-administered group of the tumor group compared to the control group, but it was confirmed that the muscle weight significantly increased in the Lactobacillus gasseri BNR17-administered group (Figure 35).

[0162] As a result of extracting proteins from the quadriceps femoris and confirming the level of myosin heavy chain (MyHC), which plays a central role in muscle contraction, the level of MyHC decreased in the solvent-administered group of the tumor group compared to the control group, but it was confirmed that the level of MyHC significantly increased in the Lactobacillus gasseri BNR17-administered group compared to the solvent-administered group of the tumor group (Figure 36).

[0163] Protein was extracted from the quadriceps femoris muscle, and the level of MyoD, which plays a central role in increasing muscle mass, was examined. As a result, the level of MyoD decreased in the solvent-administered group of the tumor group compared to the control group, but it was confirmed that the level of MyoD was significantly increased in the Lactobacillus gasseri BNR17-administered group compared to the solvent-administered group of the tumor group (Figure 37).

[0164] The increase in the levels of MyHC, which plays a central role in muscle contraction, and MyoD, which plays a central role in increasing muscle mass, suggests a direct mechanism of action for the increase in the muscle endurance, muscle strength, and muscle weight of Lactobacillus gasseri.

[0165] As a result of quantifying GDF-15 in the muscle, the level of GDF-15 in the muscle was significantly increased in the solvent-administered group of the tumor group compared to the control group, but the level of GDF-15 in the muscle was significantly decreased in the Lactobacillus gasseri BNR17-administered group (Figure 38). The results of quantifying GDF-15 in the serum showed the same pattern as the level of GDF-15 in the muscle (Figure 39).

[0166] In the suppression of sarcopenia by tumors, 10 7 cfu / mouse (2.5×10 9 cfu / human) of Lactobacillus gasseri BNR17 showed the same or superior efficacy compared to megestrol acetate (MA), which is the most commonly used drug for weight loss in cancer patients.

[0167]

[0168] Example 11: Experiment on the Efficacy of Suppressing Sarcopenia Caused by Obesity

[0169] The experimental animals were 4-week-old female Balb / c mice (18 - 20 g), supplied by Central Laboratory Animal Inc., and after being acclimated in an experimental animal breeding facility for 1 week, they were used in the experiment. During the experimental period, solid feed and water were freely available, and the temperature (22±2°C), relative humidity (60±5%), and 12-hour light-dark cycle of the breeding room were maintained.

[0170] Mice were divided into a control group and an obese group, and the obese group was divided into a vehicle-administered group and a Lactobacillus gasseri BNR17-administered group. The control group was fed a normal diet, and the obese group was fed a high fat diet (70% fat) for 8 weeks to induce obesity.

[0171] After that, the obese group was administered distilled water for 10 min, and the Lactobacillus gasseri group was administered Lactobacillus gasseri BNR17 for 10 min. 7 ~10 8 cfu / mouse (converted to human dose: 2.5 x 10 9 ~2.5×10 10 The mice were orally administered with 0.01 mg / kg of 10000 cfu / human for 8 weeks.

[0172] After the administration, the muscle endurance of the mice was measured using a treadmill machine (Columbus Instrument, USA). Muscle endurance was quantified as the maximum exercise time and maximum exercise distance until the mouse became tired and could no longer run. In addition, the forelimb muscle strength of the mice was measured using a grip strength test machine (Bioseb, France). The fat-free body mass of each mouse was measured using a dual energy X-ray absorptiometry method using an InAlyzer (Medikors, Korea) machine.

[0173]

[0174] Example 12: Confirmation of the inhibitory effect of Lactobacillus gasseri BNR17 on sarcopenia caused by obesity

[0175] As a result of measuring the muscle endurance of mice using a treadmill device, the running time and distance of the solvent-administered group in the obese group were significantly lower than those of the control group. However, it was confirmed that the muscle endurance was significantly restored in the Lactobacillus gasseri BNR17-administered group (Figs. 40 and 41). The grip strength of the mice was significantly decreased in the solvent-administered group of the obese group compared to the control group, but it was confirmed that the muscle strength was significantly restored in the Lactobacillus gasseri BNR17-administered group (Fig. 42). The lean body mass of the hind limb (Leg) measured by the dual-energy X-ray absorptiometry method was significantly decreased in the solvent-administered group of the obese group compared to the control group, but it was confirmed that it was significantly increased in the Lactobacillus gasseri BNR17-administered group (Fig. 43).

[0176]

[0177] Example 13: Experiment on the efficacy of suppressing sarcopenia due to aging

[0178] The experimental animals were 4-week-old female Balb / c mice (18 - 20 g), supplied by Central Laboratory Animal Inc., and after being acclimatized in the experimental animal breeding facility for 1 week, they were used in the experiment. During the experimental period, solid feed and water were freely available, and the temperature (22 ± 2°C), relative humidity (60 ± 5%), and 12-hour light-dark cycle of the breeding room were maintained.

[0179] The mice were divided into a control group and an aging-induced group, and the aging-induced group was further divided into a solvent (Vehicle)-administered group and a Lactobacillus gasseri BNR17-administered group. The control group was intraperitoneally injected with 200 μl of saline, and the aging-induced group was intraperitoneally injected with 200 mg / Kg of D-galactose for 6 weeks to induce aging (Chang L et al., Journal of Medicinal Food 17(3):357 - 364, 2014).

[0180] At the same time, among the aging-induced groups, distilled water was administered to the solvent (Vehicle)-administered group, and Lactobacillus gasseri BNR17 was administered to the D-galactose-administered group at a dose of 10 6 ~10 8cfu / mouse (when converted to human dosage, 2.5×10 8 ~2.5×10 10 cfu / human) and administered orally.

[0181] After the administration, the muscle endurance of the mice was measured using a treadmill device (Columbus Instrument, USA). Muscle endurance was quantified by the maximum exercise time and maximum exercise distance until the mice became tired and could no longer run. Also, the forelimb muscle strength of the mice was measured using a grip strength testing device (Bioseb, France).

[0182]

[0183] Example 14: Confirmation of the inhibitory effect of Lactobacillus gasseri BNR17 on sarcopenia due to aging

[0184] As a result of measuring the muscle endurance of the mice using a treadmill device, in the solvent administration group of the aging induction group, the treadmill running time and distance were significantly lower compared to the control group. However, in the Lactobacillus gasseri BNR17 administration group, it was confirmed that the muscle endurance was significantly restored (Figures 44 and 45). The grip strength of the mice was significantly decreased in the solvent administration group of the aging induction group compared to the control group, but it was confirmed that the muscle strength was significantly restored in the Lactobacillus gasseri BNR17 administration group (Figure 46).

[0185]

[0186] Therefore, summarizing the above content, the decrease of MyoD (Myoblast determination protein-1) which plays a major role in increasing muscle mass and MyHC (Myosin heavy chain) which plays a major role in muscle contraction acts as a direct cause of sarcopenia, which is due to the increase of MuRF1 (muscle RING-finger protein-1) and MAFbx (muscle atrophy F-box, AKA atrogin-1) that cause ubiquitin-dependent proteolysis of MyoD and MyHC and the increase of FOXO3 (Forkhead Box O3) which acts as their transcription factor.

[0187] Lactobacillus gasseri BNR17 effectively suppresses the decrease of muscle function and muscle mass by suppressing the decrease of MyHC and MyoD and the increase of MuRF1, MAFbx, and FOXO3 caused by various factors such as stress, drugs, tumors, obesity, and aging. Therefore, it may be used for pharmaceutical compositions for the prevention and treatment of sarcopenia caused by various factors including stress, drugs, tumors, obesity, and aging, and foods for improving muscle mass, muscle function, muscle strength, and muscle endurance.

[0188]

[0189] As described above, specific parts of the content of the present invention have been described in detail. However, it will be apparent to those with ordinary knowledge in the art that such specific descriptions are merely preferred embodiments and do not limit the scope of the present invention. Therefore, it can be said that the substantial scope of the present invention is defined by the appended claims and their equivalents.

[0190]

Industrial Applicability

[0191] The pharmaceutical and food compositions according to an embodiment of the present invention can maintain and enhance health and quality of life in various situations such as stress, obesity, aging, drug taking, and tumor occurrence by preventing or treating sarcopenia and improving muscle mass, muscle function, muscle strength, and muscle endurance.

[0192] The effects of the present invention are not limited to the above-described effects, and the effects not mentioned will be clearly understood by those skilled in the art from the specification of the present application.

[0193] TIFF2025518437000002.tif153164

Claims

1. A pharmaceutical composition for preventing or treating sarcopenia, comprising Lactobacillus gasseri BNR17 with deposit number KCTC 10902BP or a culture thereof.

2. The pharmaceutical composition for preventing or treating sarcopenia according to claim 1, wherein the sarcopenia is caused by stress, obesity, aging, drugs, tumors, or the like.

3. The pharmaceutical composition according to claim 1, wherein the Lactobacillus gasseri BNR17 or a culture thereof exhibits the following effects: Suppression of the decrease in MyoD (Myoblast determination protein-1); Suppression of the decrease in MyHC (Myosin heavy chain); Suppression of the increase in MuRF1 (muscle RING-finger protein-1); Suppression of the increase in MAFbx (muscle atrophy F-box, also known as atrogin-1); Suppression of the increase in FOXO3 (Forkhead Box O3); and Suppression of the increase in GFD-15 (Growth differentiation factor 15).

4. A food composition for improving the decrease in muscle mass and muscle function, comprising Lactobacillus gasseri BNR17 with deposit number KCTC 10902BP or a culture thereof.

5. The food composition for improving the decrease in muscle mass and muscle function according to claim 4, wherein the decrease in muscle mass and muscle function is caused by stress, obesity, aging, drugs, tumors, or the like.

6. The food composition according to claim 4, wherein the Lactobacillus gasseri BNR17 or a culture thereof exhibits the following effects: Suppression of the decrease in MyoD (Myoblast determination protein-1); Suppression of reduction in MyHC (Myosin heavy chain); Suppression of increase in MuRF1 (muscle RING-finger protein-1); Suppression of increase in MAFbx (muscle atrophy F-box, aka atrogin-1); Suppression of increase in FOXO3 (Forkhead Box O3); and Suppression of increase in GFD-15 (Growth differentiation factor 15).

7. A composition for improving muscle strength and muscle endurance, comprising Lactobacillus gasseri BNR17 with accession number KCTC 10902BP or a culture thereof.

8. The composition according to claim 7, wherein the Lactobacillus gasseri BNR17 or a culture thereof exhibits the following effects: Suppression of reduction in MyoD (Myoblast determination protein-1); Suppression of reduction in MyHC (Myosin heavy chain); Suppression of increase in MuRF1 (muscle RING-finger protein-1); Suppression of increase in MAFbx (muscle atrophy F-box, aka atrogin-1); Suppression of increase in FOXO3 (Forkhead Box O3); and Suppression of increase in GFD-15 (Growth differentiation factor 15).

9. An anti-cancer adjuvant comprising Lactobacillus gasseri BNR17 with accession number KCTC 10902BP or a culture thereof.

10. The anti-cancer adjuvant according to claim 9, which improves sarcopenia, reduction in muscle mass and muscle function, or reduction in muscle strength and muscle endurance caused by an anti-cancer agent.

Citation Information

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