CN119454769A - Composition for promoting gastric somatostatin secretion - Google Patents

Abstract

The problem is to provide a novel composition for promoting ghrelin secretion. The solution is to provide a composition for promoting ghrelin secretion containing bacteria belonging to Lactobacillus delbrueckii and a composition for promoting any one or more of the group consisting of promoting growth hormone secretion, inhibiting the function of brown adipose tissue, promoting gastrointestinal motility, promoting gastric acid secretion, promoting pancreatic exocrine secretion, dilating blood vessels, increasing cardiac contractility and protecting myocardial cells.

Description

Composition for promoting gastric somatostatin secretion

Technical Field

The present invention relates to a composition for promoting gastric somatostatin secretion.

Background

Gastric somatotropin is a peptide hormone secreted mainly by endocrine cells of the stomach, and has been reported to have various functions such as regulation of energy metabolism, promotion of gastric acid secretion and gastrointestinal motility, vasodilation, cardiovascular system protection, and antidiabetic effect.

Gastric somatotropin has the effect of promoting growth hormone secretion. Growth hormone and gastric somatotropin are peptide hormones, and when taken directly orally, they are decomposed by digestive enzymes, and cannot exert their effects. In addition, injection of growth hormone has various problems such as stimulant problems, safety, side effects, and the like. Therefore, a method that has high safety, can be easily ingested, and can promote endogenous secretion of growth hormone has been desired.

Patent documents 1 and 2 describe hormone secretion promoters containing skim milk or skim milk powder as an active ingredient, and the hormone mentioned in these references is referred to as a gastric somatotropin or a growth hormone. Patent document 3 describes a gastric somatostatin secretion promoter comprising whey protein hydrolysate and fermented milk protein as proteins, medium-chain fatty acid, lactophospholipid and fish oil as lipids and palatinose (registered trademark) as sugar, and patent document 4 describes an appetite-related agent comprising lactobacillus gasseri OLL2716 (FERM BP-6999) (reclassified as lactobacillus paragari (Lactobacillus paragasseri) in 2020) as an active ingredient, and describes that the appetite-related improvement is based on a gastric somatostatin secretion promoting effect. Patent document 5 describes peptides having a specific sequence of 4 to 12 amino acids in length derived from subtilisin digests of purified rice endosperm proteins, and describes that these peptides are effective in treating inappetence caused by decreased gastric somatotropin secretion.

On the other hand, lactobacillus delbrueckii (Lactobacillus delbrueckii) is 1 species of lactic acid bacteria. Patent document 6 describes a lipid metabolism improving agent containing a cell disrupted product of lactic acid bacteria as an active ingredient, wherein the average length of cells in the cell disrupted product is 0 to 70% before disruption, and examples of lactic acid bacteria include lactobacillus delbrueckii subsp bulgaricus. Patent document 7 describes fermented milk prepared using lactobacillus of lactobacillus for improving fatigue, and lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1 as lactobacillus of lactobacillus. Patent document 8 describes fermented milk for improving autonomic nerve function, which contains at least one kind of lactobacillus belonging to the genus lactobacillus selected from the group consisting of lactobacillus delbrueckii, lactobacillus delbrueckii subsp. Bulgaricus, lactobacillus grignard, lactobacillus rhamnosus and lactobacillus acidophilus and at least one kind of lactobacillus belonging to the genus lactobacillus, and describes lactobacillus delbrueckii subsp. Bulgaricus OLL1073R-1 (FERM BP-10741). Patent document 9 discloses that weight loss, disease Activity Index (DAI) decrease and intestinal lesions improvement in a mouse model of ulcerative colitis are observed by administration of a probiotic compound VSL ^#, VSL ^# comprising 8 useful bacteria including lactobacillus delbrueckii subsp bulgaricus, lactobacillus casei, lactobacillus plantarum, lactobacillus acidophilus, streptococcus thermophilus, bifidobacterium longum, bifidobacterium breve and bifidobacterium infantis. Non-patent document 1 describes that lactobacillus delbrueckii LAB4 suppresses an excessive reaction of insulin supplementation and secretion with an early increase in blood glucose level immediately after ingestion of sugar, and suppresses hypoglycemia.

Prior art literature

Patent literature

Patent document 1 Japanese patent application laid-open No. 2015-205829

Patent document 2 Japanese patent application laid-open No. 2015-205830

Patent document 3 Japanese patent publication No. 6657084 (International publication WO 2015/199192)

Patent document 4 Japanese patent No. 6813974 (Japanese patent laid-open No. 2018-8901)

Patent document 5 International publication WO2020/218450

Patent document 6 Japanese patent publication No. 5801802 (International publication WO 2011/063117)

Patent document 7 International publication WO2017/015407

Patent document 8 Japanese patent laid-open No. 2020-184906

Patent document 9 Japanese patent application laid-open No. 2021-524751

Non-patent literature

Non-patent document 1, yong Tian Shengtai Lang, daqianjia, zhi and Wu, qian Chuan Wei, cuugan Gao, also, blood glucose value in the pool, super-bin, lactic acid bacteria LAB4 and nano コ, act by super-bin and lactic acid bacteria LAB4, instron, comprehensive Medicine all-man medical treatment 20 (1) 3-12,2021.

Disclosure of Invention

Problems to be solved by the invention

The present invention aims to provide a novel composition for promoting gastric somatotropin secretion.

Solution for solving the problem

The present invention relates to the following.

<1> Use of a bacterium belonging to lactobacillus delbrueckii (Lactobacillus delbrueckii) for the manufacture of a composition for promoting the secretion of a gastric somatostatin for therapeutic or non-therapeutic use.

<2> Use of a bacterium belonging to lactobacillus delbrueckii for producing a composition for at least one selected from the group consisting of promoting growth hormone secretion, inhibiting the function of brown adipose tissue, promoting gastrointestinal motility, enhancing gastric acid secretion, enhancing pancreatic exocrine secretion, dilating blood vessels, increasing heart contractility, and protecting myocardial cells.

<3> The use according to <2>, wherein any one or more selected from the group consisting of promoting growth hormone secretion, inhibiting the function of brown adipose tissue, promoting gastrointestinal motility, causing gastric acid secretion to be enhanced, causing pancreatic exocrine secretion to be enhanced, dilating blood vessels, increasing heart contractility, and protecting myocardial cells is based on promoting gastric somatotropin secretion.

<4> The use according to any one of <1> to <3>, wherein the bacterium belonging to Lactobacillus delbrueckii is a bacterium belonging to any one of Lactobacillus delbrueckii subspecies bulgaricus (Lactobacillus delbrueckii ssp. Bulgaricus), lactobacillus delbrueckii subspecies delbrueckii (Lactobacillus delbrueckii ssp. Delbrueckii), lactobacillus delbrueckii subspecies indicus (Lactobacillus delbrueckii ssp. Indicus), lactobacillus delbrueckii subspecies lactis (Lactobacillus delbrueckii ssp. Lactis) and Lactobacillus delbrueckii subspecies Sang Ji (Lactobacillus delbrueckii ssp. Sunkii).

<5> The use according to any one of <1> to <4>, wherein the bacterium belonging to Lactobacillus delbrueckii has a 16S rRNA gene having 90% or more identity with the nucleotide sequence represented by any one of SEQ ID Nos. 1 to 5.

<6> The use according to any one of <1> to <5>, wherein the bacterium belonging to the Lactobacillus delbrueckii subsp bulgaricus is any one or more selected from the group consisting of Lactobacillus delbrueckii subsp bulgaricus 2038, lactobacillus delbrueckii subsp bulgaricus OLL1255 (accession number: NITE BP-76), lactobacillus delbrueckii subsp bulgaricus OLL1171 (accession number: NITE BP-01569), lactobacillus delbrueckii subsp bulgaricus OLL1247 (accession number: NITE BP-01814), lactobacillus delbrueckii subsp bulgaricus OLL205013 (accession number: NITE BP-02411), lactobacillus delbrueckii OLL204989 (accession number: NITE BP-02874), lactobacillus delbrueckii subsp (JCM 1012T), lactobacillus delbrueckii subsp (JCM 15610T), lactobacillus delbrueckii subsp (JCM 1248T) and Lactobacillus delbrueckii subsp Sang Ji subsp (JCM 17838T).

The use according to any one of <1> to <6>, wherein the bacterium belonging to Lactobacillus delbrueckii is a living bacterium.

The use according to any one of <1> to <7>, wherein the composition is a fermented milk free of bacteria belonging to the genus Lactobacillus paracasei.

<9> The use according to any one of <1> to <8>, wherein the bacterium belonging to Lactobacillus delbrueckii does not have a DNA composed of the sequence of SEQ ID NO. 6.

<10> Non-therapeutic use of a composition comprising a bacterium belonging to lactobacillus delbrueckii (Lactobacillus delbrueckii) for promoting the secretion of gastric somatostatin.

<11> A non-therapeutic use for any one or more selected from the group consisting of promoting growth hormone secretion, inhibiting the function of brown adipose tissue, promoting gastrointestinal motility, enhancing gastric acid secretion, enhancing pancreatic exocrine secretion, dilating blood vessels, increasing cardiac contractility, and protecting myocardial cells, which contains a composition containing a bacterium belonging to lactobacillus delbrueckii (Lactobacillus delbrueckii).

<12> The use according to <11>, wherein any one or more selected from the group consisting of promoting growth hormone secretion, inhibiting the function of brown adipose tissue, promoting gastrointestinal motility, causing gastric acid secretion to be enhanced, causing pancreatic exocrine secretion to be enhanced, dilating blood vessels, increasing heart contractility, and protecting myocardial cells is based on promoting gastric somatotropin secretion.

<13> The use according to any one of <10> -12 >, wherein the bacterium belonging to lactobacillus delbrueckii is a bacterium belonging to any one of lactobacillus delbrueckii subspecies bulgaricus (Lactobacillus delbrueckii ssp. Bulgaricus), lactobacillus delbrueckii subspecies delbrueckii (Lactobacillus delbrueckii ssp. Delbrueckii), lactobacillus delbrueckii subspecies indicus (Lactobacillus delbrueckii ssp. Indicus), lactobacillus delbrueckii subspecies lactis (Lactobacillus delbrueckii ssp. Lactis) and lactobacillus delbrueckii subspecies Sang Ji (Lactobacillus delbrueckii ssp. Sunkii).

The use according to any one of <10> to <13>, wherein the bacterium belonging to Lactobacillus delbrueckii is a 16S rRNA gene having 90% or more identity with the nucleotide sequence shown in any one of SEQ ID Nos. 1 to 5.

The use according to any one of <10> to <14>, wherein the bacterium belonging to the Lactobacillus delbrueckii subsp bulgaricus is any one or more selected from the group consisting of Lactobacillus delbrueckii subsp bulgaricus 2038, lactobacillus delbrueckii subsp bulgaricus OLL1255 (accession number: NITE BP-76), lactobacillus delbrueckii subsp bulgaricus OLL1171 (accession number: NITE BP-01569), lactobacillus delbrueckii subsp bulgaricus OLL1247 (accession number: NITE BP-01814), lactobacillus delbrueckii subsp bulgaricus OLL205013 (accession number: NITE BP-02411), lactobacillus delbrueckii OLL204989 (accession number: NITE BP-02874), lactobacillus delbrueckii subsp (JCM 1012T), lactobacillus delbrueckii subsp (JCM 15610T), lactobacillus delbrueckii subsp (JCM 1248T) and Lactobacillus delbrueckii Sang Ji subsp (JCM 17838T).

The use according to any one of <10> to <15>, wherein the bacterium belonging to Lactobacillus delbrueckii is a living bacterium.

The use according to any one of <10> to <17>, wherein the composition contains a bacterium belonging to Lactobacillus delbrueckii.

The use according to any one of <10> to <17>, wherein the composition is a fermented milk free of bacteria belonging to the genus Lactobacillus paracasei.

The use according to any one of <10> to <18>, wherein the bacterium belonging to Lactobacillus delbrueckii does not have DNA composed of the sequence of SEQ ID NO. 6.

The present invention also relates to the following.

[1] A composition for promoting gastric somatostatin secretion contains bacteria belonging to Lactobacillus delbrueckii (Lactobacillus delbrueckii).

[2] A composition for use in any one selected from the group consisting of promoting growth hormone secretion, promoting fat accumulation (inhibiting weight loss), inhibiting insulin secretion, inhibiting the function of brown adipose tissue, promoting gastrointestinal motility, promoting gastric acid secretion, promoting exocrine pancreas secretion, dilating blood vessels, increasing heart contractility, and protecting myocardial cells, which contains a bacterium belonging to Lactobacillus delbrueckii.

[3] The composition of [2], which is based on promoting gastric somatostatin secretion.

[4] The composition according to any one of [1] to [3], wherein the bacterium belonging to Lactobacillus delbrueckii is a bacterium belonging to any one of Lactobacillus delbrueckii subspecies bulgaricus (Lactobacillus delbrueckii ssp. Bulgaricus), lactobacillus delbrueckii subspecies delbrueckii (Lactobacillus delbrueckii ssp. Delbrueckii), lactobacillus delbrueckii subspecies indicus (Lactobacillus delbrueckii ssp. Indicus), lactobacillus delbrueckii subspecies lactis (Lactobacillus delbrueckii ssp. Lactis) and Lactobacillus delbrueckii subspecies Sang Ji (Lactobacillus delbrueckii ssp. Sunkii).

[5] The composition according to any one of [1] to [4], wherein the bacterium belonging to the Lactobacillus delbrueckii subsp. Bulgaricus is any one or more selected from the group consisting of Lactobacillus delbrueckii subsp. Bulgaricus 2038, lactobacillus delbrueckii subsp. Bulgaricus OLL1255 (accession number: NITE BP-76), lactobacillus delbrueckii subsp. Bulgaricus OLL1171 (accession number: NITE BP-01569), lactobacillus delbrueckii subsp. Bulgaricus OLL1247 (accession number: NITE BP-01814), lactobacillus delbrueckii subsp. Bulgaricus OLL205013 (accession number: NITE BP-02411), lactobacillus delbrueckii OLL204989 (accession number: NITE BP-02874), lactobacillus delbrueckii subsp. (JCM 1012T), lactobacillus delbrueckii subsp. Indicum (JCM 15610T), lactobacillus delbrueckii subsp (JCM 1248T) and Lactobacillus delbrueckii Sang Ji subsp (JCM 17838T).

[6] The composition according to any one of [1] to [5], wherein the bacterium belonging to Lactobacillus delbrueckii is a living bacterium.

[7] The composition according to any one of [1] to [6], which is a fermented milk free of bacteria belonging to Lactobacillus paracasei.

[8] The composition according to any one of [1] to [7], wherein the bacterium belonging to Lactobacillus delbrueckii does not have DNA composed of the sequence of SEQ ID NO. 6.

The present invention also relates to the following.

[9] A composition comprising a bacterium belonging to lactobacillus delbrueckii for use in a method of promoting the secretion of gastric somatostatin. Use of a bacterium belonging to lactobacillus delbrueckii for the manufacture of a composition for promoting the secretion of gastric somatostatin. A method or a non-therapeutic method for promoting the secretion of a gastric somatostatin, which comprises the step of administering a composition comprising a bacterium belonging to lactobacillus delbrueckii to a subject. Use or non-therapeutic use of a composition comprising a bacterium belonging to the genus lactobacillus for promoting the secretion of gastric somatostatin.

[10] A composition comprising a bacterium belonging to lactobacillus delbrueckii for use in a method selected from any one of the group consisting of promoting growth hormone secretion, promoting fat accumulation (inhibiting weight loss), inhibiting insulin secretion, inhibiting the function of brown adipose tissue, promoting gastrointestinal motility, causing gastric acid secretion to be enhanced, causing pancreatic exocrine secretion to be enhanced, dilating blood vessels, increasing cardiac contractility, and protecting myocardial cells. Use of a bacterium belonging to lactobacillus delbrueckii for the manufacture of a composition for any one selected from the group consisting of promoting growth hormone secretion, promoting fat accumulation (inhibiting weight loss), inhibiting insulin secretion, inhibiting the function of brown adipose tissue, promoting gastrointestinal motility, enhancing gastric acid secretion, enhancing pancreatic exocrine secretion, dilating blood vessels, increasing cardiac contractility, and protecting myocardial cells. A method or a non-therapeutic method for any one selected from the group consisting of promoting growth hormone secretion, promoting fat accumulation (inhibiting weight loss), inhibiting insulin secretion, inhibiting the function of brown adipose tissue, promoting gastrointestinal motility, enhancing gastric acid secretion, enhancing pancreatic exocrine secretion, dilating blood vessels, increasing cardiac contractility, and protecting myocardial cells, comprising the step of administering a composition comprising a bacterium belonging to lactobacillus delbrueckii to a subject. Use or non-therapeutic use of a composition comprising a bacterium belonging to lactobacillus delbrueckii for any of the group consisting of promoting growth hormone secretion, promoting fat accumulation (inhibiting weight loss), inhibiting insulin secretion, inhibiting the function of brown adipose tissue, promoting gastrointestinal motility, causing gastric acid secretion to be enhanced, causing pancreatic exocrine secretion to be enhanced, dilating blood vessels, increasing cardiac contractility, and protecting myocardial cells.

[11] The composition, the use in manufacture, the method or the non-therapeutic method, or the use or the non-therapeutic use according to [10], wherein any one selected from the group consisting of promoting growth hormone secretion, promoting fat accumulation (inhibiting weight loss), inhibiting insulin secretion, inhibiting the function of brown adipose tissue, promoting gastrointestinal motility, promoting gastric acid secretion, promoting pancreatic exocrine secretion, dilating blood vessels, increasing heart contractility, and protecting myocardial cells is based on promoting gastric somatotropin secretion.

[12] The composition, the use in manufacture, the method or the non-therapeutic method, or the use or the non-therapeutic use of any one of [9] to [11], wherein the bacterium belonging to Lactobacillus delbrueckii is a bacterium belonging to any one of Lactobacillus delbrueckii (Lactobacillus delbrueckii ssp. Delbrueckii), lactobacillus delbrueckii (Lactobacillus delbrueckii ssp. Indica), lactobacillus delbrueckii (Lactobacillus delbrueckii ssp. Lactis), and Lactobacillus delbrueckii Sang Ji subspecies (Lactobacillus delbrueckii ssp. Sunkii).

[13] The composition, the use in manufacture, the method or the non-therapeutic method, or the use or the non-therapeutic use according to any one of [9] to [12], wherein the bacterium belonging to the Lactobacillus delbrueckii subsp. Bulgaricus is any one selected from the group consisting of Lactobacillus delbrueckii subsp. Bulgaricus 2038, lactobacillus delbrueckii subsp. Bulgaricus OLL1255 (accession number: NITE BP-76), lactobacillus delbrueckii subsp. Bulgaricus OLL1171 (accession number: NITE BP-01569), lactobacillus delbrueckii subsp. Bulgaricus OLL1247 (accession number: NITE BP-01814), lactobacillus delbrueckii subsp. Bulgaricus OLL205013 (accession number: NITE BP-02411), lactobacillus delbrueckii OLL204989 (accession number: NITE BP-02874), lactobacillus delbrueckii subsp. Bulgaricus (JCM 1012T), lactobacillus delbrueckii subsp. Bulgaricus (JCM 15610T), lactobacillus delbrueckii subsp. Bulgaricus (JCM 1248T) and Lactobacillus delbrueckii subsp. Bulgaricus Sang Ji (JCM 17838T).

[14] The composition, use in production, method or non-therapeutic method, or use or non-therapeutic use according to any one of [9] to [13], wherein the bacterium belonging to Lactobacillus delbrueckii is a living bacterium.

[15] The composition, use in production, method or non-therapeutic method, or use or non-therapeutic use according to any one of [9] to [14], wherein the composition is a fermented milk free of bacteria belonging to Lactobacillus paracasei.

[16] The composition, the use in production, the method or the non-therapeutic method, or the use or the non-therapeutic use according to any one of [1] to [7], wherein the bacterium belonging to Lactobacillus delbrueckii does not have DNA composed of the sequence of SEQ ID NO. 6.

ADVANTAGEOUS EFFECTS OF INVENTION

According to the present invention, the secretion of the gastric somatotropin can be promoted by a highly safe component.

Drawings

FIG. 1 shows the measurement results of the mRNA expression amount of the motilin in MKN45 cells after incubation of each strain of Lactobacillus delbrueckii subsp. Bulgaricus for 4 hours or 6 hours. Mean ± SE, n=3, ^*p<0.05,^** p <0.01vs. control (based on Dunnett test)

FIG. 2 shows the results of measurement of the mRNA expression level of the chymosin using Lactobacillus delbrueckii OLL204989, lactobacillus delbrueckii subspecies JCM 1012T, lactobacillus delbrueckii subspecies JCM 15610T, lactobacillus delbrueckii subspecies JCM 1248T or Lactobacillus delbrueckii Sang Ji subspecies JCM 17838T. Mean ± SE, n=3, ^*p<0.05,^** p <0.01vs. control (based on Dunnett test)

Detailed Description

The present invention will be described in detail below.

In one embodiment, the present invention relates to a composition containing a specific bacterium. More specifically, the present invention relates to a composition for promoting the secretion of gastric somatotropin and the like, which contains a specific bacterium as an active ingredient. In the present invention, the term "arbitrary" means that the number and the kind are arbitrary.

[ Active ingredient ]

"Bacterium belonging to Lactobacillus delbrueckii"

The composition of the present invention contains a bacterium belonging to Lactobacillus delbrueckii (Lactobacillus delbrueckii (hereinafter also referred to as L.delbrueckii.) as an active ingredient. The composition is not limited to a specific subspecies as long as it is a bacterium belonging to l.delbrueckii, and can be used as an active ingredient.

The taxonomically equivalent strain of a strain (hereinafter referred to as strain S) is, for example, any of the following.

A strain which belongs to the same genus as the strain S, preferably belongs to the same species as the strain S, and which has a sequence (a V1 region, a V2 region, or all or a part of a V1 region and a V2 region, or a part comprising a V1 region and a V2 region, etc.) which is characteristic of all or a part of the 16S rRNA gene thereof, has a sequence identity of 90% or more, preferably 95% or more, more preferably 98% or more, still more preferably 98.5% or more, still more preferably more than 98.7%, still more preferably 99% or more, still more preferably 100% with the sequence of the strain S;

strains having the same bacteriological properties as strain S.

For a criterion for determining the heterogeneity of species based on the 16S rRNA gene sequence, one skilled in the art can refer to Stackebrandt E,Ebers J.Taxonomic parameters revisited:tarnished gold standards.Microbiol Today 2006;33:152-155.

(L.delbrueckii OLL204989)

As an example of a strain belonging to L.delbrueckii, OLL204989 (accession number: NITE BP-02874) and a taxonomically equivalent strain thereof are used. The International deposition (deposition date of depositors: ming's solution, budapest treaty-based International deposition date: 2019, 2 months 5) was carried out by delbrueckii OLL204989 under accession number NITE BP-02874 at the national institute of technology for evaluating articles of manufacture by independent administration patent biological depository (Fusarium graminis. Of Qian-Ye county, japan).

< Bacterium belonging to Lactobacillus delbrueckii subsp bulgaricus >

In a preferred embodiment, the bacterium belonging to l.delbrueckii in the composition of the present invention is a bacterium belonging to the subspecies bulgaricus of lactobacillus delbrueckii (hereinafter also sometimes referred to as l.delbrueckii ssp. Delbrueckii ssp. Is suitable for lactic acid bacteria of fermented milk, by using the bacterium, the fermented milk can be easily produced. The composition is not limited to a specific strain as long as it is a bacterium belonging to l.delbrueckii ssp.

As examples of strains belonging to L.delbrueckii ssp.bulgaricus, 2038, OLL1255 (accession number: NITE BP-76), OLL1171 (accession number: NITE BP-01569), OLL1247 (accession number: NITE BP-01814), OLL205013 (accession number: NITE BP-02411) and taxonomically equivalent strains of these were used.

(L.delbrueckii ssp.bulgaricus 2038)

Delbrueckii ssp.bulgaricus 2038 is isolated from the Ming's Bulgarian yogurt LB81 (Ming's Co., ltd.) and is commercially available. In addition, ming's solution (Tokyo eight Wang Zishi seven kingdoms 1-29-1 Ming's solution technology innovation center) was also stored.

Alternatively, 2038 strain can be isolated by, for example, applying a dilution of Bulgarian yogurt LB81 (manufactured by Ming et al, inc.) to an agar medium to which BCP is added and culturing at 37℃for 48 hours, and then picking up rough colonies.

The bacteriological properties of 2038 are shown below.

Form of bacillus, glucose production, GC content of 49.7%, gram positive, catalase negative, lactic acid optical rotation, D type, no growth at 15 ℃, acid formation by assimilation of glucose, lactose and the like, no spore formation and no motility.

The sequence of the 16S rRNA gene of 2038 (corresponding to positions 27 to 520 of the full length sequence of the rRNA gene) is shown in SEQ ID NO.1 of the sequence Listing.

16S rRNA Gene, lactobacillus delbrueckii subspecies bulgaricus 2038 (SEQ ID NO: 1)

gctggcggcgtgcctaatacatgcaagtcgagcgagctgaattcaaagatyccttcgggrtgatttgttggacgctagcggcggatgggtgagtaacacgtgggcaatctgccctaaagactgggataccacttggaaacaggtgctaataccggataacaacatgaatcgcatgattcaagtttgaaaggcggcgyaagctgtcactttaggatgagcccgcggcgcattagctagttggtggggtaaaggcctaccaaggcaatgatgcgtagccgagttgagagactgatcggccacattgggactgagacacggcccaaactcctacgggaggcagcagtagggaatcttccacaatggacgcaagtctgatggagcaacgccgcgtgagtgaagaaggttttcggatcgtaaagctctgttgttggtgaagaaggatagaggcagtaactggtctttatttgacggtaatcaaccagaaagtcacggctaactacgt

(L.delbrueckii ssp.bulgaricus OLL1255)

The international deposit (deposit: ming's solution, national deposit date: 2.10 in 2005, and tube transfer request receiving date based on the international deposit of Budapest treaty: 4.1 in 2009) was carried out by the institute of patent and biological deposit of independent administrative laws and human products evaluation technology (Fusarium Makino, king Kogyo, japan) under deposit number NITE BP-76 by L.delbrueckii ssp.bureau OLL1255 (deposit number: NITE BP-76).

The bacteriological properties of OLL1255 are shown below.

Form of bacillus, no gas production, gram positive, catalase negative, facultative anaerobic, no nitrate reduction, no indole generation, no hydrogen sulfide generation, lactic acid optical rotation, no growth at 15 ℃ and no spore formation and no motility.

Sugar degradability, arabinose, galactose, glucose+, salicin, sucrose, cellobiose, starch, maltose, mannitol, mannose+, lactose, raffinose, ribose-.

The sequence of the 16S rRNA gene of OLL1255 (corresponding to positions 27 to 520 of the full length sequence of the rRNA gene) is shown in SEQ ID NO. 2 of the sequence Listing.

16S rRNA Gene, lactobacillus delbrueckii subspecies bulgaricus OLL1255 (SEQ ID NO: 2)

gctggcggcgtgcctaatacatgcaagtcgagcgagctgaattcaaagatyccttcgggrtgatttgttggacgctagcggcggatgggtgagtaacacgtgggcaatctgccctaaagactgggataccacttggaaacaggtgctaataccggataacaacatgaatcgcatgattcaagtttgaaaggcggcgyaagctgtcactttaggatgagcccgcggcgcattagctagttggtggggtaaaggcctaccaaggcaatgatgcgtagccgagttgagagactgatcggccacattgggactgagacacggcccaaactcctacgggaggcagcagtagggaatcttccacaatggacgcaagtctgatggagcaacgccgcgtgagtgaagaaggttttcggatcgtaaagctctgttgttggtgaagaaggatagaggcagtaactggtctttatttgacggtaatcaaccagaaagtcacggctaactacgt

(L.delbrueckii ssp.bulgaricus OLL1171)

The International depositary (depositary: ming's solution, deposition date of International deposition based on the Budapest treaty: 2013, 3 months 13) was carried out by the national institute of technology for evaluating articles of manufacture, patent and organism depositary (Fusarium, king Kogyo, japan) under accession number NITE BP-01569, under accession number NITE BP-01569.

The sequence of the 16S rRNA gene of OLL1171 (corresponding to positions 27 to 520 of the full length sequence of the rRNA gene) is shown in SEQ ID NO. 3 of the sequence Listing.

16S rRNA Gene, lactobacillus delbrueckii subspecies bulgaricus OLL1171 (SEQ ID NO: 3)

gctggcggcgtgcctaatacatgcaagtcgagcgagctgaattcaaagatyccttcgggrtgatttgttggacgctagcggcggatgggtgagtaacacgtgggcaatctgccctaaagactgggataccacttggaaacaggtgctaataccggataacaacatgaatcgcatgattcaagtttgaaaggcggcgyaagctgtcactttaggatgagcccgcggcgcattagctagttggtggggtaaaggcctaccaaggcaatgatgcgtagccgagttgagagactgatcggccacattgggactgagacacggcccaaactcctacgggaggcagcagtagggaatcttccacaatggacgcaagtctgatggagcaacgccgcgtgagtgaagaaggttttcggatcgtaaagctctgttgttggtgaagaaggatagaggcagtaactggtctttatttgacggtaatcaaccagaaagtcacggctaactacgt

(L.delbrueckii ssp.bulgaricus OLL1247)

The International depositary (depositary: ming's solution, deposition date of International deposition based on the Budapest treaty: 2014, 3 months and 6 days) was carried out by the national institute of technology for evaluating articles of manufacture, patent and organism depositary (Fusarium, kidney, japan) under accession number NITE BP-01814.

The sequence of the 16S rRNA gene of OLL1247 (corresponding to positions 27 to 520 of the full length sequence of the rRNA gene) is shown in SEQ ID NO. 4 of the sequence Listing.

16S rRNA Gene, lactobacillus delbrueckii subspecies bulgaricus OLL1247 (SEQ ID NO: 4)

gctggcggcgtgcctaatacatgcaagtcgagcgagctgaattcaaagatyccttcgggrtgatttgttggacgctagcggcggatgggtgagtaacacgtgggcaatctgccctaaagactgggataccacttggaaacaggtgctaataccggataacaacatgaatcgcatgattcaagtttgaaaggcggcgyaagctgtcactttaggatgagcccgcggcgcattagctagttggtggggtaaaggcctaccaaggcaatgatgcgtagccgagttgagagactgatcggccacattgggactgagacacggcccaaactcctacgggaggcagcagtagggaatcttccacaatggacgcaagtctgatggagcaacgccgcgtgagtgaagaaggttttcggatcgtaaagctctgttgttggtgaagaaggatagaggcagtaactggtctttatttgacggtaatcaaccagaaagtcacggctaactacgt

(L.delbrueckii ssp.bulgaricus OLL205013)

The International depositary (depositary: ming's solution, deposition date of International deposition based on the Budapest treaty: 2017, 2 months 13) was carried out by the national institute of technology for evaluating articles of manufacture, patent and organism depositary (Fusarium, king Kogyo, japan) under accession number NITE BP-02411, L.delbrueckii ssp. Bulgarica OLL205013 (deposition number: NITE BP-02411).

The sequence of the 16S rRNA gene of OLL205013 (corresponding to positions 27 to 520 in the full-length sequence of the rRNA gene) is shown in SEQ ID NO. 5 of the sequence Listing.

16S rRNA Gene, lactobacillus delbrueckii subspecies bulgaricus OLL205013 (SEQ ID NO: 5)

gctggcggcgtgcctaatacatgcaagtcgagcgagctgaattcaaagatyccttcgggrtgatttgttggacgctagcggcggatgggtgagtaacacgtgggcaatctgccctaaagactgggataccacttggaaacaggtgctaataccggataacaacatgaatcgcatgattcaagtttgaaaggcggcgyaagctgtcactttaggatgagcccgcggcgcattagctagttggtggggtaaaggcctaccaaggcaatgatgcgtagccgagttgagagactgatcggccacattgggactgagacacggcccaaactcctacgggaggcagcagtagggaatcttccacaatggacgcaagtctgatggagcaacgccgcgtgagtgaagaaggttttcggatcgtaaagctctgttgttggtgaagaaggatagaggcagtaactggtctttatttgacggtaatcaaccagaaagtcacggctaactacgt

< Bacterium belonging to De-Lactobacillus subspecies De >

In a preferred embodiment, the bacterium belonging to L.delbrueckii in the composition of the present invention is a bacterium belonging to the De subspecies of Lactobacillus delbrueckii (Lactobacillus delbrueckii ssp. Delbrueckii (hereinafter sometimes also referred to as L.delbrueckii ssp. Delbrueckii.). In the composition, the bacterium belonging to l.delbrueckii ssp.delbrueckii is not limited to a specific strain, and various bacteria can be used as an active ingredient.

(L.delbrueckii ssp.delbrueckii JCM 1012^T)

As examples of strains belonging to L.delbrueckii ssp.delbrueckii, JCM 1012 ^T and taxonomically equivalent strains thereof can be used. Delberrueckii ssp.delberrueckii JCM 1012 ^T is available from the institute of physical and chemical independent administrative institute biological and resource center (RIKEN BRC) microbiological materials development room (Japan Collection of Microorganisms) (RIKEN BRC-JCM, japan) under JCM number JCM 1012 ^T.

< Bacterium belonging to the Indian subspecies of Lactobacillus delbrueckii >

In a preferred embodiment, the bacteria belonging to l.delbrueckii in the composition of the present invention are bacteria belonging to the subspecies india (Lactobacillus delbrueckii ssp. In the composition, the bacterium belonging to l.delbrueckii ssp.indicus is not limited to a specific strain, and various kinds of bacteria can be used as an active ingredient.

(L.delbrueckii ssp.indicus JCM 15610^T)

As an example of a strain belonging to L.delbrueckii ssp.indicus, JCM 15610 ^T and a taxonomically equivalent strain thereof are used. Delbrueckii ssp. Indicus JCM 15610 ^T is available from the institute of physical and chemical independent administration biological resource center (RIKEN BRC) microbiological materials development room (Japan Collection of Microorganisms) (RIKEN BRC-JCM, japan) under JCM code JCM 15610 ^T.

< Bacterium belonging to Lactobacillus delbrueckii subspecies lactis >

In a preferred embodiment, the bacteria belonging to l.delbrueckii in the composition of the present invention are bacteria belonging to lactobacillus delbrueckii subspecies lactis (Lactobacillus delbrueckii ssp. The composition is not limited to a specific strain as long as it is a bacterium belonging to l.delbrueckii ssp.

(L.delbrueckii ssp.lactis JCM 1248^T)

As an example of strains belonging to L.delbrueckii ssp.lactis, JCM 1248 ^T and taxonomically equivalent strains thereof are used. Delbrueckii ssp.lactis JCM 1248 ^T is available from the institute of independent administrative and physical chemistry center of biological resources (RIKEN BRC) microbiological materials development room (Japan Collection of Microorganisms) (RIKEN BRC-JCM, japan) under JCM number JCM 1248 ^T.

< Bacterium belonging to the Lactobacillus delbrueckii Sang Ji subspecies >

In a preferred embodiment, the bacterium belonging to l.delbrueckii in the composition of the present invention is a bacterium belonging to the Sang Ji subspecies lactobacillus delbrueckii (Lactobacillus delbrueckii ssp. In the composition, the bacteria belonging to L.delbrueckii ssp.sunkii are not limited to a specific strain, and various bacteria can be used as an active ingredient.

(L.delbrueckii ssp.sunkii JCM 17838^T)

As an example of a strain belonging to L.delbrueckii ssp.sunkii, JCM 17838 ^T and a taxonomically equivalent strain thereof are used. Delbrueckii ssp. Sunkii JCM 17838 ^T is available from the institute of independent administrative and physical chemistry biological resource center (RIKEN BRC) microbiological materials development room (Japan Collection of Microorganisms) (RIKEN BRC-JCM, japan) under JCM number JCM 17838 ^T.

As described above, in a preferred embodiment, the bacterium belonging to L.delbrueckii in the composition of the present invention is a bacterium belonging to any one of L.delbrueckii ssp.、L.delbrueckii ssp.bulgaricus、L.delbrueckii ssp.delbrueckii、L.delbrueckii ssp.indicus、L.delbrueckii ssp.lactis and L.delbrueckii ssp. In another embodiment, the bacterium belonging to L.delbrueckii is free of a bacterium belonging to the subspecies bulgaricus of Lactobacillus delbrueckii. In another embodiment, the bacterium belonging to L.delbrueckii in the composition of the present invention is a bacterium belonging to any one of L.delbrueckii ssp.delbrueckii, L.delbrueckii ssp.index, L.delbrueckii ssp.lactis, and L.delbrueckii ssp.sunkii.

In addition, the bacterium belonging to L.delbrueckii in the composition of the present invention may be any one or more selected from the group consisting of L.delbrueckii ssp.bulgaricu 2038, L.delbrueckii ssp.bulgaricu OLL1255 (accession number: NITE BP-76), L.delbrueckii ssp.bulgaricu OLL1171 (accession number: NITE BP-01569), L.delbrueckii ssp.bulgaricu OLL1247 (accession number: NITE BP-01814), L.delbrueckickii ssp.bulgaricu OLL205013 (accession number: NITE BP-02411), L.delbrueckicu OLL204989 (accession number: ：NITE BP-02874)、L.delbrueckii ssp.delbrueckii(JCM 1012T)、L.delbrueckii ssp.indicus(JCM 15610T)、L.delbrueckii ssp.lactis(JCM 1248T) and L.delbrueckii ssp.sun (JCM 17838T), and the composition of the present invention may be any one or more selected from the group consisting of JTE BP-01814, L.delrueckii ssp.delkui.ssp.bulicu.48 and L.delgaricu.48.

In another embodiment, the bacterium belonging to L.delbrueckii in the composition of the present invention has a 16S rRNA gene having 90% or more, preferably 95% or more, more preferably 98% or more, still more preferably 98.5% or more, still more preferably 98.7% or more, particularly preferably 99% or more, and preferably 99.5% or more identity with the base sequence represented by any one of SEQ ID NOS.1 to 5.

The composition comprising any of the above strains as an active ingredient is particularly excellent in the objective effect, and is preferable.

< DNA coding putative protein (hypothetical protein) Gene >

The present inventors have found that a DNA having a sequence described below as SEQ ID NO. 6 (DNA encoding a putative protein gene) is not included as one of the common characteristics of the strains in which the promoting effect of gastric somatotropin secretion was confirmed under the conditions of this example. The amino acid sequence of the protein (hypothetical protein) corresponding to the DNA is described in SEQ ID NO. 7 of the sequence Listing. Therefore, in a preferred embodiment, the composition may contain any bacterium belonging to lactobacillus delbrueckii and having no DNA of the following (i) as an active ingredient. In other words, in this embodiment, the bacterium belonging to lactobacillus delbrueckii contained in the composition does not contain the DNA of (i) or does not contain the strain having the DNA of (i). In another embodiment, the composition may contain any bacterium belonging to Lactobacillus delbrueckii and having no DNA of the following (ii) as an active ingredient. In another embodiment, the composition may contain any bacteria belonging to Lactobacillus delbrueckii and having no DNA of (iii) below as an active ingredient.

(I) DNA comprising the sequence of SEQ ID No. 6

(Ii) DNA comprising a sequence having at least 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or 99% or more identity with SEQ ID NO. 6

(Iii) DNA comprising sequence of 1, 1 to 2, 1 to 3, 1 to 4, 1 to 5, 1 to 6, 1 to 7, 1 to 8, 1 to 9, 1 to 10, 1 to 11, 1 to 12, 1 to 13, 1 to 14, 1 to 15, 1 to 16, 1 to 17, 1 to 18, 1 to 19, 1 to 20 or 1 to 21 bases substituted, deleted or added in SEQ ID NO. 6

In another preferred embodiment, the composition may contain any bacterium belonging to lactobacillus delbrueckii and having no protein of the following (iv) as an active ingredient. In other words, in this embodiment, the bacterium belonging to lactobacillus delbrueckii contained in the composition does not contain the protein of (iv) or does not contain the strain containing the protein of (iv). In another embodiment, the composition may contain any bacterium belonging to lactobacillus delbrueckii and having no protein of the following (v) as an active ingredient. In another embodiment, the composition may contain any bacterium belonging to lactobacillus delbrueckii and having no protein of the following (vi) as an active ingredient.

(Iv) Protein comprising sequence of SEQ ID NO. 7

(V) Protein encoded by the DNA of the above (ii)

(Vi) Protein encoded by the DNA of the above (iii)

In another embodiment, the composition may contain any bacteria that do not have a DNA encoding a protein comprising the sequence of SEQ ID NO. 7 (may contain a DNA comprising the sequence of SEQ ID NO. 6). In other words, in this embodiment, the bacterium belonging to lactobacillus delbrueckii contained in the composition does not have a DNA encoding a protein comprising the sequence of sequence No. 7 or does not contain a strain having a DNA encoding a protein comprising the sequence of sequence No. 7. In another preferred embodiment, the composition may contain any bacterium belonging to the subspecies bulgaricus of lactobacillus delbrueckii and having no DNA consisting of the sequence of sequence number 6 as an active ingredient. In another preferred embodiment, the composition may contain any bacterium belonging to the subspecies bulgaricus of lactobacillus delbrueckii and having no protein consisting of the sequence of sequence number 7 as an active ingredient.

DNA encoding hypothetical protein gene (sequence number 6)

atggttgatgagatgtaccctgaagccgagaagatcattcttgtcatagacaatcttaatacgcacaagccatcctcactatataaggctttcaaagcacgtcgaatcatcaagaagcttgagattcactatactcccaagcacggcagctggttagatatcgctgaaattgatgatgaccagacagtgtctttctcgaagaatcccggatattga

Hypothetical protein (sequence number 7)

MVDEMYPEAEKIILVIDNLNTHKPSSLYKAFKARRIIKKLEIHYTPKH GSWLDIAEIDDDQTVSFSKNPGY

The composition may contain lactic acid bacteria other than bacteria belonging to l.delbrueckii as long as the intended function is not impaired. In addition, the composition may contain microorganisms such as yeast other than the target lactic acid bacteria. Preferably, the composition comprises 1 or more lactic acid bacteria, and is free of microorganisms other than them, such as yeasts. In another preferred embodiment, the composition does not contain any one or both of lactobacillus gasseri (Lactobacillus gasseri) and lactobacillus paragrignard (Lactobacillus paragasseri). In another preferred embodiment, the composition is free of Streptococcus thermophilus (Streptococcus thermophilus). In another preferred embodiment, the composition is free of L.delbrueckii ssp.bulgaricus OLL1073R-1. In another preferred embodiment, the composition does not contain lactic acid bacteria other than bacteria belonging to the genus L. In another preferred embodiment, the composition is free of lactic acid bacteria other than bacteria belonging to the genus L. In another preferred embodiment, the composition does not contain a component that promotes the secretion of a gastric somatostatin other than a bacterium belonging to the genus L. In another preferred embodiment, the composition is free of ingredients that promote the secretion of gastric somatotropin other than bacteria belonging to the genus L.

Lactic acid bacteria (active bacteria) as active ingredients contained in the composition can be produced by culturing. The culture conditions are not particularly limited as long as the desired effect can be exhibited.

The composition of the present invention may contain the active bacteria in any form as long as the target effect can be exhibited. For example, the effective bacteria may be a culture of the effective bacteria (including the effective bacterial cells and culture supernatant) in addition to the effective bacterial cells themselves. The bacterial cells may be in a viable state (living bacterial cells) or in a dead state (dead bacterial cells) as long as the target effect can be exhibited.

The effective bacteria may be included in the composition in a dead bacteria form. Dead cells can be obtained by sterilizing the effective cells. The sterilization treatment is not particularly limited as long as the target effect can be exhibited, and heat, a germicidal lamp (UV), ozone, a chemical, high osmotic pressure, and the like can be used.

The dead bacterial cells are preferably heat-treated dead bacterial cells obtained by subjecting living bacterial cells to heat treatment. The heat treatment for obtaining the heat-treated dead cells is not particularly limited as long as the target effect can be exhibited, and may be carried out at a temperature and for a time sufficient to cause death of the effective cells used. Such conditions also depend on the effective bacteria used, but the heat treatment temperature is, for example, 55 ℃ or higher, preferably 60 ℃ or higher, more preferably 65 ℃ or higher, still more preferably 70 ℃ or higher, and may be 80 ℃ or higher, and may be 90 ℃ or higher. The upper limit of the heat treatment temperature may be suitably set, for example, 121 ℃ or lower, 100 ℃ or lower, or 90 ℃ or lower, or 80 ℃ or lower. The heating time may be 1 minute or more, 3 minutes or more, or 10 minutes or more, 15 minutes or more, 30 minutes or more, or 45 minutes or more depending on the heating temperature. The upper limit of the heat treatment time may be, for example, 120 minutes or less, 100 minutes or less, 90 minutes or less, or 80 minutes or less.

The living cells may be obtained by culturing the living cells by a known method, and may be in the form of a culture solution, or in the form of a concentrate, frozen product, or dried product of the culture solution. Alternatively, a culture medium may be subjected to centrifugation or the like to collect only cells, or a culture medium may be suspended in a buffer. Or adding (inoculating) living cells to a food material such as milk (animal milk) which is a raw material of a fermented food, thereby increasing the amount of the living cells in the composition endogenously.

The active bacteria used in the composition, whether living or dead bacteria, can be prepared in the form of a dried product, suspension, paste, gel, or the like.

[ Use ]

(Function)

In one embodiment, the composition may be used to promote gastric somatostatin secretion. Gastric somatotropin is a peptide hormone that is primarily secreted in the stomach. In addition, the compositions may also be used to aid, assist, improve or maintain gastric somatostatin secretion. In addition, the compositions may also be used to alleviate the decline in gastric auxin secretion, reduce the risk of decline in gastric auxin secretion, or help improve gastric auxin secretion.

Gastric somatotropin is known to have effects of promoting growth hormone secretion (patent documents 1 and 2), inhibiting brown adipose tissue function, promoting gastrointestinal motility, enhancing gastric acid secretion, enhancing pancreatic exocrine secretion, dilating blood vessels, increasing cardiac contractility, protecting myocardial cells, and the like (patent document 3). Accordingly, in one embodiment, the composition may be used for any one or more selected from the group consisting of promoting growth hormone secretion, inhibiting the function of brown adipose tissue, promoting gastrointestinal motility (or aiding digestion), enhancing gastric acid secretion, enhancing pancreatic exocrine secretion, dilating blood vessels, increasing cardiac contractility, and protecting myocardial cells. Or the composition may be used for regulating or helping to regulate any one or more selected from the group consisting of promoting growth hormone secretion, inhibiting the function of brown adipose tissue, promoting gastrointestinal motility, hyperacidity, vasodilation, increasing contractility of the heart, and protecting myocardial cells.

In addition, in addition to the above-described actions, gastric somatotropin is known to have the actions of promoting fat accumulation (suppressing weight loss) and suppressing insulin secretion (patent document 3). Accordingly, in one embodiment, the composition may be used for any one or more selected from the group consisting of promoting growth hormone secretion, promoting fat accumulation (suppressing weight loss), suppressing insulin secretion, suppressing the function of brown adipose tissue, promoting gastrointestinal motility (or aiding digestion), causing gastric acid secretion to be enhanced, causing pancreatic exocrine secretion to be enhanced, dilating blood vessels, increasing cardiac contractility, and protecting myocardial cells. Or the composition can be used for regulating or helping to regulate any one or more selected from the group consisting of promoting growth hormone secretion, promoting fat accumulation (inhibiting weight loss), inhibiting insulin secretion, inhibiting the function of brown adipose tissue, promoting gastrointestinal motility, causing gastric acid secretion to be enhanced, causing pancreatic exocrine secretion to be enhanced, dilating blood vessels, increasing cardiac contractility, and protecting myocardial cells.

In addition, the composition of the present invention can be used for regulating autonomic nerves, suppressing sympathetic nerves, improving cold symptoms, improving stiffness, improving gastrointestinal discomfort, improving depression exacerbation, improving dizziness exacerbation, improving heart rate acceleration, improving blood pressure elevation, improving chronic pain exacerbation, improving fatigue, improving general listlessness, improving subjective stress, improving daytime sleepiness, improving dysphoria, improving anorexia, improving thought decline, improving dry mouth, improving loss of refreshing feeling, promoting fat accumulation (suppressing weight loss), suppressing weight loss associated with ulcerative colitis, suppressing insulin secretion, and suppressing excessive insulin secretion after sugar intake.

Whether a component promotes the secretion of gastric somatotropin can be confirmed by one skilled in the art by various methods. For example, the component may be added to human stomach-derived cells such as MKN45 cells (human stomach-derived cell line), and the amount of the chyme gene expressed in the cells may be measured after an appropriate time period to evaluate the amount. The expression level of the gastric somatostatin gene can be specifically measured as the expression level of mRNA. Correction is preferably performed by using the expression level of a constitutively expressed gene, for example, beta actin (beta-actin).

(Object)

In one embodiment, the composition is suitable for ingestion by a subject in need or desiring to promote gastric somatostatin secretion. In one embodiment, the composition is suitable for ingestion by a subject having reduced gastric somatotropin secretion. In one embodiment, the composition is suitable for ingestion by a subject in need or desirous of any 1 or more selected from the group consisting of promoting growth hormone secretion, promoting fat accumulation (inhibiting weight loss), inhibiting insulin secretion, inhibiting the function of brown adipose tissue, promoting gastrointestinal motility, enhancing gastric acid secretion, enhancing pancreatic exocrine secretion, dilating blood vessels, increasing cardiac contractility, and protecting myocardial cells. The judgment of the above-mentioned diseases or conditions of the subject also includes judgment of doctors, guardians, pharmacists, etc., output results of lifestyle habits and eating habits and subjective symptom questionnaires, self judgment based on subjective symptoms, etc. The subject may be healthy (e.g., stomach healthy, without a disease to be treated, without a therapeutic drug, such as a donor of a chemotherapeutic agent). In addition, patients suffering from autonomic dysfunction, those suffering from cold, those suffering from stiffness, those suffering from depression, those suffering from dizziness, those suffering from loss of appetite and weight in summer symptoms, and those suffering from ulcerative colitis can be excluded from subjects taking the composition of the present invention.

Such subjects include adults (age 15 or older), middle-aged and elderly (age 65 or older (defined by World Health Organization (WHO)), ill and ill subjects, pregnant women, parturients, infants, and children. The composition of the present invention is suitable for long-term intake because the active ingredient is a bacterium having a high experience of use, and is therefore particularly suitable for subjects desiring to promote the secretion of gastric somatotropin in daily life.

[ Composition ]

(Food composition, etc.)

The composition of the present invention may be formulated as a food composition or a pharmaceutical composition. Food and pharmaceutical products include, unless specifically stated otherwise, those intended for use not only in humans but also in animals other than humans. The foods include, unless otherwise specified, conventional foods, functional foods, nutritional compositions, and therapeutic foods (foods for therapeutic purposes, foods prepared by doctors, diets prepared by dieticians, and the like based on the menu, dietetic foods, formulas, nursing foods, and auxiliary foods for therapeutic purposes. Food products include, unless specifically stated otherwise, not only solid products but also liquid products such as beverages, drinkers, liquid foods and soups. The functional food means a food capable of imparting a predetermined functionality to a living body, and includes, for example, all health foods such as a specific health food (special health food including additional conditions), a functional labeling food, a health functional food including a nutritional functional food, a special purpose food, a nutritional supplementary food, a health supplementary food, a supplement (e.g., a food in various dosage forms such as a tablet, a coated tablet, a sugar-coated tablet, a capsule, a liquid agent, etc.), a beauty food (e.g., a weight-reducing food), and the like. In addition, the "functional food" in the present invention includes health foods to which the health statement (HEALTH CLAIM) of food standards of the food act committee (FAO/WHO joint food standards committee) is applied.

The following are excluded from the composition of the invention:

A preparation containing a protein hydrolysate as a protein and a fermented milk protein, a medium-chain fatty acid as a lipid, and a sugar, and the fermented milk protein is derived from a fermented milk formed by fermenting skim milk using lactobacillus bulgaricus (Lactobacillus Bulgaricus), streptococcus thermophilus, or a combination thereof;

Compositions comprising Lactobacillus casei, lactobacillus plantarum, lactobacillus acidophilus, lactobacillus delbrueckii subsp. Bulgaricus, streptococcus thermophilus, bifidobacterium longum, bifidobacterium breve, and Bifidobacterium infantis.

(Route of administration)

The composition of the present invention may be administered parenterally, for example via a tube (gastric fistula, intestinal fistula), nasally, orally, preferably orally.

(Content and amount of active ingredient)

The content of the effective bacteria in the composition of the present invention is only required to be an amount that exerts the desired effect. The content of the effective bacteria in the composition can be appropriately set in consideration of various factors such as age, weight, and symptoms of the subject to be ingested and administered. One unit of the composition may be an amount to be taken and administered for 1 day or 1 time (may be taken and administered once a day, or may be administered several times a day, for example, 3 times).

In one embodiment, the content of the effective bacteria in each unit of the composition may be, for example, 1×10 ⁵ or more, 1×10 ⁶ or more, 1×10 ⁷ or more, 1×10 ⁸ or more, and, more than 5×10 ⁸, more than 5.7× 10 ⁸, more than 6×10 ⁸, more than 7×10 ⁸, 8×10 ⁸ or more, 9×10 ⁸ or more, 1×10 ⁹ or more, 5×10 ⁹ or more, preferably 1×10 ¹⁰ or more, more preferably 1×10 ¹¹ or more, and even more preferably 2×10 ¹¹ or more. the upper limit may be appropriately set, and the lower limit may be set to 1×10 ¹⁴ or less, 1×10 ¹³ or less, or 1×10 ¹² or less, for example, in any case.

In one embodiment, the intake of the active bacteria may be 1×10 ⁵/day or more, 1×10 ⁶/day or more, 1×10 ⁷/day or more, 1×10 ⁸/day or more, and, More than 5×10 ⁸/day, more than 5.7×10 ⁸/day, more than 6×10 ⁸/day, more than 7×10 ⁸/day, 8X 10 ⁸/day or more, 9X 10 ⁸/day or more, 1X 10 ⁹/day or more, and, 5X 10 ⁹ pieces/day or more, preferably 1X 10 ¹⁰ pieces/day or more, more preferably 1.3X 10 ¹⁰ pieces/day or more, still more preferably 2X 10 ¹⁰ pieces/day or more, 1X 10 ¹¹ pieces/day or more and 2X 10 ¹¹ pieces/day or more. The upper limit may be appropriately set, and the lower limit may be set to, for example, 1×10 ¹⁴ pieces/day or less, 1×10 ¹³ pieces/day or less, or 1×10 ¹² pieces/day or less in any case.

In the case of commercially available yogurt, 1×10 ⁷/g or more of l.delbrueckii ssp.bulgarisu is contained, and 1×10 ⁹ or more of l.delbrueckii ssp.bulgarisu is contained per 1 product as a result of calculation.

In addition, when the content of the effective bacteria is set to the above, 1 unit may be set to, for example, 0.5g or more, or may be set to 1g or more, 5g or more, 10g or more, 20g or more, or 30g or more, in any case. When the composition is in the form of a food such as fermented milk, 1 unit may be an amount that is easy to be taken 1 time, for example, 50g or more, 60g or more, 70g or more, 80g or more, 90g or more, or 100g or more, as the food. The upper limit may be set to be appropriately, and the lower limit may be set to be 500g or less in any case, and may be set to be 400g or less, 300g or less, 200g or less, 150g or less, 125g or less.

The composition contains effective bacteria with abundant edible experience as effective components. Thus, the composition of the present invention can be repeatedly or chronically ingested, and for example, can be continuously administered/ingested for 3 days or more, preferably 1 week or more, more preferably 15 days or more, still more preferably 3 weeks or more, 4 weeks or more, and 1 month or more.

(Other ingredients, additives)

The composition of the present invention may contain other active ingredients, nutritional ingredients, which are allowed as food or pharmaceutical products. Examples of such ingredients are amino acids (e.g., lysine, arginine, glycine, alanine, glutamic acid, leucine, isoleucine, valine), sugars (glucose, sucrose, fructose, maltose, trehalose, erythritol, maltitol, palatinose, xylitol, dextrin), electrolytes (e.g., sodium, potassium, calcium, magnesium), vitamins (e.g., vitamin a, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, biotin, folic acid, pantothenic acid, and nicotinic acids), minerals (e.g., copper, zinc, iron, cobalt, manganese), antibiotics, dietary fibers, proteins, lipids, and the like.

In addition, the composition may further comprise additives that are allowed as food or pharmaceutical. Examples of such additives are inactive carriers (solid carriers, liquid carriers), excipients, surfactants, binders, disintegrants, lubricants, co-solvents, suspending agents, coating agents, colorants, preserving agents, buffers, pH adjusters, emulsifiers, stabilizers, sweeteners, antioxidants, fragrances, sour agents, natural substances. More specifically, water, other aqueous solvents, pharmaceutically acceptable organic solvents, collagen, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, sodium alginate, water-soluble dextran, water-soluble dextrin, sodium carboxymethyl starch, pectin, xanthan gum, acacia, casein, gelatin, agar, glycerin, propylene glycol, polyethylene glycol, vaseline, paraffin, stearyl alcohol, stearic acid, human serum albumin, mannitol, sorbitol, lactose, sucralose, stevioside, aspartame, acesulfame potassium, citric acid, lactic acid, malic acid, tartaric acid, phosphoric acid, acetic acid, fruit juice, vegetable juice, and the like.

(Dosage form, morphology)

The food composition of the present invention may be in any form such as solid, liquid, mixture, suspension, powder, granule, paste, jelly, gel, capsule, etc. The food composition of the present invention may be formulated into any form such as dairy products, supplements, snack foods, beverages, supplements, seasonings, processed foods, side dishes, and soups. More specifically, the composition of the present invention may be formulated into fermented milk, lactobacillus beverage, milk beverage, refreshing beverage, ice cream, tablet, cheese, bread, biscuit (biscuits), cracker (cracker), pizza, formula milk powder, liquid diet, food for patients, nutritional food, frozen food, processed food, etc., or may be formulated into granule, powder, paste, thick liquid, etc. for ingestion by mixing with beverage or food. The fermented milk refers to fermented milk and a lactic acid bacteria beverage defined in "province (hereinafter, simply referred to as" province for milk or the like ")" concerning constituent standards of milk and dairy products and the like. The fermented milk in the province of milk and the like means a milk obtained by fermenting milk or milk containing a fat-free milk solid component equal to or more than that of lactobacillus or yeast to form a paste or liquid or freezing the same.

The pharmaceutical composition of the present invention can be formulated into any form suitable for oral administration, such as solid preparations, such as tablets, granules, powders, pills, capsules, liquid preparations, such as liquid, suspension, syrup, and the like, and gels, aerosols, and the like.

(Others)

In the production of the composition of the present invention, the stage of compounding the effective bacteria can be appropriately selected. The stage of the compounding is not particularly limited as long as the properties of the effective bacteria are not significantly impaired. For example, the composition can be produced by mixing milk, a dairy product, and water, homogenizing as needed, sterilizing, inoculating with an effective bacterium, and fermenting, thereby producing the composition in the form of fermented milk containing a sufficient amount of the effective bacterium. The milk and dairy products used as raw materials may be appropriately selected according to the effective bacteria used in fermentation. In a preferred embodiment, the milk and dairy products used as raw materials include animal-derived milk and dairy products. In addition, the milk and dairy products as raw materials may be free of vegetable milk, such as soymilk, almond milk, oat milk, coconut milk, rice milk, and hemp milk.

The composition may indicate the purpose of use (use), and may additionally indicate what is recommended for ingestion by a particular subject. The specific object may be, for example, an object described in the above item (object). The labeling may be performed directly or indirectly, and examples of the direct labeling include a record on a physical object such as a product itself, a package, a container, a label (label), or a Tag (Tag), and examples of the indirect labeling include a place or means-based advertisement/publicity activity such as a notice by an application in AI diagnosis, a web page, a store, a brochure, an exhibition, a seminar such as a media seminar, a book, a newspaper, a magazine, a television, a radio, a mail, an email, or an audio.

Examples of the uses and functions indicated in the food composition include promoting the secretion of gastric somatostatin, treating diseases or conditions which can be improved by promoting the secretion of gastric somatostatin, for example, promoting the secretion of growth hormone, promoting fat accumulation (inhibiting weight loss), inhibiting insulin secretion, inhibiting the function of brown adipose tissue, promoting the movement of the digestive tract, promoting gastric acid secretion, promoting pancreatic exocrine secretion, dilating blood vessels, increasing the contractility of the heart, protecting myocardial cells, and regulating, assisting and maintaining these, and being useful as probiotics.

In one embodiment, the indication of ingestion of the composition is recommended for the individual. Such labeling may be performed using a file issued to the object (either written or electronic), a tablet terminal of the object, a smart phone and a personal computer, SNS of the object, or the like. Such labeling may be performed together with display of the results of any examination/analysis such as blood examination and blood metabolome examination of the subject.

In one embodiment, a method for promoting the secretion of a gastric somatostatin in a subject is provided, which comprises the step of allowing the subject to ingest a composition containing a bacterium belonging to Lactobacillus delbrueckii based on the amount of the gastric somatostatin in the blood of the subject (blood concentration of the gastric somatostatin). In another embodiment, there is provided a method for promoting fat accumulation (inhibiting weight loss), a method for inhibiting insulin secretion, a method for inhibiting the function of brown adipose tissue, a method for promoting gastrointestinal motility, a method for enhancing gastric acid secretion, a method for enhancing pancreatic exocrine secretion, a method for dilating blood vessels, a method for increasing cardiac contractility, or a method for protecting myocardial cells in a subject, comprising the step of causing the subject to ingest a composition containing a bacterium belonging to Lactobacillus delbrueckii based on the amount of motilin in the blood of the subject (blood concentration of motilin). In still another embodiment, a method for providing a composition intake recommendation to a subject, a method for supporting a dietary life of a subject, or a method for supporting health of a subject, includes the step of providing a recommendation to intake a composition containing a bacterium belonging to Lactobacillus delbrueckii based on an amount of a motilin in blood of a subject (blood concentration of motilin).

In these methods, the blood of the subject is preferably collected on an empty stomach. The blood may be separated plasma. In addition, in these methods, the amount of the gastric somatostatin may be an amount of either or both of sialylated gastric somatostatin (active form) and non-sialylated gastric somatostatin. The amount of the gastric somatostatin can be measured by quantifying the amount of the gastric somatostatin in blood, performing a metabolome analysis in blood, and the like. The quantification of the gastric somatostatin can be performed by any method known to those skilled in the art, such as ELISA, HPLC, and the like. Further, the subject in these methods may be, for example, a subject whose blood concentration of gastric somatotropin is 5pg/mL or less in the fasting state.

These methods may further include, for example, the following steps:

The method comprises the steps of collecting blood from a subject, measuring the amount of a gastric somatostatin in the blood, displaying the measurement result, judging whether the subject desires or needs to promote the secretion of the gastric somatostatin based on the measurement result, displaying the judgment result, and marking a product as a composition containing a bacterium belonging to Lactobacillus delbrueckii.

Examples

EXAMPLE 1 investigation of the promoting effect of gastric somatostatin secretion by Lactobacillus delbrueckii subspecies bulgaricus

MKN45 cells were cultured on 24-well plates in RPMI-1640 medium without antibiotics for 24 hours.

The strain of lactobacillus delbrueckii subspecies bulgaricus shown in table 1 below was subjected to activation culture and main culture with MRS medium for 20 hours.

After the cultured cells were washed with PBS, they were suspended in a medium such that OD ₆₆₀ =0.5, and viable cells were added to the plates. After 4 hours and 6 hours incubation, the cells were washed 3 times with PBS, 200. Mu.L of reagent T/E solution of Maxwell RSC SIMPLYRNA CELLS KIT (Promega) and 200. Mu.L of Lysis Buffer were added, and the cells were recovered. Then, RNA extraction and cDNA conversion were performed, and the amount of the gastric auxin gene expression was measured by qPCR (SYBR Green-based intercalator method). The beta actin (beta-actin) was used for normalization and analysis by the delta-delta Ct method as a comparative quantification method.

[ Table 1]

Strains used and culture conditions

The additive can be separated from the Bulgarian yogurt LB81 (Ming's Co., ltd.).

The results are shown in FIG. 1. The amounts of the gastric auxin mRNA expressed in 2038 and OLL205013 groups were significantly increased after 4 hours compared to the control group to which no viable bacteria were added, and after 6 hours, significant increases were confirmed in P230250 group, OLL1255 group, OLL1171 group and OLL1247 group.

EXAMPLE 2 investigation of the promoting effect of gastric somatostatin secretion by various bacteria belonging to Lactobacillus delbrueckii

The gastric somatomedin secretion ability was investigated by the same method as in example 1 using the strains of lactobacillus delbrueckii, lactobacillus delbrueckii subspecies, or lactobacillus delbrueckii subspecies Sang Ji shown in table 2 below.

[ Table 2]

The species of the grass is not limited to OLL 204989.

The results are shown in FIG. 2. The amount of the gastric auxin mRNA expressed was significantly increased in all groups after 4 hours compared to the control group to which no viable bacteria had been added, and was confirmed to be significantly increased in all groups except the OLL204989 group after 6 hours.

As described above, the strain belonging to L.delbrueckii promotes the expression of the gastric somatostatin gene, and thus, it can be said that the strain belonging to L.delbrueckii can be used to promote the secretion of gastric somatostatin. Further, the gastric somatotropin has known actions of promoting growth hormone secretion (patent documents 1 and 2), promoting fat accumulation (weight loss), inhibiting insulin secretion, inhibiting the function of brown adipose tissue, promoting gastrointestinal motility, enhancing gastric acid secretion, enhancing pancreatic exocrine secretion, dilating blood vessels, increasing cardiac contractility, protecting myocardial cells, and the like (patent document 3). Therefore, it can be said that a bacterium belonging to l.delbrueckii can be used for any 1 or more selected from the group consisting of promoting growth hormone secretion, promoting fat accumulation (suppressing weight loss), suppressing insulin secretion, suppressing the function of brown adipose tissue, promoting gastrointestinal motility, causing gastric acid secretion to be enhanced, causing pancreatic exocrine secretion to be enhanced, dilating blood vessels, increasing cardiac contractility, and protecting myocardial cells.

Industrial applicability

The present invention can provide a material derived from a food ingredient or confirmed to be safe as a gastric somatostatin secretion promoter, which can help an unhealthy person to maintain and improve health and improve work efficiency. Further, according to the present invention, a food composition and a method for producing a food, which are useful for promoting the secretion of a gastric somatostatin or for maintaining and improving health of a non-ill person and improving work efficiency, can be provided.

Claims (19)

1. Use of a bacterium belonging to lactobacillus delbrueckii (Lactobacillus delbrueckii) for the manufacture of a composition for promoting the secretion of gastric somatostatin.

2. Use of a bacterium belonging to lactobacillus delbrueckii for producing a composition for at least one selected from the group consisting of promoting growth hormone secretion, inhibiting the function of brown adipose tissue, promoting gastrointestinal motility, enhancing gastric acid secretion, enhancing pancreatic exocrine secretion, dilating blood vessels, increasing cardiac contractility, and protecting myocardial cells.

3. The use according to claim 2, wherein any one or more selected from the group consisting of promoting growth hormone secretion, inhibiting the function of brown adipose tissue, promoting gastrointestinal motility, hyperacidity of pancreas, vasodilation, increasing heart contractility, and protecting myocardial cells is based on promoting gastric somatotropin secretion.

4. The use according to any one of claims 1 to 3, wherein the bacterium belonging to lactobacillus delbrueckii is a bacterium belonging to any one of lactobacillus delbrueckii subspecies bulgaricus (Lactobacillus delbrueckii ssp. Bulgaricus), lactobacillus delbrueckii subspecies delbrueckii (Lactobacillus delbrueckii ssp. Delbrueckii), lactobacillus delbrueckii subspecies indicus (Lactobacillus delbrueckii ssp. Indicus), lactobacillus delbrueckii subspecies lactis (Lactobacillus delbrueckii ssp. Lactis) and lactobacillus delbrueckii subspecies Sang Ji (Lactobacillus delbrueckii ssp. Sunkii).

5. The use according to any one of claims 1 to 3, wherein the bacterium belonging to Lactobacillus delbrueckii has a 16S rRNA gene having 90% or more identity with the nucleotide sequence shown in any one of SEQ ID Nos. 1 to 5.

6. The use according to any one of claims 1 to 3, wherein the bacterium belonging to the Lactobacillus delbrueckii subsp bulgaricus is any one or more selected from the group consisting of Lactobacillus delbrueckii subsp bulgaricus 2038, lactobacillus delbrueckii subsp bulgaricus OLL1255 (accession number: NITE BP-76), lactobacillus delbrueckii subsp bulgaricus OLL1171 (accession number: NITE BP-01569), lactobacillus delbrueckii subsp bulgaricus OLL1247 (accession number: NITE BP-01814), lactobacillus delbrueckii subsp bulgaricus OLL205013 (accession number: NITE BP-02411), lactobacillus delbrueckii OLL204989 (accession number: NITE BP-02874), lactobacillus delbrueckii subsp (JCM 1012T), lactobacillus delbrueckii subsp indica (JCM 15610T), lactobacillus delbrueckii subsp (JCM 1248T) and Lactobacillus delbrueckii subsp Sang Ji (JCM 17838T).

7. The use according to any one of claims 1 to 3, wherein the bacterium belonging to lactobacillus delbrueckii is a living bacterium.

8. The use according to any one of claims 1 to 3, wherein the composition is a fermented milk free of bacteria belonging to the genus lactobacillus.

9. The use according to any one of claims 1 to 3, wherein the bacterium belonging to Lactobacillus delbrueckii does not have DNA composed of the sequence of SEQ ID NO. 6.

10. Non-therapeutic use of a bacterium belonging to lactobacillus delbrueckii (Lactobacillus delbrueckii) for promoting the secretion of gastric somatostatin.

11. A non-therapeutic use of a bacterium belonging to Lactobacillus delbrueckii (Lactobacillus delbrueckii) for at least one member selected from the group consisting of promoting growth hormone secretion, inhibiting the function of brown adipose tissue, promoting gastrointestinal motility, promoting gastric acid secretion, promoting exocrine pancreatic secretion, dilating blood vessels, increasing cardiac contractility, and protecting myocardial cells.

12. The use according to claim 11, wherein any one or more selected from the group consisting of promoting growth hormone secretion, inhibiting the function of brown adipose tissue, promoting gastrointestinal motility, hyperacidity of pancreas, vasodilation, increasing contractility of the heart, and protecting myocardial cells is based on promoting gastric somatotropin secretion.

13. Use according to any one of claims 10-12, wherein the bacterium belonging to lactobacillus delbrueckii is a bacterium belonging to any one of lactobacillus delbrueckii subspecies bulgaricus (Lactobacillus delbrueckii ssp. Bulgaricus), lactobacillus delbrueckii subspecies delbrueckii (Lactobacillus delbrueckii ssp. Delbrueckii), lactobacillus delbrueckii subspecies indicus (Lactobacillus delbrueckii ssp. Indicus), lactobacillus delbrueckii subspecies lactis (Lactobacillus delbrueckii ssp. Lactis) and lactobacillus delbrueckii subspecies Sang Ji (Lactobacillus delbrueckii ssp. Sunkii).

14. The use according to any one of claims 10 to 12, wherein the bacterium belonging to lactobacillus delbrueckii is a 16S rRNA gene having 90% or more identity with the base sequence represented by any one of sequence numbers 1 to 5.

15. The use according to any one of claims 10 to 12, wherein the bacterium belonging to the subspecies bulgaricus is any one or more selected from the group consisting of subspecies bulgaricus 2038, subspecies bulgaricus OLL1255 (accession number: NITE BP-76), subspecies bulgaricus OLL1171 (accession number: NITE BP-01569), subspecies bulgaricus OLL1247 (accession number: NITE BP-01814), subspecies bulgaricus OLL205013 (accession number: NITE BP-02411), subspecies bulgaricus OLL204989 (accession number: NITE BP-02874), subspecies delbrueckii (JCM 1012T), subspecies lactobacillus delbrueckii (JCM 15610T), subspecies lactobacillus delbrueckii (JCM 1248T) and subspecies delbrueckii Sang Ji (JCM 17838T).

16. The use according to any one of claims 10 to 12, wherein the bacteria belonging to lactobacillus delbrueckii are living bacteria.

17. The use according to any one of claims 10 to 12, wherein the composition comprises a bacterium belonging to lactobacillus delbrueckii.

18. Use according to claim 17, wherein the composition is a fermented milk free of bacteria belonging to the genus lactobacillus paracasei.

19. The use according to any one of claims 10 to 12, wherein the bacterium belonging to lactobacillus delbrueckii does not have a DNA consisting of the sequence of sequence No. 6.