Glucose metabolism improving composition

Abstract

To provide a human glucose metabolism improving composition containing lactic acid bacteria of Lactobacillus.SOLUTION: A composition comprising lactic acid bacteria of Lactobacillus is fed to a person, to improve the glucose metabolism of the person.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a composition for improving glucose metabolism in humans. [Background technology]

[0002] The increase in the number of patients with lifestyle-related diseases such as obesity and diabetes, which, in combination with obesity, cause metabolic syndrome, has become a major problem worldwide, as it leads to a deterioration in the public's health and increased medical costs. Moderate exercise and a balanced diet are important for preventing metabolic syndrome, but it is also known that consuming foods and beverages containing functional ingredients effective in preventing metabolic syndrome is effective (Non-Patent Document 1). Today, there are a variety of products available containing food ingredients that have the function of preventing or improving metabolic syndrome, but most only act as symptomatic treatments, such as promoting fat burning or inhibiting absorption, and it is difficult to say that they fundamentally improve metabolic syndrome by normalizing sugar and lipid metabolism.

[0003] Chronic inflammation in adipose tissue is known to be one of the causes of impaired glucose and lipid metabolism. Specifically, increased levels of inflammatory cytokines such as monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) promote macrophage infiltration into adipose tissue, resulting in decreased production of hormones necessary for normal glucose and lipid metabolism (Non-Patent Documents 2 and 3).

[0004] It has been known that certain lactic acid bacteria improve sugar and lipid metabolism in mice (Patent Document 1, Non-Patent Documents 4 and 5).

[0005] However, from the perspective of health promotion, methods to effectively improve glucose metabolism in humans are still needed, and suppressing inflammation in patients with lifestyle-related diseases is an important issue. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] International Publication No. 2012 / 014971 [Non-patent literature]

[0007] [Non-Patent Document 1] Egawa, K. et al. Verification of the body fat reducing effect and safety of green tea drink containing quercetin glycoside (enzyme-modified isoquercitrin) in obese individuals. Jpn Pharmacol Ther (Pharmacology and Therapy) 40:495-03, 2012 [Non-patent document 2] Xu H et al. “Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance” J Clin Invest, 112:1821-1830, 2003 [Non-patent document 3] Weisberg SP et al. “CCR2 modulates inflammatory and metabolic effects of high-fat feeding” J Clin Invest, 116:115-124, 2006 [Non-patent document 4] T. Toshimitsu et al. “Identification of Lactobacillus plantarum strain that meliorates chronic inflammation and metabolic disorders in obese and type 2 diabetic mice” J Dairy Sci, 99:933-946, 2016 [Non-Patent Document 5] Tohru Sakai et al. “Lactobacillus plantarum OLL2712 regulates glucose metabolism in C57BL / 6 mice fed a high-fat diet” J Nutr Sci Vitaminol, 59, 144-147, 2013

[0008] An object of the present invention is to provide a composition for effectively improving glucose metabolism in humans.

[0009] As a result of intensive research, the present inventors have found that lactic acid bacteria belonging to the genus Lactobacillus have the activity of significantly reducing specific inflammatory cytokines in humans, and can improve sugar metabolism in humans. The present invention is based on these findings.

[0010] According to the present invention, the following inventions are provided. [1] A composition for improving human sugar metabolism, comprising lactic acid bacteria belonging to the genus Lactobacillus. [2] An anti-inflammatory composition for humans containing lactic acid bacteria belonging to the genus Lactobacillus. [3] The composition described in [1] or [2], wherein the lactic acid bacteria are lactic acid bacteria having the activity of reducing the amount of at least one inflammatory cytokine selected from Monocyte Chemotactic Protein-1 (MCP-1) and interleukin-6 (IL-6) in human blood. [4] The composition according to any one of [1] to [3], wherein the lactic acid bacterium is Lactobacillus plantarum. [5] The composition according to any one of [1] to [4], wherein the lactic acid bacteria comprise killed cells of the lactic acid bacteria. [6] The composition according to any one of [1] to [5], wherein the lactic acid bacteria comprise heat-killed cells. [7] The composition according to any one of [1] to [6], wherein the composition is a food composition. [8] The composition according to any one of [1] to [6], wherein the composition is a pharmaceutical composition. [9] The composition described in any one of [1] to [8], wherein the lactic acid bacterium has a 16S rRNA gene that has 90% or more homology with the base sequence represented by SEQ ID NO: 1.

[10] The composition described in any one of [1] to [9], wherein the lactic acid bacterium is Lactobacillus plantarum OLL2712 strain deposited under accession number FERM BP-11262.

[0011] According to the present invention, it is possible to significantly reduce specific inflammatory cytokines associated with chronic inflammation of adipose tissue and abnormalities in glucose metabolism in humans, thereby improving glucose metabolism.

[0012] Composition for improving sugar metabolism According to one embodiment of the present invention, there is provided a composition for improving sugar metabolism in humans, comprising lactic acid bacteria belonging to the genus Lactobacillus (hereinafter also referred to as "lactic acid bacteria").

[0013] According to one embodiment, the lactic acid bacteria belonging to the genus Lactobacillus contained in the composition of the present invention are preferably lactic acid bacteria that have the activity of reducing the amount of at least one inflammatory cytokine selected from MCP-1 and IL-6 in human blood.The lactic acid bacteria are preferably lactic acid bacteria that have the activity of selectively reducing the amount of at least one of these inflammatory cytokines in the blood, and more preferably lactic acid bacteria that have the activity of selectively reducing the amount of both of these inflammatory cytokines in the blood.In addition, since MCP-1 and IL-6 are known to cause inflammation in adipose tissue and cause abnormalities in glucose and lipid metabolism, the use of lactic acid bacteria that have the activity of reducing the amount of MCP-1 and / or IL-6 in the blood can not only improve glucose metabolism but also suppress inflammation, particularly suppress inflammation in adipose tissue, and improve lipid metabolism.

[0014] As used herein, "reducing" inflammatory cytokines means that stimulation with lactic acid bacteria or a composition containing lactic acid bacteria results in a statistically significant (i.e., beyond the margin of error) reduction in the blood levels of each inflammatory cytokine in a stimulated subject. Furthermore, "selectively reducing" MCP-1 and IL-6 means that stimulation with lactic acid bacteria or a composition containing lactic acid bacteria results in a significant reduction in MCP-1 and / or IL-6, while other inflammatory cytokines are not significantly reduced in a stimulated subject. Statistical analysis can be performed using methods known to those skilled in the art, such as repeated measures one-way analysis of variance and paired t-tests with Bonferroni correction. Furthermore, "reducing activity" with respect to blood levels of MCP-1 and IL-6 refers to the ability to significantly reduce the levels of MCP-1 and IL-6, respectively. The presence or absence of the activity to reduce blood levels of MCP-1 and IL-6 is specifically determined by the methods described in the Examples.

[0015] The glucose metabolism-improving composition of the present invention is effective in both humans with normal and abnormal glucose metabolism, but is particularly effective in humans with abnormal glucose metabolism. Furthermore, the glucose metabolism-improving composition of the present invention can improve glucose metabolism regardless of the blood MCP-1 and IL-6 levels of the subject. That is, the glucose metabolism-improving effect is achieved in both subjects with low blood MCP-1 and IL-6 levels (low inflammation) and subjects with high blood MCP-1 and IL-6 levels (high inflammation), but is particularly pronounced in subjects with high inflammation. Applying the composition of the present invention to humans with high inflammation is preferable from the perspective of promoting health by simultaneously suppressing inflammation and promoting glucose metabolism. As used herein, "low inflammation" refers to a state in which the blood MCP-1 concentration is less than 5 pg / mL and / or the blood IL-6 concentration is less than 0.5 pg / mL. Furthermore, "hyperinflammation" refers to a state in which the blood MCP-1 concentration is 5 pg / mL or higher and / or the blood IL-6 concentration is 0.5 pg / mL or higher.

[0016] The lactic acid bacteria contained in the composition of the present invention are not particularly limited as long as they belong to the genus Lactobacillus.Preferably, the lactic acid bacteria belonging to the genus Lactobacillus are lactic acid bacteria that have the activity of reducing the amount of at least one inflammatory cytokine selected from MCP-1 and IL-6 in human blood. Examples of lactic acid bacteria belonging to the genus Lactobacillus include Lactobacillus delbrueckii subsp. burgaricus, Lactobacillus delbrueckii subsp. lactis, Lactobacillus casei, Lactobacillus helveticus, Lactobacillus acidophilus, Lactobacillus crispatus, Lactobacillus amylovorus, Lactobacillus gallinarum, Lactobacillus gasseri, and Lactobacillus oris. oris, Lactobacillus rhamnosus, Lactobacillus johnsonii, Lactobacillus fermentum, Lactobacillus brevis, Lactobacillus plantarum, Lactobacillus pentosus, Lactobacillus paraplantarum, Lactobacillus paracollinoides, Lactobacillus hammesii, etc.Of these lactic acid bacteria, Lactobacillus plantarum is preferred, and Lactobacillus plantarum OLL2712 strain is more preferred.

[0017] The Lactobacillus plantarum OLL2712 strain was deposited at the International Patent Organism Depositary of the National Institute of Advanced Industrial Science and Technology (6-1 Central, Higashi 1-chome, Tsukuba City, Ibaraki Prefecture, Japan) on July 2, 2010, and was subsequently transferred to international deposition and assigned the accession number FERM BP-11262. As stated in Budapest Notification No. 282 (http: / / www.wipo.int / treaties / en / notifications / budapest / treaty_budapest_282.html), the National Institute of Technology and Evaluation (IPOD, NITE) has taken over the patent microorganism deposit business from the National Institute of Advanced Industrial Science and Technology (AIST), and Lactobacillus plantarum OLL2712 strain is currently deposited at the National Institute of Technology and Evaluation (IPOD, NITE) (Room 120, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture) under the accession number FERM BP-11262.

[0018] The lactic acid bacteria contained in the composition of the present invention can also be strains substantially equivalent to the deposited strain. Substantially equivalent strains refer to, for example, the above-mentioned strains of lactic acid bacteria belonging to the genus Lactobacillus, whose 16S rRNA gene base sequence has 90% or more, preferably 98% or more, and more preferably 99% or more homology with the 16S rRNA gene base sequence (SEQ ID NO: 1) of the deposited strain, and preferably have the same bacteriological properties as the strain. A strain with the same bacteriological properties is preferably a strain that has the same activity as the deposited strain in terms of reducing the amount of at least one inflammatory cytokine selected from MCP-1 and IL-6 in human blood. Furthermore, the lactic acid bacteria contained in the composition of the present invention can also be strains bred from the deposited strain or a substantially equivalent strain by mutation, genetic recombination, natural mutant selection, etc., as long as the effects of the present invention are achieved.

[0019] The lactic acid bacteria contained in the composition of the present invention include, for example, cultures containing lactic acid bacteria cells, as well as the lactic acid bacteria cells themselves. While either live or killed lactic acid bacteria cells can be used as the lactic acid bacteria cells, killed cells are preferred, and killed cells obtained by heat-treating live cells (heat-killed cells) are more preferred. That is, the lactic acid bacteria contained in the composition of the present invention preferably include killed cells, and more preferably heat-killed cells. The number of passages of the lactic acid bacteria is not particularly limited as long as the effects of the present invention are achieved, but is, for example, 1 to 30, preferably 5 to 15, and more preferably 11 to 13.

[0020] The conditions for culturing lactic acid bacteria are not particularly limited as long as the effects of the present invention are achieved, and can be the conditions typically used for culturing lactic acid bacteria. For example, a medium can be prepared by dissolving whey powder or whey protein concentrate in sterilized water, digesting the mixture with protease A, adding yeast extract, fish extract, and MnSO4, and then adding various nutrients (vitamins, minerals, fatty acid esters), adjusting the pH to 6.7 with NaOH, and then sterilizing the mixture in an autoclave. The pH during culture can be adjusted to 4.8 to 6.8. K2CO3 can be used to adjust the pH. The temperature during culture can be 29 to 40°C.

[0021] The heat treatment for obtaining heat-killed bacteria is not particularly limited as long as the effects of the present invention are achieved, and the heat treatment is carried out under conditions that are normally used to sterilize lactic acid bacteria.

[0022] In addition to the above-mentioned heat treatment, lactic acid bacteria that have been subjected to treatments such as concentration, dilution, freezing, drying, and powdering can also be used.

[0023] The lactic acid bacteria contained in the composition of the present invention may be those prepared by the above-mentioned culture or various treatments, or commercially available compositions containing lactic acid bacteria may be used.

[0024] In the composition of the present invention, the number of lactic acid bacteria per mass of the composition is not particularly limited as long as the effects of the present invention are exhibited. 6 ~10 14 pieces / g, more preferably 10 7 ~1×10 13 pieces / g, more preferably 10 8 ~10 12 pieces / g, particularly preferably 10 8 ~10 10 In the composition of the present invention, the dry mass of bacterial cells per mass of solid content in the composition is preferably 0.01 to 100% by mass, more preferably 1 to 80% by mass, and even more preferably 10 to 40% by mass.

[0025] The composition of the present invention may contain components other than lactic acid bacteria, as long as they do not impair the effects of the present invention. Examples of components other than lactic acid bacteria include medium components, additives suitable for oral tube administration, solvents such as water, carbohydrates, proteins, lipids, vitamins, minerals, biologically essential trace metals (manganese sulfate, zinc sulfate, magnesium chloride, potassium carbonate, etc.), flavorings, hygienically or pharmaceutically acceptable carriers, food additives, etc.

[0026] Examples of carbohydrates include sugars, modified starch (dextrin, soluble starch, British starch, oxidized starch, starch ester, starch ether, etc.), dietary fiber, and the like.

[0027] Examples of proteins include whole milk powder, skim milk powder, partially skim milk powder, casein, whey powder, whey protein, whey protein concentrate, whey protein isolate, α-casein, β-casein, κ-casein, β-lactoglobulin, α-lactalbumin, lactoferrin, soy protein, egg protein, meat protein and other animal and plant proteins, their hydrolysates, butter, milk minerals, cream, whey, non-protein nitrogen, sialic acid, phospholipids, lactose and other milk-derived components.

[0028] Examples of lipids include animal fats and oils such as lard, fish oil, and fractionated, hydrogenated, and interesterified oils thereof; and vegetable fats and oils such as palm oil, safflower oil, corn oil, rapeseed oil, coconut oil, fractionated, hydrogenated, and interesterified oils thereof.

[0029] Examples of vitamins include vitamin A, carotenes, B vitamins, vitamin C, D vitamins, vitamin E, K vitamins, vitamin P, vitamin Q, niacin, nicotinic acid, pantothenic acid, biotin, inositol, choline, and folic acid.

[0030] Examples of minerals include calcium, potassium, magnesium, sodium, copper, iron, manganese, zinc, and selenium.

[0031] The composition of the present invention can be produced by blending, in addition to lactic acid bacteria belonging to the genus Lactobacillus, pharmaceutically acceptable carriers and / or additives, food hygienically acceptable carriers and / or additives, etc. Thus, according to another aspect of the present invention, there is provided a method for producing a composition for improving sugar metabolism, which comprises blending lactic acid bacteria belonging to the genus Lactobacillus.

[0032] According to one embodiment of the present invention, the composition for improving glucose metabolism of the present invention can be provided as a food composition. The food composition of the present invention may be used for suppressing an increase in blood glucose level, promoting a decrease in blood glucose level, maintaining normal blood glucose level, suppressing an increase in blood insulin level, promoting a decrease in blood insulin level, maintaining normal insulin level, or for preventing and / or treating diabetes, obesity, metabolic syndrome, or dyslipidemia.

[0033] The food composition of the present invention may be in any form as long as it contains lactic acid bacteria, such as a solution, suspension, emulsion, powder, paste, semi-solid product, or solid product that can be taken orally or through a tube. Specific examples of foods include milk, milk drinks, soft drinks, fermented milk, lactic acid bacteria drinks, dairy drinks, yogurt, cheese, ice cream, frozen desserts, chocolate, tablets, gummies, candy, bread, biscuits, crackers, pizza crust, infant formula, liquid milk, liquid diet, food for the sick, nutritional foods, frozen foods, processed foods, seasonings, and other commercially available foods.

[0034] The food composition of the present invention can be made into a food or beverage labeled with uses such as improving glucose metabolism, inhibiting MCP-1 production, inhibiting IL-6 production, and inhibiting inflammation. The food or beverage can be labeled with such uses as "improving glucose metabolism," "inhibiting increases in blood glucose levels," "lowering blood glucose levels," "maintaining normal blood glucose levels," "inhibiting increases in blood insulin levels," "maintaining normal insulin levels," "lowering HbA1c," "improving insulin resistance," "preventing diabetes, obesity, and metabolic syndrome," "assisting the function of the hormone (insulin) that lowers blood glucose levels," "inhibiting MCP-1 production," "inhibiting IL-6 production," "inhibiting inflammation," and "anti-inflammatory." Labels other than these can also be used as long as they describe the effects achieved by inhibiting MCP-1 production and / or IL-6 production.

[0035] In this specification, "indication" means any act intended to inform consumers of the above-mentioned uses, and any indication that can recall or infer the above-mentioned uses falls under the "indication" of the present invention, regardless of the purpose of the indication, the content of the indication, the object or medium on which it is displayed, etc. However, it is preferable to display the use in an expression that allows consumers to directly recognize the above-mentioned uses.

[0036] The labeling is preferably one approved by the government or the like (e.g., labeling approved under various government systems and made in a manner based on such approval). Examples include labeling as a health food, functional food, functional food with function claims, enteral nutritional food, special dietary use food, food for the sick, functional nutrient food, and quasi-drug. Other examples include labeling approved by the Ministry of Health, Labor and Welfare, such as a food for specified health uses (FOSHU) or labeling approved under similar systems. Examples of the latter include labeling as a food for specified health uses, a conditional food for specified health uses (FOSHU), a label indicating an effect on the structure or function of the body, and a label indicating disease risk reduction. More specifically, labeling as a food for specified health uses (particularly a label indicating health uses) as defined in the Enforcement Regulations of the Health Promotion Act (Ministry of Health, Labor and Welfare Ordinance No. 86 of April 30, 2003), and similar labeling, etc.

[0037] According to another aspect of the present invention, the composition for improving glucose metabolism of the present invention can be provided as a pharmaceutical composition. The pharmaceutical composition of the present invention may be used for suppressing an increase in blood glucose levels, promoting a decrease in blood glucose levels, maintaining normal blood glucose levels, suppressing an increase in blood insulin levels, promoting a decrease in blood insulin levels, maintaining normal insulin levels, anti-inflammatory purposes, or for the prevention and / or treatment of diabetes, obesity, metabolic syndrome, and dyslipidemia. The pharmaceutical composition of the present invention can be produced according to standard manufacturing procedures for such foods, except for the inclusion of lactic acid bacteria. Here, the pharmaceutical composition refers to the composition of the present invention prepared as an oral or parenteral formulation according to conventional methods. The formulation may be carried out using additives acceptable for formulation. Examples of additives acceptable for formulation include excipients, stabilizers, preservatives, humectants, emulsifiers, lubricants, sweeteners, colorants, flavorings, buffers, antioxidants, and pH adjusters. When the pharmaceutical composition is an oral preparation, it can take the form of a solid preparation such as a tablet, powder, fine granules, granules, capsules, pills, or sustained-release preparation, or a liquid preparation such as a solution, suspension, or emulsion. When the pharmaceutical composition is a parenteral preparation, it can take the form of an injection, suppository, or the like. From the viewpoint of ease of ingestion (administration) to a subject, oral preparations are preferred for pharmaceutical compositions.

[0038] Furthermore, according to another aspect of the present invention, there is provided a composition for reducing MCP-1 and / or IL-6 in humans, comprising lactic acid bacteria belonging to the genus Lactobacillus.

[0039] The intake amount of the composition of the present invention is not particularly limited as long as the effects of the present invention are achieved, and can be appropriately adjusted depending on the age, health condition, body weight, etc. of the person taking it. Typically, it is 0.01 to 10,000 mg / kg body weight per day, preferably 0.1 to 1,000 mg / kg body weight, more preferably 0.5 to 300 mg / kg body weight, and even more preferably 1 to 100 mg / kg body weight. Furthermore, the dry mass of the lactic acid bacteria is preferably 0.001 to 1,000 mg / kg body weight, more preferably 0.01 to 100 mg / kg body weight, more preferably 0.05 to 30 mg / kg body weight, and even more preferably 0.1 to 10 mg / kg body weight. Furthermore, the number of lactic acid bacteria is preferably 1 x 10 4 ~1×10 12 per kg body weight, preferably 10 5 ~10 11 per kg body weight, more preferably 10 6 ~10 10 pcs / kg body weight, particularly preferably 10 6 ~10 8 Pieces / kg body weight.

[0040] To maximize the effectiveness of the composition of the present invention, it is preferable to continuously ingest (administer) it for a long period of time, specifically, for at least three days, and more preferably for at least one week. Examples of the administration period include 1 to 6 weeks, 1 to 12 weeks, 2 to 10 weeks, 4 to 10 weeks, and 4 to 12 weeks. As used herein, "continuously" means that a predetermined amount of the composition of the present invention is continuously ingested every day.

[0041] According to another aspect of the present invention, there is provided a method for improving carbohydrate metabolism in a human, comprising administering to the human an effective amount of a lactic acid bacterium belonging to the genus Lactobacillus. In addition, according to a preferred aspect of the present invention, the method is a method for improving inflammation in a human.

[0042] According to one embodiment of the present invention, "improvement of glucose metabolism" includes the improvement of abnormal glucose metabolism, activation or promotion of low glucose metabolism, maintenance of normal glucose metabolism, or prevention of decline. The cause of abnormal or declined glucose metabolism is not particularly limited, but lifestyle habits are a typical example. Examples of the glucose metabolism-improving effects of the composition of the present invention include suppressing increases in blood glucose levels, reducing blood glucose levels, maintaining normal blood glucose levels, suppressing increases in blood insulin levels, reducing blood insulin levels, and maintaining normal blood insulin levels. As used herein, "improvement" not only includes the meaning of "treatment," which involves stopping, alleviating, or delaying the progression or worsening of abnormalities or diseases through medical intervention, but also includes the meaning of stopping, alleviating, or delaying the progression or worsening of abnormalities or diseases through non-medical intervention. Furthermore, "improvement" also includes the meaning of "prevention," which involves preparing for anticipated worsening of abnormalities or diseases and preventing the onset or recurrence of abnormalities or diseases through non-medical or medical intervention.

[0043] Furthermore, humans to be inoculated with lactic acid bacteria are preferably highly inflammatory. In this specification, the blood MCP-1 concentration in highly inflammatory individuals is typically 5 pg / mL or higher, preferably 10 pg / mL or higher, and more preferably 15 pg / mL. There is no particular upper limit to the blood MCP-1 concentration in highly inflammatory individuals, but it is preferably 1000 pg / mL or lower, and more preferably 500 pg / mL or lower. These upper and lower limits can be combined. Furthermore, the blood IL-6 concentration in highly inflammatory individuals is typically 0.5 pg / mL or higher, preferably 1.0 pg / mL or higher, and more preferably 1.5 pg / mL or higher. There is no particular upper limit to the blood IL-6 concentration in highly inflammatory individuals, but it is preferably 100 pg / mL or lower, and more preferably 50 pg / mL or lower. These upper and lower limits can be combined.

[0044] In the method for improving sugar metabolism, the dosage and administration period of the lactic acid bacteria are not particularly limited as long as the effects of the present invention are achieved, and can be appropriately adjusted depending on the age, health condition, weight, etc. of the subject. Typically, in the method of the present invention, the dosage and administration period of the lactic acid bacteria are the same as those of the lactic acid bacteria in the composition of the present invention.

[0045] Furthermore, according to another aspect of the present invention, there is provided a method for treating and / or preventing diseases and / or disorders caused by abnormalities in sugar metabolism in a human, which comprises having the human ingest an effective amount of a composition containing lactic acid bacteria belonging to the genus Lactobacillus.

[0046] Diseases and disorders caused by abnormalities in glucose metabolism include, but are not limited to, diabetes, obesity, metabolic syndrome, and the like.

[0047] According to another aspect of the present invention, there is provided use of lactic acid bacteria belonging to the genus Lactobacillus for improving sugar metabolism.

[0048] According to another aspect of the present invention, there is provided use of a lactic acid bacterium belonging to the genus Lactobacillus for the production of a composition for improving glucose metabolism. [Example]

[0049] The present invention will be specifically described based on the following examples, but the present invention is not limited to these examples.

[0050] Example 1: Confirmation of the sugar metabolism improving effect of a composition containing lactic acid bacteria (1) Subject selection (screening) Subjects for the confirmation test of the glucose metabolism improvement effect were selected based on the following inclusion criteria A and exclusion criteria B. A: Selection criteria - Subjects who have received a full explanation of the purpose and content of this study, are able to consent, fully understand the study, and have volunteered voluntarily and given written consent to participate. Healthy men and women aged 35 to 65 -Persons with fasting blood glucose levels of 105 mg / dL or more and less than 130 mg / dL at the time of screening B: Exclusion criteria -People undergoing drug treatment or outpatient treatment -Persons with a serious medical history that may affect the results of the study - Subjects who had the habit of consuming yogurt or lactic acid bacteria drinks at least twice a week for the three months prior to the screening test -Those who have taken or taken medicines, quasi-drugs, health foods, or foods for specified health uses in their daily lives in the three months prior to the screening test that may affect the test results Heavy alcohol drinkers (those who drink an average of more than 60g of pure alcohol per day) -Those who have participated in other clinical trials within one month prior to obtaining consent to participate in this study, or who plan to participate in other clinical trials after obtaining consent to participate in this study. -Other individuals who are deemed inappropriate as subjects by the investigator

[0051] Thirty subjects (22 men, 8 women) were selected from 221 volunteers based on the above criteria. The subjects' ages were 52.5±8.1 years (51.9±8.7 years for men, 54.3±6.3 years for women).

[0052] (2) Preparation of the composition The raw materials (acidulant, sweetener, stabilizer, fruit juice, flavoring, lactic acid bacteria cells, and water) were mixed to obtain a composition of the present invention (a colorless, transparent grapefruit-flavored soft drink), and approximately 100 mL of the composition was bottled (hereinafter also referred to as the "test composition"). The amount of lactic acid bacteria (heat-treated Lactobacillus plantarum OLL2712 strain (accession number: FERM BP-11262) cells in the test composition was approximately 10 10 The heat treatment of the lactic acid bacteria was carried out by concentrating the bacterial cells to the above concentration, suspending them in ion-exchanged water, and heating them at 95°C for 3 minutes.

[0053] (3) Effect on inflammatory cytokines The effect of the composition of the present invention on the blood levels of inflammatory cytokines was evaluated according to the following procedure. First, the test composition was administered once daily at random for 12 weeks. Blood samples were taken at 0, 4, 8, and 12 weeks after the start of administration, and serum concentrations of the following cytokines related to glucose metabolism were measured using a Bio-Plex multiplex system. In addition, administration of the test composition was discontinued 12 weeks after the start of administration, and similar measurements were performed 4 weeks after discontinuation. Monocyte chemotactic protein-1 (MCP-1) Interleukin-6 (IL-6) Interleukin-8 (IL-8) ·Tumor necrosis factor (TNF-α) Interleukin-1β (IL-1β) Interleukin-17 (IL-17)

[0054] The measured values ​​for each inflammatory cytokine at each time point were evaluated using one-way repeated measures analysis of variance and paired t-tests with Bonferroni correction. The results are shown in Table 1. All values ​​in the table are in pg / mL. [Table 1]

[0055] As shown in Table 1, the levels of MCP-1 and IL-6 in the blood were significantly reduced after initiating ingestion of the test composition compared to before initiation. Specifically, the levels of MCP-1 in the blood were significantly reduced compared to before initiation at 4, 8, and 12 weeks after initiating ingestion of the test composition, and were also significantly reduced compared to before initiation at 4 weeks after discontinuing ingestion. Furthermore, the levels of IL-6 in the blood were significantly reduced compared to before initiation at 4 weeks after initiating ingestion of the test composition. Meanwhile, the levels of IL-8, TNF-α, IL-1β, and IL-17 in the blood did not change significantly at 4, 8, or 12 weeks after initiating ingestion. These results demonstrate that the composition of the present invention selectively reduces the levels of specific inflammatory cytokines (MCP-1 and IL-6).

[0056] In addition, all subjects were measured for blood levels of inflammatory cytokines (MCP-1 and IL-6) before starting the test composition. They were divided into two groups: those with blood levels of either inflammatory cytokine above the mean (high inflammation group, n = 19 (14 men, 5 women), mean MCP-1 concentration: 23.92 ± 7.95 pg / mL, mean IL-6 concentration: 2.83 ± 0.56 pg / mL) and those with blood levels below the mean (low inflammation group, n = 11 (8 men, 3 women), mean MCP-1 concentration: 0.02 ± 0.02 pg / mL, mean IL-6 concentration: 0.28 ± 0.18 pg / mL). Fasting plasma glucose (FPG) and insulin resistance index (HOMA-IR) were measured for each group. Many subjects in the high inflammation group had insulin resistance (HOMA-IR ≥ 2.0) before starting the test composition. The results for fasting plasma glucose (FPG) levels and insulin resistance index (HOMA-IR) are shown in Tables 2 and 3, respectively.

[0057] [Table 2]

[0058] [Table 3]

[0059] As shown in Tables 2 and 3, in both the low-inflammatory and high-inflammatory groups, blood MCP-1 and IL-6 levels tended to be maintained or decreased after ingestion of the test composition compared to baseline. In particular, in the high-inflammatory group, which is prone to developing abnormal glucose metabolism, blood MCP-1 levels were significantly reduced 8 and 12 weeks after ingestion of the test composition compared to baseline, and blood IL-6 levels were significantly reduced 8 weeks after ingestion of the test composition compared to baseline, but were reduced, albeit not significantly, by 12 weeks. These results demonstrate that the composition of the present invention selectively reduces the levels of specific inflammatory cytokines (MCP-1 and IL-6) in humans, particularly in highly inflammatory individuals prone to developing abnormal glucose metabolism. In relation to the above results, it is known that the incidence of inflammatory states increases as fasting blood glucose levels approach diabetic levels from normal, and that the progression to hyperinflammatory states accelerates as the inflammatory state worsens. Therefore, the results in Tables 2 and 3, which show that the levels of MCP-1 and IL-6 in the blood of the low-inflammation group were maintained by ingestion of the composition of the present invention, suggest that the composition of the present invention can suppress the increase in MCP-1 and IL-6 in humans with a low inflammation state, and can suppress the worsening of the inflammatory state and the resulting abnormalities in glucose metabolism.

[0060] (4) Evaluation of the effect of improving glucose metabolism Using the same method as described in (3) above, the sugar metabolism improving effect of the composition of the present invention was evaluated based on the following indexes. Fasting blood glucose (FPG) levels Blood glycated albumin (GA) levels Blood hemoglobin A1c (HbA1c) levels Blood insulin levels Insulin Resistance Index (HOMA-IR) Quantitative Insulin Sensitivity Index (QUICKI)

[0061] Specifically, the above indices were measured for each blood sample taken from the subjects at Health Science Research Institute Co., Ltd. Specifically, plasma FPG levels, serum GA levels, and whole blood HbA1c levels were measured by enzymatic methods using an automated biochemical analyzer. Serum insulin levels were measured by CLIA (chemiluminescence immunoassay) using a fully automated chemiluminescence immunoassay device. HOMA-IR and QUICKI were calculated using the following formulas: HOMA-IR = (fasting blood insulin concentration (μU / mL)) × (fasting blood glucose level (mg / dl)) / 405 QUICKI = 1 / [log(fasting blood insulin concentration (μU / mL)) + log(fasting blood glucose level (mg / dL))]

[0062] Measurements for each index at each time point were evaluated by repeated measures one-way analysis of variance and paired t-tests with Bonferroni correction. The results are shown in Table 4. [Table 4]

[0063] As shown in Table 4, fasting blood glucose levels and blood glycoalbumin levels significantly improved (decreased) 4 and 8 weeks after the start of test composition intake compared to before intake. Furthermore, HOMA-IR and QUICKI values, which are indicators of insulin resistance, significantly improved 12 weeks after the start of test composition intake compared to before intake. No significant changes were observed in blood HbA1c levels at 4, 8, or 12 weeks after the start of intake. However, multiple comparison analysis revealed a significant improvement (decreased) at 12 weeks after the start of intake compared to 4 weeks after the start of intake. Since blood HbA1c levels reflect the average blood glucose level from 1 to 2 months prior to measurement, the results of the blood HbA1c levels and the results of other indicators are not considered to be inconsistent. These results demonstrate that the composition of the present invention improves glucose metabolism in humans.

[0064] In addition, fasting plasma glucose (FPG) and insulin resistance index (HOMA-IR) were measured in each of the low- and high-inflammation groups using the same method as described in (3) above. The results for FPG and HOMA-IR are shown in Tables 5 and 6, respectively.

[0065] [Table 5]

[0066] [Table 6]

[0067] As shown in Tables 5 and 6, in both the low-inflammatory group and the high-inflammatory group, both fasting blood glucose levels and HOMA-IR values ​​tended to be maintained or decreased after ingestion of the test composition compared to before ingestion. In particular, in the high-inflammatory group, which is prone to developing abnormalities in glucose metabolism, fasting blood glucose levels improved (decreased) significantly 8 and 12 weeks after ingestion of the test composition compared to before ingestion, and HOMA-IR values ​​improved (decreased), although not significantly, 8 weeks after ingestion of the test composition compared to before ingestion, and improved (decreased) significantly 12 weeks after ingestion compared to before ingestion. These results demonstrate that the composition of the present invention maintains or improves glucose metabolism in humans, particularly in humans with a high inflammation state, which is prone to developing abnormalities in glucose metabolism.

[0068] These results demonstrate that the use of the composition of the present invention can selectively reduce specific inflammatory cytokines that cause abnormalities in glucose metabolism in humans, thereby improving glucose metabolism. [Industrial Applicability]

[0069] According to the present invention, it is possible to significantly reduce specific inflammatory cytokines that cause abnormalities in glucose metabolism in humans, thereby improving glucose metabolism.

Claims

1. A composition for improving human sugar metabolism, comprising lactic acid bacteria belonging to the genus Lactobacillus.

2. An anti-inflammatory composition for humans comprising lactic acid bacteria belonging to the genus Lactobacillus.

3. The composition according to claim 1 or 2, wherein the lactic acid bacteria are lactic acid bacteria having an activity to reduce the amount of at least one inflammatory cytokine selected from MCP-1 and IL-6 in human blood.

4. The composition according to any one of claims 1 to 3, wherein the lactic acid bacterium is Lactobacillus plantarum.

5. The composition according to any one of claims 1 to 4, wherein the lactic acid bacteria comprise killed cells of the lactic acid bacteria.

6. The composition according to any one of claims 1 to 5, wherein the lactic acid bacteria comprise heat-killed bacteria.

7. The composition according to any one of claims 1 to 6, wherein the composition is a food composition.

8. The composition according to any one of claims 1 to 6, wherein the composition is a pharmaceutical composition.

9. The composition according to any one of claims 1 to 8, wherein the lactic acid bacterium has a 16S rRNA gene that has 90% or more homology with the base sequence represented by SEQ ID NO:

1.

10. The composition according to any one of claims 1 to 9, wherein the lactic acid bacterium is Lactobacillus plantarum strain OLL2712 deposited under accession number FERM BP-11262.

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