Composition for promoting aromatic lactic acid compound production

Abstract

To provide a composition that can be used for specific purposes, such as a composition for promoting production of an aromatic lactic acid compound or for yielding effects based on promoted production of an aromatic lactic acid compound.SOLUTION: A composition contains indigestible oligosaccharide such as lactulose and Bifidobacterium bacteria such as Bifidobacterium breve.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a composition that can be used for specific purposes, such as a composition for promoting the production of aromatic lactic acid compounds or for obtaining effects based on the promotion of the production of aromatic lactic acid compounds. [Background technology]

[0002] Indole-3-lactic acid (ILA), a type of aromatic lactic acid compound, is known to be a key component of the lactic acid metabolism of Bifidobacterium species commonly isolated from the intestines of human infants (e.g., Bifidobacterium longum). ILA can be produced by Bifidobacterium longum subsp. longum, Bifidobacterium longum subsp. infantis, Bifidobacterium breve, and Bifidobacterium bifidum (Non-Patent Document 1). ILA can have the function of improving neurite outgrowth, for example (Non-Patent Document 2). ILA can also have the function of regulating immune balance, for example (Non-Patent Document 3). ILA can also act as an agonist of the aryl hydrocarbon receptor (AhR) in intestinal epithelial cells and neurons, thereby exerting anti-inflammatory effects, etc. (Non-Patent Documents 2 and 4). [Prior art documents] [Non-patent literature]

[0003] [Non-Patent Document 1] Sakurai T. et al. Production of Indole-3-Lactic Acid by Bifidobacterium Strains Isolated from Human Infants. Microorganisms. 2019 Sep 11;7(9). [Non-patent document 2] Chyn Boon Wong et al. Potential Effects of Indole-3-Lactic Acid, a Metabolite of Human Bifidobacteria, on NGF-Induced Neurite Outgrowth in PC12 Cells. Microorganisms. 2020 Mar; 8(3): 398. [Non-patent document 3] Bethany M. Henrick et al. Bifidobacteria-mediated immune system imprinting early in life, Cell. 2021 July; 184: 1-15. [Non-patent document 4] Ehrlich et al. Indole-3-lactic acid associated with Bifidobacterium-dominated microbiota significantly decreases inflammation in intestinal epithelial cells. BMC Microbiology. 2020 20:357. Summary of the Invention [Problem to be solved by the invention]

[0004] An object of the present invention is to provide a composition that can be used for specific purposes, such as a composition for promoting the production of aromatic lactic acid compounds or for obtaining effects based on the promotion of the production of aromatic lactic acid compounds. [Means for solving the problem]

[0005] The present inventors have conducted extensive research to solve the above problems, and as a result have found that the combined use of indigestible oligosaccharides such as lactulose and Bifidobacterium breve bacteria such as Bifidobacterium breve promotes the production of aromatic lactic acid compounds such as indole-3-lactic acid (ILA) and 4-hydroxyphenyllactic acid (HPLA), thereby completing the present invention.

[0006] That is, the present invention can be exemplified as follows. [1] A composition for promoting the production of aromatic lactic acid compounds, comprising the following components (A) and (B): (A) Indigestible oligosaccharides; (B) Bifidobacterium bacteria. [2] The composition, wherein the aromatic lactic acid compound is indole-3-lactic acid or 4-hydroxyphenyl lactic acid. [3] The composition, wherein the indigestible oligosaccharide is one or more oligosaccharides selected from the group consisting of milk oligosaccharides, fructooligosaccharides, galactooligosaccharides, xylooligosaccharides, mannooligosaccharides, cellooligosaccharides, lactoferrin oligosaccharides, and raffinose. [4] The composition, wherein the indigestible oligosaccharide is lactulose. [5] The composition, wherein the component (B) is Bifidobacterium breve. [6] The composition, wherein the component (B) is Bifidobacterium breve FERM BP-11175. [7] The composition, which is a food or beverage composition. [8] The composition, wherein the composition is a pharmaceutical composition. [Effects of the Invention]

[0007] According to the present invention, it is possible to provide a composition that can be used for specific purposes, such as a composition for promoting the production of aromatic lactic acid compounds or for obtaining effects based on the promotion of the production of aromatic lactic acid compounds. [Brief explanation of the drawings]

[0008] [Figure 1]Figure showing the results of 4-hydroxyphenyllactic acid (HPLA) production by the combined use of lactulose and Bifidobacterium breve in neutral culture. [Figure 2] Figure showing the results of indole-3-lactic acid (ILA) production by the combined use of lactulose and Bifidobacterium breve in neutral culture. [Figure 3] Figure showing the results of indole-3-acetic acid (IAA) production by the combined use of lactulose and Bifidobacterium breve in neutral culture. [Figure 4] Figure showing the results of 4-hydroxyphenyllactic acid (HPLA) production by the combined use of lactulose and Bifidobacterium breve in monoculture. [Figure 5] Figure showing the results of indole-3-lactic acid (ILA) production by the combined use of lactulose and Bifidobacterium breve in monoculture. [Figure 6] Figure showing the results of indole-3-acetic acid (IAA) production by the combined use of lactulose and Bifidobacterium breve in monoculture. DETAILED DESCRIPTION OF THE INVENTION

[0009] The present invention will be described in detail below.

[0010] <1> Active ingredient In the present invention, the following components (A) and (B) are used as active ingredients: (A) Indigestible oligosaccharides; (B) Bifidobacterium bacteria.

[0011] That is, components (A) and (B) are collectively referred to as "active ingredients." The active ingredients can be used, for example, in vivo. That is, the active ingredients can be used, for example, by administering them to a subject.

[0012] By using an active ingredient, specifically by administering the active ingredient to a subject, the production of aromatic lactic acid compounds may be promoted in the subject, that is, an effect of promoting the production of aromatic lactic acid compounds may be obtained. This effect is referred to as the "effect of promoting the production of aromatic lactic acid compounds." This is also referred to as "a method for promoting the production of aromatic lactic acid compounds." Specifically, the use of an active ingredient may have the effect of promoting the production of aromatic lactic acid compounds compared to a method in which the active ingredient is not used. Examples of a method in which neither of the components (A) nor (B) is used, or a method in which only one of the components (A) and (B) is used, are included. Examples of a method in which the active ingredient is not used include a method in which neither of the components (A) nor (B) is used. The production of aromatic lactic acid compounds may be promoted, for example, in the intestines of a subject. Examples of the intestines include the small intestine and the large intestine. The aromatic lactic acid compounds may be produced, for example, by administered Bifidobacterium bacteria. That is, by using the aromatic lactic acid compounds in combination with indigestible oligosaccharides, for example, the production of aromatic lactic acid compounds by the administered Bifidobacterium bacteria may be promoted. Specifically, the aromatic lactic acid compounds may be produced in the intestines of a subject by administered Bifidobacterium bacteria. Furthermore, the aromatic lactic acid compounds may be produced, for example, by bacteria that naturally inhabit the intestines of a subject. That is, administration of an active ingredient may promote, for example, the production of aromatic lactic acid compounds by bacteria naturally present in the intestines of a subject. The aromatic lactic acid compound production-promoting effect can be confirmed, for example, by confirming an increase in the amount of aromatic lactic acid compounds in a subject due to administration of the active ingredient. Specifically, the aromatic lactic acid compound production-promoting effect can be confirmed, for example, when the amount of aromatic lactic acid compounds in a sample obtained from the subject after administration of the active ingredient is greater than the amount of aromatic lactic acid compounds in a sample obtained from the subject before administration of the active ingredient. The subject before administration of the active ingredient may preferably be the same individual as the subject to which the active ingredient is administered, but before administration of the active ingredient. However, the subject before administration of the active ingredient may also be, for example, a different individual from the subject to which the active ingredient is administered and not to which the active ingredient is administered. Furthermore, the subject before administration of the active ingredient may also be, for example, a group of subjects to which the active ingredient is not administered. The sample used to confirm the aromatic lactic acid compound production-promoting effect is not particularly limited as long as it contains an aromatic lactic acid compound. Examples of samples used to confirm the aromatic lactic acid compound production-promoting effect include blood samples such as whole blood and plasma, and feces.

[0013] The term "aromatic lactic acid compound" refers to a lactic acid compound containing a cyclic unsaturated hydrocarbon. More specifically, the term "aromatic lactic acid compound" may refer to a lactic acid compound having a benzene ring. Examples of aromatic lactic acid compounds include indole-3-lactic acid (ILA), 4-hydroxyphenyl lactic acid (HPLA), and 3-phenyl lactic acid (PLA). Preferred examples of aromatic lactic acid compounds include indole-3-lactic acid (ILA) and 4-hydroxyphenyl lactic acid (HPLA). The amount of aromatic lactic acid compounds can be measured, for example, by known methods for measuring the amount of compounds. Such methods include HPLC, UPLC, LC / MS, and GC / MS. The use of an active ingredient may promote the production of one type of aromatic lactic acid compound, or may promote the production of two or more types of aromatic lactic acid compounds. The use of an active ingredient may promote the production of one or more aromatic lactic acid compounds selected from, for example, ILA, HPLA, and PLA. Preferably, the use of an active ingredient may promote the production of ILA and / or HPLA.

[0014] Furthermore, by utilizing an active ingredient, specifically by administering the active ingredient to a subject, for example, an effect based on the promotion of aromatic lactic acid compound production may be obtained. Examples of effects based on the promotion of aromatic lactic acid compound production include effects on symptoms and diseases that can be prevented, improved, and / or treated by aromatic lactic acid compounds. Examples of effects based on the promotion of aromatic lactic acid compound production include effects on the prevention, improvement, and / or treatment of symptoms and diseases that can be prevented, improved, and / or treated by aromatic lactic acid compounds.

[0015] ILA may have the function of improving neurite outgrowth, for example (Non-Patent Document 2: Chyn Boon Wong et al. Potential Effects of Indole-3-Lactic Acid, a Metabolite of Human Bifidobacteria, on NGF-Induced Neurite Outgrowth in PC12 Cells. Microorganisms. 2020 Mar; 8(3): 398.). Therefore, promoting the production of aromatic lactic acid compounds may improve neurite outgrowth. For example, an effect of improving neurite outgrowth may be obtained in a subject in which the production of aromatic lactic acid compounds is promoted (i.e., a subject to which the active ingredient is administered). This effect is also referred to as a "neurite outgrowth improving effect." In other words, an effect based on the promotion of the production of aromatic lactic acid compounds includes a neurite outgrowth improving effect.

[0016] Improvement in neurite outgrowth may be an indicator of neuronal differentiation. Therefore, neuronal differentiation may be promoted by using an active ingredient, specifically by administering the active ingredient to a subject, i.e., an effect of promoting neuronal differentiation may be obtained. This effect is also referred to as a "neuronal differentiation promoting effect." In other words, an effect based on promoting the production of aromatic lactic acid compounds includes a neuronal differentiation promoting effect. In other words, improvement in neurite outgrowth may be obtained by promoting neuronal differentiation. In other words, the neurite outgrowth improving effect may be an example of a neuronal differentiation promoting effect. The neuronal differentiation promoting effect can be confirmed, for example, by confirming the neurite outgrowth improving effect.

[0017] The neuronal differentiation promoting effect can also be confirmed, for example, by confirming an increase in acetylcholinesterase (AchE) activity in a subject. Specifically, the neuronal differentiation promoting effect can be confirmed, for example, when the AchE activity in a sample obtained from a subject after administration of an active ingredient is greater than the AchE activity in a sample obtained from the subject before administration of the active ingredient. AchE activity can be measured, for example, using an Amplite Fluorimetric Acetylcholinesterase Assay Kit (AAT Bioquest, Sunnyvale, CA, USA). The sample used to confirm the neuronal differentiation promoting effect is not particularly limited, as long as it contains neurons. The sample can be obtained, for example, by biopsy from a subject.

[0018] Furthermore, by utilizing the active ingredient, specifically by administering the active ingredient to a subject, effects based on the promotion of neuronal differentiation and / or the improvement of neurite outgrowth may be obtained. The promotion of neuronal differentiation and / or the improvement of neurite outgrowth may, for example, protect and / or improve neural function. That is, the promotion of neuronal differentiation and / or the improvement of neurite outgrowth may, for example, prevent, improve, and / or treat symptoms associated with nerve disorders. That is, effects based on the promotion of aromatic lactic acid compound production (specifically, effects based on the promotion of neuronal differentiation and / or the improvement of neurite outgrowth) include the effects of protecting neural function, improving neural function, and preventing, improving, and / or treating symptoms associated with nerve disorders. Symptoms associated with nerve disorders may or may not be disease. In other words, symptoms associated with nerve disorders may or may not be caused by disease. Symptoms associated with nerve disorders include neurodegenerative diseases, or in other words, symptoms caused by neurodegenerative diseases. Neurodegenerative diseases include diseases involving disorders of neuronal differentiation or disorders of neurite outgrowth.Specific examples of neurodegenerative diseases include Alzheimer's disease (AD), dementia (dementia with Lewy bodies (DLB), etc.), frontotemporal lobar degeneration (FTLD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), Huntington's disease, dystonia, transmissible spongiform encephalopathy (TSE), chorea-acanthocytosis (ChAc), adrenoleukodystrophy (ALD), multiple system atrophy (MSA), and spinocerebellar degeneration (SCD). These include spinal and bulbar muscular atrophy (SBMA), spinal muscular atrophy (SMA), Charcot-Marie-Tooth disease (CMT), and Batten disease.

[0019] It has been reported that kynurenine, a tryptophan metabolite, can cross the blood-brain barrier (Psychoneuroendocrinology. 2018;94:1-10. doi:10.1016 / j.psyneuen.2018.04.019.). Therefore, it is expected that aromatic lactic acid compounds such as ILA can cross the blood-brain barrier.

[0020] ILA may regulate the immune balance of newborn infants by, for example, promoting the production of immunoregulatory galectin-1, thereby reducing Th2 and Th17 cytokines and inducing Th1 cytokines such as interferon-β (Bethany M. Henrick et al., Bifidobacteria-Mediated Immune System Imprinting Early in Life, Cell. 2021 July; 184: 1-15.). Therefore, promoting the production of aromatic lactic acid compounds may improve immune function in subjects whose production of aromatic lactic acid compounds is promoted (i.e., subjects to whom the active ingredient is administered), i.e., may provide an immune function-improving effect. This effect is also referred to as an "immune function-improving effect." In other words, an example of an effect based on promoting the production of aromatic lactic acid compounds is an immune function-improving effect. The immune function-improving effect may be obtained, for example, in infants. Improvement of immune function may provide, for example, the effect of preventing, ameliorating, and / or treating symptoms and diseases associated with immune abnormalities. That is, effects based on the promotion of the production of aromatic lactic acid compounds (specifically, the effect of improving immune function) include the prevention, amelioration, and / or treatment of symptoms and diseases associated with immune abnormalities. Examples of symptoms and diseases associated with immune abnormalities include allergies and autoimmune diseases. Examples of allergies include atopic dermatitis, allergic rhinitis, allergic conjunctivitis, allergic gastroenteritis, bronchial asthma, childhood asthma, food allergies, drug allergies, and urticaria. Examples of autoimmune diseases include Graves' disease, rheumatoid arthritis, Hashimoto's thyroiditis, type 1 diabetes, systemic lupus erythematosus, and vasculitis.

[0021] ILA is known to act as an agonist of the aryl hydrocarbon receptor (AhR) in intestinal epithelial cells and neurons, thereby exerting anti-inflammatory effects, for example (Ehrlich et al. Indole-3-lactic acid associated with Bifidobacterium-dominated microbiota significantly decreases inflammation in intestinal epithelial cells. BMC Microbiology. 2020 20:357. and Wong et al. Potential Effects of Indole-3-Lactic Acid, a Metabolite of Human Bifidobacteria, on NGF-Induced Neurite Outgrowth in PC12 Cells. Microorganisms. 2020 Mar; 8(3): 398.). Therefore, by promoting the production of aromatic lactic acid compounds, for example, anti-inflammatory, antioxidant, and / or antibacterial effects may be obtained in subjects in which the production of aromatic lactic acid compounds is promoted (i.e., subjects to which the active ingredient has been administered). That is, effects based on the promotion of aromatic lactic acid compound production include anti-inflammatory effects, antioxidant effects, and antibacterial effects. Anti-inflammatory, antioxidant, and / or antibacterial effects may result in, for example, the prevention, amelioration, and / or treatment of inflammation and inflammatory diseases. That is, effects based on the promotion of aromatic lactic acid compound production (specifically, anti-inflammatory, antioxidant, or antibacterial effects) include the prevention, amelioration, and / or treatment of inflammation and inflammatory diseases. Examples of inflammation and inflammatory diseases include encephalitis, osteomyelitis, meningitis, neuritis, dermatitis, myositis, hepatitis, pancreatitis, vascular inflammation (arteritis, phlebitis, capillitis, etc.), heart inflammation (endocarditis, myocarditis, pericarditis, etc.), eye inflammation (dacryoadenitis, keratitis, retinitis, conjunctivitis, etc.), ear inflammation (otitis externa, otitis media, otitis interna, etc.), respiratory inflammation (sinusitis, rhinitis, pharyngitis, laryngitis, bronchitis, pneumonia, etc.), oral inflammation (stomatitis, glossitis, tonsillitis, etc.), digestive inflammation (esophagitis, gastritis, enteritis, appendicitis, etc.), and urinary inflammation (nephritis, cystitis, prostatitis, etc.).

[0022] The present invention may provide use of an active ingredient for achieving the effects exemplified above. That is, the present invention may provide use of an active ingredient for promoting aromatic lactic acid compound production, promoting neuronal differentiation, improving neurite outgrowth, preventing, ameliorating, and / or treating symptoms associated with neurological disorders, improving immune function, anti-inflammatory, antioxidant, and / or antibacterial. The present invention may also provide use of an active ingredient for manufacturing a composition for promoting aromatic lactic acid compound production, promoting neuronal differentiation, improving neurite outgrowth, preventing, ameliorating, and / or treating symptoms associated with neurological disorders, improving immune function, anti-inflammatory, antioxidant, and / or antibacterial.

[0023] The present invention may provide an active ingredient used to achieve the effects exemplified above. That is, the present invention may provide an active ingredient used for promoting aromatic lactic acid compound production, promoting neuronal differentiation, improving neurite outgrowth, preventing, ameliorating, and / or treating symptoms associated with neuropathy, improving immune function, anti-inflammatory, antioxidant, and / or antibacterial purposes. The present invention may also provide an active ingredient used for manufacturing a composition for promoting aromatic lactic acid compound production, promoting neuronal differentiation, improving neurite outgrowth, preventing, ameliorating, and / or treating symptoms associated with neuropathy, improving immune function, anti-inflammatory, antioxidant, and / or antibacterial purposes.

[0024] The active ingredient may be used for therapeutic or non-therapeutic purposes, i.e., the effects exemplified above may be obtained for therapeutic or non-therapeutic purposes, unless otherwise specified.

[0025] "Therapeutic purposes" may refer to a concept including, for example, medical procedures, and specifically, may refer to a concept including treatment of the human body through therapy.

[0026] "Non-therapeutic purposes" may refer to, for example, a concept that does not include medical procedures, and more specifically, a concept that does not include therapeutic treatment of the human body. Non-therapeutic purposes include health promotion and cosmetic purposes.

[0027] "Prevention of a symptom or disease" may mean, for example, preventing and / or delaying the onset of a symptom or disease, or reducing the likelihood of onset of a symptom or disease. "Amelioration of a symptom or disease" or "treatment of a symptom or disease" may mean, for example, improvement of a symptom or disease, prevention or delay of worsening of a symptom or disease, or prevention or delay of progression of a symptom or disease. "Amelioration of a symptom or disease" may particularly refer to these events, which are achieved for non-therapeutic purposes. "Treatment of a symptom or disease" may particularly refer to these events, which are achieved for therapeutic purposes.

[0028] Examples of resistant oligosaccharides include milk oligosaccharides, fructooligosaccharides, galactooligosaccharides, mannooligosaccharides, cellooligosaccharides, xylooligosaccharides, lactosucrose, and raffinose. In one embodiment, examples of resistant oligosaccharides include milk oligosaccharides, fructooligosaccharides, galactooligosaccharides, mannooligosaccharides, xylooligosaccharides, lactosucrose, and raffinose. The degree of polymerization of the resistant oligosaccharides may be, for example, 2 to 10 residues, 2 to 7 residues, or 2 to 5 residues. The degree of polymerization of the resistant oligosaccharides may be, for example, 2 residues, 3 residues, or 4 residues. Examples of milk oligosaccharides include oligosaccharides that can be produced using milk as a raw material. Specific examples of milk oligosaccharides include oligosaccharides that can be produced using lactose as a raw material. More specific examples of milk oligosaccharides include lactulose. Fructooligosaccharides include those in which one or more fructose residues are bonded to the fructose residue of sucrose. Specific examples of fructooligosaccharides include 1-kestose (also called "GF2"), nystose (also called "GF3"), 1-kestose (also called "GF4"), 1-kestose (also called "GF5"), 1-kestose (also called "GF6"), 1-kestose (also called "GF7"), 1-kestose (also called "GF8"), 1-kestose (also called "GF9"), 1-kestose (also called "GF10"), 1-kestose (also called "GF11"), 1-kestose (also called "GF12"), 1-kestose (also called "GF13"), 1-kestose (also called "GF14"), 1-kestose (also F -β-fructofuranosylnystose (1 Fβ-beta-fructofuranosylnystose; also referred to as "GF4"). Galactooligosaccharides include those in which one or more galactose residues are linked to the galactose residue of lactose. Specific examples of galactooligosaccharides include 4'-galactosyllactose. Mannooligosaccharides include oligosaccharides that can be produced by the degradation of mannan. Specific examples of mannooligosaccharides include mannobiose, mannotriose, mannotetraose, mannopentaose, mannohexaose, mannoheptaose, mannooctaose, mannononaose, and mannodecaose. Cellooligosaccharides include oligosaccharides that can be produced by the degradation of cellulose. Specific examples of cellooligosaccharides include cellobiose, cellotriose, and cellotetraose. Cellobiose is a particular example of cellooligosaccharides. Xylooligosaccharides include oligosaccharides that can be produced by the decomposition of xylan. Specific examples of xylooligosaccharides include xylobiose, xylotriose, and xylotetraose. Xylooligosaccharides particularly include xylobiose. As the indigestible oligosaccharides, one type of oligosaccharide may be used, or two or more types of oligosaccharides may be used in combination.

[0029] The resistant oligosaccharides may be commercially available or may be obtained by appropriate production. For example, commercially available lactulose products include milk oligosaccharide MLS (registered trademark)-50 and milk oligosaccharide MLC (registered trademark)-97 (both manufactured by Morinaga Milk Industry Co., Ltd.). The method for producing the resistant oligosaccharides is not particularly limited. Resistant oligosaccharides can be produced by known methods, for example. Specifically, resistant oligosaccharides can be produced by, for example, chemical synthesis, enzymatic reaction, or extraction. For example, lactulose can be produced using lactose as a raw material by the methods described in Japanese Patent Application Laid-Open No. 3-169888 or Japanese Patent Application Laid-Open No. 6-228179. The resistant oligosaccharides may be purified to a desired degree or not. That is, purified products or materials containing resistant oligosaccharides may be used as the resistant oligosaccharides. The content of indigestible oligosaccharides in the material may be, for example, 10% by weight or more, 30% by weight or more, 50% by weight or more, 70% by weight or more, or 90% by weight or more relative to the dry weight of the material.

[0030] When a material containing indigestible oligosaccharides is used, the amount of indigestible oligosaccharides (e.g., the content in the composition of the present invention or the dosage in the method of the present invention) is calculated based on the amount of indigestible oligosaccharides themselves contained in the material.

[0031] Bifidobacterium bacteria include Bifidobacterium longum, Bifidobacterium breve, Bifidobacterium bifidum, Bifidobacterium adolescentis, Bifidobacterium angulatum, Bifidobacterium dentium, Bifidobacterium pseudocatenulatum, Bifidobacterium animalis, and Bifidobacterium pseudolongum. Examples of the genus Bifidobacterium include Bifidobacterium pseudolongum and Bifidobacterium thermophilum. Examples of the genus Bifidobacterium include Bifidobacterium breve. As the genus Bifidobacterium, one type of bacterium may be used, or two or more types of bacteria may be used in combination.

[0032] "Bifidobacterium longum" includes strains classified into any subspecies of Bifidobacterium longum, such as B. longum subsp. longum, B. longum subsp. infantis, and B. longum subsp. suis. "Bifidobacterium animalis" includes strains classified into any subspecies of Bifidobacterium animalis, such as B. animalis subsp. lactis. "Bifidobacterium pseudolongum" includes strains classified into any subspecies of Bifidobacterium pseudolongum, such as B. pseudolongum subsp. globosum and B. pseudolongum subsp. pseudolongum.

[0033] The Bifidobacterium bacterium may be, for example, a bacterium capable of producing an aromatic lactic acid compound such as ILA. The Bifidobacterium bacterium may be, for example, a bacterium capable of producing an aromatic lactic acid compound from a carbon source and / or tryptophan. Specifically, the Bifidobacterium bacterium may be a bacterium capable of producing an aromatic lactic acid compound in a subject when administered to the subject. More specifically, the Bifidobacterium bacterium may be a bacterium capable of producing an aromatic lactic acid compound in the intestine of a subject when administered to the subject. For example, infant-type human-residential bifidobacteria (HRB) have been reported to produce significantly higher concentrations of ILA than adult-type HRB and non-HRB (Sakurai et al., Production of Indole-3-Lactic Acid by Bifidobacterium Strains Isolated from Human Infants. Microorganisms. 2019 Sep 11;7(9).). Therefore, infant-type HRB are particularly important Bifidobacterium species. Examples of infant-type HRB include Bifidobacterium longum (e.g., Bifidobacterium longum subsp. longum and Bifidobacterium longum subsp. infantis), Bifidobacterium breve, and Bifidobacterium bifidum.

[0034] Bifidobacterium longum, specifically BB536 (NITE BP-02621), ATCC 15697, ATCC 15707, ATCC 25962, ATCC 15702, ATCC 27533, M-63 (NITE BP-02623), BG7, DSM 24736, SBT 2928, NCC 490 (CNCM I-2170), and NCC 2705 (CNCM I-2618). Bifidobacterium longum may be used in combination with one strain or two or more strains.

[0035] Specific examples of Bifidobacterium breve include M-16V (NITE BP-02622), MCC1274 (FERM BP-11175), ATCC 15700, B632 (DSM 24706), Bb99 (DSM 13692), ATCC 15698, DSM 24732, UCC2003, YIT4010, YIT4064, BBG-001, BR-03, C50, and R0070. Examples of Bifidobacterium breve include MCC1274 (FERM BP-11175). Bifidobacterium breve may be used alone or in combination of two or more strains.

[0036] Examples of Bifidobacterium bifidum include ATCC 29521, NITE BP-02429, NITE BP-02431, OLB6378, and BF-1. Examples of Bifidobacterium adolescentis include ATCC 15703. Examples of Bifidobacterium dentium include DSM 20436. Examples of Bifidobacterium animalis include DSM 10140, Bb-12, DN-173 010, GCL2505, and CNCM I-3446. Examples of Bifidobacterium pseudolongum include JCM 5820 and ATCC 25526. Examples of Bifidobacterium thermophilum include ATCC 25525.

[0037] Bifidobacterium breve MCC1274 (FERM BP-11175) was internationally deposited on August 25, 2009, in accordance with the Budapest Treaty with the Patent Organism Deposit Center of the National Institute of Advanced Industrial Science and Technology (currently the Patent Organism Deposit Center (IPOD) of the National Institute of Technology and Evaluation, Japan; postal code: 292-0818; address: Room 120, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan), and has been assigned the accession number FERM BP-11175.

[0038] These strains are available from, for example, the American Type Culture Collection (ATCC, Address: 10801 Strains can be obtained from the Belgian Coordinated Collections of Microorganisms (BCCM, Address: Rue de la Science 8, 1000 Brussels, Belgium), the Belgian Coordinated Collections of Microorganisms (BCCM, Address: Rue de la Science 8, 1000 Brussels, Belgium), the German Collection of Microorganisms and Cell Cultures (DSMZ, Address: Inhoffenstr. 7B, D38124 Braunschweig, Germany), the Japan Collection of Microorganisms (JCM, Postal Code: 305-0074, Address: Microbial Materials Development Division, RIKEN BioResource Research Center, 3-1-1 Takanodai, Tsukuba, Ibaraki, Japan), or from the depository institutions where the respective strains were deposited.

[0039] The strains identified by the strain names exemplified above are not limited to the strains themselves deposited or registered with a designated institution under those strain names (hereinafter, for convenience of explanation, also referred to as "deposited strains"), but also include strains that are substantially equivalent to those deposited strains (hereinafter, also referred to as "derived strains"). For example, "Bifidobacterium breve MCC1274 (FERM BP-11175)" refers not only to the strain deposited at the depository under the accession number FERM BP-11175, but also to strains substantially equivalent to the deposited strain. A "strain substantially equivalent to the deposited strain" refers to a strain that belongs to the same species as the deposited strain, has the function of an active ingredient (i.e., the function of promoting the production of aromatic lactic acid compounds in combination with indigestible oligosaccharides), has a nucleotide sequence of its 16S rRNA gene that is preferably 99.86% or more, more preferably 99.93% or more, and even more preferably 100% identical to the nucleotide sequence of the 16S rRNA gene of the deposited strain, and preferably has the same biological properties as the deposited strain. A strain substantially equivalent to the deposited strain may be, for example, a derivative strain obtained using the deposited strain as a parent strain. Derivative strains include strains bred from the deposited strain and strains that naturally arise from the deposited strain. Breeding methods include modification by genetic engineering techniques and modification by mutation treatment. Mutation treatments include X-ray irradiation, ultraviolet irradiation, and treatment with mutagens (N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), ethyl methanesulfonate (EMS), methyl methanesulfonate (MMS), etc.). Strains naturally derived from the deposited strain include strains naturally derived during use of the deposited strain. Use of the deposited strain includes culturing (e.g., subculturing) the deposited strain. Derivative strains may be constructed by one type of modification, or by two or more types of modifications.

[0040] Bifidobacterium bacteria may be commercially available or may be obtained by appropriate manufacturing process. Commercially available Bifidobacterium bacteria include Bifidobacterium longum subsp. longum BB536, Bifidobacterium breve M-16V, Bifidobacterium breve MCC1274, and Bifidobacterium longum subsp. infantis M-63, all manufactured by Morinaga Milk Industry Co., Ltd.

[0041] The term "bifidobacterium bacteria" as an active ingredient may refer to bacterial cells of Bifidobacterium bacteria. Bifidobacterium bacteria can be easily obtained by culturing Bifidobacterium bacteria. The culturing method is not particularly limited as long as it allows the proliferation of Bifidobacterium bacteria. As the culturing method, for example, a method commonly used for culturing Bifidobacterium bacteria can be used as is, or with appropriate modifications. The culture temperature may be, for example, 25 to 50°C, preferably 35 to 42°C. The culture may be preferably carried out under anaerobic conditions, for example, while aerating with anaerobic gas such as carbon dioxide. Alternatively, the culture may be carried out under microaerobic conditions, such as liquid static culture. The culture may be carried out, for example, until the Bifidobacterium bacteria have proliferated to a desired level.

[0042] The medium used for culturing is not particularly limited as long as it allows the proliferation of Bifidobacterium bacteria. For example, media commonly used for culturing Bifidobacterium bacteria can be used as is or with appropriate modifications. The medium may contain, for example, a carbon source, a nitrogen source, inorganic salts, organic components, milk components, or a combination thereof. Examples of carbon sources include sugars such as galactose, glucose, fructose, mannose, cellobiose, maltose, lactose, sucrose, trehalose, starch, starch hydrolysates, and blackstrap molasses. These sugars can be used depending on the assimilation ability of Bifidobacterium bacteria. Examples of nitrogen sources include ammonia, ammonium salts such as ammonium sulfate, ammonium chloride, and ammonium nitrate, or nitrates. Examples of inorganic salts include sodium chloride, potassium chloride, potassium phosphate, magnesium sulfate, calcium chloride, calcium nitrate, manganese chloride, and ferrous sulfate. Examples of organic ingredients include peptone, soybean flour, defatted soybean meal, meat extract, and yeast extract. Examples of dairy ingredients include milk proteins. Examples of dairy proteins include casein, whey, and their hydrolyzates. These ingredients may be used alone or in appropriate combinations. Specific examples of media that can be used to culture Bifidobacterium include Reinforced Clostridial medium, de Man, Rogosa, and Sharpe medium (MRS medium), modified MRS medium (mMRS medium), TOS propionate medium (TOSP medium), and TOS propionate mupirocin medium (TOSP Mup medium).

[0043] The Bifidobacterium bacteria may be the Bifidobacterium bacteria themselves or a fraction containing the Bifidobacterium bacteria. That is, for example, a culture solution of Bifidobacterium bacteria may be used as is, or bacterial cells recovered from the culture solution may be used. Furthermore, the bacterial cells or a fraction containing the Bifidobacterium bacteria may be subjected to a treatment before use. The treatment is not particularly limited as long as it does not impair the desired effect, such as the effect of promoting aromatic lactic acid compound production. Preferably, the treatment does not significantly reduce the viability of the bacterial cells. Examples of treatment include dilution, concentration, freezing, and drying. That is, examples of Bifidobacterium bacteria (specifically, Bifidobacterium bacteria) include a culture solution of Bifidobacterium bacteria, bacterial cells recovered from the culture solution, and processed products thereof (dilutions, concentrates, frozen products, dried products, etc.). Specific examples of treatment include freezing of the culture solution, spray drying, freeze-drying, and the oil drop method. The bacterial cells contain live bacterial cells, and may or may not contain dead bacterial cells.

[0044] <2> Compositions of the Invention The composition of the present invention is a composition containing an active ingredient.

[0045] That is, the composition of the present invention is a composition containing the following components (A) and (B): (A) indigestible oligosaccharides; (B) Bifidobacterium bacteria.

[0046] The composition of the present invention can be administered to a subject. Specifically, the composition of the present invention can be administered to a subject as described in the method of the present invention. The composition of the present invention can be used, for example, to achieve the effects exemplified above.

[0047] By utilizing the composition of the present invention, specifically by administering the composition of the present invention to a subject, the production of aromatic lactic acid compounds may be promoted in the subject, i.e., an aromatic lactic acid compound production promoting effect may be obtained. That is, the composition of the present invention may be, for example, a composition for promoting the production of aromatic lactic acid compounds. Furthermore, the composition of the present invention may be, for example, a composition for use in promoting the production of aromatic lactic acid compounds.

[0048] Furthermore, by utilizing the composition of the present invention, specifically by administering the composition of the present invention to a subject, for example, an effect based on the promotion of aromatic lactic acid compound production may be obtained. That is, the composition of the present invention may be, for example, a composition for obtaining an effect based on the promotion of aromatic lactic acid compound production. Furthermore, the composition of the present invention may be, for example, a composition for use in achieving an effect based on the promotion of aromatic lactic acid compound production. A composition for obtaining an effect based on the promotion of aromatic lactic acid compound production may be an example of a composition for promoting aromatic lactic acid compound production.

[0049] By utilizing the composition of the present invention, specifically by administering the composition of the present invention to a subject, for example, neurite outgrowth may be improved in the subject, i.e., a neurite outgrowth improving effect may be obtained. That is, the composition of the present invention may be, for example, a composition for improving neurite outgrowth. Furthermore, the composition of the present invention may be, for example, a composition for use in improving neurite outgrowth. The composition for improving neurite outgrowth may be an example of a composition for promoting aromatic lactic acid compound production.

[0050] By utilizing the composition of the present invention, specifically by administering the composition of the present invention to a subject, for example, neuronal differentiation may be promoted, i.e., a neuronal differentiation promoting effect may be obtained. That is, the composition of the present invention may be, for example, a composition for promoting neuronal differentiation. Furthermore, the composition of the present invention may be, for example, a composition for use in promoting neuronal differentiation. A composition for improving neurite outgrowth may be an example of a composition for promoting neuronal differentiation. A composition for improving neurite outgrowth may be an example of a composition for promoting aromatic lactic acid compound production.

[0051] By using the compositions of the present invention, specifically by administering the compositions of the present invention to a subject, effects based on, for example, the promotion of neuronal differentiation and / or the improvement of neurite outgrowth may be obtained. That is, the compositions of the present invention may be, for example, compositions for obtaining effects based on the promotion of neuronal differentiation and / or the improvement of neurite outgrowth. Furthermore, the compositions of the present invention may be, for example, compositions for use in achieving effects based on the promotion of neuronal differentiation and / or the improvement of neurite outgrowth. Specifically, the compositions of the present invention may be, for example, compositions for preventing, ameliorating, and / or treating symptoms associated with neurological disorders. Furthermore, specifically, the compositions of the present invention may be, for example, compositions for use in the prevention, amelioration, and / or treatment of symptoms associated with neurological disorders. A composition for obtaining effects based on the promotion of neuronal differentiation and / or the improvement of neurite outgrowth (such as a composition for preventing, ameliorating, and / or treating symptoms associated with neurological disorders) may be an example of a composition for promoting neuronal differentiation and / or a composition for improving neurite outgrowth. A composition for obtaining effects based on promoting neuronal differentiation and / or improving neurite outgrowth (such as a composition for preventing, ameliorating, and / or treating symptoms associated with neurological disorders) may be an example of a composition for promoting aromatic lactic acid compound production.

[0052] By utilizing the composition of the present invention, specifically by administering the composition of the present invention to a subject, for example, immune function may be improved, i.e., an immune function improving effect may be obtained. That is, the composition of the present invention may be, for example, a composition for improving immune function. Furthermore, the composition of the present invention may be, for example, a composition for use in improving immune function. The composition for improving immune function may be an example of a composition for promoting aromatic lactic acid compound production.

[0053] By utilizing the composition of the present invention, specifically by administering the composition of the present invention to a subject, for example, anti-inflammatory, antioxidant, and / or antibacterial effects may be obtained. That is, the composition of the present invention may be, for example, an anti-inflammatory, antioxidant, and / or antibacterial composition. Furthermore, the composition of the present invention may be, for example, a composition for use in anti-inflammatory, antioxidant, and / or antibacterial applications. An anti-inflammatory, antioxidant, and / or antibacterial composition may be an example of a composition for promoting aromatic lactic acid compound production.

[0054] The subject to which the composition of the present invention is administered can be subject to the same descriptions as those for the subject to which the active ingredient in the method of the present invention is administered.

[0055] The composition of the present invention may be, for example, a food or drink composition, a pharmaceutical composition, or a feed composition. The composition of the present invention may be, in particular, a food or drink composition or a pharmaceutical composition. That is, the composition of the present invention may contain, for example, a compound having an aromatic lactic acid compound (for example, an aromatic lactic acid compound) for obtaining the effects exemplified above. The compositions of the present invention may be food and beverage compositions for use in achieving the effects exemplified above (e.g., for promoting aromatic lactic acid compound production, promoting neuronal differentiation, improving neurite outgrowth, preventing, ameliorating, and / or treating symptoms associated with neuropathy, improving immune function, anti-inflammatory, antioxidant, and / or antibacterial). Furthermore, the compositions of the present invention may be food and beverage compositions for use in achieving the effects exemplified above (e.g., for promoting aromatic lactic acid compound production, promoting neuronal differentiation, improving neurite outgrowth, preventing, ameliorating, and / or treating symptoms associated with neuropathy, improving immune function, anti-inflammatory, antioxidant, and / or antibacterial). Furthermore, the compositions of the present invention may be pharmaceutical compositions for achieving the effects exemplified above (e.g., for promoting aromatic lactic acid compound production, promoting neuronal differentiation, improving neurite outgrowth, preventing, ameliorating, or treating symptoms associated with neuropathy, improving immune function, anti-inflammatory, antioxidant, and / or antibacterial). The composition of the present invention may also be a pharmaceutical composition for use in achieving the effects exemplified above (e.g., use in promoting the production of aromatic lactic acid compounds, use in promoting neuronal differentiation, use in improving neurite outgrowth, use in preventing, ameliorating, and / or treating symptoms associated with neurological disorders, use in improving immune function, anti-inflammatory use, antioxidant use, and / or antibacterial use). The composition of the present invention may also be a feed composition for achieving the effects exemplified above (e.g., for promoting the production of aromatic lactic acid compounds, promoting neuronal differentiation, improving neurite outgrowth, preventing, ameliorating, and / or treating symptoms associated with neurological disorders, improving immune function, anti-inflammatory use, antioxidant use, and / or antibacterial use). Furthermore, the composition of the present invention may be, for example, a feed composition for use in achieving the effects exemplified above (e.g., use in promoting the production of aromatic lactic acid compounds, use in promoting neuronal differentiation, use in improving neurite outgrowth, use in preventing, ameliorating, and / or treating symptoms associated with neurological disorders, use in improving immune function, use in anti-inflammatory, antioxidant, and / or antibacterial use).The composition of the present invention, which is a food or drink composition, a pharmaceutical composition, or a feed composition, is also referred to as the "food or drink composition of the present invention," the "pharmaceutical composition of the present invention," or the "feed composition of the present invention," respectively.

[0056] The composition of the present invention may consist of an active ingredient, or may contain additional ingredients in addition to the active ingredient.

[0057] The additional component is not particularly limited as long as it does not impair the desired effect, such as the effect of promoting aromatic lactic acid compound production. Any additional component that is acceptable depending on the mode of use of the composition of the present invention can be used. Examples of the additional component include components that can be incorporated into foods and beverages, pharmaceuticals, or feeds. Specific examples of the additional component include the components exemplified for the food and beverage compositions, pharmaceutical compositions, or feed compositions described below. The additional component may be a single component, or a combination of two or more components.

[0058] The contents and ratios of the components (i.e., the active ingredient and optionally additional ingredients) in the composition of the present invention are not particularly limited, as long as the desired effect, such as the effect of promoting aromatic lactic acid compound production, is achieved. The contents and ratios of the components in the composition of the present invention can be appropriately set depending on various conditions, such as the type of active ingredient, the type of additional ingredient, the type, dosage form, and method of use of the composition of the present invention, the type, age, and health condition of the subject to be administered.

[0059] The total content of the active ingredients in the composition of the present invention is greater than 0% by weight and less than 100% by weight. The total content of the active ingredients in the composition of the present invention may be, for example, 0.1% by weight or more, 0.5% by weight or more, 1% by weight or more, 5% by weight or more, 10% by weight or more, 30% by weight or more, 50% by weight or more, 70% by weight or more, or 90% by weight or more, or 100% by weight or less, 99.99% by weight or less, 99% by weight or less, 90% by weight or less, 70% by weight or less, 50% by weight or less, 30% by weight or less, 10% by weight or less, 5% by weight or less, or 1% by weight or less, or any compatible combination thereof.

[0060] The content of component (A) in the composition of the present invention may be, for example, 0.1 wt% or more, 0.3 wt% or more, 0.5 wt% or more, 1 wt% or more, 5 wt% or more, 10 wt% or more, 30 wt% or more, 50 wt% or more, 70 wt% or more, or 90 wt% or more, or 99.99 wt% or less, 99 wt% or less, 90 wt% or less, 70 wt% or less, 50 wt% or less, 30 wt% or less, 10 wt% or less, 5 wt% or less, or 1 wt% or less, or any compatible combination thereof. Specifically, the content of component (A) in the composition of the present invention may be, for example, 0.1 to 50 wt%, preferably 0.3 to 20 wt%, and more preferably 0.5 to 10 wt%.

[0061] The content of component (B) in the composition of the present invention is, for example, 1 × 10 in terms of the viable cell count of Bifidobacterium. 4 cells / g or more, 1×10 5 cells / g or more, 1×10 6 cells / g or more, 1×10 7 cells / g or more, or 1×10 8 cells / g or more, and may be 1×10 13 cells / g or less, 1×10 12 cells / g or less, or 1 x 10 11 The content of component (B) in the composition of the present invention may be, for example, 1 × 10 cells / g or less, calculated as the viable cell count of Bifidobacterium bacteria. 4 ~1×10 13 cells / g, 1 × 10 5 ~1×10 13 cells / g, 1 × 10 6 ~1×10 12 cells / g, preferably 1 x 10 7 ~1×10 11 cells / g, more preferably 1×10 8 ~1×10 10The dosage range may be cells / g. In the dosage ranges exemplified above, "cells" may be read as "cfu." "cfu" stands for colony forming unit.

[0062] The content of the active ingredient in the composition of the present invention may be set, for example, so as to achieve the dosage of the active ingredient mentioned in the method of the present invention.

[0063] The shape of the composition of the present invention is not particularly limited. As the shape of the composition of the present invention, any shape acceptable depending on the mode of use of the composition of the present invention can be adopted. Specific examples of the shape of the composition of the present invention include the shapes exemplified for food and beverage compositions, pharmaceutical compositions, and feed compositions described below.

[0064] <Food and drink composition> The food and drink composition of the present invention is not particularly limited as long as it contains an active ingredient. The food and drink composition may be provided in any form, such as a liquid, paste, solid, or powder.

[0065] The food and beverage composition may be, for example, a food or beverage itself, or a material used in the production of a food or beverage. Examples of such materials include seasonings, food additives, and other food ingredients. Specific examples of food and beverage compositions include flour products, instant foods, processed agricultural products, processed marine products, processed livestock products, dairy products (fermented milk, cheese, infant formula, etc.), oils and fats, basic seasonings, complex seasonings, frozen foods, confectioneries, beverages, and other commercially available foods and beverages. Examples of food and beverage compositions include dairy products such as fermented milk. Specific examples of food and beverage compositions include health foods, functional foods, enteral nutritional foods, special dietary foods, health-promoting foods (foods for specified health uses, foods with nutrient functions, foods with functional claims, etc.), nutritional supplements, and quasi-drugs. The food and beverage composition may also be a supplement, such as a tablet supplement.

[0066] The food and drink composition of the present invention can be produced, for example, by combining an active ingredient with an additional ingredient. The operation of combining an active ingredient with an additional ingredient is also referred to as "addition of an active ingredient." The method for producing the food and drink composition of the present invention is not particularly limited. The food and drink composition of the present invention can be produced, for example, using the same raw materials as ordinary foods and drinks and by the same method as ordinary foods and drinks, except for the addition of the active ingredient. The same applies when the food and drink composition of the present invention is produced as a material used in the production of foods and drinks. The addition of the active ingredient is carried out during the production process of the food and drink composition. The addition of the active ingredient may be carried out at any stage of the process. The active ingredient may be added, for example, during or after the production of the food or beverage composition. That is, for example, the food or beverage composition of the present invention may be produced by adding the active ingredient to a food or beverage that has been prepared in advance. The food or beverage composition of the present invention may also be produced through a fermentation process using the active ingredient (specifically, a fermentation process using component (B)). Food and beverage compositions produced through a fermentation process include fermented products such as fermented milk and probiotic drinks. That is, the active ingredient (specifically, component (B)) may be used, for example, as a starter for producing a fermented product. Naturally, the active ingredient can also be added to a fermented product that has been prepared in advance.

[0067] The food and beverage composition of the present invention can also be used to produce another food and beverage composition. That is, for example, when the food and beverage composition of the present invention is provided as a material (seasoning, food additive, other food and beverage raw material, etc.) used in the production of a food or beverage, another food and beverage composition may be produced by adding the food and beverage composition of the present invention. Such another food and beverage composition is also an example of the food and beverage composition of the present invention. With regard to the addition of the food and beverage composition of the present invention in the production of a food and beverage composition, the description regarding the addition of an active ingredient in the production of a food and beverage composition can be applied mutatis mutandis.

[0068] The food and drink composition of the present invention may be provided and sold as a food and drink labeled with the intended use (including health use), such as for promoting aromatic lactic acid compound production, for promoting nerve cell differentiation, for improving neurite outgrowth, for preventing, improving, and / or treating symptoms associated with nerve disorders, for improving immune function, for anti-inflammatory, antioxidant, and / or antibacterial purposes, etc. The food and drink composition of the present invention may be provided and sold as a food and drink labeled with the intended target.

[0069] "Representation" includes all actions to inform consumers of the aforementioned uses, and any expression that can recall or infer the aforementioned uses falls under "representation" regardless of the purpose, content, object, or medium of the representation. In particular, representation may be made using expressions that enable consumers to directly recognize the aforementioned uses.

[0070] Specific examples of labeling include the act of transferring, delivering, displaying for transfer or delivery, or importing a product related to the food and beverage composition of the present invention or a product package on which the above-mentioned use is written, as well as the act of displaying or distributing an advertisement, price list, or transaction document related to the product and writing the above-mentioned use therein, or the act of providing the information containing the above-mentioned use by electromagnetic means (such as the Internet). Examples of labeling include, in particular, labeling on packaging, containers, catalogs, pamphlets, promotional materials (such as POP) at sales sites, or other documents.

[0071] Examples of labeling include labeling as health foods, functional foods, enteral nutritional foods, special dietary foods, health functional foods (foods for specified health uses, foods with nutrient functions, foods with functional claims, etc.), dietary supplements, and quasi-drugs. Labeling may preferably be labeling approved by the government or the like (e.g., labeling approved under various systems established by the government and made in a manner based on such approval). Examples of labeling approved by the government or the like (e.g., the Consumer Affairs Agency) include labeling approved under systems for health functional foods (foods for specified health uses, foods with nutrient functions, foods with functional claims, etc.) and similar systems. Specific examples of labeling approved by the Consumer Affairs Agency include labeling as a food for specified health uses, labeling as a conditional food for specified health uses, labeling claiming an effect on the structure or function of the body, labeling claiming disease risk reduction, and labeling claiming functionality based on scientific evidence. More specifically, the labeling approved by the Consumer Affairs Agency includes labeling as a food for specified health uses (especially labeling for health uses) and similar labeling as stipulated in the Cabinet Office Ordinance on Permission for Labeling for Special Uses Provided for in the Health Promotion Act (Cabinet Office Ordinance No. 57 of August 31, 2009). Specific examples of labeling include "The combination of bifidobacteria and indigestible oligosaccharides promotes the production of ILA in the intestines" and "Promotes the production of ILA, which is known to regulate immune balance."

[0072] The content of the active ingredient in the food and drink composition of the present invention may be, for example, within the range described above. In particular, the content of component (B) in the food and drink composition of the present invention is, for example, 1 × 10 in terms of the viable cell count of Bifidobacterium bacteria. 4 ~1×10 13 cells / g, 1 × 10 5 ~1×10 13 cells / g, 1 × 10 6 ~1×10 12 cells / g, preferably 1 x 10 7 ~1×10 11 cells / g, more preferably 1×10 8 ~1×10 10It may be cells / g.

[0073] <Pharmaceutical Composition> The pharmaceutical composition of the present invention is not particularly limited as long as it contains an active ingredient.

[0074] The pharmaceutical composition of the present invention may be appropriately formulated into a desired dosage form. The dosage form of the pharmaceutical composition of the present invention is not particularly limited. The dosage form of the pharmaceutical composition of the present invention can be appropriately selected depending on various conditions such as the administration method. The pharmaceutical composition of the present invention may be for oral administration or for parenteral administration. The pharmaceutical composition of the present invention may particularly be for oral administration. In the case of oral administration, dosage forms include solid preparations such as powders, granules, tablets, and capsules, and liquid preparations such as solutions, syrups, suspensions, and emulsions. In the case of parenteral administration, dosage forms include suppositories and ointments.

[0075] The method of formulation is not particularly limited. Formulation can be carried out, for example, by a known method depending on the dosage form. Physiologically acceptable additives can be used in formulation. Examples of additives include various organic and inorganic components. Specific examples of additives include excipients, binders, disintegrants, lubricants, stabilizers, flavorings, pH adjusters, colorants, diluents, surfactants, and solvents. These additives can be appropriately selected depending on various conditions, such as the dosage form.

[0076] Examples of excipients include sugar derivatives such as lactose, sucrose, glucose, mannitol, and sorbitol; starch derivatives such as corn starch, potato starch, α-starch, dextrin, and carboxymethyl starch; cellulose derivatives such as crystalline cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, carboxymethyl cellulose, and carboxymethyl cellulose calcium; gum arabic; dextran; pullulan; silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate, and magnesium aluminometasilicate; phosphate derivatives such as calcium phosphate; carbonate derivatives such as calcium carbonate; and sulfate derivatives such as calcium sulfate.

[0077] Examples of binders include gelatin, polyvinylpyrrolidone, macrogol, and the like, in addition to the above-mentioned excipients.

[0078] Disintegrants include the above-mentioned excipients as well as chemically modified starch or cellulose derivatives such as croscarmellose sodium, carboxymethyl starch sodium, and cross-linked polyvinylpyrrolidone.

[0079] Lubricants include talc; stearic acid; metal stearates such as calcium stearate and magnesium stearate; colloidal silica; waxes such as beech and gazel; boric acid; glycol; carboxylic acids such as fumaric acid and adipic acid; sodium carboxylates such as sodium benzoate; sulfates such as sodium sulfate; leucine; lauryl sulfates such as sodium lauryl sulfate and magnesium lauryl sulfate; silicic acids such as silicic anhydride and silicic acid hydrate; and starch derivatives.

[0080] Stabilizers include parahydroxybenzoates such as methylparaben and propylparaben. alcohols such as chlorobutanol, benzyl alcohol, and phenylethyl alcohol; benzalkonium chloride; acetic anhydride; and sorbic acid.

[0081] Flavoring agents include sweeteners, acidulants, and fragrances.

[0082] The content of the active ingredient in the pharmaceutical composition of the present invention may be, for example, within the range described above. The content of component (B) in the pharmaceutical composition of the present invention is, in particular, 1 x 10 in terms of the viable cell count of Bifidobacterium. 4 ~1×10 13 cells / g, 1 × 10 5 ~1×10 13 cells / g, 1 × 10 6 ~1×10 12 cells / g, preferably 1 x 10 7 ~1×10 11 cells / g, more preferably 1×108 ~1×10 10 It may be cells / g.

[0083] <Feed composition> The feed composition of the present invention is not particularly limited as long as it contains an active ingredient. Examples of the feed composition include pet food and livestock feed. The feed composition may be provided in any form, such as powder, granules, crumbles, pellets, cubes, paste, or liquid.

[0084] The feed composition of the present invention can be produced, for example, by combining the active ingredient with an additional ingredient. The process of combining the active ingredient with an additional ingredient is also referred to as "addition of the active ingredient." The method for producing the feed composition of the present invention is not particularly limited. The feed composition of the present invention can be produced, for example, using the same raw materials as for ordinary feed and by the same method as for ordinary feed, except for the addition of the active ingredient. The active ingredient may be added at any stage in the production process of the feed composition. For example, the active ingredient may be added during or after the production of the feed composition. That is, for example, the feed composition of the present invention may be produced by adding the active ingredient to a pre-prepared feed. Alternatively, the feed composition of the present invention may be produced via a fermentation process using the active ingredient (specifically, a fermentation process using component (B)). An example of a feed composition produced via a fermentation process is silage.

[0085] <3> Methods of the Invention The method of the present invention is a method comprising administering an active ingredient to a subject. This step is also referred to as an "administration step." The subject to which the active ingredient is administered is also referred to as an "administration subject."

[0086] That is, the method of the present invention comprises administering the following components (A) and (B) to a subject: (A) Indigestible oligosaccharides; (B) Bifidobacterium bacteria.

[0087] The method of the present invention can be carried out, for example, to obtain the effects exemplified above.

[0088] By utilizing the method of the present invention, specifically by administering an active ingredient to a subject, the production of aromatic lactic acid compounds in the subject may be promoted, i.e., the effect of promoting the production of aromatic lactic acid compounds may be obtained. In other words, the method of the present invention may be, for example, a method for promoting the production of aromatic lactic acid compounds.

[0089] Furthermore, by utilizing the method of the present invention, specifically by administering an active ingredient to a subject, for example, an effect based on the promotion of aromatic lactic acid compound production may be obtained. That is, the method of the present invention may be, for example, a method for obtaining an effect based on the promotion of aromatic lactic acid compound production. A method for obtaining an effect based on the promotion of aromatic lactic acid compound production may be an example of a method for promoting the production of aromatic lactic acid compounds.

[0090] By utilizing the method of the present invention, specifically by administering an active ingredient to a subject, For example, neurite outgrowth may be improved in the subject, i.e., a neurite outgrowth-improving effect may be obtained. That is, the method of the present invention may be, for example, a method for improving neurite outgrowth. The method for improving neurite outgrowth may be an example of a method for promoting production of an aromatic lactic acid compound.

[0091] By utilizing the method of the present invention, specifically by administering an active ingredient to a subject, for example, neuronal differentiation may be promoted, i.e., a neuronal differentiation promoting effect may be obtained. That is, the method of the present invention may be, for example, a method for promoting neuronal differentiation. A method for improving neurite outgrowth may be an example of a method for promoting neuronal differentiation. A method for promoting neuronal differentiation may be an example of a method for promoting the production of aromatic lactic acid compounds.

[0092] By using the methods of the present invention, specifically by administering an active ingredient to a subject, effects based on, for example, the promotion of neuronal differentiation and / or the improvement of neurite outgrowth may be obtained. That is, the methods of the present invention may be, for example, methods for obtaining effects based on the promotion of neuronal differentiation and / or the improvement of neurite outgrowth. Specifically, the methods of the present invention may be, for example, methods for preventing, ameliorating, and / or treating symptoms associated with neurological disorders. A method for obtaining effects based on the promotion of neuronal differentiation and / or the improvement of neurite outgrowth (e.g., a method for preventing, ameliorating, and / or treating symptoms associated with neurological disorders) may be an example of a method for promoting neuronal differentiation or a method for improving neurite outgrowth. A method for obtaining effects based on the promotion of neuronal differentiation and / or the improvement of neurite outgrowth (e.g., a method for preventing, ameliorating, and / or treating symptoms associated with neurological disorders) may be an example of a method for promoting aromatic lactic acid compound production.

[0093] By utilizing the method of the present invention, specifically by administering an active ingredient to a subject, for example, immune function may be improved, i.e., an immune function improving effect may be obtained. That is, the method of the present invention may be, for example, a method for improving immune function. The method for improving immune function may be an example of a method for promoting the production of aromatic lactic acid compounds.

[0094] By utilizing the method of the present invention, specifically by administering an active ingredient to a subject, for example, an anti-inflammatory effect, an antioxidant effect, and / or an antibacterial effect may be obtained. That is, the method of the present invention may be, for example, a method for anti-inflammatory, antioxidant, and / or antibacterial effects. The method for anti-inflammatory, antioxidant, and / or antibacterial effects may be an example of a method for promoting the production of aromatic lactic acid compounds.

[0095] It should be noted that "administering an active ingredient to a subject" can be used interchangeably with or equivalent to "allowing a subject to ingest the active ingredient." Intake may be voluntary (i.e., free intake) or forced (i.e., forced intake). That is, the administration step may be, for example, a step of supplying the active ingredient (which may be incorporated into food, drink, or feed) to a subject, thereby allowing the subject to ingest the active ingredient freely. Administration may be oral administration or parenteral administration. Administration may typically be oral administration. Parenteral administration includes tube administration, rectal administration, and intranasal administration.

[0096] The conditions for administering the active ingredient (e.g., the subject, administration period, number of administrations, dosage, and other conditions related to administration) are not particularly limited as long as the desired effect, such as the effect of promoting aromatic lactic acid compound production, is achieved. The conditions for administering the active ingredient can be appropriately set depending on various conditions, such as the type of active ingredient, the type, age, and health condition of the subject.

[0097] The subject of administration is not particularly limited as long as the desired effect, such as the effect of promoting the production of aromatic lactic acid compounds, is achieved. The subject of administration includes mammals. Mammals include humans, monkeys, and the like. Examples of mammals include primates such as chimpanzees, rodents such as mice, rats, hamsters, and guinea pigs, and various other mammals such as rabbits, horses, cows, sheep, goats, pigs, dogs, and cats. Mammals include, in particular, humans. The subject (e.g., a mammal) may be, for example, a pet animal, livestock, or a laboratory animal. The subject may be a male or female subject. The subject may be of any age, for example, an infant, child, adult, middle-aged or elderly person, or elderly person. The subject may be, for example, a healthy subject or an unhealthy subject. An unhealthy subject may be a subject exhibiting symptoms associated with a neurological disorder. The subject may be, for example, a subject in need of prevention, amelioration, and / or treatment of symptoms associated with a neurological disorder.

[0098] The dosage of component (A) may be, for example, 0.1 mg / kg body weight / day or more, 0.5 mg / kg body weight / day or more, 1 mg / kg body weight / day or more, 5 mg / kg body weight / day or more, 10 mg / kg body weight / day or more, 50 mg / kg body weight / day or more, 100 mg / kg body weight / day or more, 200 mg / kg body weight / day or more, or 300 mg / kg body weight / day or less, 200 mg / kg body weight / day or less, 100 mg / kg body weight / day or less, 50 mg / kg body weight / day or less, 10 mg / kg body weight / day or less, 5 mg / kg body weight / day or less, or 1 mg / kg body weight / day or less, or any compatible combination thereof. Specifically, the dosage of the active ingredient may be, for example, 0.1 to 300 mg / kg body weight / day, preferably 1 to 300 mg / kg body weight / day, more preferably 10 to 100 mg / kg body weight / day.

[0099] The dose of component (B) is, for example, 1 x 10 viable bacteria of the genus Bifidobacterium. 6 cells / kg body weight / day or more, 1×10 7 cells / kg body weight / day or more, or 1 × 10 8 cells / kg body weight / day or more, but not more than 1 x 10 12 cells / kg body weight / day or less, 1×10 11 cells / kg body weight / day or less, or 1 x 10 11 The dosage of component (B) may be, for example, 1 x 10 cells / kg body weight / day or less, or any combination thereof that is not inconsistent with the dosage. 6 ~1×10 12 cells / kg body weight / day, preferably 1 × 10 7 ~1×10 11 cells / kg body weight / day, preferably 1×10 8 ~1×10 10 The term "cells" in the above-exemplified ranges of dosage may be read as "cfu."

[0100] The administration period of the active ingredient may be, for example, 1 day or more, 3 days or more, 1 week or more, 2 weeks or more, 4 weeks or more, 2 months or more, 3 months or more, 4 months or more, 6 months or more, 9 months or more, or 12 months or more, or 10 years or less, 5 years or less, 1 year or less, or 6 months or less, or any compatible combination thereof. The active ingredient may be administered, for example, throughout the subject's lifetime or for a portion of the subject's lifetime. The active ingredient may be administered, for example, until at least the desired effect, such as the effect of promoting aromatic lactic acid compound production, is achieved. The active ingredient may be administered, for example, daily or once every few days. The active ingredient may particularly be administered daily. The dosage of the active ingredient at each administration may or may not be constant. The active ingredients (A) and (B) may be administered simultaneously or may not be administered simultaneously. The active ingredients (A) and (B) may particularly be administered simultaneously.

[0101] For example, the active ingredient may be administered to a subject directly, or may be prepared as a composition containing the active ingredient, such as a food or beverage composition, a pharmaceutical composition, or a feed composition, and then administered to a subject. The description of the composition of the present invention applies mutatis mutandis to compositions containing the active ingredient. The active ingredient may be administered alone or in combination with additional components. Examples of additional components include foods, beverages, pharmaceuticals, feed, and components contained therein. Furthermore, the description of the additional components contained in the composition of the present invention applies mutatis mutandis to additional components used in the method of the present invention.

[0102] The active ingredient can be administered to a subject, for example, by using the composition of the present invention (specifically, by administering the composition of the present invention to a subject). That is, one embodiment of the method of the present invention may be a method comprising administering the composition of the present invention to a subject. That is, the "active ingredient" can be administered to a subject using the composition of the present invention. "Administration of a component" also includes administration of the composition of the present invention. The administration conditions of the composition of the present invention (e.g., administration subject, administration period, administration frequency, dosage, and other administration conditions) are not particularly limited as long as the desired effect, such as the effect of promoting aromatic lactic acid compound production, is achieved. The administration conditions of the composition of the present invention can be appropriately set depending on various conditions, such as the type and content of the active ingredient, the type and content of the additional ingredient, the type and dosage form of the composition, the type, age, and health condition of the administration subject. The administration conditions of the composition of the present invention can be applied mutatis mutandis to the descriptions of the administration conditions of the active ingredient. That is, the composition of the present invention may be administered to, for example, subjects such as those exemplified above. Furthermore, the dosage of the composition of the present invention can be set so as to obtain, for example, the dosage of the active ingredient exemplified above. Furthermore, the composition of the present invention may be administered alone or in combination with an additional ingredient.

[0103] <4> Method for producing aromatic lactic acid compound The active ingredient can also be used in vitro. The active ingredient can be used, for example, to produce aromatic lactic acid compounds. That is, another embodiment of the method of the present invention may be a method for producing aromatic lactic acid compounds, comprising culturing Bifidobacterium bacteria in a medium containing indigestible oligosaccharides. The indigestible oligosaccharides, Bifidobacterium bacteria, and aromatic lactic acid compounds are as described above. As the Bifidobacterium bacteria, bacteria capable of producing aromatic lactic acid compounds such as ILA may be selected.

[0104] The culture conditions are not particularly limited as long as a medium containing indigestible oligosaccharides is used and aromatic lactic acid compounds are produced. The culture conditions for obtaining the above-mentioned Bifidobacterium bacteria can be applied mutatis mutandis, except that a medium containing indigestible oligosaccharides is used. The medium may or may not contain a carbon source other than the indigestible oligosaccharides.

[0105] The concentration of resistant oligosaccharides in the medium is not particularly limited, as long as aromatic lactic acid compounds are produced. The concentration of resistant oligosaccharides in the medium may be, for example, 0.1% by weight or more, 0.2% by weight or more, 0.3% by weight or more, 0.5% by weight or more, 0.7% by weight or more, or 1% by weight or more, or 30% by weight or less, 20% by weight or less, 15% by weight or less, 10% by weight or less, 7% by weight or less, 5% by weight or less, 3% by weight or less, 2% by weight or less, or 1% by weight or less, or any compatible combination thereof. Specifically, the concentration of resistant oligosaccharides in the medium may be, for example, 0.1 to 30% by weight, preferably 0.2 to 20% by weight, and more preferably 0.5 to 10% by weight. The resistant oligosaccharides may be contained in the medium in the concentration range exemplified above at the start of culture, and / or may be added during culture to achieve the concentration range exemplified above.

[0106] The resistant oligosaccharides may or may not be present in the medium throughout the entire culture period. For example, the resistant oligosaccharides may or may not be present in the medium at a predetermined concentration range, such as the concentration ranges exemplified above, throughout the entire culture period. That is, the resistant oligosaccharides may be present in the medium at a concentration outside the predetermined concentration range, such as the concentration ranges exemplified above, during a portion of the culture period. The resistant oligosaccharides may be in short supply during a portion of the culture period. "Insufficient" means that the required amount is not met, and may mean, for example, that the concentration in the medium is zero. For example, the resistant oligosaccharides may or may not be present in the medium from the start of culture. If the resistant oligosaccharides are not present in the medium at the start of culture, they are supplied to the medium after the start of culture. The timing of supply can be appropriately determined depending on various conditions, such as the culture time. The resistant oligosaccharides may be supplied to the medium after the Bifidobacterium bacteria have grown sufficiently, for example. Furthermore, for example, the resistant oligosaccharides may be consumed during culture, resulting in a concentration of zero in the medium. A "partial period" may refer to, for example, 50% or less, 30% or less, 20% or less, 10% or less, 5% or less, or 1% or less of the total culture period. Thus, even if the resistant oligosaccharides are insufficient for a partial period, as long as there is a culture period in the medium containing the resistant oligosaccharides, this is included in "culturing Bifidobacterium bacteria in a medium containing the resistant oligosaccharides." The resistant oligosaccharides may generally be contained in the medium at least throughout the desired period for the production of aromatic lactic acid compounds.

[0107] By culturing Bifidobacterium bacteria in this manner, aromatic lactic acid compounds are produced, and thus a culture containing aromatic lactic acid compounds can be obtained.

[0108] The production of aromatic lactic acid compounds can be confirmed by known techniques used for detecting or identifying compounds, such as HPLC, UPLC, LC / MS, GC / MS, and NMR.

[0109] The aromatic lactic acid compound can be appropriately recovered from the culture (specifically, from the medium). That is, the method for producing an aromatic lactic acid compound may further include recovering the aromatic lactic acid compound from the culture. The recovery of the aromatic lactic acid compound can be carried out, for example, by a known method used for separating and purifying compounds. Such methods include an ion exchange resin method, a membrane treatment method, a precipitation method, an extraction method, a distillation method, and a crystallization method. The aromatic lactic acid compound may be purified to a desired purity. [Example]

[0110] The present invention will now be described in more detail with reference to the following non-limiting examples.

[0111] Test Example 1: Neutralization culture 100 ml of the mixture from Section A of YCFA medium shown in Table 1 was placed in a pH-controllable culture vessel, Bio Jr. 8 (BJR-25NA1S-8M, Biot Co., Ltd.). 0.2 g each of glucose, cellobiose, and maltose (all Fujifilm Wako Pure Chemical Industries) or 1 g of lactulose powder (Morinaga Milk Industry Co., Ltd.) was added and autoclaved at 115°C for 20 minutes. Then, 0.1 mL each of vitamins I and II, which had been aseptically filter-sterilized, and 1 mL of L-cysteine ​​solution were added. Finally, a medium containing 0.2% (w / v) glucose, 0.2% (w / v) cellobiose, and 0.2% (w / v) maltose as carbon sources, and a medium containing 1% (w / v) lactulose as a carbon source were obtained. The medium was then conditioned anaerobic by overnight carbon dioxide gas replacement, and 100 μl of fecal solution pre-diluted to 10% (w / v) with saline was inoculated with 1 mL of Bifidobacterium breve MCC 1274 (FERM BP-11175) pre-cultured in MRS medium (Difco) supplemented with 0.05% L-cysteine. The medium was then anaerobically cultured at 37°C for 24 hours, while controlling the pH with 1 M Na2CO3 solution to maintain a pH above 6. A control culture was also obtained by anaerobically culturing the medium under the same conditions without inoculation of Bifidobacterium breve MCC 1274 (FERM BP-11175).

[0112] [Table 1]

[0113] [Table 2]

[0114] [Table 3]

[0115] Test Example 2: Pretreatment of culture supernatant for LC-MS analysis The culture medium obtained in Test Example 1 was centrifuged (10,000 g, 4°C, 3 minutes), and the supernatant was collected. A 1:2.5:1 mixture of ultrapure water, methanol, and chloroform (all from Fujifilm Wako Pure Chemical Corporation) was used as the extraction solvent, and this was mixed with 100 μL of the supernatant and stirred using a vortex. The mixture was then rotated at 20 rpm for 30 minutes, centrifuged (13,000 g, 4°C, 10 minutes), and 1200 μL of the supernatant was collected. 500 μL of HPLC-grade ultrapure water was added to the supernatant, and the mixture was stirred using a vortex. After centrifugation (13,000 g, 4°C, 10 minutes), a hole was punctured in the cap of a 2 mL tube with a syringe needle, and 1200 μL of the supernatant was collected. The mixture was then evaporated by a centrifugal evaporator for at least 30 minutes, frozen overnight in a deep freezer (-80°C), and then lyophilized to dryness. 200 to 500 μL of HPLC-grade ultrapure water (containing 0.1 mg / mL of internal standard) was added to the dried product and stirred using a vortex. The stirred solution was passed through a 0.22 μm filter (manufactured by Merck Millipore) into an analytical glass vial and used as a sample.

[0116] Test Example 3: LC-MS analysis of culture supernatant LC-MS analysis was performed using an XBridge BEH C18 column (130 Å, 5 μm, 4.6 mm x 150 mm, Waters) connected to a Vanquish HPLC system (Thermo Fisher Scientific) and a TSQ Fortis triple quadrupole mass spectrometer (Thermo Fisher Scientific). The mobile phases were A: ultrapure water with 0.1% ammonium acetate (Merck) and B: methanol with 0.1% ammonium formate (Merck) and 0.1% formic acid (Fujifilm Wako Pure Chemical Corporation). A 10 μL injection of the sample was performed on the column equilibrated at 2% B. The elution was performed with a gradient gradient of 55% B over 45 minutes. The amounts of HPLA, ILA, and indole-3-acetic acid (IAA) in each sample were analyzed. The analytical conditions are shown in Table 4. Each sample was analyzed in triplicate. The analytical results (average values ​​of three analyses) are shown in Figures 1–3. In the figures, "GMC + 1274" indicates the condition in which MCC 1274 was inoculated with a combination of glucose, cellobiose, and maltose as the carbon source; "MLC + 1274" indicates the condition in which MCC 1274 was inoculated with lactulose as the carbon source; "GMC" indicates the condition in which MCC 1274 was inoculated with a combination of glucose, cellobiose, and maltose as the carbon source without inoculation; and "MLC" indicates the condition in which MCC 1274 was inoculated with lactulose as the carbon source without inoculation. MLC + 1274 (the condition in which MCC 1274 was inoculated with lactulose as the carbon source) dramatically increased HPLA and ILA production compared to the other conditions. On the other hand, MLC + 1274 did not increase IAA production compared to the other conditions. These results demonstrate that the combined use of indigestible oligosaccharides such as lactulose and Bifidobacterium breve promotes the production of aromatic lactic acid compounds such as ILA and HPLA.

[0117] [Table 4]

[0118] Test Example 4: Monoculture test Monoculture tests were conducted on two conditions: one in which Bifidobacterium breve MCC 1274 (FERM BP-11175) was inoculated with a combination of glucose, cellobiose, and maltose as the carbon source (GMC+1274), and the other in which Bifidobacterium breve MCC 1274 (FERM BP-11175) was inoculated with lactulose as the carbon source (MLC+1274). Specifically, Bifidobacterium breve MCC 1274 (FERM BP-11175) was cultured using the same procedures as in Test Example 1, except that feces was not inoculated. The culture supernatant was then pretreated for LC-MS analysis and analyzed by LC-MS using the same procedures as in Test Examples 2 and 3. The analytical results (average values ​​of three analyses) are shown in Figures 4 to 6. In the figure, "GMC + 1274" indicates the condition in which MCC 1274 was inoculated with a combination of glucose, cellobiose, and maltose as the carbon source, while "MLC + 1274" indicates the condition in which MCC 1274 was inoculated with lactulose as the carbon source. MLC + 1274 (MCC 1274 inoculated with lactulose as the carbon source) dramatically increased HPLA and ILA production compared with GMC + 1274 (MCC 1274 inoculated with a combination of glucose, cellobiose, and maltose as the carbon source). On the other hand, MLC + 1274 did not increase IAA production compared with GMC + 1274. These results demonstrate that the combined use of indigestible oligosaccharides, such as lactulose, and Bifidobacterium species, such as Bifidobacterium breve, promotes the production of aromatic lactic acid compounds, such as ILA and HPLA.

Claims

1. A composition for promoting the production of an aromatic lactic acid compound, comprising the following components (A) and (B), wherein the aromatic lactic acid compound is indole-3-lactic acid or 4-hydroxyphenyl lactic acid: (A) lactulose; (B) Bifidobacterium breve FERM BP-11175.

2. The composition according to claim 1 , wherein the composition is a food or beverage composition.

3. The composition of claim 1 , wherein the composition is a pharmaceutical composition.

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