Composition for promoting d-serine-producing bacteria growth

Abstract

To favorably promote growth of D-serine-producing bacteria.SOLUTION: A composition for promoting D-serine-producing bacteria growth comprising sialic acid and a casein-derived peptide, wherein the content of the sialic acid is 0.5 mmol / g or more and less than 1 mmol / g.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a composition for promoting the growth of D-serine-producing bacteria. [Background technology]

[0002] The human intestine is home to 1,000 species and 40 trillion bacteria, forming a complex symbiotic relationship known as the intestinal microbiota. The intestinal bacteria that make up the intestinal microbiota contribute to the maintenance and promotion of human health by producing a variety of metabolic products. In particular, D-serine, a type of D-amino acid, has been reported to play a role in defense against pathogenic bacteria in the intestinal tract and to protect kidney function (Non-Patent Documents 1 and 2). Furthermore, D-serine has been reported to be involved in the control of psychiatric disorders through its return to the brain (Non-Patent Document 3).

[0003] D-serine-producing bacteria with remarkable D-serine productivity have been reported, including Focaicola dorei and Focaicola vulgatus, and Bacteroides uniformis, both of which belong to the genus Focaicola. However, these species are highly sensitive to oxygen, making it difficult to distribute them as live bacterial preparations like lactic acid bacteria and bifidobacteria. Furthermore, there is a lack of experience in human consumption. Therefore, there is a need to find a composition that promotes the growth of D-serine-producing bacteria normally present in the human intestine. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] ISME J.2015 Mar;9(4):1052. [Non-patent document 2] kidney360.2021 Aug:2(10):1611-1624. [Non-patent document 3] FEBS J.2008 Jul:275(14):3514-3526. Summary of the Invention [Problem to be solved by the invention]

[0005] An objective of the present invention is to preferably promote the growth of D-serine-producing bacteria. [Means for solving the problem]

[0006] A composition for promoting the growth of D-serine-producing bacteria according to aspect 1 comprises sialic acid and a casein-derived peptide, and the content of the sialic acid is 0.5 mmol / g or more and less than 1 mmol / g.

[0007] A second aspect is the composition for promoting the growth of D-serine-producing bacteria of the first aspect, wherein the nitrogen content of the casein-derived peptide is 8% by mass or more and 16% by mass or less. A third aspect is the composition for promoting the growth of D-serine-producing bacteria according to the first aspect, wherein the D-serine-producing bacteria is at least one species selected from the group consisting of Phocaecola dorei, Phocaecola vulgatus, and Bacteroides uniformis.

[0008] The composition for improving infection defense against pathogenic bacteria in the intestinal tract or the composition for alleviating infection defense against pathogenic bacteria in the intestinal tract of aspect 4 is summarized as comprising the composition for enhancing D-serine concentration of aspects 1 to 3.

[0009] The composition for improving the protective effect of renal function or the composition for alleviating the protective effect of renal function of aspect 5 is summarized as comprising the composition for enhancing D-serine concentration of aspects 1 to 3. A composition for controlling and improving a psychiatric and neurological disorder or a composition for controlling and alleviating a psychiatric and neurological disorder according to a sixth aspect is summarized as comprising a composition for increasing D-serine concentration according to any one of the first to third aspects.

[0010] A seventh aspect of the method for producing at least one of a D-serine-producing bacterium and a culture of a D-serine-producing bacterium is characterized in that the D-serine-producing bacterium is at least one species selected from the group consisting of Focaecola dorei, Focaecola vulgatus, and Bacteroides uniformis, and a medium containing sialic acid and a casein-derived peptide is used. [Effects of the Invention]

[0011] According to the composition for promoting the growth of D-serine-producing bacteria of the present invention, the growth of D-serine-producing bacteria can be favorably promoted. DETAILED DESCRIPTION OF THE INVENTION

[0012] A specific embodiment of the composition for promoting the growth of D-serine-producing bacteria according to the present invention will be described below. The composition for promoting the growth of D-serine-producing bacteria contains sialic acid and a casein-derived peptide.

[0013] The above components contained in the composition for promoting the growth of D-serine-producing bacteria will be described below. <Sialic acid> Sialic acid is a negatively charged nine-carbon sugar and is a general term for modified neuraminic acid having an amino group and a carboxy group. Sialic acid also includes substances in which the amino group or hydroxy group of neuraminic acid is substituted. Specific examples of sialic acid include N-acetylneuraminic acid (NeuAc), N-glycolylneuraminic acid (NeuGc), and deaminoneuraminic acid (KDN). Among these, N-acetylneuraminic acid is a major sialic acid found in various biological species. In vivo, sialic acid exists in a free state as well as in the molecular forms of oligosaccharides, glycoproteins, glycopeptides, and glycolipids. Specific examples of glycopeptides include N-acetylneuraminic acid-linked glycopeptides. It is preferable that the sialic acid contains at least one of N-acetylneuraminic acid and N-acetylneuraminic acid-linked glycopeptides.

[0014] The content of sialic acid in the composition for promoting the growth of D-serine-producing bacteria is 0.5 mmol / g or more and less than 1 mmol / g. <Casein-derived peptides> Casein is a type of milk protein found in dairy products. Milk proteins are broadly divided into whey, also known as milk serum, and casein.

[0015] Casein-derived peptides are produced by acid hydrolysis of casein, protease treatment, microbial fermentation, etc. Among these, casein-derived peptides are preferably degradation products produced by protease treatment.

[0016] Specific examples of casein-derived peptides include casamino acids and tryptone. The nitrogen content of the casein-derived peptide in the composition for promoting the growth of D-serine-producing bacteria is not particularly limited, but is preferably, for example, 8% by mass or more and 16% by mass or less.

[0017] <sugar> The composition for promoting the growth of D-serine-producing bacteria may contain sugars in addition to the above-mentioned sialic acid and casein-derived peptides.

[0018] The sugar is not particularly limited, and can be a monosaccharide, a disaccharide, an oligosaccharide, etc. The oligosaccharide means a saccharide oligomer in which several monosaccharides are linked together by glycosidic bonds.

[0019] Specific examples of sugars include galacto-N-biose, lactose, galactose, sialyllactose, sialylgalactose, etc. Galacto-N-biose is a disaccharide formed by β1-3 linkage between galactose and N-acetylgalactosamine. Among these, the sugar is preferably at least one selected from galacto-N-biose, lactose, and galactose. Note that the above sugars do not include sialic acid. Furthermore, the above sialyllactose and sialylgalactose contain both sialic acid and a sugar.

[0020] <Form of the composition for promoting the growth of D-serine-producing bacteria> The composition for promoting the growth of D-serine-producing bacteria may be a mixture of the above sialic acid and a peptide derived from casein, or may be a compound formed by the binding of sialic acid and a peptide derived from casein.

[0021] Also, the composition for promoting the growth of D-serine-producing bacteria may be a mixture of the above sialic acid, a peptide derived from casein, and sugar, or may be a compound formed by the binding of sialic acid, a peptide derived from casein, and sugar.

[0022] The composition for promoting the growth of D-serine-producing bacteria shall mean a composition capable of growing D-serine-producing bacteria. Specifically, it shall mean that the growth promotion rate when cultured in a test medium to which the above composition is added is statistically significantly increased compared to the growth promotion rate when cultured in a control medium to which the above composition is not added. The growth promotion rate is calculated from the turbidity difference before and after culture. The composition for promoting the growth of D-serine-producing bacteria shall include those that promote the growth of D-serine-producing bacteria in the intestinal tract of humans or non-human animals.

[0023] Also, in the present embodiment, the "composition" shall include things that animals (including humans) such as pharmaceuticals, foods and drinks, and feeds can ingest. Examples of the bacterial species of D-serine-producing bacteria in the composition for promoting the growth of D-serine-producing bacteria include the following.

[0024] <D-serine-producing bacteria> Examples of D-serine-producing bacteria include bacteria belonging to the genera Collinsella, Bacteroides, Phocaeicola, Parabacteroides, Blautia, Dorea, Ruminococcus, Roseburia, Agathobacter, Streptococcus, Clostridium, Flavonifractor, Coprococcus, and Faecalibacterium. Here, the term "Enterobacteria species" refers to bacterial species that have a nucleotide sequence identity of 97% or more, more preferably 98% or more, and even more preferably 99% or more of the 16S ribosomal RNA gene with each type strain.

[0025] In the composition for promoting the growth of D-serine-producing bacteria, the D-serine-producing bacteria may be a single species of bacteria from the species included in each of the above genera, or a combination of two or more species of bacteria.

[0026] The D-serine-producing bacterium is preferably at least one selected from Phocaeicola dorei, Phocaeicola vulgatus, and Bacteroides uniformis.

[0027] The bacterial culture refers to a culture of bacteria in a medium such as a known preparation, food or drink, feed, or food-grade material. The culture may be a product of further processing, such as concentration, drying, or freeze-drying, of the cultured bacterial cells. The culture may be a suspension containing the cultured bacterial cells and the medium, or may be a supernatant of the culture.

[0028] Sialic acid and casein-derived peptides can promote the growth of the D-serine-producing bacteria, thereby favorably increasing the D-serine concentration. That is, the composition for promoting the growth of D-serine-producing bacteria can be used to protect against infections from pathogenic bacteria in the intestinal tract, protect kidney function, and control neuropsychiatric disorders.

[0029] The method for culturing the D-serine-producing bacteria will now be described. <Culture method> The D-serine-producing bacteria can be cultured using media generally used for culturing enterobacteria. Examples of media generally used for culturing enterobacteria include YCFA medium (JCM medium number 1130), EG medium (JCM medium number 14), GAM bouillon, modified GAM bouillon, etc. The medium may be a liquid medium, a solid medium, or a semi-solid medium.

[0030] The culture temperature is not particularly limited, but may be 36 to 38°C, which is a temperature close to human body temperature, and 37°C is preferred. The large intestine is in an anoxic state, and the intestinal bacteria that grow there are obligate anaerobes. Therefore, it is necessary to maintain an anoxic state in the medium and in the medium air layer using nitrogen gas. In addition, since carbon dioxide and hydrogen gases produced by intestinal bacteria are also present in the intestine, it is preferable to include these gases. Examples of the ratio include 80-90% nitrogen, 5-10% carbon dioxide, and 5-10% hydrogen.

[0031] The incubation time is not particularly limited, but it is preferable to continue incubation until turbidity can be visually confirmed. <Other ingredients> The composition for promoting the growth of D-serine-producing bacteria may contain other ingredients as long as the ingredients do not interfere with the effects of the composition. Examples of other ingredients include excipients, binders, disintegrants, lubricants, flavorings, suspending agents, and coating agents. The composition can also be formulated into tablets, capsules, granules, powders, dusts, syrups, and other formulations.

[0032] Hereinafter, application forms of the composition for promoting the growth of D-serine-producing bacteria will be described. <Application form> The application form of the composition for promoting the growth of D-serine-producing bacteria is not particularly limited, and it may be applied, for example, as a feed composition for promoting the growth of D-serine-producing bacteria (hereinafter also referred to as a feed composition), a pharmaceutical composition for promoting the growth of D-serine-producing bacteria (hereinafter also referred to as a pharmaceutical composition), or a food composition for promoting the growth of D-serine-producing bacteria (hereinafter also referred to as a food composition). Pharmaceutical compositions include quasi-drug compositions. The composition for promoting the growth of D-serine-producing bacteria is also applied as a composition for improving infection defense against pathogenic bacteria in the intestinal tract or a composition for alleviating infection defense against pathogenic bacteria in the intestinal tract. It is also applied as a composition for enhancing D-serine concentration. It is also applied as a composition for improving renal function protective action or a composition for alleviating renal function protective action. It is also applied as a composition for controlling and improving psychiatric and neurological disorders or a composition for controlling and alleviating psychiatric and neurological disorders.

[0033] Hereinafter, the use of the composition for promoting the growth of D-serine-producing bacteria will be described. <Application> The use of the composition for promoting the growth of D-serine-producing bacteria is not particularly limited, and the composition may be incorporated into feed or food and drink products, or may be added to raw materials during the production process of feed or food and drink products.

[0034] Specific examples of foods and beverages include, but are not limited to, dairy products such as cheese, fermented milk, dairy lactic acid bacteria drinks, lactic acid bacteria drinks, butter, margarine, etc. Other examples include beverages such as milk drinks, fruit juice drinks, and soft drinks, processed egg products such as jelly, candy, pudding, and mayonnaise, and sweets and breads such as butter cake. Further examples include various types of powdered milk, infant foods, nutritional compositions, etc.

[0035] The classification of the above-mentioned food and drink is not particularly limited, and it can be used as a general food, a health functional food, a food for special uses, etc. Furthermore, as a health functional food, it can be used as a food for specified health uses, a food with nutrient function claims, a food with functional claims, etc.

[0036] When indicating the intended use of the composition for promoting the growth of D-serine-producing bacteria, the indication may be one stipulated by various laws, enforcement regulations, guidelines, etc. The indication of the intended use may be, for example, indicated on packaging such as wrapping or containers, as well as on advertising media such as pamphlets.

[0037] The recipient of the composition for promoting the growth of D-serine-producing bacteria is not particularly limited, and it can be administered to humans. The recipient may also be an animal other than a human (e.g., a dog, a cat, a horse, or a rabbit). When the recipient is a human, it can be administered to, for example, a minor under 20 years of age, an adult, or an elderly person over 65 years of age.

[0038] <Actions and Effects of the Embodiment> The operation and effects of this embodiment will be described. (1) A composition for promoting the growth of D-serine-producing bacteria contains sialic acid and a casein-derived peptide. The sialic acid content is 0.5 mmol / g or more and less than 1 mmol / g. This composition can favorably promote the growth of D-serine-producing bacteria. Furthermore, by favorably promoting the growth of D-serine-producing bacteria, the D-serine concentration can be favorably increased.

[0039] (2) The nitrogen content of the casein-derived peptide is 8% by mass or more and 16% by mass or less, which can more suitably promote the growth of D-serine-producing bacteria. (3) The D-serine-producing bacterium is preferably at least one selected from the group consisting of Focaecola dorei, Focaecola vulgatus, and Bacteroides uniformis. The composition for promoting the growth of D-serine-producing bacteria containing the above-mentioned components can suitably promote the growth of these D-serine-producing bacteria.

[0040] (4) The composition for promoting the growth of D-serine-producing bacteria can contribute to the prevention of infections against pathogenic bacteria in the intestinal tract, the protection of kidney function, the control of psychiatric and neurological disorders, etc. by favorably promoting the growth of D-serine-producing bacteria.

[0041] Specifically, it can contribute to improving the defense against infections caused by pathogenic bacteria in the intestinal tract and reducing the susceptibility to infections caused by pathogenic bacteria in the intestinal tract (also referred to as "alleviating the defense against infections").

[0042] It can also contribute to improving the protective effect of renal function and mitigating the susceptibility to decline in renal function (also referred to as "mitigation of the protective effect of renal function"). It can also contribute to improving the control of neuropsychiatric disorders and reducing the likelihood of their worsening (also referred to as "control and reduction of neuropsychiatric disorders").

[0043] <Example of change> This embodiment can be modified as follows: This embodiment and the following modifications can be combined and implemented within the scope of technical compatibility.

[0044] In this embodiment, the composition for promoting the growth of D-serine-producing bacteria does not contain lactic acid bacteria or bifidobacteria, but is not limited to this embodiment. The composition for enhancing the D-serine concentration may contain lactic acid bacteria or bifidobacteria. [Example]

[0045] Examples will be given below to more specifically explain the configuration and effects of the present invention, but the present invention is not limited to these examples. <Test Example 1> 1. Selection of D-serine-producing bacteria and preparation of freeze-concentrated cells (1) Obtaining D-serine-producing bacteria Among D-serine-producing bacteria, 12 strains corresponding to Phocaeicola dorei, Phocaeicola vulgatus, and Bacteroides uniformis were obtained from the Microbial Materials Development Division of the RIKEN BioResource Research Center (hereinafter also referred to as JCM) or the Leibniz Institute for Microbiology and Materials Science (hereinafter also referred to as DSMZ) in Germany.

[0046] (2) Preparation of D-serine-producing bacteria The above 12 bacterial species were cultured in modified GAM bouillon medium (product code 05433, Nissui). The composition of the modified GAM bouillon medium used is shown in Table 1.

[0047] [Table 1]

[0048] The modified GAM broth medium was sterilized by heat treatment at 115°C for 15 minutes. The 12 D-serine-producing strains were inoculated into individual sterilized media and anaerobically cultured overnight at 37°C using an anaerobic workstation (Concept 400, Central Scientific Trading Co., Ltd.). The anaerobic workstation operation was performed by aerating with a mixed gas. The anaerobic gas ratios were 80% (v / v) nitrogen, 10% (v / v) carbon dioxide, and 10% (v / v) hydrogen. The resulting culture was then subcultured in fresh modified GAM broth medium and adjusted to a turbidity of 1.0 (OD600) at 600 nm using an absorbance meter (Ultrospec 2100, Biochrom).

[0049] (3) Medium preparation The medium prepared in Experimental Example 1 was prepared by adding sialic acid (product code 08371-36, Nacalai Tesque) to a modified GAM bouillon medium to a final concentration of 0.5 mmol / g.

[0050] Experimental Example 2 was prepared by adding sialic acid to a modified GAM broth medium to a final concentration of 1 mmol / g and casamino acids (product number 223050, Gibco Bacto) to a nitrogen content of 16% by mass.

[0051] The medium prepared in Experimental Example 3 was prepared by adding sialic acid to a modified GAM bouillon medium to a final concentration of 1 mmol / g and tryptone (product number 211705, Gibco Bacto) so that the nitrogen content was 16% by mass.

[0052] A medium prepared as Experimental Example 4 was prepared by adding sialic acid to a modified GAM bouillon medium to a final concentration of 0.5 mmol / g and casamino acids to a nitrogen content of 8 mass %. A medium prepared as Experimental Example 5 was prepared by adding sialic acid to a modified GAM bouillon medium to a final concentration of 0.5 mmol / g and casamino acids to a nitrogen content of 16 mass %.

[0053] A medium prepared as Experimental Example 6 was prepared by adding sialic acid to a modified GAM bouillon medium to a final concentration of 0.5 mmol / g and tryptone to a nitrogen content of 16 mass %. In addition, modified GAM broth medium was used as a control medium.

[0054] (4) Cultivation of each D-serine-producing bacterium The D-serine-producing bacteria prepared in (2) above were inoculated into the above Experimental Examples 1 to 6 and the control medium to a final concentration of 1% by volume, and anaerobically cultured at 37°C for 16 hours. Thereafter, the difference in turbidity (ΔOD600) before and after culture was calculated. The growth promotion rate was calculated by dividing the ΔOD600 in Experimental Examples 1 to 6 by the ΔOD600 in the control medium.

[0055] <Test Example 2> (1) Obtaining D-serine-producing bacteria D-serine-producing bacteria were obtained in the same manner as in Test Example 1.

[0056] (2) Preparation of D-serine-producing bacteria Each D-serine-producing bacterium was prepared in the same manner as in Test Example 1. (3) Medium preparation Experimental Example 7 was prepared by adding a casein-derived sialic acid-bound glycopeptide composition (Megmilk Snow Brand) to a modified GAM bouillon medium to a concentration of 0.5% by volume. The sialic acid-bound glycopeptide composition is a compound formed by the binding of sialic acid, a casein-derived peptide, and a sugar. The sialic acid-bound glycopeptide composition is characterized by having a sialic acid content of 0.5 mmol / g or more and less than 1 mmol / g, and a nitrogen content of 8% by mass or more and 16% by mass or less.

[0057] In addition, modified GAM broth medium was used as a control medium. (4) Structure of the sialic acid-linked glycopeptide composition A specific embodiment of a sialic acid-bound glycopeptide composition is a peptide having at least one amino acid residue of a threonine residue or a serine residue, with a sialic acid bound to the hydroxyl group of the amino acid residue, and the glycan has at least one of the following glycans (a) to (e):

[0058] (a)Neu5Acα2-3Galβ1-3(Neu5Acα2-6)GalNAcα1 (b)Galβ1-3(Neu5Acα2-6)GalNAcα1 (c)Neu5Acα2-3Galβ1-3GalNAcα1 (d)Neu5Acα2-3Galβ1-3(O-Ac-Neu5Acα2-6)GalNAcα1 (e)Neu5Acα2-3Galβ1-3(O-diAc-Neu5Acα2-6)GalNAcα1 (5) Method for producing a sialic acid-bound glycopeptide composition First, the milk raw material was adjusted to a pH of less than 4, and then ultrafiltered using a membrane with a molecular weight cutoff of 10,000 to 50,000 to obtain a permeate. Thereafter, preferably, the membrane was again adjusted to a pH of 4 or higher, and the permeate was desalted using a membrane with a molecular weight cutoff of 50,000 or less, and further concentrated to prepare a κ-casein glycomacropeptide (hereinafter also referred to as GMP). The κ-casein glycomacropeptide thus obtained was treated with an endoprotease or exoprotease, and the resulting treated product was subjected to ultrafiltration with a molecular weight cutoff of 500 to 3,000. A sialic acid-linked glycopeptide composition was produced by the above steps.

[0059] (6) Cultivation of each D-serine-producing bacterium The proliferation promotion rate in Experimental Example 7 was calculated in the same manner as in Test Example 1. <Test Example 3> (1) Obtaining D-serine-producing bacteria D-serine-producing bacteria were obtained in the same manner as in Test Example 1.

[0060] (2) Preparation of D-serine-producing bacteria Each D-serine-producing bacterium was prepared in the same manner as in Test Example 1. (3) Medium preparation A medium prepared as Experimental Example 8 was prepared by adding casamino acids to a modified GAM bouillon medium so that the nitrogen content was 8% by mass.

[0061] A medium prepared as Experimental Example 9 was prepared by adding casamino acids to a modified GAM bouillon medium so that the nitrogen content was 16% by mass. A medium prepared as Experimental Example 10 was prepared by adding tryptone to a modified GAM bouillon medium so that the nitrogen content was 16% by mass.

[0062] In addition, modified GAM broth medium was used as a control medium. (4) Cultivation of each D-serine-producing bacterium The proliferation promotion rates in Experimental Examples 8 to 10 were calculated in the same manner as in Test Example 1.

[0063] <Test Results> The components contained in the compositions for promoting the growth of D-serine-producing bacteria, the species, strain number, and growth promotion rate of the D-serine-producing bacteria in Experimental Examples 1 to 6 are shown in Table 2. The components contained in the composition for promoting the growth of D-serine-producing bacteria in Experimental Example 7, the species, strain number, and growth promotion rate of the D-serine-producing bacteria are shown in Table 3. The components contained in the compositions for promoting the growth of D-serine-producing bacteria in Experimental Examples 8 to 10, the species, strain number, and growth promotion rate of the D-serine-producing bacteria are shown in Table 4.

[0064] In Tables 2 and 4, the components contained in each composition for promoting the growth of D-serine-producing bacteria, the species and strain number of the D-serine-producing bacteria, and the growth promotion rate are listed in the "Composition for promoting the growth of D-serine-producing bacteria," "Containing species," "Strain number," and "Growth promotion rate" columns, respectively. The "Composition for promoting the growth of D-serine-producing bacteria" column is further divided into "Sialic acid," "Casamino acid," and "Tryptone" columns, with "〇" indicating that each component is contained and "-" indicating that it is not contained. The "Sialic acid" and "Casamino acid" columns are further divided into columns according to concentration.

[0065] In Table 3, the components contained in each composition for promoting the growth of D-serine-producing bacteria, the species of D-serine-producing bacteria, the strain number, and the growth promotion rate are listed in the "Composition for promoting the growth of D-serine-producing bacteria," "Containing species," "Strain number," and "Growth promotion rate" columns, respectively. In the "Composition for promoting the growth of D-serine-producing bacteria," if the component is contained, it is marked with "〇," and if it is not contained, it is marked with "-."

[0066] [Table 2]

[0067] [Table 3]

[0068] [Table 4]

[0069] For the growth promotion rates of Experimental Examples 1 to 7, p values ​​were calculated relative to the growth promotion rate of the control medium. The p-value for the proliferation promotion rate in Experimental Example 1 was 0.15. The p-value for the proliferation promotion rate in Experimental Example 2 was 0.15.

[0070] The p-value for the proliferation promotion rate in Experimental Example 3 was 0.12. The p-value for the proliferation promotion rate in Experimental Example 4 was 0.01. The p-value for the proliferation promotion rate in Experimental Example 5 was 0.01.

[0071] The p-value for the proliferation promotion rate in Experimental Example 6 was 0.0079. The p-value for the proliferation promotion rate in Experimental Example 7 was less than 0.0001. The p-value for the proliferation promotion rate in Experimental Example 8 was 0.54.

[0072] The p-value for the proliferation promotion rate in Experimental Example 9 was 1.00. The p-value for the proliferation promotion rate in Experimental Example 10 was 0.35. The p-value of the growth promotion rate in Experimental Example 1 was 0.05 or more, indicating no significant difference, confirming that sialic acid alone had no effect on promoting the growth of D-serine-producing bacteria.

[0073] The p-values ​​of the growth promotion rates in Experimental Examples 8 to 10 were 0.05 or more, indicating no significant difference, confirming that casein-derived components alone had no effect on promoting the growth of D-serine-producing bacteria.

[0074] The p-values ​​for the growth promotion rates in Experimental Examples 4 to 7 were less than 0.05, confirming that the growth promotion rates for D-serine-producing bacteria were statistically significantly higher for the compositions for promoting the growth of D-serine-producing bacteria in Experimental Examples 4 to 7. This confirms that casein-derived components with specific nitrogen contents, along with sialic acid, are necessary for growth promotion in D-serine-producing bacteria.

[0075] The p-values ​​for the growth promotion rates in Experimental Examples 2 and 3 were 0.05 or greater, indicating no significant difference. This confirms that when the sialic acid content is 1 mmol / g, there is no effect on promoting the growth of D-serine-producing bacteria, even if casein-derived components are included.

[0076] From the above, it was confirmed that a specific content of sialic acid and a specific nitrogen content of casein-derived components are required for the promotion of growth in D-serine-producing bacteria. [Industrial Applicability]

[0077] According to the present invention, it is possible to obtain a composition for promoting the growth of D-serine-producing bacteria, which contains sialic acid and a casein-derived peptide as active ingredients. It is also possible to provide foods, beverages, pharmaceuticals, and feeds for promoting the growth of D-serine-producing bacteria.

Claims

1. Contains sialic acid and casein-derived peptides, A composition for promoting the growth of D-serine-producing bacteria, characterized in that the content of sialic acid is 0.5 mmol / g or more and less than 1 mmol / g.

2. 2. The composition for promoting the growth of D-serine-producing bacteria according to claim 1, wherein the nitrogen content of the casein-derived peptide is 8% by mass or more and 16% by mass or less.

3. 2. The composition for promoting the growth of D-serine-producing bacteria according to claim 1, wherein the D-serine-producing bacteria is at least one selected from the group consisting of Phocaecola dorei, Phocaecola vulgatus, and Bacteroides uniformis.

4. A composition for improving infection defense against pathogenic bacteria in the intestinal tract, or a composition for alleviating infection defense against pathogenic bacteria in the intestinal tract, comprising the composition for promoting the growth of D-serine-producing bacteria according to any one of claims 1 to 3.

5. A composition for improving or alleviating renal function protective effect, comprising the composition for promoting the growth of D-serine-producing bacteria according to any one of claims 1 to 3.

6. A composition for controlling and improving a psychiatric and neurological disorder, or a composition for controlling and alleviating a psychiatric and neurological disorder, comprising the composition for promoting the growth of D-serine-producing bacteria according to any one of claims 1 to 3.

7. A method for producing at least one of a D-serine-producing bacterium and a culture of a D-serine-producing bacterium, comprising: the D-serine-producing bacterium is at least one selected from the group consisting of Phocaecola dorei, Phocaecola vulgatus, and Bacteroides uniformis; A method for producing at least one of a D-serine producing bacterium and a culture of a D-serine producing bacterium, which is characterized by using a medium containing sialic acid and a peptide derived from casein.

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