Composition for improving vascular endothelial function

Abstract

In one embodiment, the problem to be solved by the present invention is to provide a novel means for improving vascular endothelial function. In one embodiment, the present invention provides a composition for improving vascular endothelial function comprising bifidobacteria and a water-soluble dietary fiber.

Description

Technical Field

[0001] This invention relates to a composition for improving vascular endothelial function. Background Technology

[0002] Cardiovascular disease (CVD) has become a leading cause of death worldwide, with a particularly significant impact on low- and middle-income countries. An estimated 17.9 million people died from CVD in 2019, representing 32% of all deaths globally. Despite current prevention and treatment strategies, CVD mortality is projected to increase further over the next decade. Atherosclerosis is an inflammatory disease of the cardiovascular system characterized by narrowing of the arterial lumen due to plaque formation, the progression of which directly leads to the development of CVD. Endothelial dysfunction contributes to plaque formation and disease progression, thereby leading to the development of atherosclerosis.

[0003] Similarly, the association between CVD and metabolic syndrome has been widely reported. Metabolic syndrome is a clinical condition associated with at least three of the following metabolic risk factors: excess visceral fat (abdominal obesity), insulin resistance, hyperglycemia, hypertension, and dyslipidemia (i.e., high triglyceride levels and low high-density lipoprotein (HDL) cholesterol). These components of metabolic syndrome have been found to impair endothelial function, and patients with metabolic syndrome are known to experience vascular endothelial dysfunction at a high frequency. In these cases, there is a strong need to develop novel approaches to improve vascular endothelial function.

[0004] Reference List

[0005] Patent documents

[0006] Patent Document 1: JP2021-169517A

[0007] Patent Document 2: JP5881801B

[0008] Non-patent literature

[0009] Non-patent literature 1: J Biosci Bioeng. 2012; 113: 587-91.

[0010] Non-patent literature 2: Sci Rep. 2017; 7: 43522.

[0011] Non-patent literature 3: Food Sci Nutr. 2019; 7: 1828-37.

[0012] Non-patent literature 4: Scientific Reports.; volume 4, Article number: 4548 (2014).

[0013] Non-patent literature 5: Hypertension. 2018; 72: 1060-71.

[0014] Non-patent literature 6: Biosci Microbiota Food Health. 2016; 35(4): 163-171.

[0015] Non-patent literature 7: Genome Biol. 2022 Apr 14; 23(1): 95.

[0016] Non-patent literature 8: Microbiome. 2021 Apr 29; 9(1):95. doi: 10.1186 / s40168-021-01048-3.

[0017] Non-patent document 9: The Japanese Circulation Society and the Japanese Society for Vascular Failure (eds.), "Kekkan Fuzen no Seirigakuteki Shindan Shishin" [Physiological Diagnostic Guidelines for Vascular Failure], Life Science Publishing Co., Ltd., 2021.

[0018] Non-patent literature 10: Am J Clin Nutr. 2018; 107: 965-83. Summary of the Invention

[0019] Technical issues

[0020] The problem to be solved by the present invention is to provide a novel means for improving vascular endothelial function.

[0021] Solution to the problem

[0022] In light of the above, the inventors conducted extensive research and discovered that the combination of bifidobacteria and water-soluble dietary fiber can improve vascular endothelial function. This invention is based on this novel discovery. Therefore, this invention provides the following items:

[0023] Project 1. A composition for improving vascular endothelial function, comprising bifidobacteria and water-soluble dietary fiber.

[0024] Project 2. The composition according to Project 1, wherein improving vascular endothelial function includes reducing blood LDL-c levels or reducing PAI-1 levels, or both.

[0025] Project 3. A composition for maintaining or preventing the decline of vascular flexibility or elasticity, comprising bifidobacteria and water-soluble dietary fiber.

[0026] Project 4. A composition for the prevention of arteriosclerosis, comprising bifidobacteria and water-soluble dietary fiber.

[0027] Project 5. A composition for improving kidney function, comprising bifidobacteria and water-soluble dietary fiber.

[0028] Item 6. A composition according to any one of Items 1 to 5, wherein the water-soluble dietary fiber comprises inulin.

[0029] Item 7. A composition according to any one of Items 1 to 6, wherein the Bifidobacteria have the ability to proliferate in the intestine.

[0030] Project 8. A composition according to any one of Projects 1 to 7, wherein Bifidobacterium has an anti-metabolic syndrome effect.

[0031] Item 9. A composition according to any one of Items 1 to 8 is a food.

[0032] Item 10. The composition according to any one of items 1 to 9 further comprises arginine.

[0033] Project 11. Use of Bifidobacteria and water-soluble dietary fiber in the manufacture of compositions for improving vascular endothelial function.

[0034] Project 12. As per the purpose of Project 11, improving vascular endothelial function includes reducing blood LDL-c levels or reducing PAI-1 levels, or both.

[0035] Project 13. Use of Bifidobacteria and water-soluble dietary fiber in the manufacture of compositions for maintaining or preventing the decline of vascular flexibility or elasticity.

[0036] Project 14. Use of Bifidobacteria and water-soluble dietary fiber in the manufacture of compositions for the prevention of arteriosclerosis.

[0037] Project 15. Use of Bifidobacteria and water-soluble dietary fiber in the manufacture of compositions for improving kidney function.

[0038] Project 16. Use of water-soluble dietary fiber in the manufacture of compositions for improving vascular endothelial function, the compositions comprising Bifidobacteria.

[0039] Item 17. As per the purpose of Item 16, improving vascular endothelial function includes reducing blood LDL-c levels or reducing PAI-1 levels, or both.

[0040] Item 18. Use of water-soluble dietary fiber in the manufacture of compositions for maintaining or preventing the decline of vascular flexibility or elasticity, the compositions comprising Bifidobacteria.

[0041] Project 19. Use of water-soluble dietary fiber in the manufacture of compositions for the prevention of arteriosclerosis, the compositions comprising Bifidobacteria.

[0042] Project 20. Use of water-soluble dietary fiber in the manufacture of compositions for improving kidney function, the compositions containing Bifidobacteria.

[0043] Project 21. Use of Bifidobacterium in the manufacture of compositions for improving vascular endothelial function, the compositions comprising water-soluble dietary fiber.

[0044] Project 22. As per the purpose of Project 21, improving vascular endothelial function includes reducing blood LDL-c levels or reducing PAI-1 levels, or both.

[0045] Item 23. Use of Bifidobacterium in the manufacture of compositions for maintaining or preventing the decline of vascular flexibility or elasticity, the compositions comprising water-soluble dietary fiber.

[0046] Project 24. Use of Bifidobacteria in the manufacture of compositions for the prevention of arteriosclerosis, the compositions comprising water-soluble dietary fiber.

[0047] Project 25. Use of Bifidobacterium in the manufacture of compositions for improving kidney function, the compositions comprising water-soluble dietary fiber.

[0048] Item 26. As used in any of Items 11 to 25, wherein the water-soluble dietary fiber contains inulin.

[0049] Item 27. According to any of the uses in Items 11 to 26, wherein Bifidobacteria have the ability to proliferate in the gut.

[0050] Item 28. According to any of the uses in Items 11 to 27, Bifidobacterium has an anti-metabolic syndrome effect.

[0051] Item 29. The use of any one of items 11 to 28, wherein the composition is a food.

[0052] Item 30. The use of any one of items 11 to 29, wherein the composition further comprises arginine.

[0053] Project 31. A method for improving vascular endothelial function, comprising administering an effective amount of bifidobacteria and water-soluble dietary fiber to a subject in need.

[0054] Project 32. According to the method of Project 31, improving vascular endothelial function includes reducing blood LDL-c levels or reducing PAI-1 levels, or both.

[0055] Project 33. A method for maintaining or preventing the decline of vascular flexibility or elasticity, comprising administering an effective amount of bifidobacteria and water-soluble dietary fiber to a subject in need.

[0056] Project 34. A method for preventing arteriosclerosis, comprising administering an effective amount of bifidobacteria and water-soluble dietary fiber to a subject in need.

[0057] Project 35. A method for improving renal function, comprising administering an effective amount of bifidobacteria and water-soluble dietary fiber to a subject in need.

[0058] Item 36. The method according to any one of Items 31 to 35, wherein the water-soluble dietary fiber contains inulin.

[0059] Project 37. The method of any one of Projects 31 to 36, wherein Bifidobacteria have the ability to proliferate in the intestine.

[0060] Project 38. According to the method of any one of Projects 31 to 37, Bifidobacterium has an anti-metabolic syndrome effect.

[0061] Project 39. The method of any one of Projects 31 to 38, wherein Bifidobacteria and water-soluble dietary fiber are ingested in the form of food.

[0062] Item 40. The method according to any one of items 31 to 39 also includes the application of arginine.

[0063] Project 41. A combination of Bifidobacteria and water-soluble dietary fiber for improving vascular endothelial function.

[0064] Project 42. A combination of Project 41, wherein improving vascular endothelial function includes reducing blood LDL-c levels or reducing PAI-1 levels, or both.

[0065] Project 43. A combination of Bifidobacteria and water-soluble dietary fiber for maintaining or preventing the decline of vascular flexibility or elasticity.

[0066] Project 44. A combination of Bifidobacteria and water-soluble dietary fiber for the prevention of arteriosclerosis.

[0067] Project 45. A combination of Bifidobacteria and water-soluble dietary fiber for improving kidney function.

[0068] Item 46. A combination of any of items 41 to 45, wherein the water-soluble dietary fiber contains inulin.

[0069] Item 47. A combination of any of Items 41 to 46, wherein Bifidobacteria have the ability to proliferate in the gut.

[0070] Item 48. A combination of any of Items 41 to 47, wherein Bifidobacterium has an anti-metabolic syndrome effect.

[0071] Item 49. A combination of any of items 41 to 48 constitutes food.

[0072] Item 50. It also contains arginine, based on any combination of items 41 to 49.

[0073] Project 51. Water-soluble dietary fiber for use in combination with Bifidobacteria to improve vascular endothelial function.

[0074] Project 52. According to Project 41, water-soluble dietary fiber, which improves vascular endothelial function, includes reducing blood LDL-c levels or reducing PAI-1 levels, or both.

[0075] Item 53. Water-soluble dietary fiber used in combination with Bifidobacteria to maintain vascular flexibility or elasticity, or to prevent its decline.

[0076] Item 54. Water-soluble dietary fiber used in combination with Bifidobacteria to prevent arteriosclerosis.

[0077] Item 55. Water-soluble dietary fiber used in combination with Bifidobacteria to improve kidney function.

[0078] Item 56. Soluble dietary fiber according to any one of items 51 to 55, wherein the soluble dietary fiber contains inulin.

[0079] Item 57. Water-soluble dietary fiber according to any one of Items 51 to 56, wherein Bifidobacteria have the ability to proliferate in the gut.

[0080] Item 58. Water-soluble dietary fiber according to any one of items 51 to 57, in which Bifidobacteria have an anti-metabolic syndrome effect.

[0081] Item 59. Water-soluble dietary fiber according to any one of items 51 to 58 is a food.

[0082] Item 60. Water-soluble dietary fiber according to any one of items 51 to 59, which is used for further combination with arginine.

[0083] Project 61. Bifidobacteria for use in combination with water-soluble dietary fiber to improve vascular endothelial function.

[0084] Project 62. Based on Bifidobacteria in Project 61, which improve vascular endothelial function include reducing blood LDL-c levels or reducing PAI-1 levels, or both.

[0085] Item 63. Bifidobacteria used in combination with water-soluble dietary fiber to maintain or prevent the decline of vascular flexibility or elasticity.

[0086] Item 64. Bifidobacteria for use in combination with water-soluble dietary fiber to prevent arteriosclerosis.

[0087] Project 65. Bifidobacteria used in combination with water-soluble dietary fiber to improve kidney function.

[0088] Item 66. Bifidobacteria according to any one of Items 61 to 65, wherein the water-soluble dietary fiber contains inulin.

[0089] Item 67. Bifidobacteria according to any one of Items 61 to 66, which have the ability to proliferate in the intestine.

[0090] Item 68. Bifidobacteria according to any one of Items 61 to 67 have an anti-metabolic syndrome effect.

[0091] Item 69. Bifidobacteria according to any one of items 61 to 68 are food.

[0092] Item 70. Bifidobacteria according to any one of Items 61 to 69, which are used for further combination with arginine.

[0093] Beneficial effects of the invention

[0094] This invention can provide a novel means for improving vascular endothelial function. Attached Figure Description

[0095] Figure 1 The flowchart illustrating the process from subject recruitment to analysis in this embodiment is shown.

[0096] Figure 2The effects of consuming test foods containing GCL2505 and inulin on fecal microbiota are shown in the subgroup analysis populations (test food group: n=22, placebo group: n=21). Box plots represent the 5th percentile, 95th percentile, interquartile range (25% to 75%), and median. A) α-diversity (Chao1). B) β-diversity (principal component analysis of Bray-Curtis distance at the genus level). C) Relative abundance of Bifidobacterium animalis at week 12. Data were analyzed using LinDA. Detailed Implementation

[0097] Composition for improving vascular endothelial function

[0098] This invention provides a composition for improving vascular endothelial function, comprising Bifidobacteria and water-soluble dietary fiber. Examples of Bifidobacteria in this invention include, but are not particularly limited to, *Bifidobacterium animalis*, *Bifidobacterium adolescentis*, *Bifidobacterium bifidum*, *Bifidobacterium breve*, *Bifidobacterium catenulatum*, *Bifidobacterium longum*, and *Bifidobacterium pseudocatenulatum*, with *Bifidobacterium animalis* being preferred. Among *Bifidobacterium animalis*, *Bifidobacterium animalis* subsp. *lactis* is preferred. The Bifidobacteria are preferably those capable of proliferating in the intestine. More specifically, the Bifidobacteria are preferably those capable of increasing the total number of Bifidobacteria in the intestine. For example, the ability to proliferate in the intestine can be determined by measuring the number of Bifidobacteria in a fecal sample using real-time PCR. More specifically, the measurement and evaluation can be performed according to the method described in Non-Patent Document 1. In this invention, if proliferation in the intestine is confirmed by the above method, Bifidobacteria are selected as the preferred Bifidobacteria of this invention. Preferably, the bacteria are capable of proliferation such that the number of Bifidobacteria becomes two times or more, preferably five times or more, more preferably ten times or more, compared to the number of bacteria ingested as measured by the above method. Furthermore, in this invention, Bifidobacteria are preferably those with anti-metabolic syndrome effects. The anti-metabolic syndrome effect can be confirmed, for example, by measuring visceral fat area. More specifically, the measurement and evaluation can be performed according to the method described in Non-Patent Document 6. In this invention, if a reduction in visceral fat area is confirmed by the above method, Bifidobacteria are selected as the preferred Bifidobacteria of this invention. Bifidobacteria are preferably those that, when measured by the above method, reduce the visceral fat area to 0.98 times or less, more preferably 0.96 times or less. In a preferred embodiment of the invention, an example of Bifidobacterium includes GCL2505, which belongs to the subspecies of Bifidobacterium animalis (Lactobacillus lactis). Strain GCL2505 is deposited with accession number FERM ABP-21918. This strain was deposited on February 17, 2010, under the Treaty of Budapest at the Patent Microbial Collection Center of the National Institute for Technical Evaluation (NITE) of Japan (Room 120, 2-5-8 Wataru, Kisarazu City, Chiba Prefecture, Japan, 292-0818).

[0099] The number of Bifidobacteria in the compositions of the present invention is not limited and can be appropriately set in the range of, for example, 10 million / g, preferably 30 million / g, more preferably 50 million / g, even more preferably 80 million / g or more, and particularly preferably 100 million / g or more. There is also no particular upper limit, for example, 10 trillion / g or less, 100 billion / g or less, or 10 billion / g or less. In a typical embodiment of the present invention, live Bifidobacteria are used.

[0100] Examples of water-soluble dietary fibers include inulin, indigestible dextrin, water-soluble soybean polysaccharides, polydextrose, sodium alginate, psyllium husk, fucoidan, brown algae starch, sodium carboxymethyl cellulose, pullulan, gelatin, and low molecular weight hemicellulose, with inulin being preferred. These water-soluble dietary fibers can be used alone or in combination of various types.

[0101] The content of water-soluble dietary fiber in the composition of the present invention is not limited. For example, it can be set in the range of 0.5 to 10 wt%, preferably 1 to 5 wt%, more preferably 1.5 to 3 wt%, based on the total mass of the composition.

[0102] In this invention, the combination of Bifidobacterium and water-soluble dietary fiber, which are the active ingredients of the invention, can be used in the form of a composition for improving vascular endothelial function. Alternatively, this combination can be used in the form of a composition in combination with various pharmaceutically acceptable carriers or carriers that can be added to food (e.g., isotonic agents, chelating agents, stabilizers, pH adjusters, preservatives, antioxidants, solubilizers, thickeners, excipients, and binders). In embodiments containing various carriers, the total content of Bifidobacterium and water-soluble dietary fiber in the composition is not limited and can be suitably set in the range of, for example, 50% or more by mass, 60% or more by mass, 70% or more by mass, 80% or more by mass, 90% or more by mass, 95% or more by mass, 99% or more by mass, etc.

[0103] Examples of isotonic agents include sugars such as glucose, trehalose, lactose, fructose, mannitol, xylitol, and sorbitol; polyols such as glycerol, polyethylene glycol, and propylene glycol; and inorganic salts such as sodium chloride, potassium chloride, and calcium chloride. These isotonic agents can be used alone or in combination of two or more.

[0104] Examples of chelating agents include edetates, such as disodium edetate, sodium calcium edetate, trisodium edetate, tetrasodium edetate, and calcium edetate, as well as ethylenediaminetetraacetic acid, hypozoxytriacetic acid or its salts, sodium hexametaphosphate, and citric acid. These chelating agents can be used alone or in combination of two or more.

[0105] Examples of stabilizers include sodium bisulfite.

[0106] Examples of pH adjusters include acids such as hydrochloric acid, carbonic acid, acetic acid, and citric acid; alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkali metal carbonates or bicarbonates such as sodium carbonate; alkali metal acetates such as sodium acetate; alkali metal citrates such as sodium citrate; and bases such as tromethamine. These pH adjusters can be used alone or in combination of two or more.

[0107] Examples of preservatives include sorbic acid, potassium sorbate, parabens (such as methylparaben, ethylparaben, propylparaben, and butylparaben), quaternary ammonium salts (such as chlorhexidine gluconate, benzalkonium chloride, benzyl chloride, and cetylpyridinium chloride), alkyl polyaminoethyl glycine, chlorobutanol, polyquaternary ammonium salts, polyhexamethylene biguanide, and chlorhexidine. These preservatives can be used alone or in combination of two or more.

[0108] Examples of antioxidants include sodium bisulfite, dried sodium sulfite, sodium metabisulfite, and mixed tocopherol concentrates. These antioxidants can be used alone or in combination of two or more.

[0109] Examples of solubilizers include sodium benzoate, glycerin, D-sorbitol, glucose, propylene glycol, hydroxypropyl methylcellulose, polyvinylpyrrolidone, polyethylene glycol, and D-mannitol. These solubilizers can be used alone or in combination of two or more.

[0110] Examples of thickeners include polyethylene glycol, methylcellulose, ethylcellulose, sodium carboxymethylcellulose, xanthan gum, sodium chondroitin sulfate, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, and polyvinyl alcohol. These thickeners can be used alone or in combination of two or more.

[0111] Examples of excipients include lactose, corn starch, L-cysteine, trehalose, maltitol, and sorbitol. These excipients can be used alone or in combination of two or more.

[0112] Examples of adhesives include crystalline cellulose, starch, sucrose, hydroxypropyl cellulose, gelatin, gum arabic, polyvinylpyrrolidone, pullulan, dextrin, cyclodextrin, methylcellulose, ethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinyl alcohol, and polyethylene glycol. These adhesives can be used alone or in combination of two or more.

[0113] Ingestion of the compositions of the present invention by subjects (preferably mammals, such as humans) can improve vascular endothelial function. Patent Document 1 discloses in Example 2 that ingestion twice daily (after breakfast and dinner) of a live bacterial powder of a group of Bifidobacterium animalis subsp. lactis LKM512 strain (approximately 6 × 10⁻⁶) 9 A combination of Bifidobacterium (1 packet x 1 packet) and arginine tablets (100 mg / tablet x 3 tablets) for 8 weeks resulted in improved vascular endothelial function (EndoPAT measurement). However, Patent Document 1 also discloses that in a placebo group where LKM512 strain was combined with starch (but not arginine tablets), vascular endothelial function did not improve. Therefore, Patent Document 1 discloses that vascular endothelial function was not improved when Bifidobacterium was used alone. Furthermore, to date, including Patent Document 1, there are no reports on improving vascular endothelial function by combining Bifidobacterium with water-soluble dietary fiber. Therefore, the effects of the present invention are unforeseen in the prior art.

[0114] Patent document 2 discloses that arginine intake increases the concentration of polyamines (putrescine) in intestinal bacterial metabolites, while non-patent document 4 discloses that combined intake of LKM512 strain and arginine leads to an upregulation of polyamines (putrescine). Therefore, this indicates that the increase in EndoPAT measurements due to combined intake of LKM512 strain and arginine is due to the production of polyamines (putrescine) through arginine intake. The effect achieved by this invention through the combination of Bifidobacterium and water-soluble dietary fiber is not due to the production of polyamines (putrescine), but rather through a completely different mechanism than arginine administration to improve vascular endothelial function; therefore, the combination of this invention is useful.

[0115] The intake of the composition of the present invention is not limited. The daily intake of Bifidobacterium, as the active ingredient, can be appropriately set in the range of, for example, 10 million to 10 trillion, preferably 100 million to 1 trillion, more preferably 1 billion to 100 billion, even more preferably 5 billion to 30 billion, and particularly preferably 10 billion to 20 billion Bifidobacterium. The intake of the composition of the present invention based on the weight of Bifidobacterium is also not limited. The daily intake of Bifidobacterium, as the active ingredient, can be appropriately set in the range of, for example, 1 mg to 10 g, preferably 10 mg to 1000 mg, more preferably 40 mg to 300 mg, even more preferably 200 mg or more.

[0116] In addition to the aforementioned Bifidobacteria, the compositions of the present invention may also contain substances known to improve vascular endothelial function. Examples of known substances that improve vascular endothelial function include arginine, pine bark-derived proanthocyanidins, black soybean polyphenols, and skipjack tuna-derived elastin peptides. These substances may be used alone or in combination of two or more.

[0117] The compositions of the present invention are preferably oral compositions. Oral compositions include food or beverage compositions and pharmaceutical compositions. In the present invention, food or beverage compositions include health functional foods (foods with nutritional function claims, foods for specific health purposes, and foods with functional claims).

[0118] Examples of food or beverage compositions include beverages such as vegetable juice beverages, fruit juice beverages, mixed vegetable and fruit juice beverages, fermented milk beverages, and almond-containing beverages; and foods such as ice cream, frozen fruit syrups, candies, gummies, almond-containing foods, biscuits (e.g., cream-filled biscuits), chocolate (including quasi-chocolate), and fermented dairy products (yogurt and cheese). Ice cream is preferably lactic acid ice cream (e.g., lactic acid ice cream containing fermented milk). Quasi-chocolate includes corn-containing quasi-chocolate. Dairy products include fermented milk, ice cream, and milk beverages. The food or beverage compositions of the present invention also include supplements, etc.

[0119] Other compositions, etc.

[0120] While the invention has been described above with reference to some embodiments, it is not limited to these embodiments. For example, as demonstrated in the embodiments described below, according to the invention, the combination of Bifidobacterium and water-soluble dietary fiber can improve vascular flexibility (generally the degree of vasodilation after vasoconstriction). In this invention, the term "vascular" in phrases such as "vascular endothelial function" and "vascular flexibility" is not particularly limited, and includes, for example, blood vessels of the brain, heart, etc. Furthermore, in this invention, "vascular" and "blood vessel" are not limited, and include, for example, arteries. The combination of Bifidobacterium and water-soluble dietary fiber can improve vascular elasticity. Therefore, it is expected that this combination will have a preventive effect on such vascular conditions affected by aging, etc. Therefore, in one embodiment, the invention provides a composition for maintaining vascular flexibility or elasticity, or preventing its decline, comprising Bifidobacterium and water-soluble dietary fiber. Vascular flexibility (or elasticity) can be measured, for example, by a flow-mediated dilation (FMD) test. Maintaining vascular flexibility (or elasticity) or preventing its decline means, for example, maintaining an FMD value at 4% or greater (preferably 6% or greater, more preferably 7% or greater) or increasing an FMD value from 4% or greater (preferably 6% or greater, more preferably 7% or greater) (Non-Patent Document 5). As demonstrated in the examples below, the combination of Bifidobacteria and water-soluble dietary fiber improves vascular endothelial function and reduces blood LDL-c levels. Therefore, according to the present invention, the risk of arteriosclerosis can be reduced. Therefore, in one embodiment, the present invention provides a composition for preventing arteriosclerosis comprising Bifidobacteria and water-soluble dietary fiber. Furthermore, as demonstrated in the examples below, the combination of Bifidobacteria and water-soluble dietary fiber improves vascular flexibility as measured by an FMD test; since there are existing reports on the correlation between FMD measurements and renal function, improving vascular endothelial dysfunction can reduce the risk of kidney disease. Therefore, the present invention provides a composition for improving renal function comprising Bifidobacteria and water-soluble dietary fiber. In these embodiments, the type and amount of Bifidobacteria and water-soluble dietary fiber used, the conditions of other ingredients, etc., can be the same as those described in the "Compositions for Improving Vascular Endothelial Function" section.

[0121] In another embodiment, the present invention provides the use of Bifidobacterium and water-soluble dietary fiber in the manufacture of compositions for improving vascular endothelial function; the use of Bifidobacterium and water-soluble dietary fiber in the manufacture of compositions for maintaining vascular flexibility or elasticity, or preventing their decline; the use of Bifidobacterium and water-soluble dietary fiber in the manufacture of compositions for preventing arteriosclerosis; the use of Bifidobacterium and water-soluble dietary fiber in the manufacture of compositions for improving renal function; the use of Bifidobacterium in the manufacture of compositions for improving vascular endothelial function, the compositions comprising water-soluble dietary fiber; and the use according to item 21, wherein improving vascular endothelial function includes reducing blood LD50. L-c level or decreased PAI-1 level, or both; use of Bifidobacterium in the manufacture of compositions for maintaining or preventing the decline of vascular flexibility or elasticity, the compositions comprising soluble dietary fiber; use of Bifidobacterium in the manufacture of compositions for preventing arteriosclerosis, the compositions comprising soluble dietary fiber; use of Bifidobacterium in the manufacture of compositions for improving renal function, the compositions comprising soluble dietary fiber; a method for improving vascular endothelial function, comprising administering an effective amount of Bifidobacterium and soluble dietary fiber to a subject in need; a method for maintaining or preventing the decline of vascular flexibility or elasticity, comprising administering an effective amount of Bifidobacterium... A method for preventing arteriosclerosis, comprising administering an effective amount of Bifidobacterium and water-soluble dietary fiber to a subject in need; a method for improving renal function, comprising administering an effective amount of Bifidobacterium and water-soluble dietary fiber to a subject in need; a combination of Bifidobacterium and water-soluble dietary fiber for improving vascular endothelial function; a combination of Bifidobacterium and water-soluble dietary fiber for maintaining or preventing the decline of vascular flexibility or elasticity; a combination of Bifidobacterium and water-soluble dietary fiber for preventing arteriosclerosis; a combination of Bifidobacterium and water-soluble dietary fiber for improving renal function; for use in Water-soluble dietary fiber used in combination with Bifidobacteria to improve vascular endothelial function; water-soluble dietary fiber used in combination with Bifidobacteria to maintain or prevent the decline of vascular flexibility or elasticity; water-soluble dietary fiber used in combination with Bifidobacteria to prevent arteriosclerosis; water-soluble dietary fiber used in combination with Bifidobacteria to improve renal function; Bifidobacteria used in combination with water-soluble dietary fiber to improve vascular endothelial function; Bifidobacteria used in combination with water-soluble dietary fiber to maintain or prevent the decline of vascular flexibility or elasticity; Bifidobacteria used in combination with water-soluble dietary fiber to prevent arteriosclerosis; and Bifidobacteria used in combination with water-soluble dietary fiber to improve renal function.

[0122] In these embodiments, the details (type, amount, etc.) of Bifidobacterium, soluble dietary fiber, and optional other ingredients, the method of use (medicine, food, and beverage, etc.), and the purpose of use (improving vascular endothelial function, preventing arteriosclerosis, improving renal function, etc.) are the same as described above. In this invention, examples of subjects suitable for administering (or ingesting) Bifidobacterium and soluble dietary fiber include mammals, such as humans, mice, rats, and guinea pigs (preferably humans). In the case of human subjects, examples include, but are not particularly limited to, humans who do not suffer from arteriosclerosis, kidney disease, hypertension, etc. While the age of the subject is not particularly limited, examples of age include age groups where vascular endothelial function, renal function, etc., are generally considered to decline with age. In a non-limiting preferred embodiment, subjects of this invention include humans (especially middle-aged and elderly individuals) who have not yet developed arteriosclerosis, kidney disease, hypertension, etc.

[0123] The specific embodiments of the present invention will now be described in more detail with reference to the examples. However, the present invention is not limited to these examples.

[0124] Example

[0125] A randomized, double-blind, placebo-controlled, parallel-group comparative study was conducted to examine the effects of GCL2505 and inulin, which have anti-metabolic syndrome effects, on vascular endothelial function, thereby assessing their potential to reduce the risk of atherosclerosis.

[0126] Subjects (target population for analysis)

[0127] In this study, all participants signed written informed consent forms based on the Declaration of Helsinki. Participants were Japanese men and women aged 40 to 65 years showing a declining trend in vascular endothelial function, meeting the inclusion criteria but not the exclusion criteria, and deemed eligible by the principal investigator. The inclusion criteria are as follows:

[0128] (1) Those who fully understand the meaning, content and purpose of the test and provide written informed consent to participate in the test;

[0129] (2) Japanese men and women aged 40 to 65 years at the time of screening;

[0130] (3) Individuals with high levels of pentameric protein 3 (PTX3) at the time of screening; and

[0131] (4) Individuals with a high LDL-cholesterol to HDL-cholesterol ratio (L / H ratio) at the time of screening.

[0132] The exclusion criteria are as follows:

[0133] (1) Individuals for whom FMD measurement is difficult to perform on the right arm;

[0134] (2) Individuals who are currently receiving treatment, medication, or lifestyle guidance from a doctor regarding hypertension, dyslipidemia, or diabetes;

[0135] (3) Those with a history of bronchial diseases (such as asthma, tuberculosis or pleurisy);

[0136] (4) Those who use pacemakers or defibrillators;

[0137] (5) Individuals suffering from severe cerebrovascular disease, heart disease, liver disease, kidney disease, gastrointestinal disease, or infectious diseases that require reporting;

[0138] (6) Those with a history of major gastrointestinal surgery (such as gastrectomy, gastrointestinal anastomosis or intestinal resection);

[0139] (7) Individuals with significant abnormalities in blood pressure measurement, physical measurements, or blood tests;

[0140] (8) Those suffering from severe anemia;

[0141] (9) Premenopausal or postmenopausal women with significant physical changes;

[0142] (10) Individuals at risk of exhibiting allergic symptoms to drugs or foods (especially milk components);

[0143] (11) Individuals who are taking or plan to take antibiotics from 12 weeks prior to the start of intake until the end of the test;

[0144] (12) Those who regularly take medications that affect bowel movements (e.g., probiotics, laxatives, antidiarrheals);

[0145] (13) Those who are unable to stop consuming yogurt, lactic acid bacteria beverages or health foods with intestinal regulating effects (containing ingredients such as lactic acid bacteria, bifidobacteria, oligosaccharides and foods rich in dietary fiber) during the test period;

[0146] (14) Smokers, heavy drinkers, or those with extremely irregular lifestyles;

[0147] (15) Women who have donated 400 mL of blood within 16 weeks before starting intake, men who have donated 400 mL of blood within 12 weeks before starting intake, people who have donated 200 mL of blood within 4 weeks before starting intake, or people who have donated blood components within 2 weeks before starting intake.

[0148] (16) Women who are pregnant or suspected of being pregnant, or who are breastfeeding;

[0149] (17) Individuals who participated in other clinical trials, observational studies, clinical trials, or home use tests from four weeks prior to the start of the testing period until the end of the intake period; and

[0150] (18) Any other person deemed unqualified by the principal investigator.

[0151] An overview of the testing period is as follows: Figure 1 The flowchart is shown. In this study, 149 participants were screened. Screening results showed that 60 participants met the criteria: 30 were assigned to the test food group and 30 to the placebo group. By the end of the test, three participants withdrew for personal reasons (n=1 in the test food group and n=2 in the placebo group). Additionally, one participant discontinued based on adherence criteria. After the entire test was completed, one participant was excluded due to a confirmed medical condition unrelated to the test but potentially affecting the results. Therefore, a total of 55 subjects (27 in the test food group and 28 in the placebo group) were included in the target population for analysis.

[0152] Participants in both the test food group and the placebo group consumed a beverage with the composition shown in Table 1 below once daily. While the dietary menu excluding the beverage was not restricted, prohibited items were set, including foods containing lactic acid bacteria. Beverage consumption continued for 84 days.

[0153] Table 1

[0154]

[0155] Table 2 below provides an overview of the background and safety assessment of subjects in the target population for the complete analysis. Table 3 shows the FMD and blood component measurements in the test food group (active) and placebo group (placebo) in the target population for the complete analysis.

[0156] Table 2

[0157]

[0158] Table 3

[0159]

[0160] Table 4 below shows the FMD and blood component measurements in the test food group (active) and the placebo group (placebo) in the subject population with an FMD (%) of 4% or greater at week 0.

[0161] Table 4

[0162]

[0163] Security assessment

[0164] The safety of the target population analyzed was confirmed (Table 2), and no clinically significant problems were found. Furthermore, no side effects or medically problematic adverse events were observed. Therefore, the dairy beverage used in the test is considered safe for consumption.

[0165] FMD

[0166] FMD was measured on days 0, 56, and 84 of the test, according to the following method. For the measurements, a UNEX-EF18VG (UNEX Corporation) was used. Measurements were performed using the right arm. First, the diameter of the right brachial artery was measured at rest, then the right forearm was occluded for 5 minutes. After the occlusion was released, the diameter of the vessel at maximum dilation was measured again. The percentage dilation of the vessel diameter relative to the resting diameter is expressed as FMD (%).

[0167] The increase in FMD (%) at week 12 in the test food group was confirmed in the group of subjects with an FMD (%) of 4% or greater at week 0 (0.88% ± 2.23%). Furthermore, there was a statistically significant difference in the change in FMD (%) from week 0 to week 12 between the test food group and the placebo group (-0.68% ± 2.81%) (p = 0.046 by Student's t-test) (Table 4). In the target population analyzed, an increase in FMD (%) was observed in the test food group at week 12 (1.05 ± 2.21%). The change in FMD (%) from week 0 to week 12 in the test food group was greater than that in the placebo group (-0.26% ± 2.87%) (p = 0.065 by Student's t-test) (Table 3).

[0168] fecal microbiota

[0169] Fecal microbiota were detected in the subgroups at weeks 0 and 12 using shotgun metagenomic analysis. Alpha-diversity (Chao1) and β-diversity analyses were performed to compare the fecal microbiota between the two groups. Interestingly, no differences were observed between or within the two groups at weeks 0 and 12. Figure 2 (A and B). However, the relative abundance of Bifidobacterium animalis in the gut of the test food group was 0.061% ± 0.002% at week 0, increasing to 1.503% ± 0.018% at week 12. In the placebo group, its abundance was 0.085% ± 0.004% at week 0 and 0.014% ± 0.001% at week 12. For the compositional data, the difference in abundance between the two groups was assessed using a linear model for differential abundance (LinDA) and the p-value was corrected using the Benjamini-Hochberg procedure to minimize the false discovery rate (Non-Patent Literature 7). At week 12, there was a statistically significant difference in the relative abundance of Bifidobacterium animalis between the test food group and the placebo group (p = 5.62 × 10⁻⁶). -9 () Figure 2 C).

[0170] Test methods

[0171] Fecal sample collection

[0172] Stool samples were collected by participants at home using a stool collector containing RNAlater stabilization solution (Invitrogen, Carlsbad, CA) from three days prior to their scheduled arrival date until the morning of week 0, week 8, and week 12. Stool samples were stored in a home refrigerator and cooled with refrigerant on the day of testing before being brought to the laboratory.

[0173] Fecal DNA Extraction

[0174] Bacterial DNA was extracted from a 10-fold dilution of a fecal sample using the method described above (Non-Patent Document 8) using the ISOSPIN Fecal DNA Kit (Nippon Gene Co., Ltd., Tokyo, Japan). Specifically, the sample (200 μL of fecal dilution in this case), 700 μL of FE1 buffer, and 10 μL of RNase were added to a test tube containing magnetic beads. Cells were lysed using a FastPrep-24 (MP Biomedicals, Irvine, CA) at 6 m / s for 1 minute. This beading was repeated three times, with the sample held at room temperature for 5 minutes during this period. Subsequently, 90 μL of FE2 buffer was added, and the sample was centrifuged at 12,000 × g for 15 minutes. The supernatant (up to 500 μL) was collected and mixed with FB buffer and isopropanol, each at 0.4 times the volume of the resulting supernatant. Finally, the sample was loaded onto a centrifuge column and washed according to the manufacturer's instructions. The purified DNA was eluted with 50 μL Tris-EDTA buffer (pH 8.0).

[0175] Shotgun library construction and sequencing

[0176] Unless otherwise specified, construct metagenomic sequencing libraries according to the manufacturer's instructions using the QIAseq FX DNA Library Kit (Qiagen, Hilden, Germany). Briefly, each fragmentation reaction (50 μL) contains 10× FX buffer, 10 μL FX enzyme mixture, and 500 ng DNA template, and is incubated at 32°C for 9 minutes. For adaptor ligation, add 5 μL of adaptor, along with 20 μL DNA ligase buffer, 10 μL DNA ligase, and 15 μL RNase-free H2O, and incubate at 20°C for 15 minutes. Adaptor-ligated fragments are purified and size-selected sequentially using an Agencourt AMPure XP PCR purification system (Beckman Coulter, Brea, CA) with 1x and 0.8x volumes of magnetic bead solution, and eluted with 10 mM Tris-HCl buffer.

[0177] Quality control of metagenomic reads

[0178] Metagenomic read quality control and adaptor sequence trimming were performed using fastp (version 0.20.0). Reads smaller than 50 bp were excluded from further analysis. The remaining reads were aligned to the human (hg38) and phiX phage genomes using minimap2 (version 2.17), and aligned reads were excluded. Reads whose pairs were excluded during the filtering step were also removed.

[0179] Construction and functional annotation of non-redundant gene sets

[0180] The non-redundant gene set was constructed based on HMP and population-level metagenomic data. All genes were clustered using cd-hit (version 4.8.1) with a 95% identity threshold. Functional annotation of the non-redundant genes was performed using eggNOG-mapper (version 2.1.9) based on the eggNOG orthologous database (version 5.0.2). Sequence searches were performed using DIAMOND (version 2.0.15).

[0181] Sample classification and functional spectrum

[0182] Using a biomarker-based approach, taxonomic profiles at the species and genus levels were obtained using mOTUs2 (version 3.0.3). To quantify gene function, metagenomic reads were aligned to non-redundant genes using minimap2 with an identity threshold of 95% or higher, and the number of reads aligned to each gene was counted. The number of multiple-aligned reads was assigned to the aligned genes based on the ratio of unique aligned reads to the number of genes. The counts were normalized per million transcripts to form a per-million-transcripts matrix.

[0183] Body parameters

[0184] In participants with a FMD (%) of 4% or greater at week 0, the test food group showed a decrease in total blood cholesterol levels (week 8: -2.75 ± 11.51 mg / dL, week 12: -3.75 ± 21.09 mg / dL), with a greater change from week 0 to week 8 than the placebo group (3.87 ± 13.74 mg / dL) (p = 0.081 by Student's t-test). The test food group also showed a decrease in blood LDL-c levels (week 8: -4.17 ± 9.18 mg / dL, week 12: -4.29 ± 15.14 mg / dL). The change in blood LDL-c levels from week 0 to week 8 was statistically significant between the test food group and the placebo group (3.57 ± 10.93 mg / dL) (p = 0.012 by Student's t-test). The change in blood LDL-c levels in the test food group from week 0 to week 12 was greater than that in the placebo group (2.14 ± 9.73 mg / dL) (p = 0.092 via Student's t-test). Blood PAI-1 levels decreased in the test food group (week 8: -1.83 ± 5.25 ng / mL, week 12: -1.25 ± 4.66 ng / mL). The change in blood PAI-1 levels in the test food group from week 0 to week 8 was greater than that in the placebo group (0.52 ± 2.61 ng / mL) (p = 0.058 via Student's t-test), and the change in blood PAI-1 levels in the test food group from week 0 to week 12 was greater than that in the placebo group (0.86 ± 3.12 ng / mL) (p = 0.076 via Student's t-test) (Table 4).

[0185] Based on the above tests, the effects of consuming yogurt containing Bifidobacterium animalis subsp. lactis GCL2505 and inulin on vascular endothelial function in healthy adults were studied.

[0186] Flow-mediated dilation (FMD) was used in this test. FMD is a vascular endothelial function test that utilizes the flow-dependent vasodilatory response that occurs after the upper arm occlusion is released. Increased blood flow after occlusion release creates shear stress on the vascular endothelium, leading to the production of vasodilators such as nitric oxide. These substances act on the vascular smooth muscle adjacent to the vascular endothelium, causing relaxation and triggering a vasodilatory response. The ratio of the vessel diameter at maximum dilation to the resting vessel diameter is defined as FMD (%). In cases of vascular endothelial dysfunction, the bioavailability of nitric oxide produced and released by the vascular endothelium is reduced, resulting in a weakened vasodilatory response and a low FMD (%). FMD is considered non-invasive, low in patient burden, and useful for assessing the risk of CVD (Non-Patent Literature 9).

[0187] In this study, the FMD (%) of the test food group increased by 0.85% after consuming yogurt containing GCL2505 and inulin for 12 weeks. Furthermore, the FMD (%) change in the test food group from week 0 to week 12 was significantly greater than that in the placebo group.

[0188] Analysis of the fecal microbiota of the subjects showed that GCL2505 and inulin had no effect in α-diversity and β-diversity analyses. It has been reported that dietary fiber intervention in healthy humans increases the abundance of specific bacteria without affecting gut microbiota diversity (Non-Patent Literature 10). The lack of change in fecal microbiota may be because the subjects in this study were healthy and did not have gut microbiota dysbiosis. The relative abundance of Bifidobacterium animalis increased only in the gut of the active group subjects, and not in the placebo group. In other words, the ingested GCL2505 survived and reached the gut. The increased relative abundance of Bifidobacterium animalis in the gut may increase the production of acetic acid (a major SCFA).

[0189] In this study, the effect on blood LDL cholesterol (LDL-c) levels in the test food group was confirmed. LDL-c deposited on the vascular wall is converted into oxidized LDL, and this stimulation leads to endothelial cell dysfunction and increased expression of adhesion factors. Oxidized LDL is taken up by macrophages and participates in foam cell formation, thereby sustaining the growth of atherosclerotic lesions by promoting local and systemic plaque inflammation. Specifically, the improvement in endothelial function observed in this study may be attributed to a decrease in blood LDL-c levels. Furthermore, in this study, the blood plasminogen activator inhibitor-1 (PAI-1) level in the test food group was lower than that in the placebo group (week 8, p = 0.058; week 12, p = 0.076). PAI-1 is a cytokine that regulates the fibrinolytic system and strongly inhibits thrombolysis by blocking tissue plasminogen activator (t-PA, a known fibrinolytic agent). Previous reports have indicated that elevated PAI-1 levels are associated with atherosclerotic thrombosis, and that PAI-1 levels are elevated in patients with obese metabolic syndrome and type II diabetes. Specifically, it can be argued that the improvement in vascular endothelial function due to the intake of GCL2505 and inulin is achieved by reducing visceral fat, thereby lowering blood PAI-1 levels and activating the fibrinolytic system. Furthermore, given the reported positive correlation between visceral fat and blood LDL-c levels, in this study, the visceral fat quality of the test food group with lowered blood LDL-c levels was likely affected.

[0190] It is hypothesized that GCL2505 and inulin improve vascular endothelial function through a two-step mechanism. Step 1: Ingestion of GCL2505 and inulin reduces visceral fat by altering the gut microbiota. Clinical studies have demonstrated that daily consumption of yogurt containing GCL2505 reduces abdominal visceral fat mass. Furthermore, Horiuchi et al. demonstrated that in GPR43 knockout mice, administration of GCL2505 increased the count of Bifidobacterium lactis in the gut and the concentration of acetic acid in plasma, subsequently modulating host energy metabolism in a GPR43-dependent manner (e.g., inhibiting body fat accumulation, improving insulin sensitivity, and enhancing systemic fatty acid metabolism). GPR43 is a member of the G protein-coupled receptor family and is known as a short-chain fatty acid receptor in the host. Acetic acid has been reported to inhibit fat accumulation by activating GPR43 in adipocytes and regulating insulin signaling in adipocytes. Step 2: Prevention of vascular endothelial dysfunction through the following sub-steps triggered by reducing visceral fat: 1) By reducing blood lipid levels and consequently lowering blood LDL-c levels through reducing visceral fat: LDL-c is a pathogenic factor in plaque formation, and its synthesis is related to the amount of free fatty acids released from visceral adipose tissue; and 2) By reducing visceral fat, inhibition of plasminogen activator inhibitor-1 (PAI-1) expression: PAI-1 is an adipokine produced by adipocytes that regulates the fibrinolytic system and is closely related to atherosclerosis. In this test, GCL2505 and inulin have been demonstrated to promote vascular endothelial function through their inhibitory effects on fat accumulation.

[0191] The above results indicate that consuming a probiotic beverage containing GCL2505 and inulin reduces visceral fat, thereby improving vascular endothelial function. Since a meta-analysis reported that a 1% increase in FMD (%) led to a reduction of approximately 13% in the risk of CVD, the findings of this study are considered clinically significant. Furthermore, given the reported correlation between FMD (%) and renal function, improving vascular endothelial dysfunction may also reduce the risk of kidney disease. Therefore, because this combination has the potential to reduce the risk of CVD and multiple other diseases, and makes a significant contribution to promoting health, the results obtained in this study are considered clinically significant. PCT / RO / 134 form

Claims

1. A composition for improving vascular endothelial function, comprising bifidobacteria and water-soluble dietary fiber.

2. The composition according to claim 1, wherein the improvement of vascular endothelial function comprises reducing blood LDL-c levels or reducing PAI-1 levels, or both.

3. A composition for maintaining or preventing the decline of vascular flexibility or elasticity, comprising bifidobacteria and water-soluble dietary fiber.

4. A composition for preventing arteriosclerosis, comprising bifidobacteria and water-soluble dietary fiber.

5. A composition for improving kidney function, comprising bifidobacteria and water-soluble dietary fiber.

6. The composition according to any one of claims 1 to 5, wherein the water-soluble dietary fiber comprises inulin.

7. The composition according to any one of claims 1 to 5, wherein the Bifidobacterium has the ability to proliferate in the intestine.

8. The composition according to any one of claims 1 to 5, wherein the Bifidobacterium has an anti-metabolic syndrome effect.

9. The composition according to any one of claims 1 to 5, wherein it is a food product.

10. The composition according to any one of claims 1 to 5, further comprising arginine.

11. Use of Bifidobacteria and water-soluble dietary fiber in the manufacture of compositions for improving vascular endothelial function.

12. The use according to claim 11, wherein the improvement of vascular endothelial function includes reducing blood LDL-c levels or reducing PAI-1 levels, or both.

13. Use of Bifidobacteria and water-soluble dietary fiber in the manufacture of compositions for maintaining or preventing the decline of vascular flexibility or elasticity.

14. Use of Bifidobacteria and water-soluble dietary fiber in the manufacture of compositions for the prevention of arteriosclerosis.

15. Use of Bifidobacteria and water-soluble dietary fiber in the manufacture of compositions for improving renal function.

16. Use of water-soluble dietary fiber in the manufacture of compositions for improving vascular endothelial function, said compositions comprising Bifidobacteria.

17. The use according to claim 16, wherein the improvement of vascular endothelial function comprises reducing blood LDL-c levels or reducing PAI-1 levels, or both.

18. Use of water-soluble dietary fiber in the manufacture of compositions for maintaining or preventing the decline of vascular flexibility or elasticity, said compositions comprising Bifidobacteria.

19. Use of water-soluble dietary fiber in the manufacture of compositions for the prevention of arteriosclerosis, said compositions comprising Bifidobacteria.

20. Use of water-soluble dietary fiber in the manufacture of compositions for improving kidney function, said compositions comprising Bifidobacteria.

21. The use according to any one of claims 11 to 20, wherein the water-soluble dietary fiber comprises inulin.

22. The use according to any one of claims 11 to 20, wherein the Bifidobacterium has the ability to proliferate in the intestine.

23. The use according to any one of claims 11 to 20, wherein the Bifidobacterium has an anti-metabolic syndrome effect.

24. The use according to any one of claims 11 to 20, wherein the composition is a food product.

25. The use according to any one of claims 11 to 20, wherein the composition further comprises arginine.

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