Composition for reducing advanced glycation end products

Abstract

The purpose of the present invention is to provide a novel probiotic that is not readily affected by stomach acids or bile acids and can reduce the amounts of multiple types of advanced glycation end products (AGEs) and / or dimethylarginine metabolites. Provided is a composition that includes Heyndrickxia bacteria and is to be used to reduce AGEs and / or dimethylarginine metabolites.

Description

Composition for reducing advanced glycation end products

[0001] The present invention relates to a composition for reducing advanced glycation end products and / or dimethylarginine metabolites. More particularly, the present invention relates to a composition for reducing advanced glycation end products and / or dimethylarginine metabolites, comprising a bacterium of the genus Heyndrickxia, preferably Heyndrickxia coagulans (synonyms: Bacillus coagulans, Weizmannia coagulans).

[0002] Advanced glycation end products (AGEs) are substances formed as a result of the Maillard reaction (a non-enzymatic glycation reaction of proteins) between amino acid groups, such as lysine residues in proteins, and reducing sugars, which occurs without the action of enzymes; they are irreversible reaction products. Some guanidino compounds are known to function as precursors of AGEs and are sometimes considered to be compounds related to AGE production in the broad sense. Once produced in the body or taken into the body, these advanced glycation end products (AGEs) (hereinafter, including compounds related to AGE production in the broad sense) accumulate in tissues and cause abnormal changes in tissue structure and function. Therefore, they are thought to be one of the causes of diabetic complications such as diabetic retinopathy, diabetic neuropathy, diabetic cataracts, and diabetic nephropathy, as well as diabetes, chronic kidney disease, heart disease, vascular disease, glycation, aging, and other conditions. In recent years, it has been pointed out that a Western-style diet and the intake of processed foods increase the amount of advanced glycation end products in the body, raising the risk of various chronic diseases. Coupled with the growing health consciousness, this has become one of the substances attracting attention today.

[0003] Dimethylarginine metabolites (asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA)) are metabolites liberated during protein degradation following enzymatic methylation of arginine residues in proteins. Both are constitutively produced in the body. ADMA is known to cause vascular endothelial dysfunction by inhibiting nitric oxide (NO) synthesis. Furthermore, because SDMA is primarily excreted by the kidney, its blood concentration increases with declining renal function. Therefore, ADMA and SDMA are considered to be clinically significant as risk indicators for cardiovascular disease and renal function markers, respectively. In recent years, the accumulation of these dimethylarginine metabolites has been reported to be involved in pathologies such as chronic inflammation, oxidative stress, and endothelial dysfunction. These metabolites, along with AGEs, are attracting increasing attention from the perspective of preventing and slowing the progression of chronic diseases.

[0004] Probiotics are live microorganisms that have beneficial effects on the host when ingested in sufficient amounts, and their supplementation can promote the health of the intestinal flora. To date, lactic acid bacteria such as Lactococcus lactis KF140, Lactobacillus paracasei TCI708, Lactobacillus paracasei KF00816, and Lactobacillus pentosus KF8, and Bacillus subtilis KF11 have been reported. It has been reported that the ingestion / administration of ketamine (KF11) or the like can reduce Nε-(carboxymethyl)lysine (CML), which is one of the advanced glycation end products (Patent Documents 1 to 3).

[0005] However, some probiotics are easily destroyed by gastric acid or bile acid, making it difficult to continuously deliver sufficient amounts of live bacteria to the intestines through oral ingestion or administration. Furthermore, no probiotics are known that can reduce the amounts of multiple types of advanced glycation end products and / or dimethylarginine metabolites.

[0006] Therefore, there has been a strong demand in this field for new probiotics that are less susceptible to the effects of gastric acid and bile acid and that are capable of reducing the amounts of multiple types of advanced glycation end products and / or reducing the amount of dimethylarginine metabolites.

[0007] Hindrixia coagulans SANK70258 (synonyms: Bacillus coagulans SANK70258, Weizmannia coagulans SANK70258) is a spore-forming lactic acid bacterium with high lactic acid production ability that was isolated from green malt in 1949. A food preparation containing Hindrixia coagulans SANK70258 (trade name: Lacris) has been on the market for over 50 years since 1966.

[0008] Special table 2020-515296 publication Special table 2022-528040 publication CN112239732 publication

[0009] A main object of the present invention is to provide a new probiotic that is less susceptible to the effects of gastric acid and bile acid and that is capable of reducing the amounts of multiple types of advanced glycation end products and / or reducing the amount of dimethylarginine metabolites.

[0010] As a result of intensive research to solve the above-mentioned problems, the present inventors have found that Hindrixia coagulans, a spore-forming probiotic, is less susceptible to the effects of gastric acid and bile acid, and that oral ingestion / administration of the probiotic can reduce the amounts of multiple types of advanced glycation end products and / or reduce the amount of dimethylarginine metabolites.

[0011] The present invention is based on these novel findings and includes the following: [1] A composition for use in reducing advanced glycation end products, comprising a bacterium of the genus Heyndrickxia. [2] The composition of [1], wherein the bacterium of the genus Heyndrickxia is Heyndrickxia coagulans. [3] The composition of [1] or [2], wherein the advanced glycation end products comprise one or more selected from the group consisting of Nε-(carboxymethyl)lysine, Nω-carboxymethylarginine, and pyrraline. [4] Any of the compositions of [1] to [3], wherein the daily dosage of the Hindrixia coagulans is 1 to 2 billion cfu (colony formation units) in terms of viable cell count. [5] The composition according to any one of [1] to [4], wherein the Hindrixia coagulans is SANK70258 strain, P-22 strain, lilac-01 strain, SIM-7 DSM14043 strain, C101 strain, NBRC12583 strain, GBI-1 strain, GBI-20 strain, GBI-30 strain, GBI-40 strain, or a mutant strain derived from these strains.

[0012] [6] A composition for use in reducing advanced glycation end products and dimethylarginine metabolites, comprising a bacterium of the genus Heyndrixia. [7] The composition of [6], wherein the advanced glycation end products comprise one or more selected from the group consisting of Nε-(carboxymethyl)lysine, Nω-carboxymethylarginine, and pyrraline. [8] The composition of [6] or [7], wherein the dimethylarginine metabolites comprise one or more selected from the group consisting of symmetric dimethylarginine (hereinafter SDMA) and asymmetric dimethylarginine (hereinafter ADMA). [9] The composition of any of [6] to [8], wherein the bacterium of the genus Heyndrixia is Heyndrixia coagulans.

[10] The composition of any of [6] to [9], wherein the daily dose of Heyndrixia coagulans is 10 to 2 billion cfu in terms of viable cell count.

[0013]

[11] A composition for use in reducing dimethylarginine metabolites, comprising a bacterium of the genus Hindrixia.

[12] The composition of

[11] , wherein the dimethylarginine metabolites comprise one or more selected from the group consisting of SDMA and ADMA.

[13] The composition of

[11] or

[12] , wherein the bacterium of the genus Hindrixia is Hindrixia coagulans.

[14] Any of the compositions of

[11] to

[13] , wherein the daily dosage of the bacterium of the genus Hindrixia is 10 to 20 billion cfu in terms of viable cell count.

[0014]

[15] Any of the compositions of [1] to

[14] , which is orally administered.

[16] Any of the compositions of [1] to

[15] , which is a food product.

[17] Any of the compositions of [1] to

[15] , which is a beverage.

[18] Any of the compositions of [1] to

[15] , which is a supplement.

[19] Any of the compositions of [1] to

[15] , which is a feed, a feed additive, or a pet food composition.

[0015]

[20] An agent for reducing advanced glycation end products, comprising bacteria of the genus Hindrixia.

[21] The agent for reducing advanced glycation end products according to

[20] , wherein the bacteria of the genus Hindrixia is Hindrixia coagulans.

[22] The agent for reducing advanced glycation end products according to

[20] or

[21] , wherein the advanced glycation end products comprise one or more selected from the group consisting of Nε-(carboxymethyl)lysine, Nω-carboxymethylarginine, and pyrraline.

[23] The agent for reducing advanced glycation end products according to any of

[20] to

[22] , wherein the daily application amount of the Hindrixia coagulans is 10 to 2 billion cfu in terms of viable cell count.

[24] The reducer according to any one of

[20] to

[23] , wherein the Hindrixia coagulans is SANK70258 strain, P-22 strain, lilac-01 strain, SIM-7 DSM14043 strain, C101 strain, NBRC12583 strain, GBI-1 strain, GBI-20 strain, GBI-30 strain, GBI-40 strain, or a mutant strain derived from these strains.

[0016]

[25] An agent for reducing advanced glycation end products and dimethylarginine metabolites, comprising bacteria of the genus Hindrixia.

[26] The agent of

[25] , wherein the advanced glycation end products comprise one or more selected from the group consisting of Nε-(carboxymethyl)lysine, Nω-carboxymethylarginine, and pyrraline.

[27] The agent of

[25] or

[26] , wherein the dimethylarginine metabolites comprise one or more selected from the group consisting of SDMA and ADMA.

[28] The agent of any of

[25] to

[27] , wherein the bacteria of the genus Hindrixia is Hindrixia coagulans.

[29] The agent of any of

[25] to

[28] , wherein the daily dose of Hindrixia coagulans to be administered is 10 to 2 billion cfu in terms of viable cell count.

[0017]

[30] A dimethylarginine metabolite reducer comprising a bacterium of the genus Hindrixia.

[31] The reducer of

[30] , wherein the dimethylarginine metabolite comprises one or more selected from the group consisting of SDMA and ADMA.

[32] The reducer of

[30] or

[31] , wherein the bacterium of the genus Hindrixia is Hindrixia coagulans.

[33] The reducer of any of

[30] to

[32] , wherein the daily application dose of the bacterium of the genus Hindrixia is 10 to 20 billion cfu in terms of viable cell count.

[0018]

[34] A reducing agent according to any one of

[20] to

[33] , which is orally administered.

[35] A food product comprising the reducing agent according to any one of

[20] to

[34] .

[36] A beverage comprising the reducing agent according to any one of

[20] to

[34] .

[37] A supplement comprising the reducing agent according to any one of

[20] to

[34] .

[38] A feed, a feed additive, or a pet food composition comprising the reducing agent according to any one of

[20] to

[34] .

[0019]

[39] A method for reducing advanced glycation end products, comprising the step of orally administering a composition containing bacteria of the genus Hindrixia to a subject.

[40] The method of

[39] , wherein the bacteria of the genus Hindrixia is Hindrixia coagulans.

[41] The method of

[39] or

[40] , wherein the advanced glycation end products comprise one or more selected from the group consisting of Nε-(carboxymethyl)lysine, Nω-carboxymethylarginine, and pyrraline.

[42] Any of the methods

[39] to

[41] , wherein the daily application dose of Hindrixia coagulans is 10 to 2 billion cfu in terms of viable cell count.

[43] Any of the methods according to

[39] to

[42] , wherein the Hindrixia coagulans is SANK70258 strain, P-22 strain, lilac-01 strain, SIM-7 DSM14043 strain, C101 strain, NBRC12583 strain, GBI-1 strain, GBI-20 strain, GBI-30 strain, GBI-40 strain, or a mutant strain derived from these strains.

[0020]

[44] A method for reducing advanced glycation end products and dimethylarginine metabolites, comprising the step of orally administering a composition containing Hindrixia bacteria to a subject.

[45] The method of

[44] , wherein the advanced glycation end products comprise one or more selected from the group consisting of Nε-(carboxymethyl)lysine, Nω-carboxymethylarginine, and pyrraline.

[46] The method of

[44] or

[45] , wherein the dimethylarginine metabolites comprise one or more selected from the group consisting of SDMA and ADMA.

[47] Any of the methods of

[44] to

[46] , wherein the Hindrixia bacteria is Hindrixia coagulans.

[48] Any of the methods of

[44] to

[47] , wherein the daily dose of Hindrixia coagulans administered is 10 to 2 billion cfu in terms of viable cell count.

[0021]

[49] A method for reducing dimethylarginine metabolites, comprising the step of orally administering a composition containing Hindrixia bacteria to a subject.

[50] The method of

[49] , wherein the dimethylarginine metabolites include one or more selected from the group consisting of SDMA and ADMA.

[51] Any of the methods of

[49] or

[50] , wherein the Hindrixia bacteria is Hindrixia coagulans.

[52] Any of the methods

[49] to

[51] , wherein the daily dose of Hindrixia coagulans administered is 10 to 2 billion cfu in terms of viable cell count.

[0022]

[53] The method of any one of

[39] to

[52] , wherein the composition is a food product.

[54] The method of any one of

[39] to

[52] , wherein the composition is a beverage.

[55] The method of any one of

[39] to

[52] , wherein the composition is a supplement.

[56] The method of any one of

[39] to

[52] , wherein the composition is a feed, a feed additive, or a pet food composition.

[0023]

[57] A composition for treating, alleviating, or preventing a disease or symptom caused by advanced glycation end products, comprising a bacterium of the genus Hindrixia.

[58] The composition of

[57] , wherein the bacterium of the genus Hindrixia is Hindrixia coagulans.

[59] The composition of

[57] or

[58] , wherein the disease or symptom is diabetic complications such as diabetic retinopathy, diabetic neuropathy, diabetic cataract, and diabetic nephropathy, diabetes, chronic kidney disease, heart disease, vascular disease, glycation / aging, or the like.

[60] The composition of any of

[57] to

[59] , wherein the advanced glycation end products comprise one or more selected from the group consisting of Nε-(carboxymethyl)lysine, Nω-carboxymethylarginine, and pyrraline.

[61] Any of the compositions of

[57] to

[60] , wherein the daily dose of the Hindrixia coagulans to be administered is 10 to 2 billion cfu in terms of viable cell count.

[62] The composition of any of

[57] to

[61] , wherein the Hindrixia coagulans is SANK70258 strain, P-22 strain, lilac-01 strain, SIM-7 DSM14043 strain, C101 strain, NBRC12583 strain, GBI-1 strain, GBI-20 strain, GBI-30 strain, GBI-40 strain, or a mutant strain derived from these strains.

[0024]

[63] A composition for treating, alleviating, or preventing a disease or symptom caused by advanced glycation end products and dimethylarginine metabolites, comprising a bacterium of the genus Hindrixia.

[64] The composition of

[63] , wherein the disease or symptom is diabetic complications such as diabetic retinopathy, diabetic neuropathy, diabetic cataract, and diabetic nephropathy, diabetes, chronic kidney disease, heart disease, vascular disease, glycation and aging, vascular endothelial dysfunction, arteriosclerosis, or the like.

[65] The composition of

[63] or

[64] , wherein the advanced glycation end products comprise one or more selected from the group consisting of Nε-(carboxymethyl)lysine, Nω-carboxymethylarginine, and pyrraline.

[66] The composition of any of

[63] to

[65] , wherein the dimethylarginine metabolites comprise one or more selected from the group consisting of SDMA and ADMA.

[67] The composition of any of

[63] to

[66] , wherein the bacterium of the genus Hindrixia is Hindrixia coagulans.

[68] The composition according to any one of

[63] to

[67] , wherein the daily dose of Hindrixia coagulans is 10 to 2 billion cfu in terms of viable cell count.

[0025]

[69] A composition for treating, alleviating, or preventing a disease or symptom caused by dimethylarginine metabolites, comprising a bacterium of the genus Hindrixia.

[70] The composition of

[69] , wherein the disease or symptom is chronic kidney disease, heart disease, vascular disease, vascular endothelial dysfunction, arteriosclerosis, etc.

[71] The composition of

[69] or

[70] , wherein the dimethylarginine metabolites comprise one or more selected from the group consisting of SDMA and ADMA.

[72] The composition of any of

[69] to

[71] , wherein the bacterium of the genus Hindrixia is Hindrixia coagulans.

[73] Any of the compositions of

[69] to

[72] , wherein the daily dosage of the bacterium of the genus Hindrixia is 10 to 20 billion cfu in terms of viable cell count.

[0026]

[74] Any of the compositions of

[57] to

[73] , which is orally administered.

[75] Any of the compositions of

[57] to

[74] , which is a food product.

[76] Any of the compositions of

[57] to

[74] , which is a beverage.

[77] Any of the compositions of

[57] to

[74] , which is a supplement.

[78] Any of the compositions of

[57] to

[74] , which is a pharmaceutical product.

[79] Any of the compositions of

[57] to

[74] , which is a feed, feed additive, or pet food composition.

[0027]

[80] A method for treating, alleviating, or preventing a disease or symptom caused by advanced glycation end products, comprising the step of orally administering a composition containing Hindrixia bacteria to a subject.

[81] The method of

[80] , wherein the Hindrixia bacteria is Hindrixia coagulans.

[82] The method of

[80] or

[81] , wherein the disease or symptom is diabetic complications such as diabetic retinopathy, diabetic neuropathy, diabetic cataract, and diabetic nephropathy, diabetes, chronic kidney disease, heart disease, vascular disease, glycation / aging, or the like.

[83] Any of the methods of

[80] to

[82] , wherein the advanced glycation end products comprise one or more selected from the group consisting of Nε-(carboxymethyl)lysine, Nω-carboxymethylarginine, and pyrraline.

[84] Any of the methods of

[80] to

[83] , wherein the daily dose of Hindrixia coagulans administered is 10 to 2 billion cfu in terms of viable cell count.

[85] Any of the methods according to

[80] to

[84] , wherein the Hindrixia coagulans is SANK70258 strain, P-22 strain, lilac-01 strain, SIM-7 DSM14043 strain, C101 strain, NBRC12583 strain, GBI-1 strain, GBI-20 strain, GBI-30 strain, GBI-40 strain, or a mutant strain derived from these strains.

[0028]

[86] A method for treating, alleviating, or preventing a disease or symptom caused by advanced glycation end products and dimethylarginine metabolites, comprising the step of orally administering a composition containing Hindrixia bacteria to a subject.

[87] The method of

[86] , wherein the disease or symptom is diabetic complications such as diabetic retinopathy, diabetic neuropathy, diabetic cataract, and diabetic nephropathy, diabetes, chronic kidney disease, heart disease, vascular disease, glycation and aging, vascular endothelial dysfunction, arteriosclerosis, or the like.

[88] The method of

[86] or

[87] , wherein the advanced glycation end products comprise one or more selected from the group consisting of Nε-(carboxymethyl)lysine, Nω-carboxymethylarginine, and pyrraline.

[89] Any of the methods

[86] to

[88] , wherein the dimethylarginine metabolites comprise one or more selected from the group consisting of SDMA and ADMA.

[90] The method according to any one of

[86] to

[89] , wherein the bacterium of the genus Hindrixia is Hindrixia coagulans.

[91] The method according to any one of

[86] to

[90] , wherein the daily dose of Hindrixia coagulans is 10 to 2 billion cfu in terms of viable cell count.

[0029]

[92] A method for treating, alleviating, or preventing a disease or symptom caused by dimethylarginine metabolites, comprising the step of orally administering a composition containing Hindrixia bacteria to a subject.

[93] The method of

[92] , wherein the disease or symptom is chronic kidney disease, heart disease, vascular disease, vascular endothelial dysfunction, arteriosclerosis, or the like.

[94] The method of

[92] or

[93] , wherein the dimethylarginine metabolites include one or more selected from the group consisting of SDMA and ADMA.

[95] Any of the methods of

[92] to

[94] , wherein the Hindrixia bacteria is Hindrixia coagulans.

[96] Any of the methods of

[92] to

[95] , wherein the daily dose of Hindrixia coagulans administered is 10 to 2 billion cfu in terms of viable cell count.

[0030]

[97] Any of the methods

[80] to

[96] , wherein the composition is a food product.

[98] Any of the methods

[80] to

[96] , wherein the composition is a beverage.

[99] Any of the methods

[80] to

[96] , wherein the composition is a supplement.

[100] Any of the methods

[80] to

[96] , wherein the composition is a pharmaceutical product.

[101] Any of the methods

[80] to

[96] , wherein the composition is a feed, a feed additive, or a pet food composition.

[0031]

[102] Use of a bacterium of the genus Hindrixia in the manufacture of a medicament for use in a method for reducing advanced glycation end products.

[103] The use according to

[102] , wherein the bacterium of the genus Hindrixia is Hindrixia coagulans.

[104] The use according to

[102] or

[103] , wherein the advanced glycation end products comprise one or more selected from the group consisting of Nε-(carboxymethyl)lysine, Nω-carboxymethylarginine, and pyrraline.

[105] The use according to any of

[102] to

[104] , wherein the daily application amount of the Hindrixia coagulans in the method is 10 to 2 billion cfu in terms of viable cell count.

[106] The use of any of

[102] to

[105] , wherein the Hindrixia coagulans is SANK70258 strain, P-22 strain, lilac-01 strain, SIM-7 DSM14043 strain, C101 strain, NBRC12583 strain, GBI-1 strain, GBI-20 strain, GBI-30 strain, GBI-40 strain, or a mutant strain derived from these strains.

[0032]

[107] Use of a bacterium of the genus Hindrixia in the manufacture of a medicament for use in a method for reducing advanced glycation end products and dimethylarginine metabolites.

[108] The use of

[107] , wherein the advanced glycation end products comprise one or more selected from the group consisting of Nε-(carboxymethyl)lysine, Nω-carboxymethylarginine, and pyrraline.

[109] The use of

[107] or

[108] , wherein the dimethylarginine metabolites comprise one or more selected from the group consisting of SDMA and ADMA.

[110] The use of any of

[107] to

[109] , wherein the bacterium of the genus Hindrixia is Hindrixia coagulans.

[111] The use of any of

[107] to

[110] , wherein the daily dosage of the Hindrixia coagulans in the method is 10 to 2 billion cfu in terms of viable cell count.

[0033]

[112] Use of a bacterium of the genus Hindrixia in the manufacture of a medicament for use in a method for reducing dimethylarginine metabolites.

[113] The use of

[112] , wherein the dimethylarginine metabolites include one or more selected from the group consisting of SDMA and ADMA.

[114] The use of

[112] or

[113] , wherein the bacterium of the genus Hindrixia is Hindrixia coagulans.

[115] The use of any of

[112] to

[114] , wherein the daily dosage of the Hindrixia coagulans in the method is 10 to 2 billion cfu in terms of viable cell count.

[0034]

[116] Use of a bacterium of the genus Hindrixia in the manufacture of a medicament for use in a method for treating, alleviating, or preventing a disease or symptom caused by advanced glycation end products.

[117] The use of

[116] , wherein the bacterium of the genus Hindrixia is Hindrixia coagulans.

[118] The use of

[116] or

[117] , wherein the disease or symptom is diabetic complications such as diabetic retinopathy, diabetic neuropathy, diabetic cataract, and diabetic nephropathy, diabetes, chronic kidney disease, heart disease, vascular disease, glycation / aging, etc.

[119] The use of any of

[116] to

[118] , wherein the advanced glycation end products comprise one or more selected from the group consisting of Nε-(carboxymethyl)lysine, Nω-carboxymethylarginine, and pyrraline.

[120] The use of any of

[116] to

[119] , wherein the daily dose of the Hindrixia coagulans in the method is 1 to 2 billion cfu in terms of viable cell count.

[121] The use of any of

[116] to

[120] , wherein the Hindrixia coagulans is SANK70258 strain, P-22 strain, lilac-01 strain, SIM-7 DSM14043 strain, C101 strain, NBRC12583 strain, GBI-1 strain, GBI-20 strain, GBI-30 strain, GBI-40 strain, or a mutant strain derived from these strains.

[0035]

[122] Use of a bacterium of the genus Hindrixia in the manufacture of a medicament for use in a method for treating, alleviating, or preventing a disease or symptom caused by advanced glycation end products and dimethylarginine metabolites.

[123] The use according to

[122] , wherein the disease or symptom is diabetic complications such as diabetic retinopathy, diabetic neuropathy, diabetic cataract, and diabetic nephropathy, diabetes, chronic kidney disease, heart disease, vascular disease, glycation and aging, vascular endothelial dysfunction, arteriosclerosis, etc.

[124] The use according to

[122] or

[123] , wherein the advanced glycation end products comprise one or more selected from the group consisting of Nε-(carboxymethyl)lysine, Nω-carboxymethylarginine, and pyrraline.

[125] The use according to any of

[122] to

[124] , wherein the dimethylarginine metabolites comprise one or more selected from the group consisting of SDMA and ADMA.

[126] The use of any of

[122] to

[125] , wherein the bacterium of the genus Hindrixia is Hindrixia coagulans.

[127] The use of any of

[122] to

[126] , wherein the daily dose of the Hindrixia coagulans in the method is 10 to 2 billion cfu in terms of viable cell count.

[0036]

[128] Use of a bacterium of the genus Hindrixia in the manufacture of a medicament for use in a method for treating, alleviating, or preventing a disease or symptom caused by a dimethylarginine metabolite.

[129] The use of

[128] , wherein the disease or symptom is chronic kidney disease, heart disease, vascular disease, vascular endothelial dysfunction, arteriosclerosis, etc.

[130] The use of

[128] or

[129] , wherein the dimethylarginine metabolite comprises one or more selected from the group consisting of SDMA and ADMA.

[131] The use of any of

[128] to

[130] , wherein the bacterium of the genus Hindrixia is Hindrixia coagulans.

[132] The use of any of

[128] to

[131] , wherein the daily dose of the Hindrixia coagulans in the method is 10 to 2 billion cfu in terms of viable cell count.

[0037] This specification includes the contents of the specification and the like of Japanese Patent Application No. 2024-102888, filed on June 26, 2025, which is the priority document of this application. All publications, patents, and patent applications cited in this specification are hereby incorporated by reference in their entirety.

[0038] According to the present invention, it is possible to provide a new probiotic that is less susceptible to the effects of gastric acid and bile acid and is capable of reducing the amounts of multiple types of advanced glycation end products and / or reducing the amount of dimethylarginine metabolites.

[0039] Figure 1 is a graph showing the quantification results of (A) Nε-(carboxymethyl)lysine, (B) SDMA, (C) Nω-carboxymethylarginine, and (D) pyrraline in the feces of the placebo group and the test food group at weeks 0 and 8, with the values ​​at weeks 0 and 8 expressed as relative quantitative values. Each graph shows the mean and standard error. Figure 2 is a graph showing the mean change in (A) ADMA measurement values ​​(relative quantification) in the plasma of the placebo group and the test food group from week 0 to week 8, and (B) the sum of the mean changes in ADMA and SDMA from week 0 to week 8.

[0040] Preferred embodiments for carrying out the present invention will be described below. Note that the embodiment described below is an example of a typical embodiment of the present invention, and the scope of the present invention should not be construed as being narrow.

[0041] Bacteria of the genus Hindrixia are rod-shaped bacteria belonging to the family Heyndrickxiaceae in the order Bacillales. In the present invention, any Hindrixia bacteria capable of reducing advanced glycation end products and / or dimethylarginine metabolites can be used. Examples of Hindrixia bacteria that can be used in the present invention include Hindrixia coagulans, Hindrixia oleronia, Hindrixia acidicola, Hindrixia sporothermodurans, and Hindrixia vini, and one or more selected from these bacteria can be used in combination. Preferably, in the present invention, the Hindrixia bacteria is Hindrixia coagulans.

[0042] Hindrixia coagulans is a lactic acid bacterium belonging to the spore-forming lactic acid bacteria, and is highly resistant to dry conditions, heat, and acid. Even when orally ingested / administered, it reaches the intestine without being killed by gastric acid or bile, germinates in the intestine to become vegetative cells, and then proliferates to produce lactic acid. Due to these characteristics, Hindrixia coagulans is more resistant than Lactobacillus bacteria, and it is expected to be sufficiently effective even when administered in relatively small amounts. In addition, there are several synonyms for Hindrixia coagulans, such as Bacillus coagulans and Weizmannia coagulans. In the present invention, "Hindrixia coagulans" is a concept that includes these previously known synonyms as well as further synonyms associated with species name changes.

[0043] Examples of Hindrixia coagulans include Hindrixia coagulans strains SANK70258, P-22, lilac-01, SIM-7 DSM14043, C101, NBRC12583, GBI-1, GBI-20, GBI-30, and GBI-40, of which Hindrixia coagulans strain SANK70258 is preferred in terms of stable supply and ease of acquisition. Furthermore, mutant strains derived from these strains may also be used as long as they have the effect of reducing advanced glycation end products and / or dimethylarginine metabolites.

[0044] Commercially available Hindrixia coagulans can be used (for example, Mitsubishi Chemical Corporation's "Lacris-S," "Lacris-15," and "Feed Lacris-10," as well as products from Kerry Inc., SABINSA, Aterio Bio, UNIQUEBIOTECH, Asahi Biocycle, Jiangsu Wecare Biotechnology Co., Ltd. / Wecare Probiotics Co., Ltd., etc.). These may be appropriately cultured in an appropriate medium and used.

[0045] In the present invention, the fungus of the genus Hindrixia, preferably Hindrixia coagulans, can be used in the form of a fungus body, a component thereof, contents or secretions thereof, or a culture composition of spore-forming bacteria. The fungus body may be killed, live, or a mixture thereof, but live bacteria are preferred.

[0046] Advanced glycation end products include Nε-(carboxymethyl)lysine, Nω-carboxymethylarginine, pyrraline, pentosidine, argpyrimidine, N-carboxyethyllysine, crosslin, GA-pyridine, glucospan, GOLD (glycol-lysine dimer), MOLD (methylglycol-lysine dimer), MG-H1 (N-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine), 3DG-H (3-deoxyglucosone), Examples of the carboxymethyl lysine include Nε-(carboxymethyl)lysine, Nω-carboxymethylarginine, and pyrraline, and preferably includes one or more selected from the group consisting of Nε-(carboxymethyl)lysine, Nω-carboxymethylarginine, and pyrraline.

[0047] Dimethylarginine metabolites are metabolic products released during protein degradation after enzymatic methylation of arginine residues in proteins. Examples of dimethylarginine metabolites include asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). Reducing dimethylarginine metabolites may reduce the burden on the kidneys and vascular system, potentially reducing cardiovascular risk and the risk of renal dysfunction.

[0048] SDMA is a dimethylarginine metabolite that is primarily excreted via the kidney. Because blood levels increase with a decrease in glomerular filtration rate (GFR), SDMA has attracted attention as a biomarker sensitively reflecting declining renal function. In addition to its application in the early diagnosis of chronic kidney disease (CKD) in humans, SDMA is also used in veterinary medicine for the early detection and monitoring of renal disease in pets such as dogs and cats, making it a highly useful indicator in clinical settings. Reduction of SDMA is expected to contribute to reducing renal excretion load and maintaining renal function.

[0049] ADMA, another dimethylarginine metabolite, is primarily metabolized in the liver by dimethylarginine dimethylaminohydrolase (DDAH), but is also partially excreted through the kidneys. ADMA inhibits nitric oxide (NO) synthase (NOS), and numerous studies have shown its association with vascular endothelial dysfunction, arteriosclerosis, and cardiovascular disease. Therefore, reducing ADMA may contribute to maintaining vascular endothelial function and reducing cardiovascular risk.

[0050] The mechanism by which oral ingestion / administration of Hindrixia bacteria or a composition containing Hindrixia bacteria can reduce advanced glycation end products and dimethylarginine metabolites is unclear, but it is presumed to be due to changes in the overall metabolic pathways resulting from an improvement in the intestinal environment.

[0051] Oral ingestion / administration of the composition for reducing advanced glycation end products and / or dimethylarginine metabolites and the agent for reducing advanced glycation end products and / or dimethylarginine metabolites of the present invention (hereinafter also referred to as "the composition of the present invention, etc.") is observed to reduce the amount of advanced glycation end products and / or dimethylarginine metabolites in a subject.

[0052] Subjects include not only humans but also animals such as pets, livestock, and poultry. Examples of animals include mammals (dogs, cats, pigs, cows, goats, sheep, horses, donkeys, rats, mice, guinea pigs, hamsters, rabbits, etc.), birds (e.g., chickens, quails, turkeys, ducks, ducklings, parrots, parakeets, etc.), reptiles (e.g., crocodiles, snakes, lizards, turtles, etc.), amphibians, and fish, but are not limited to these. Preferably, the subject is a mammal, including a human, and more preferably a human.

[0053] A reduction in the amount of advanced glycation end products and / or dimethylarginine metabolites can be observed up to 8 weeks after ingestion / administration of the composition of the present invention, however, the period until a reduction in the amount of advanced glycation end products and / or dimethylarginine metabolites can be observed after ingestion / administration of the composition may vary depending on the applied dose.

[0054] The amount of advanced glycation end products and / or dimethylarginine metabolites in a subject may be reduced to, for example, 90% or less, 80% or less, 70% or less, 60% or less, 50% or less, or 40% or less at 8 weeks after intake / administration compared to the amount at the start of intake / administration (week 0; defined as 100%). However, the extent of reduction in the amount of advanced glycation end products and / or dimethylarginine metabolites may vary depending on the applied dose and / or the type of advanced glycation end products and / or dimethylarginine metabolites.

[0055] The effect of the composition, etc. of the present invention in reducing the amount of advanced glycation end products and / or dimethylarginine metabolites can be evaluated by comparing the amount of advanced glycation end products and / or dimethylarginine metabolites in samples collected from a subject before and after the start of ingestion / administration of the composition, etc. The amount of advanced glycation end products and / or dimethylarginine metabolites in a sample can be quantified using a method commonly used for protein purification and quantification, and can be performed by combining one or more methods selected from, for example, ammonium sulfate precipitation, precipitation separation, filtration, chromatography (column chromatography, high-performance liquid chromatography (HPLC), etc.), capillary electrophoresis, mass spectrometry, enzyme-linked immunosorbent assay (ELISA), Western blotting, flow cytometry, etc.

[0056] The sample may contain advanced glycation end products and / or dimethylarginine metabolites, and examples thereof include blood, serum, plasma, saliva, tears, urine, and feces collected from a subject, with feces being preferred.

[0057] The composition etc. according to the present invention may contain bacteria other than those of the genus Hindrixia. Examples of other bacteria include lactic acid bacteria, butyric acid-producing bacteria, bifidobacteria, bacillus bacteria, natto bacteria, koji mold, yeast, etc. Examples of lactic acid bacteria include bacteria of the genus Lactobacillus and Lactococcus.

[0058] Examples of bacteria of the genus Lactobacillus include Lactobacillus casei, Lactobacillus paracasei, Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus gasseri, Lactobacillus plantarum, and Lactobacillus pentosus.

[0059] Examples of bacteria of the genus Lactococcus include Lactococcus lactis, Lactococcus plantrum, Lactococcus garvieae, and Lactococcus raffinolactis.

[0060] When bacteria other than those of the genus Hindrixia are included, the proportion of bacteria of the genus Hindrixia, preferably Hindrixia coagulans, to the total amount of bacteria is usually 1% by weight or more, preferably 10% by weight or more, preferably 50% by weight or more, and usually 100% by weight or less.

[0061] The composition of the present invention may contain salts such as sodium salts, potassium salts, calcium salts, magnesium salts, etc.; amino acids such as lysine, methionine, threonine, tryptophan, and valine; organic acids such as tannic acid; vitamin A, vitamin D, vitamin E, vitamin K, vitamin B1, vitamin B2, vitamin B6, vitamin B 12 It may also contain vitamins such as niacin, pantothenic acid, biotin, folic acid, and ascorbic acid.

[0062] The composition according to the present invention may contain, as necessary, a stabilizer, an excipient, a pH adjuster, etc. Examples of the stabilizer include silicic anhydride, and examples of the excipient include grains such as corn, wheat, soybeans, and milo; sugars such as lactose, sucrose, and glucose; vegetable oil cakes such as soybean meal, corn gluten meal, sesame oil cake, corn farm meal, rapeseed oil cake, and distillers' residue; bran such as wheat bran, rice bran, defatted rice bran, and corn gluten feed; animal materials such as fish meal; vegetable oils and fats such as palm oil, lard, and corn oil; starches such as corn starch and potato starch; minerals such as calcium carbonate; vitamins such as vitamin E; dextrin, corn stir liquor, paprika extract, and alfalfa meal.

[0063] The composition of the present invention is preferably one that is orally ingested / administered, and specific oral compositions can take the form of pharmaceuticals, foods, beverages, and supplements. The agent for reducing advanced glycation end products and / or dimethylarginine metabolites of the present invention can also be added to foods, beverages, and supplements for oral ingestion / administration.

[0064] The "medicine" of the present invention may be in any form, such as tablets, granules, powders, sugar-coated tablets, capsules, syrups, suspensions, liquids, emulsions, etc. Furthermore, to protect the drug from gastric acid and allow it to act in the intestines, it may be in the form of an enteric-coated drug with different solubility at different pH levels.

[0065] The term "food" as used herein includes health foods, functional foods, health claim foods (foods for specified health uses, foods with nutrient functions, foods with functional claims, etc.), health supplements, and nutritional supplements. The form of the food can be selected appropriately, such as solid, liquid, or paste.

[0066] The term "drinks" as used herein includes soft drinks, dairy drinks, and alcoholic drinks.

[0067] The "supplement" of the present invention may be in any form, such as tablets, granules, powders, sugar-coated tablets, capsules, syrups, suspensions, liquids, emulsions, etc. Furthermore, to protect the supplement from gastric acid and allow it to act in the intestines, it may be in the form of an enteric-coated agent with different solubility at different pH levels.

[0068] The above-mentioned pharmaceuticals, foods, beverages, and supplements include not only those for humans but also those for animals. For example, the composition of the present invention can be in the form of a feed, a feed additive, or a pet food composition, and the agent for reducing advanced glycation end products and / or dimethylarginine metabolites of the present invention can be added to a feed, a feed additive, or a pet food composition.

[0069] The dosage of Hindrixia sp., preferably Hindrixia coagulans, is 1 x 10 viable bacteria per day. 7 colony forming units (cfu) or more, preferably 1 x 10 8 cfu or more, with an upper limit of 5 x 10 10 More specifically, the amount of Hindrixia bacteria, preferably Hindrixia coagulans, to be applied is 1 x 10 viable bacteria per day. 8 cfu ~ 2 x 10 9 It is said to be around cfu.

[0070] The amount of Hindrixia bacteria, preferably Hindrixia coagulans, in the composition of the present invention can be appropriately determined depending on the application amount described above. For example, 6 cfu / g or more 1.0×10 11 cfu / g or less, preferably 1.0 x 10 7 cfu / g or more 1.0×10 10 cfu / g or less.

[0071] The period of intake / administration of Hindrixia bacteria, preferably Hindrixia coagulans, is not particularly limited, but as a guideline for obtaining the effect of reducing advanced glycation end products and / or dimethylarginine metabolites, it is set to 4 weeks or more, preferably 8 weeks or more, and more preferably 12 weeks or more, and there is no upper limit to the intake period.

[0072] The compositions and the like according to the present invention can be used to treat, alleviate, or prevent diseases or symptoms caused by advanced glycation end products and / or dimethylarginine metabolites. Because advanced glycation end products and / or dimethylarginine metabolites are irreversible reaction products, once produced in the body or taken up into the body, they accumulate in tissues, abnormally altering the structure and function of tissues and causing various diseases and symptoms, such as diabetic complications such as diabetic retinopathy, diabetic neuropathy, diabetic cataracts, and diabetic nephropathy, diabetes, chronic kidney disease, heart disease, vascular disease, glycation, and aging. Oral ingestion / administration of the compositions and the like according to the present invention to a subject, as described above, can reduce the levels of advanced glycation end products and / or dimethylarginine metabolites in the subject, thereby treating, alleviating, or preventing various diseases and symptoms caused by advanced glycation end products and / or dimethylarginine metabolites. The present invention will be described below with reference to examples, but the present invention is not limited to these examples.

[0073] The following test was carried out to examine changes in the amounts of AGEs and dimethylarginine metabolites in feces and plasma due to the ingestion of Hindrixia coagulans.

[0074] I. Methods <Test Method> Eighty Japanese women aged 30 to 65 years who reported experiencing rough skin were selected through a screening test. Forty subjects were assigned to each of two groups: a placebo group and a group receiving a test food containing Hindrixia coagulans (test food group). A placebo-controlled, randomized, double-blind, parallel-group comparative study was conducted with 8 weeks of continuous intake of Hindrixia coagulans. <Subjects> Healthy adult women (aged 30 to 65 years), 40 subjects receiving the test food (1 discontinued, dropped out, or excluded, 39 valid data), and 40 subjects receiving the control food (4 discontinued, dropped out, or excluded, 36 valid data). <Intake Period> 8 weeks <Test Food> The composition is shown in Table 1 below. Both groups took one capsule per day. Hindrixia coagulans was administered using Mitsubishi Chemical Corporation's "Lacris-15" at a viable bacterial count of 1 billion cfu / day.

[0075] <Collection of Fecal Samples> Fecal samples were collected from the subjects at the start of the study, and after 4 and 8 weeks. To measure the amounts of AGEs and dimethylarginine metabolites in the feces of the placebo group and the test food group, comprehensive measurements of metabolites in the feces were conducted. The specific method is shown below.

[0076] <Collection of fecal samples for metabolite measurement and measurement of metabolites> Subjects collected marble-sized feces at home using a spoon-shaped stool collection container 1 to 3 days before the test date and froze them in their home freezer. They brought the frozen samples to the test site and submitted them to the test administrator. The test administrator sent the samples frozen to HMT (Human Metabolome Technologies, Inc., Japan). <Comprehensive analysis of metabolites> Comprehensive analysis of metabolites (feces) was outsourced to HMT. Metabolites in feces were comprehensively measured using CE-TOFMS or LC-MS to obtain data (Soga T, Heiger DN: Amino acid analysis by capillary electrophoresis electrospray ionization mass spectrometry. Anal. Chem. 2000, 72:1236-1241; Soga T, Ohashi Y, Ueno Y, Naraoka H, ​​Tomita M, Nishioka T: Quantitative metabolome analysis using capillary electrophoresis mass spectrometry. J. Proteome Res. 2003, 2:488-494). Specifically, metabolite measurement results were obtained using the following methods.

[0077] (Metabolite extraction from feces) Approximately 30 mg of feces was mixed with 500 μL of Milli-Q water containing an internal standard (H3304-1002, HMT, Tsuruoka, Yamagata Prefecture). The mixture was centrifuged at 2,300 × g and 4°C for 5 minutes, and 350 μL of the supernatant was centrifuged using a Millipore 5 kDa cutoff filter (ULTRAFREE MC PLHCC, HMT) at 9,100 × g and 4°C for 120 minutes to remove macromolecules. 80 μL of the filtrate was mixed with 20 μL of Milli-Q water and subjected to measurement.

[0078] <Plasma Sample Collection> Plasma samples were collected from the subjects at the start of the study and after 8 weeks. To measure the levels of AGEs and dimethylarginine metabolites in the plasma of the placebo group and the test food group, comprehensive measurements of metabolites in the plasma were performed. The specific method is shown below.

[0079] <Collection of plasma samples for metabolite measurement> Subjects underwent blood collection at the testing site. (Sample processing) EDTA-2K (5 mL) was used for the blood collection tube. After blood was collected at the testing site, the tube was thoroughly mixed by inversion and then quickly placed in an ice-filled test tube rack to rapidly cool the blood collection tube. Within 6 hours of collection, the blood was centrifuged (1500 g x 15 minutes), and plasma was collected in multiple 0.5 mL tubes. The samples were then promptly frozen and stored at -20°C. The samples were shipped in a frozen state to HMT (Human Metabolome Technologies, Inc., Japan).

[0080] (Metabolite extraction from plasma) 50 μL of plasma was added to 200 μL of methanol solution prepared so that the concentration of the internal standard (H3304-1002, HMT, Tsuruoka City, Yamagata Prefecture) was 20 μM, and the mixture was stirred. 150 μL of Milli-Q water was added to the mixture, and the mixture was stirred. The entire amount was transferred to a Millipore 5 kDa cutoff filter (ULTRAFREE MC PLHCC, HMT). The mixture was centrifuged at 9,100 × g and 4°C for 120 minutes, and the ultrafiltrate was dried and dissolved again in Milli-Q water before being subjected to measurement.

[0081] (Metabolite Measurement and Analysis) Metabolites were measured using the fecal and plasma samples. Metabolite analysis was performed using a capillary electrophoresis time-of-flight mass spectrometer (CE-TOFMS) with the Basic Scan package from HMT, as previously described (Ohashi Y, Hirayama A, Ishikawa T, Nakamura S, Shimizu K, Ueno Y, Tomita M, Soga T: Depiction of metabolome changes in histidine-starved Escherichia coli by CE-TOFMS. Mol. Biosyst. 2008, 4:135-147.). CE-TOFMS analysis was performed using an Agilent 6210 time-of-flight mass spectrometer (Agilent Technologies, Inc.) connected to an Agilent CE capillary electrophoresis system. The system was controlled by Agilent G2201AA ChemStation software version B.03.01 (Agilent Technologies) and connected to a fused silica capillary (50 μm i.d. × 80 cm total length) using a commercially available electrophoresis buffer (H3301-1001 for cation analysis, HMT) as the electrolyte.The spectrometer was scanned from m / z 50 to 1,000, and peaks were extracted using the automated integration software MasterHands (Keio University, Tsuruoka, Yamagata Prefecture, Japan). Peak information, such as m / z, peak area, and migration time (MT), was obtained (Sugimoto M, Wong DT, Hirayama A, Soga T, Tomita M: Capillary electrophoresis mass spectrometry-based saliva metabolomics identified oral, breast, and pancreatic cancer-specific profiles. Metabolomics 2010, 6:78-95). Signal peaks corresponding to isotopomers, adduct ions, and other product ions of known metabolites were excluded, and the remaining peaks were annotated based on their m / z values ​​and MT according to the HMT metabolite database. Relative quantification of each metabolite was calculated by normalizing the annotated peak area to the internal standard and sample amount.

[0082] II. Results <Comparison of AGEs and dimethylarginine metabolites in feces between groups> When AGEs and dimethylarginine metabolites detected in the feces of 10 or more subjects were extracted, four types of AGEs and dimethylarginine metabolites were found: Nε-(carboxymethyl)lysine, SDMA, Nω-carboxymethylarginine, and pyrraline. The comparison results for these between the groups at 0 and 8 weeks are shown in Figure 1.

[0083] The relative amounts of Nε-(carboxymethyl)lysine at week 8 were calculated for the placebo group and the test food group, with week 0 as the baseline. The change in the placebo group was 108%, while the change in the test food group was 54% (Figure 1(A)).

[0084] When the relative amounts of SDMA at week 8 were calculated for the placebo group and the test food group, with week 0 as the reference, the change in the placebo group was 105%, while the change in the test food group was 73% (Figure 1(B)).

[0085] When the relative amounts of Nω-carboxymethylarginine at week 8 were calculated for the placebo group and the test food group, with week 0 as the baseline, the change in the placebo group was 87%, while the change in the test food group was 74% (Figure 1(C)).

[0086] When the relative amounts of pyrraline at week 8 were calculated for the placebo group and the test food group, with week 0 as the reference point, the change in the placebo group was 114%, while the change in the test food group was 80% (Figure 1(D)).

[0087] These results demonstrate that the intake of Hindrixia coagulans has a reducing effect on all four types of AGEs and dimethylarginine metabolites in feces: Nε-(carboxymethyl)lysine, SDMA, Nω-carboxymethylarginine, and pyrraline. Furthermore, the levels of Nε-(carboxymethyl)lysine, SDMA, and pyrraline increased in the placebo group over the eight-week period, whereas they decreased in the Hindrixia coagulans group, demonstrating a further reduction effect.

[0088] Comparison of AGEs and dimethylarginine metabolites in plasma between groups When AGEs and dimethylarginine metabolites detected in the plasma of 10 or more subjects were extracted, SDMA and ADMA were found. The results of a comparison of the changes in these metabolites from week 0 to week 8 are shown in Figure 2.

[0089] For ADMA, the change in relative quantitative values ​​from week 0 to week 8 was calculated for each subject in the placebo group and the test food group, and the average values ​​were compared. The placebo group showed an increase at week 8, while the test food group showed a decrease at week 8. If the size of the graph for the test food group is 1, the size of the placebo group was approximately 22.6 (Figure 2(A)).

[0090] For ADMA and SDMA, the changes in relative quantitative values ​​from week 0 to week 8 were calculated for each subject in the placebo group and the test food group, and the sum of the average values ​​was compared.The placebo group showed an increase at week 8, while the test food group showed a decrease at week 8. If the size of the graph for the test food group is 1, the size of the placebo group was approximately 0.8 (Figure 2(B)).

[0091] These results demonstrate that the intake of Hindrixia coagulans has the effect of reducing ADMA, as well as SDMA and ADMA in plasma.

Claims

1. A composition for use in reducing advanced glycation end products (AGEs), comprising a fungus of the genus Heyndrixia.

2. The composition according to claim 1, wherein the Hindrixia fungus is Hindrixia coagulans.

3. The composition of claim 1, wherein the advanced glycation end products comprise one or more selected from the group consisting of Nε-(carboxymethyl)lysine, Nω-carboxymethylarginine, and pyrraline.

4. The composition according to claim 2, wherein the daily dose of Hindrixia coagulans is 1 to 2 billion cfu (colony formation units) in terms of viable cell count.

5. The composition according to claim 4, wherein the Hindrixia coagulans is strain SANK70258, strain P-22, strain lilac-01, strain SIM-7 DSM14043, strain C101, strain NBRC12583, strain GBI-1, strain GBI-20, strain GBI-30, strain GBI-40, or a mutant strain derived from any of these strains.

6. A composition for use in reducing advanced glycation end products and dimethylarginine metabolites, comprising a bacterium of the genus Heyndrixia.

7. The composition of claim 6, wherein the advanced glycation end products comprise one or more selected from the group consisting of Nε-(carboxymethyl)lysine, Nω-carboxymethylarginine, and pyrraline.

8. The composition of claim 7, wherein the dimethylarginine metabolites include one or more selected from the group consisting of SDMA and ADMA.

9. The composition according to claim 8, wherein the Hindrixia fungus is Hindrixia coagulans.

10. The composition according to claim 9, wherein the daily dose of Hindrixia coagulans is 1 to 2 billion cfu in terms of viable cell count.

11. A composition for use in reducing dimethylarginine metabolites, comprising a Hindrixia sp. bacterium.

12. The composition of claim 11, wherein the dimethylarginine metabolites include one or more selected from the group consisting of SDMA and ADMA.

13. The composition of claim 12, wherein the Hindrixia fungus is Hindrixia coagulans.

14. The composition according to claim 13, wherein the daily dose of Hindrixia coagulans is 1 to 2 billion cfu in terms of viable cell count.

15. The composition according to any one of claims 1 to 14, which is a food product.

16. The composition according to any one of claims 1 to 14, which is a beverage.

17. The composition according to any one of claims 1 to 14, which is a supplement.

18. The composition of any one of claims 1 to 14, which is a feed, feed additive, or pet food composition.

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