Nutritional pulse

Abstract

To provide improvement in an intestinal environment or prevention or therapy of intestinal environment-related diseases which includes modifying epigenetics and / or reducing energy metabolism, and to provide a technique for unexpectedly remarkable increasing an intestinal lactic acid bacterium.SOLUTION: The present disclosure provides a method for improvement in an intestinal environment or prevention or therapy of intestinal environment-related diseases which includes modifying epigenetics and / or reducing energy metabolism.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present disclosure relates to techniques for improving intestinal environment or preventing or treating intestinal environment-related diseases, comprising modifying epigenetics and / or suppressing energy metabolism. [Background technology]

[0002] So far, information regarding the intestinal environment in relation to tryptophan and methionine has been known (Non-Patent Documents 1 to 3). [Prior art documents] [Non-patent literature]

[0003] [Non-Patent Document 1] Chen S, Wang M, Yin L, Ren W, Bin P, Xia Y, Liu G, Yang H, Tan B, Yin Y. Effects of dietary tryptophan supplementation in the acetic acid-induced colitis mouse model. Food Funct. 2018 Aug 15;9(8):4143-4152. [Non-Patent Document 2] Li J, Kong D, Wang Q, Wu W, Tang Y, Bai T, Guo L, Wei L, Zhang Q, Yu Y, Qian Y, Zuo S, Liu G, Liu Q, Wu S, Zang Y, Zhu Q, Jia D, Wang Y, Yao W, Ji Y, Yin H, Nakamura M, Lazarus M, Breyer RM, Wang L, Yu Y. Niacin ameliorates ulcerative colitis via prostaglandin D2-mediated D prostanoid receptor 1 activation. EMBO Mol Med. 2017 May;9(5):571-588. doi: 10.15252 / emmm.201606987. Erratum in: EMBO Mol Med. 2020 Dec 7;12(12):e13487. [Non-Patent Document 3] Zhu S, Li J, Bing Y, Yan W, Zhu Y, Xia B, Chen M. Diet-Induced Hyperhomocysteinaemia Increases Intestinal Inflammation in an Animal Model of Colitis. J Crohns Colitis. 2015 Sep;9(9):708-19. Summary of the Invention [Means for solving the problem]

[0004] The present disclosure relates to a method for improving an intestinal environment, including modifying epigenetics and / or suppressing energy metabolism, or for preventing or treating an intestinal environment-related disease. The present disclosure relates to a technique for unexpectedly and significantly increasing intestinal lactic acid bacteria.

[0005] The present disclosure provides the following: (Item 1A) A method for improving the intestinal environment or for preventing or treating an intestinal environment-related disease, comprising administering at least one amino acid or substance related to amino acid metabolism (presumably niacin) and / or lipid or substance related to lipid metabolism in an amount less than that normally required. (Item 1B) A method for improving intestinal environment or for preventing or treating intestinal environment-related diseases, comprising modifying epigenetics and / or suppressing energy metabolism. (Item 2A) The method according to any one of the preceding items, wherein the amino acid or amino acid metabolism-related substance (assuming niacin) includes methionine, tryptophan, and / or niacin. (Item 2B) The method according to any one of the above items, wherein the modification or suppression comprises ingesting the substance related to epigenetics and / or energy metabolism in an amount less than that normally required. (Item 3) The method according to any one of the preceding items, wherein the alteration or suppression comprises ingesting at least one of methionine, tryptophan, and / or niacin in an amount less than that normally required. (Item 4) The method according to any one of the preceding items, wherein the alteration or suppression comprises ingesting a total amount of methionine, tryptophan, and niacin, and the equivalent amounts of related substances, that is less than the amount normally required. (Item 5) The method according to any one of the preceding items, wherein the alteration or suppression comprises providing less methionine than normally required, or providing less tryptophan and niacin than normally required. (Item 6) The method according to any one of the preceding claims, wherein the intake is less than 90%, less than 50%, or less than 30% of the requirement. (Item 7) The method according to any one of the preceding claims, wherein the intake is substantially zero. (Item 8) The method according to any one of the preceding items, wherein, except for step A), the subject is provided with a normal diet free of the deficiency. (Item 9) The method according to any one of the preceding items, wherein step A) is carried out for 14 to 33 days. (Item 10) The method according to any one of the preceding items, wherein the lack means less than the amount normally required. (Item 11) The method according to any one of the preceding items, wherein the lack means less than half the amount normally required. The method according to any one of the preceding items, wherein the absence described in (Item 12) means complete absence of ingestion. (Item 13) The method according to any one of the preceding items, wherein the improvement of the intestinal environment includes an increase in lactic acid bacteria. (Item 14) The method according to any one of the preceding items, wherein the intestinal environment-related disease includes at least one selected from an autoimmune disease and an inflammatory disease. (Item 15) The method according to any one of the preceding items, wherein the intestinal environment-related disease includes at least one selected from inflammatory bowel disease (IBD), obesity, cancer, fatty liver, and dyslipidemia. (Item 16A) A diet, medicine or composition for improving the intestinal environment or for preventing or treating intestinal environment-related diseases, characterized in that it is configured to modify epigenetics and / or suppress energy metabolism in a diet that provides normal nutrition. (Item 16B) A diet, medicine or composition for improving the intestinal environment or for preventing or treating intestinal environment-related diseases, characterized in that it is configured to provide substances related to epigenetics and / or energy metabolism in amounts less than those normally required in a diet providing normal nutrition. (Item 17) A diet, medicine or composition described in any one of the above items, characterized in that it is configured to provide a total amount of methionine, tryptophan, and niacin, as well as the equivalent amounts of related substances, in an amount less than that normally required in a diet providing normal nutrition. (Item 18) A diet, medicine or composition described in any one of the above items, characterized in that it is configured to provide at least one of methionine, tryptophan and / or niacin in an amount less than the amount normally required in a diet providing normal nutrition. (Item 19) A food, medicine or composition described in any one of the above items, wherein the intake amount is less than 50%, 30% or 20% of the total amount. (Item 20) A diet, medicine or composition described in any one of the above items, wherein the intake is substantially zero. (Item 20A) 21. The diet, medicament or composition according to item 20, comprising one or more of the features of one or more of the above items. (Item 21) A method for designing a diet, medicine or composition for improving the intestinal environment or for preventing or treating an intestinal environment-related disease, the method comprising calculating a diet, medicine or composition configured to modify epigenetics and / or suppress energy metabolism in a diet that provides normal nutrition. (Item 21A) 22. The method according to claim 21, comprising one or more features of one or more of the preceding items. (Item 22) A program for causing a computer to implement a method for designing a diet, medicine or composition for improving the intestinal environment or for preventing or treating an intestinal environment-related disease, the method comprising: calculating a diet configured to modify epigenetics and / or suppress energy metabolism in a diet, medicine or composition that provides normal nutrition; and displaying the calculated diet. (Item 22A) 23. The program according to item 22, comprising one or more features of one or more of the above items. (Item 23) A device for designing a diet for improving an intestinal environment or for preventing or treating an intestinal environment-related disease, the device including: a calculation unit that calculates a diet configured to modify epigenetics and / or suppress energy metabolism in a diet, medicine, or composition that provides normal nutrition; and a display unit that displays the calculated diet, medicine, or composition. (Item 23A) 24. The device according to item 23, comprising one or more features of one or more of the items above. (Item 24) A medicine or food that lacks at least one amino acid or fat, or a component related to the metabolism of these. (Item 25) The pharmaceutical or food product according to item X, wherein the amino acid or fatty acid or component is an essential component for a subject.

[0006] It is contemplated that the present disclosure may provide one or more of the above features in combinations other than those specifically described. Still further embodiments and advantages of the present disclosure will be recognized by those skilled in the art upon reading and understanding the following detailed description, if necessary. Effect of the Invention

[0007] The present disclosure unexpectedly provides a technology that contributes to improving the intestinal environment or preventing or treating intestinal environment-related diseases. In particular, it has been shown that lactic acid bacteria are unexpectedly improved and inflammatory bowel diseases are significantly improved. [Brief description of the drawings]

[0008] [Figure 1] FIG. 1 is a diagram showing the energy metabolism-related mechanisms of the present disclosure. [Diagram 2] FIG. 2 shows the experimental procedure of Example 1. [Diagram 3] FIG. 3 shows the results of 16S rRNA analysis performed using fecal samples from the mice drinking dextran sulfate sodium (DSS) in Example 1. [Figure 4] FIG. 4 shows the results of examining body weight on the 14th day after the start of feeding with the deficient feed in Example 1. [Diagram 5] FIG. 5 shows the experimental procedure of Example 2. [Figure 6] FIG. 6 shows the results of 16S rRNA analysis carried out using each fecal sample in Example 2. [Figure 7] FIG. 7 shows the graph results of the changes in body weight in Example 2. [Figure 8] FIG. 8 shows the experimental procedure of Example 3. [Figure 9] FIG. 9 shows the results of 16S rRNA analysis of fecal samples taken 5 days after the return to regular feed and before the return to regular feed in Example 3, where the deprivation period was set to 2 days, 9 days, and 14 days. [Figure 10] FIG. 10 is a graph showing the weight of mice under each condition. [Figure 11] FIG. 11 illustrates an example of a hardware configuration of the composition adjustment support server of the present disclosure. [Figure 12] FIG. 12 illustrates an example user information table of the present disclosure. [Figure 13] FIG. 13 shows a meal information table of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] Throughout this specification, the singular expression should be understood to include the concept of the plural form, unless otherwise specified. Thus, the singular article (e.g., in the case of English, "a", "an", "the", etc.) should be understood to include the concept of the plural form, unless otherwise specified. In addition, it should be understood that the terms used in this specification are used in the sense commonly used in the field, unless otherwise specified. Therefore, unless otherwise defined, all technical terms and scientific and technical terms used in this specification have the same meaning as commonly understood by those skilled in the art to which this disclosure belongs. In case of conflict, the specification (including definitions) will take precedence.

[0010] (definition) First, terms and general techniques used in this disclosure are explained.

[0011] As used herein, "inhibition of energy metabolism" refers to a decrease in energy metabolism. From a biological perspective, energy metabolism generally refers to the process of taking in and taking out energy by synthesizing and decomposing substances at the cellular level. For example, it includes the process of synthesizing adenosine triphosphate (ATP), which is chemical energy, by decomposing neutral fats. Factors related to the inhibition of energy metabolism include, but are not limited to, tryptophan, methionine, niacin, homocysteine, nicotinamide riboside, nicotinamide mononucleotide, N'-formylkynurenine, kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxyanthranilic acid, 2-amino-3-carboxymuconic acid semialdehyde, and quinolinic acid.

[0012] In this specification, "epigenetic modification" refers to a mechanism by which cells control the function of genes without changing the base sequence of DNA. Epigenetic changes affect the synthesis of proteins in cells to determine whether genes are on or off. A representative example of epigenetic modification is "DNA methylation," which can directly or indirectly affect histone modifications (methylation, acetylation, phosphorylation, etc.). Although we do not wish to be bound by theory, with regard to the relationship with representative examples such as methionine, tryptophan, and niacin, methylation enzymes use S-adenosylmethionine (SAM) to methylate substrates, but SAM is produced only from methionine. Therefore, the supply of methionine is essential for epigenetic modification. The supply of tryptophan and niacin promotes the production of nicotinamide from NAD+, and the consumption of SAM by nicotinamide-N-methyltransferase (NNMT) progresses, so tryptophan and niacin affect the supply of SAM, which is a source of methyl groups.

[0013] Therefore, preferably, epigenetic modification may be to make at least one of methionine, tryptophan, and / or niacin ingested in an amount less than that which is normally required, and more preferably, to make the total amount of methionine, tryptophan, and niacin, and the equivalent amounts of substances related thereto, ingested in an amount less than that which is normally required.For example, when adding other substances than methionine, tryptophan, and niacin, it is possible to assume that SAM, SAH, etc. are also added to the target, without wishing to be bound by theory.In this case, the total amount (also called total amount) may be, for example, said to be less than the standard amount of methionine, for example.The conversion value can be calculated by comparing molecular weights, and the molecular weight of methionine can be converted using 149.21, 398.44, and 384.412 for the molecular weight of methionine, SAM, and SAH. In this way, it can be calculated as follows: "The tryptophan equivalent amount of a substance (g) = mass of a substance added (g) × molecular weight of tryptophan ÷ molecular weight of a substance," and "The niacin equivalent amount of a substance (g) = mass of a substance added (g) × molecular weight of niacin ÷ molecular weight of a substance."

[0014] In this case, the examples show a complex system of tryptophan and niacin, and the converted amount can be calculated, for example, as Trp amount + Nia amount + converted amount = a certain value or less (in this case, all amounts can be converted to NAD+ converted amount), or Trp amount + converted amount = a certain value or less, or Nia amount + converted amount = a certain value or less, etc.

[0015] As used herein, the term "amino acid or an amino acid metabolism-related substance" refers to any substance related to amino acids constituting a living body or metabolism. Preferably, in the present disclosure, the amino acid or an amino acid metabolism-related substance is an essential amino acid or an essential amino acid metabolism-related substance.

[0016] As used herein, "essential amino acids or substances related to essential amino acid metabolism" refers to amino acids essential for life or substances related to amino acid metabolism, including isoleucine, leucine, valine, histidine, lysine, methionine, tryptophan, phenylalanine, threonine, etc. Essential substances related to amino acid metabolism include various vitamins, such as water-soluble vitamins (e.g., vitamin C, vitamin B1, vitamin B2, vitamin B6, vitamin B12, niacin, pantothenic acid, folic acid, biotin), fat-soluble vitamins (vitamin A, vitamin D, vitamin E, vitamin K), etc. The vitamin B group, including niacin, is involved in energy production and may be preferably used in the present disclosure.

[0017] In the present specification, the term "intestinal environment" refers to an intestinal ecosystem formed between intestinal bacteria or between intestinal bacteria and host cells. The intestinal environment is regulated by "intestinal flora" or "intestinal (micro) flora", and "intestinal flora" or "intestinal (micro) flora" refers to all bacteria in the intestine. Since the intestinal environment is controlled by mutual communication between the intestinal flora or intestinal bacterial flora and the host, disturbance or deterioration of the intestinal flora or intestinal bacterial flora causes disturbance or deterioration of the intestinal environment. Therefore, in the present disclosure, "disturbance or deterioration of the intestinal environment" includes disturbance or deterioration of the intestinal environment due to disturbance of the intestinal flora or intestinal bacterial flora. Disturbance or deterioration of the intestinal environment has an adverse effect on the host. Examples of adverse effects on the host include inflammation caused in the intestinal mucosa.

[0018] In the present specification, "improvement of intestinal environment" includes improvement of intestinal flora or intestinal bacterial flora. Improvement of intestinal flora or intestinal bacterial flora may be either an increase in the number or ratio of bacteria (good bacteria) useful to the host, or an inhibition of a decrease in the number or ratio of bacteria useful to the host, making the intestinal flora or intestinal bacterial flora normal or close to normal, and inhibiting adverse effects on the host. In the present disclosure, it is intended that lactic acid bacteria are particularly increased. Examples of inhibiting adverse effects on the host include inhibition of inflammation in the intestinal mucosa. That is, the intestinal environment improver of the present disclosure may be an intestinal environment improver that increases the number or ratio of bacteria useful to the host, or an intestinal environment improver that inhibits a decrease in the number or ratio of bacteria useful to the host.

[0019] Examples of bacteria useful to the host include lactic acid bacteria such as Lactobacillus bacteria, Bifidobacterium bacteria, and Streptococcus bacteria, which are also used as probiotics.

[0020] In the present specification, the term "intestinal environment-related disease" includes any disease, disorder, symptom, etc. related to the intestinal environment, including, for example, inflammatory bowel disease (IBD), obesity, cancer, fatty liver, dyslipidemia, hay fever, atopic dermatitis, stress-induced sleep disorder, etc. In addition, disturbance or deterioration of the intestinal flora or intestinal bacterial flora has been reported to be involved in allergies, enteritis, exacerbation of intestinal bleeding, intestinal permeability, obesity, diabetes, etc., and improvement of disturbance or deterioration of the intestinal flora or intestinal bacterial flora is expected to improve these symptoms. There are no particular limitations on the cause of disturbance or deterioration of the intestinal environment, and examples of such causes include eating habits, smoking, stress, drug administration, etc., but the technology of the present disclosure is preferably applied to disturbance or deterioration of the intestinal environment caused by drug administration.

[0021] In the present specification, "configured to modify epigenetics and / or suppress energy metabolism" refers to any aspect configured to modify epigenetics and / or suppress energy metabolism. Although not limited thereto, for example, at least one of methionine, tryptophan, and / or niacin may be ingested in an amount less than the amount normally required, but this is not limited thereto, and it may be completely not ingested. For example, in a specific embodiment, in addition to completely zero, the following may be mentioned: for example, based on the components of the feed used, methionine is calculated as 4.5 g per kg, tryptophan is calculated as 2.1 g per kg, and niacin is calculated as 10 g per kg as a vitamin mix, and in the case of half the amount, methionine is calculated as 2.25 g per kg, tryptophan is calculated as 1.05 g per kg, and niacin is calculated as a vitamin mix as 5 g per kg. *In the case of a 90% reduction, methionine is calculated as 0.45g per kg, tryptophan is calculated as 0.21g per kg, and niacin is calculated as 1g per kg as a vitamin mix. In the case of a 10% reduction, methionine is calculated as 4.05g per kg, tryptophan is calculated as 1.89g per kg, and niacin is calculated as 9g per kg as a vitamin mix. These can also be combined. Examples of combinations include methionine deficiency only, tryptophan and niacin deficiency, and methionine, tryptophan, and niacin deficiency.

[0022] As used herein, the term "dietary composition that modifies epigenetics and / or suppresses energy metabolism" refers to any dietary composition that modifies epigenetics and / or suppresses energy metabolism, and refers to a composition that is broken down into nutrients to modify epigenetics and / or suppress energy metabolism. Such a dietary composition may be one that adjusts the following nutrients. Such nutrients involved in epigenetics include folic acid, vitamins B12, B6, B2, B3, methionine, serine, glycine, histidine, threonine, betaine, choline, and α-ketoglutaric acid. Lysine-specific demethylase-1 (LSD1 or KDM1A), one of the epigenetic modification enzymes, controls the expression of energy metabolism-related genes (Hino S, Sakamoto A, Nagaoka K, Anan K, Wang Y, Mimasu S, Umehara T, Yokoyama S, Kosai K, Nakao M. FAD-dependent lysine-specific demethylase-1 regulates cellular energy expenditure. Nat Commun. 2012 Mar 27;3:758). Therefore, epigenetic-related nutrients also indirectly affect the expression of energy metabolism-related genes (Figure 1 shows a schematic diagram based on Otani Rie, Murakami T, Kato Hisanori (2013) Mechanism of lifestyle-related disease caused by protein nutrition: Nutritional memory imprinted from fetal to neonatal periods. Chemistry and Biology, 51, 785-788.).

[0023] As used herein, the term "medicine that modifies epigenetics and / or suppresses energy metabolism" refers to any medicine that is configured to modify epigenetics and / or suppress energy metabolism, including those that are composed of nutrients that modify epigenetics and / or suppress energy metabolism as components of the medicine. Such components can include KDM1A inhibitors. KDM1A inhibitors act on KDM1A to inhibit demethylation of methylated histones, and examples thereof include Seclidemstat (available from MedChemExpress) and GSK2879552 dihydrochloride (available from MedChemExpress).

[0024] In this specification, "instructions" (including package inserts and labels used by the U.S. FDA, etc.) are descriptions of a method of using the present disclosure that is explained to a physician or other user. The instructions include a statement instructing administration of the medicament, etc. of the present disclosure. The instructions may also include a statement instructing intravenous administration, etc. (e.g., by injection, etc.) as the administration site. The instructions are prepared in accordance with a format prescribed by a supervisory agency of the country in which the present disclosure is implemented (e.g., the Ministry of Health, Labor and Welfare in Japan, the Food and Drug Administration (FDA) in the United States, etc.), and it is clearly stated that the instructions have been approved by the supervisory agency. The instructions are so-called package inserts or labels, and may be provided in paper media, but are not limited thereto, and may also be provided in the form of, for example, electronic media (e.g., a homepage provided on the Internet, PDF, email, etc.).

[0025] (Preferred embodiment) A description of a preferred embodiment is given below, but it should be understood that this embodiment is an example of the present disclosure and the scope of the present disclosure is not limited to such a preferred embodiment. It should also be understood that those skilled in the art can easily make modifications, changes, etc. within the scope of the present disclosure by referring to the following preferred examples. Therefore, it is clear that those skilled in the art can make appropriate modifications within the scope of the present disclosure by taking into account the description in this specification. It is also understood that the following embodiments of the present disclosure can be used alone or in combination.

[0026] (epigenetic modification, suppression of energy metabolism, lack of amino acids and amino acid-related substances) In one aspect, the present disclosure provides a method for improving intestinal environment or preventing or treating intestinal environment-related diseases, comprising providing at least one amino acid or amino acid metabolism-related substance (considering niacin) in an amount less than that normally required.

[0027] In another aspect, there is provided a composition or a combination thereof that provides at least one amino acid or amino acid metabolism-related substance (assuming niacin) in an amount less than that normally required, for improving the intestinal environment or for preventing or treating an intestinal environment-related disease.

[0028] In another aspect, the present disclosure provides a method for improving intestinal environment or for preventing or treating intestinal environment-related diseases, comprising modifying epigenetics and / or suppressing energy metabolism.

[0029] In another aspect, the present disclosure provides a composition or a combination thereof that is provided to modify epigenetics and / or suppress energy metabolism, and is for improving the intestinal environment or for preventing or treating intestinal environment-related diseases. The composition may be provided in the form of a medicine, a diet, a complete nutritional diet, a gastrostomy, or the like.

[0030] (Detailed explanation of epigenetic modification and energy metabolism suppression) In one embodiment, in a diet that provides normal nutrition, epigenetics can be modified and / or energy metabolism can be suppressed as follows. Without wishing to be bound by theory, methylation enzymes methylate substrates using S-adenosylmethionine (SAM), which is produced only from methionine. Therefore, deficiency of methionine reduces the amount of SAM synthesis, promoting the modification of epigenetic methylation modification. Since NAD+ required for energy metabolism is supplied from tryptophan and niacin, deficiency of tryptophan and niacin suppresses energy metabolism.

[0031] Although not wishing to be bound by theory, an increase in lactobacillus is expected to improve IBD, and is also expected to be effective in preventing obesity. Regarding the expected effect of an increase in lactobacillus, for example, a mouse experiment showed that a deficiency caused weight loss ("In Vivo Functional Properties of Dairy Bacteria" Microorganisms. 2023 Jul 11;11(7):1787.), and the effect of the present disclosure on obesity is reasonably expected. It is also known that Lactobacillus johnsonii enhances the effect of immune checkpoint inhibitors (CTLA-4) in cancer treatment, and from these, the present disclosure is expected to act on cancer as well ("Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy" Science. 2020 Sep 18;369(6510):1481-1489.). It is also expected to be effective against fatty liver ("Protective Effects of Lactobacillus gasseri against High-Cholesterol Diet-Induced Fatty Liver and Regulation of Host Gene Expression Profiles" Int J Mol Sci. 2023 Jan 20;24(3):2053.).In addition, it is expected to be effective against dyslipidemia (Li X, Xiao Y, Huang Y, Song L, Li M, Ren Z. "Lactobacillus gasseri RW2014 Ameliorates Hyperlipidemia by Modulating Bile Acid Metabolism and Gut Microbiota Composition in Rats" Nutrients. 2022 Nov 22;14(23):4945.), and it is reasonably expected to be effective against IBD ("The Lactobacillus gasseri G098 Strain Mitigates Symptoms of DSS-Induced Inflammatory Bowel Disease in Mice" Nutrients. 2022 Sep 10;14(18):3745.). There are many types of lactic acid bacteria, which were classified into major categories and were reclassified in 2020, but regardless of this classification, any lactic acid bacteria is expected to be effective.

[0032] Although we do not wish to be bound by theory, Ligilactobacillus murinus (Lactobacillus murinus) was the majority in DSS drinking water IBD model mice (approximately 80% in 1KR, approximately 50% in 2KR, and approximately 20% in 3KR). In addition, approximately 40% of Lactococcus garvieae was detected in 2KR (this bacterium was originally found as a fish pathogen, but also had antibacterial activity). ("Heat, cold, acid, and bile salt induced differential proteomic responses of a novel potential probiotic Lactococcus garvieae C47 isolated from camel milk" Food Chem. 2022 Dec 15;397:133774.). From the above, it is expected that the diet will have an effect. A small increase in the lactic acid bacteria Lactobacillus murinus was observed in cancer model mice treated with immune checkpoint inhibitors ("Anti-PD-L1 Antibody and / or 17β-Estradiol Treatment Induces Changes in the Gut Microbiome in MC38 Colon Tumor Model" Cancer Res Treat. 2023 Jul;55(3):894-909.). In addition, in deficiency experiments in normal mice not drinking DSS as in Examples 2-3 of the present specification (BALB / c), Lactobacillus johnsonii (approximately 15% in 1KR, approximately 15% in 2KR, and approximately 25% in 3KR) and Lactobacillus_gasseri (approximately 2% in 1KR, approximately 5% in 2KR, and approximately 10% in 3KR) were detected. As mentioned in the references in Answer 1, Lactobacillus johnsonii is a bacterium that is expected to have anticancer activity when used in combination with immune checkpoint inhibitors, and Lactobacillus gasseri is a bacterium that is expected to be effective against fatty liver and dyslipidemia. It is understood that various lactic acid bacteria are effective in this way, and it can be said that the effects of the present disclosure are reasonably expected.

[0033] There is no other data showing that the proportion of lactobacillus in the intestine increases when methionine is returned to normal diet from a deficiency state, so this dietary method that can be expected to have such an effect is unexpected. If the host's gene expression is severe, tryptophan and niacin, or tryptophan, niacin, and methionine are preferable. It is not necessary to return from "deficiency" to "normal," and the effect is achieved even if the diet is left deficient. This is because, although I do not wish to be bound by theory, the results of the analysis of gene expression in the intestinal cells of the host (mouse) showed that the antioxidant power of the intestinal cells increased both when the diet was deficient and when it was returned to normal. Therefore, in terms of gene expression on the host side, it does not matter whether the diet is returned to normal or not (as long as it is within 2 weeks). Based on the experimental results, it is recommended to return the diet to normal to increase the proportion of lactobacillus. An increase in the proportion of lactobacillus has been observed with other deficiencies, and both are expected to be effective.

[0034] In addition, in the case of both tryptophan and niacin deficiency and only one of them being deficient, the present disclosure clearly demonstrates that the condition of both tryptophan and niacin deficiency is effective, and even if only one of them is deficient, it is expected to be effective. From the viewpoint of NAD+ production, according to the metabolic pathway diagram, NAD+ is produced if either tryptophan or niacin is present, so it is understood that sufficient effect cannot be obtained with only one of them.

[0035] Without wishing to be bound by theory, the present disclosure found activation of the signal transduction pathway related to antioxidant power. Therefore, it is presumed that an anti-inflammatory effect can be expected. The expression of IL-10, an anti-inflammatory cytokine, increased, albeit at a very small amount, in IBD model mice in a "deficiency state." When the mice were fed a normal diet, the expression level increased in methionine deficiency, decreased in tryptophan and niacin deficiency, and increased in methionine, tryptophan, and niacin deficiency. A correlation with the increase in lactic acid bacteria has also been suggested (the gene expression level of each cytokine can be accounted for), and from past research reports on lactic acid bacteria, it is believed that the increase in lactic acid bacteria contributes to the anti-inflammatory effect.

[0036] As shown in the present disclosure, in order to increase lactic acid bacteria in the intestines, it is usually necessary to externally ingest lactic acid bacteria or oligosaccharides that can only be metabolized by lactic acid bacteria; however, what was unexpected and remarkable in this study was that an increase in lactic acid bacteria in the intestines was observed without taking these methods.

[0037] Methionine deficiency suppresses "Epigenetic Modifications", tryptophan and niacin deficiency suppresses "Energy Metabolism", and it can be said that methionine, tryptophan and niacin deficiency suppress "Epigenetic Modifications" and "Energy Metabolism". Since S-adenosylmethionine (SAM) is produced only from methionine, and NAD+ is produced only from tryptophan metabolism or niacin metabolism, there is no need to deplete components other than methionine, tryptophan and niacin, but it is expected that depletion of these components will be effective.

[0038] I don't want to be bound by theory, but I think that weight loss can be a health hazard for healthy people (those with normal weight), but beneficial for obese people. For example, in a mouse experiment, about 40% of mice died after 18 days of deprivation, but 100% survived within 2 weeks. It is thought that there is no problem if the deprivation period is set appropriately. Another feature is that it can achieve weight loss by burning fat under milder conditions than fasting (in the sense that it does not cut off all nutrients, but only cut off the three elements methionine, tryptophan, and niacin).

[0039] In this disclosure, we performed RNA-seq on cells in the intestine of IBD model mice in particular, and it is believed that enhanced antioxidant activity can be applied to the treatment or prevention of IBD.

[0040] Although not intended to be limiting, the present disclosure is based on experiments using IBD model mice drinking dextran sulfate sodium (DSS) or normal mice to examine gene expression in intestinal cells and the intestinal bacterial flora, and it is understood that this is effective against IBD.

[0041] As described herein, in addition to tryptophan, methionine, and niacin, it is expected that the effects will be obtained by depleting homocysteine, nicotinamide riboside, nicotinamide mononucleotide, N'-formylkynurenine, kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxyanthranilic acid, 2-amino-3-carboxymuconic acid semialdehyde, and quinolinic acid. In a preferred embodiment, it is advantageous to deplete at least one of tryptophan, methionine, and niacin. Without wishing to be bound by theory, homocysteine ​​is produced by the metabolism of methionine, and nicotinamide riboside and nicotinamide mononucleotide are produced by the metabolism of niacin. The others (N'-formylkynurenine, kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxyanthranilic acid, 2-amino-3-carboxymuconic acid semialdehyde, quinolinic acid) are produced by the metabolism of tryptophan, and therefore even if only these are deficient, as long as there is no deficiency in methionine, niacin, or tryptophan upstream in the metabolic pathway, they will be used as raw materials for production. Therefore, it is understood that a deficiency of methionine, niacin, or tryptophan is effective, but it is also understood that the present invention is not limited to this.

[0042] In one embodiment, it can be confirmed that the improvement of the intestinal environment or the prevention or treatment of intestinal environment-related diseases has been achieved as follows. In addition to the increase in lactic acid bacteria, whether the patient is aware that the itching and pain caused by inflammation has subsided, whether the patient feels that stress has been relieved and that they have slept well, etc. It can be judged whether the quality of life (QOL) of the patient has improved.

[0043] (Amino acids and amino acid metabolism-related substances) In one embodiment, the amino acid or amino acid metabolism related substance is exemplified by methionine, tryptophan, homocysteine, nicotinamide riboside, nicotinamide mononucleotide and / or niacin or a combination thereof.

[0044] Suppression of amino acids or substances related to amino acid metabolism can be achieved, for example, by ingesting at least one of methionine, tryptophan, and / or niacin in an amount less than the normally required amount. The amount of amino acids or substances related to amino acid metabolism such as methionine, tryptophan, and / or niacin that is normally required for a subject to be treated can be calculated by referring to nutritional literature known in the art.

[0045] For example, such calculations can be done as follows. https: / / www.tyojyu.or.jp / net / kenkou-tyoju / eiyouso / tanpaku-amino.html can be used as a reference. Of the amino acids, nine types - valine, leucine, isoleucine, threonine, methionine, lysine, phenylalanine, tryptophan, and histidine - cannot be synthesized in the body in the required amounts, so they must usually be ingested through food. These amino acids are called essential amino acids. There are 11 non-essential amino acids that can be synthesized in the body: glycine, alanine, glutamic acid, glutamine, serine, aspartic acid, asparagine, tyrosine, cysteine, arginine, and proline. According to the Japanese Dietary Reference Intakes, the ideal daily protein requirement is 13-20% of energy intake for those aged 18-49, 14-20% for those aged 50-64, and 15-20% for those aged 65 or older. The recommended amount is 65g per day for men aged 18-64, 60g for men aged 65 or older, and 50g per day for women aged 18 or older. The required amount of the amino acids covered by this disclosure is based on these documents, and the purpose of this disclosure can be achieved by ingesting less than these amounts (https: / / www.tyojyu.or.jp / net / kenkou-tyoju / eiyouso / tanpaku-amino.html). In the tables of these documents, the estimated average required amount in Tables 1-1 and 1-2, in particular, can be divided by 20 (there are 20 types of amino acids). For men, 50÷20 is 2.5g. For women, 40÷20 is 2g.

[0046] Niacin can be explained as follows, referring to https: / / www.tyojyu.or.jp / net / kenkou-tyoju / eiyouso / vitamin-niacin.html etc. In other words, niacin is one of the water-soluble B vitamins, and is a general term for nicotinic acid and nicotinamide. Furthermore, since niacin is synthesized in the body from tryptophan, an amino acid, it is expressed in niacin equivalents, taking into account the tryptophan content. As 60 mg of tryptophan is equivalent to 1 mg of niacin, the niacin equivalent (mgNE) is expressed by the following formula: Niacin equivalent (mgNE) = niacin (mg) + 1 / 60 tryptophan (mg) Niacin is a water-soluble vitamin B group and is the general term for nicotinic acid and nicotinamide.

[0047] Niacin is a vitamin involved in energy metabolism, so the estimated average requirement is calculated as 4.8 mg per 1,000 kcal of energy. The recommended amount is calculated by multiplying this estimated average requirement, which is estimated to meet the needs of half of the population, by the recommended amount calculation coefficient of 1.2, which is the amount that is thought to meet the needs of approximately 97.5% of people. The amount of niacin required per day (recommended amount) is 15 mg NE for men aged 18-49, 14 mg NE for men aged 50-74, and 13 mg NE for those aged 75 and over, 11 mg NE for women aged 18-29, 12 mg NE for women aged 30-49, 11 mg NE for women aged 50-74, and 10 mg NE for women aged 75 and over.

[0048] A deficiency of niacin can cause a disease called pellagra, but this can be managed by monitoring the condition. A provisional value can be calculated by dividing the estimated average requirement in Tables 1-1 and 1-2 above by 20 (there are 20 types of amino acids). For men, 50÷20 = 2.5g. For women, 40÷20 = 2g.

[0049] (energy metabolism suppression or epigenetic modification) Energy metabolism inhibition or epigenetic modification can be achieved by providing components associated with energy metabolism inhibition or epigenetic modification, such as methionine, tryptophan, and / or niacin, or a combination thereof, in amounts less than those normally required in normal nutritional intake.

[0050] In one embodiment, the present disclosure provides a diet for improving intestinal environment or for preventing or treating intestinal environment-related diseases, characterized in that at least one of methionine, tryptophan, and / or niacin is provided in an amount less than the amount normally required in a diet providing normal nutrition. Such a diet is assumed to be provided consecutively, but is not limited thereto, and may be configured to provide at least one of methionine, tryptophan, and / or niacin in an amount less than the amount normally required as a result of the sum of two or more meals.

[0051] In one embodiment, modification or suppression in this disclosure includes providing less methionine than would normally be required, or providing less tryptophan and niacin than would normally be required.

[0052] In a specific embodiment, the intake amount is: Methionine: Less than 2.5g / day (body weight 60kg) Tryptophan, less than 2.5g / day (body weight 60kg) Niacin: Less than 13 mg / day (body weight 60 kg) Examples are given below.

[0053] These amounts may be increased by as much as 5%, 10%, 15%, or 20%.

[0054] In one embodiment, in the present disclosure, the intake amount is substantially zero, because by making it zero, the deficiency effect is enhanced and a significant increase in lactic acid bacteria is observed.

[0055] (Administration Method) In one embodiment, as an example of a method for implementing the present disclosure, the present disclosure provides, for example, a method for treating, preventing, or improving a subject, comprising the step of A) having the subject ingest a diet that is deficient in at least one amino acid or fat, or a component related to the metabolism of these, in the normal diet.

[0056] As used herein, "lack" means less than the amount normally required; such required amounts are well known in the art and references cited in this specification may be found therein.

[0057] In one embodiment, the present disclosure relates to having the subject consume a normal diet (also referred to as a restricted diet in this specification) that does not include the above deficiencies, except for step A).

[0058] In another embodiment, the present disclosure provides that the A) step is carried out for 15 to 33 days. These upper and lower limits can be set arbitrarily, and the lower limit can be 7 days, 10 days, 12 days, 15 days, 18 days, 21 days, 25 days, 28 days, 30 days, etc., and the upper limit can be 25 days, 28 days, 30 days, 33 days, 35 days, 40 days, 45 days, 50 days, etc. For example, in Example 1, the deprivation period is 28 days, and the animals are returned to normal feed and reared for 5 days. In Example 2, the animals are reared on normal feed for 2 days after 13 days of deprivation. In Example 3, the animals can be reared on normal feed for 5 days after 14 days of deprivation, 9 days of deprivation, and 2 days of deprivation.

[0059] In a preferred embodiment, the deficiency may be less than the amount normally required. In one embodiment, the lack of the present disclosure may be less than half the amount normally required. It is understood that even a decrease in the amount of about half the amount required will produce the intended effect of the present disclosure on enterobacteria.

[0060] In another embodiment, the absence in the present disclosure may be a complete absence of intake, for example, but not limited to, a 20% reduction from the normal amount.

[0061] (For increasing lactic acid bacteria) In one aspect, the improvement of the intestinal environment in the present disclosure includes an increase in lactic acid bacteria.

[0062] In one embodiment, the intestinal environment-related disease targeted by the present disclosure includes at least one selected from autoimmune disease and inflammatory disease. Without wishing to be bound by theory, the reason why these diseases can be treated includes, but is not limited to, the promotion of intestinal protease secretion, which breaks down proteins that cause inflammation, and the adjustment of the balance of immune cells by changes in the intestinal flora.

[0063] In one embodiment, the intestinal environment-related disease targeted by the present disclosure includes at least one selected from inflammatory bowel disease (IBD), obesity, cancer, fatty liver, and dyslipidemia. Without wishing to be bound by theory, these diseases can be treated, for example, by enhancing the effect of immune checkpoint inhibitors, which are anticancer drugs, or by promoting the burning of fat accumulated in the body. Examples of such treatments include, but are not limited to, promoting changes in the intestinal environment and adjusting the balance of immune cells.

[0064] In one aspect, the present disclosure can be provided as a meal set, which can achieve energy metabolism suppression or epigenetic modification based on the overall intake of the meal set.

[0065] In one embodiment, the energy metabolism inhibition or epigenetic modification inhibition in the present disclosure includes ingesting less methionine than normally required, or ingesting less tryptophan and niacin than normally required. Such an embodiment can be provided as a meal set. Specific amounts envisioned here include methionine, less than 2.5 g / day (60 kg body weight), tryptophan, less than 2.5 g / day (60 kg body weight), niacin, less than 13 mg / day (60 kg body weight), etc., and preferably, the intake is substantially zero.

[0066] In one embodiment, the dietary set of the present disclosure achieves an improvement in the intestinal environment, and the improvement includes an increase in lactic acid bacteria. Since the lactic acid bacteria is improved, intestinal environment-related diseases can be improved, and at least one selected from autoimmune diseases and inflammatory diseases can be treated or prevented, and such diseases include at least one selected from inflammatory bowel disease (IBD), obesity, cancer, fatty liver, and dyslipidemia.

[0067] (Amino acid-deficient medicines, foods, and compositions) In one aspect, the present disclosure provides medicines, foods, and compositions that lack a specific ingredient.

[0068] In one aspect, the present disclosure may be a medicine or food that lacks at least one amino acid or fat or component related to their metabolism.Such amino acid or fatty acid or component may be an essential component for a subject.Such essential components may include methionine, tryptophan, niacin, homocysteine, nicotinamide riboside, nicotinamide mononucleotide, N'-formylkynurenine, kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxyanthranilic acid, 2-amino-3-carboxymuconic acid semialdehyde, quinolinic acid, etc.

[0069] (Administration Method) In one aspect, the present disclosure provides a method for treating, preventing or improving a subject, comprising the step of A) making the subject consume a normal diet so that at least one of amino acid or fat or components related to the metabolism thereof is absent.Medicine or diet can be configured to realize the present disclosure and realize the method.

[0070] In one embodiment, in the present disclosure, except for step A), a normal diet without the above deficiency may be consumed, or a diet that realizes the above deficiency may be consumed. Such administration of step A) is carried out for 15 to 33 days.

[0071] Therefore, in another aspect, there is provided a medicine or food lacking at least one of the amino acids or fats or components related to their metabolism, characterized in that the medicine or food is used to cause a subject to consume a normal diet, but during a certain period of time, the subject is provided with a diet lacking at least one of the amino acids or fats or components related to their metabolism.

[0072] In one embodiment, the present disclosure provides a medicine or food product lacking at least one amino acid. Preferably, the amino acid is essential for a subject, e.g., Amino acids include methionine, tryptophan, homocysteine, nicotinamide riboside, nicotinamide mononucleotide, N'-formylkynurenine, kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxyanthranilic acid, 2-amino-3-carboxymuconic acid semialdehyde, and quinolinic acid.

[0073] In one embodiment, the medicine or food contains standard dietary components (thionine, tryptophan) and an improved diet lacking homocysteine, nicotinamide riboside, nicotinamide mononucleotide, N'-formylkynurenine, kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxyanthranilic acid, 2-amino-3-carboxymuconic acid semialdehyde, and quinolinic acid.

[0074] In another aspect, the present disclosure provides a medicine or food product lacking at least one component involved in amino acid or fatty acid metabolism, including niacin and other analogs (nicotinamide riboside, nicotinamide mononucleotide, etc.).

[0075] In one embodiment, the medicament or food of the present disclosure is for the treatment or prevention of an autoimmune disease. In a preferred embodiment, the autoimmune disease includes inflammatory bowel disease.

[0076] (Aspects of Absence) In one embodiment, the absence in the present disclosure means less than the amount normally required, or the absence may mean less than half the amount normally required. Alternatively, the absence in the present disclosure may mean not taking it at all. It is understood that these may be taken in any form as long as the desired improvement of the intestinal environment is achieved.

[0077] (Medicine) The composition for improving the intestinal environment of the present disclosure may contain other optional components within a range that does not impair the effects of the present disclosure. The optional components include binders, excipients, lubricants, flavors, flavorings (sweeteners, acidulants, etc.), dyes, stabilizers, coating agents, plasticizers, masking agents, etc., and may be used alone or in appropriate amounts in combination of two or more.

[0078] Examples of binders that can be used include starch, alpha-starch, sucrose, gelatin, powdered gum arabic, methylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, pullulan, and dextrin.

[0079] Examples of excipients that can be used include low-substituted hydroxypropylcellulose, corn starch, lactose, talc, crystalline cellulose (such as Ceolus), powdered sugar, sugar alcohols such as mannitol, and light anhydrous silicic acid.

[0080] Examples of lubricants include magnesium stearate, calcium stearate, polyethylene glycol, talc, stearic acid, sucrose fatty acid esters, sodium stearyl fumarate, etc. Examples of flavorings include menthol, limonene, plant essential oils (peppermint oil, mint oil, lychee oil, orange oil, lemon oil, etc.), etc.

[0081] Examples of sweeteners include sodium saccharin, aspartame, stevia, dipotassium glycyrrhizinate, acesulfame potassium, thaumatin, and sucralose.

[0082] As the acidulant, for example, citric acid, tartaric acid, malic acid, succinic acid, fumaric acid, lactic acid, or salts thereof can be used. Examples of coating agents that can be used include hydroxypropylmethylcellulose, hydroxyethylcellulose, polyvinyl alcohol, carboxymethylcellulose, ethylcellulose, and Opadry (trade name) (manufactured by Nippon Colorcon LLC).

[0083] As the plasticizer, for example, polyethylene glycol, triacetin, etc. can be used.

[0084] As the masking agent, for example, titanium oxide, talc, etc. can be used.

[0085] The administration form of the present disclosure is not particularly limited. For example, oral administration (e.g., oral administration, sublingual administration, etc.), parenteral administration (intravenous administration, intramuscular administration, subcutaneous administration, transdermal administration, nasal administration, pulmonary administration, etc.) and the like can be mentioned. Among these, less invasive administration forms are preferred, and oral administration (ingestion) is more preferred from the viewpoint of effectively improving the disturbance or deterioration of the intestinal environment.

[0086] Examples of dosage forms of oral administration agents (internal preparations) or compositions for oral administration (internal compositions) include liquid (liquid), syrup (syrup), tablet (tablet, tablet), capsule (capsule), powder (granule, fine granule), soft capsule (soft capsule with gelatin base or the like), hard capsule (hard capsule), liquid (liquid), syrup (syrup), solid, semi-liquid, cream, and paste forms.

[0087] The method of making the present disclosure into a formulation is not particularly limited, and can be carried out by a conventional method according to the formulation.For example, when an active ingredient is used in the present disclosure, the active ingredient can be mixed with other ingredients as is, or a part or all of the ingredients can be granulated or coated and then mixed to produce a granular mixture, which can be used as a granular agent (granules, fine granules, powders).In addition, the granular mixture can be compressed into tablets, and further coated as necessary to make tablets.

[0088] (Embodiment for meals) In one aspect, the present disclosure can be provided in the form of a meal. Such forms include those provided in a fixed format, such as solid food or liquid food, and examples thereof include CalorieMate (Otsuka Pharmaceutical) and SoyJoy (Otsuka Pharmaceutical). In such cases, the method of administration can be specified so that a deficiency of the components of the present disclosure is achieved. Examples of such products include, for example, those with the following component composition:

[0089] [Table 1]

[0090] can be assumed. Solid nutritional supplements that are deficient in methionine, tryptophan, and niacin. Examples include CalorieMate (Otsuka Pharmaceutical) and SoyJoy (Otsuka Pharmaceutical).

[0091] (Medicinal embodiment) In one aspect, the present disclosure can be provided in the form of a medicine. Such forms include nutritional supplements, in which case the method of administration can be specified to implement the deficiency of the components of the present disclosure. Examples of such products include liquid nutritional supplements that are deficient in methionine, tryptophan, and niacin. Examples include Ensure Liquid (Abbott) and Racol NF Combined Enteral Liquid (Otsuka Pharmaceutical).

[0092] For example, the composition of products such as Ensure Liquid (sodium caseinate, sodium calcium caseinate, soy protein isolate, corn oil, soy lecithin, dextrin, refined white sugar, retinol palmitate, cholecalciferol, tocopherol acetate, phytonadione, ascorbic acid, thiamine hydrochloride, riboflavin, pyridoxine hydrochloride, cyanocobalamin, choline chloride, folic acid, nicotinamide, calcium pantothenate, biotin, sodium bicarbonate, magnesium chloride, potassium citrate) It can be implemented by deleting the missing components of the present disclosure from among the components (calcium phosphate, tricalcium phosphate, potassium chloride, sodium citrate hydrate, zinc sulfate hydrate, ferrous sulfate hydrate, manganese chloride, copper sulfate) or the component composition (protein, fat, carbohydrate, vitamin A, vitamin D, vitamin E, vitamin K, vitamin C, vitamin B1, vitamin B2, vitamin B6, vitamin B12, choline, folic acid, niacin, pantothenic acid, biotin, sodium, potassium, chlorine, calcium, phosphorus, magnesium, manganese, copper, zinc, iron). (https: / / www.abbott.co.jp / content / dam / corp / abbott / ja-jp / our-products / ani / if-ensure-14.pdf may be referenced.

[0093] In another aspect, the present disclosure provides a device or system for designing a diet for improving the intestinal environment or for preventing or treating an intestinal environment-related disease, the device including a calculation unit that calculates a diet (also called a "component-adjusted" diet) that is configured to modify epigenetics and / or suppress energy metabolism and / or adjust amino acids or fats or components related to these metabolisms in a diet that provides normal nutrition, and a display unit that displays the calculated diet. Such a design can be realized as follows.

[0094] A device or system according to one embodiment of the present disclosure is a system for assisting in adjusting dietary components, comprising one or more computer processors, which, in response to execution of readable instructions, perform the steps of calculating or determining the modification of epigenetics and / or the suppression of energy metabolism and / or the adjustment of amino acids or fats or components related to the metabolism thereof in a diet providing normal nutrition, and presenting to the user a screen on which a predetermined object having an appearance based on the calculation or determination is displayed.

[0095] It is theoretically possible to create an AI using supervised machine learning with input data representing the amount of nutrition of each component, including the Western components that are the subject of this disclosure, taken in a meal, and output data representing specific parameters, and to predict the output from input data that has no answer. It is understood that this requires a certain amount of data and can be implemented by incorporating AI-related techniques.

[0096] In another aspect, the present disclosure provides a method for designing a diet for improving intestinal environment or for preventing or treating intestinal environment-related diseases, the method comprising calculating a diet that provides normal nutrition and is configured to modify epigenetics and / or suppress energy metabolism and / or adjust amino acids or fats or components related to these metabolisms (also referred to as a "component-adjusted" diet).

[0097] A method according to one embodiment of the present disclosure is executed by one or more computers to assist in adjusting meal components, comprising the steps of calculating or determining an adjustment to meal components, and presenting to the user a screen on which a predetermined object having an appearance based on the adjustment or determination of the meal components is displayed.

[0098] In another aspect, the present disclosure provides a program for causing a computer to execute a method for designing a diet for improving intestinal environment or for preventing or treating an intestinal environment-related disease, the method comprising: calculating a diet that provides normal nutrition, and that is configured to modify epigenetics, and / or suppress energy metabolism, and / or adjust amino acids or fats, or components related to these metabolism (also referred to as a "component-adjusted" diet); and displaying the calculated diet.

[0099] A program according to one embodiment of the present disclosure is a program for assisting in calorie management, which causes one or more computers to execute the steps of calculating or determining adjustments to meal components and presenting to the user a screen on which a predetermined object having an appearance based on the calculation or determination is displayed.

[0100] Specific embodiments will be described below with reference to the drawings.

[0101] First, a description will be given of the hardware configuration of the composition adjustment support server 10. The server 10 is configured as a general computer, and as shown in Fig. 11, includes a computer processor 11, a main memory 12, an input / output I / F 13, a communication I / F 14, and a storage (storage device) 15, and these components are electrically connected via a bus or the like (not shown).

[0102] The computer processor 11 is configured as a CPU, a GPU, or the like, and loads various programs stored in a storage 15 or the like into a main memory 12, and executes various instructions included in the programs. The main memory 12 is configured, for example, by a DRAM or the like.

[0103] The input / output I / F 13 includes various input / output devices for exchanging information with an operator, etc. The input / output I / F 13 includes, for example, an information input device such as a keyboard or a pointing device (e.g., a mouse, a touch panel, etc.), an audio input device such as a microphone, and an image input device such as a camera. The input / output I / F 13 also includes an image output device such as a display, and an audio output device such as a speaker.

[0104] The communication I / F 14 is implemented as hardware such as a network adapter, various communication software, or a combination of these, and is configured to realize wired or wireless communication via a communication network 20 or the like.

[0105] The storage 15 is composed of, for example, a magnetic disk, a flash memory, etc. The storage 15 stores various programs including an operating system, various data, etc. For example, as shown in FIG. 11, the storage 15 has a user information table 151 (illustrated in FIG. 12) that manages information about users of the ingredient adjustment support service, a meal information table 152 (illustrated in FIG. 13) that manages information about meals, a task information table 153 that manages information about tasks (e.g., exercise) for consuming calories, a meal management table 154 for each user that manages information about meals for each user, and a task management table 155 for each user that manages information about tasks for each user. In addition, for example, the storage 15 stores a server-side program 40 according to an embodiment of the present disclosure. The program 40 is a program for causing a computer to function as a part or all of a system for providing an ingredient adjustment support service. At least a part of the server-side program 40 can be configured to be executed on the user terminal 30 side via a web browser or other application.

[0106] In this embodiment, the composition adjustment support server 10 may be configured using a plurality of computers each having the above-mentioned hardware configuration. For example, the server 10 may be configured by one or a plurality of server devices.

[0107] The composition adjustment support server 10 configured in this manner has functions as a web server and an application server, executes various processes in response to requests from a web browser or other applications installed in the user terminal 30, and transmits screen data (e.g., HTML data) and control data according to the results of the processes to the user terminal 30. The user terminal 30 displays a web page or other screen based on the received data.

[0108] Next, a description will be given of the hardware configuration of the user terminal 30. The user terminal 30 is configured as a general computer, and as shown in Fig. 11, includes a computer processor 31, a main memory 32, an input / output I / F 33, a communication I / F 34, and a storage (storage device) 35, and these components are electrically connected via a bus or the like (not shown).

[0109] The computer processor 31 is configured as a CPU, a GPU, or the like, and loads various programs stored in a storage 35 or the like into a main memory 32 and executes various instructions included in the programs. The main memory 32 is configured, for example, by a DRAM or the like.

[0110] The input / output I / F 33 includes various input / output devices for exchanging information with an operator, etc. The input / output I / F 33 includes, for example, an information input device such as a keyboard or a pointing device (e.g., a mouse, a touch panel, etc.), an audio input device such as a microphone, and an image input device such as a camera. The input / output I / F 33 also includes an image output device such as a display, and an audio output device such as a speaker.

[0111] The communication I / F 34 is implemented as hardware such as a network adapter, various communication software, or a combination of these, and is configured to realize wired or wireless communication via the communication network 20 or the like.

[0112] The storage 35 is configured by, for example, a magnetic disk or a flash memory, etc. The storage 35 stores various programs including an operating system, various data, etc. The programs stored in the storage 35 can be downloaded from an application market, etc., and installed.

[0113] In this embodiment, the user terminal 30 may be configured as a smartphone, a tablet terminal, a wearable device, a personal computer, or the like.

[0114] A user operating the user terminal 30 configured in this manner can use the ingredient adjustment support service provided by the server 10 by communicating with the server 10 via a web browser or other application installed in the storage 35, etc.

[0115] Next, the functions of the thus configured ingredient adjustment support server 10 of this embodiment will be described. The computer processor 11 of the server 10 is configured to function as an ingredient adjustment support unit 111 by executing commands included in a program (for example, at least a part of the server-side program 40) loaded into the main memory 12, as shown in Fig. 11. The ingredient adjustment support unit 111 also has a meal registration unit 112 and a task registration unit 113.

[0116] The component adjustment support unit 111 is configured to execute various processes related to the support of the component adjustment of the user. For example, the component adjustment support unit 111 transmits screen data and control data of various screens related to the support of the component adjustment to the user terminal 30, executes various processes in response to an operation input by the user via the screen displayed on the user terminal 30, and transmits screen data and control data according to the results of the processes to the user terminal 30.

[0117] The meal registration unit 112 is configured to execute various processes related to meal registration. For example, the meal registration unit 112 registers the meal contents (menu) input by the user in the per-user meal management table 154. The input meal contents are, for example, individually selected by the user from a plurality of meals (menus) managed in the meal information table 152, or are automatically identified through analysis of a photographed image of the meal (menu).

[0118] The task registration unit 113 is configured to execute various processes related to task registration. For example, the task registration unit 113 registers a task set for a user in the per-user task management table 155. The task to be set is, for example, individually selected by the user from among a plurality of tasks managed in the task information table 153, or is automatically specified according to a predetermined rule.

[0119] In this embodiment, the ingredient adjustment support unit 111 is configured to determine the difference between the calorie consumption and calorie intake of the user in a predetermined period. For example, the ingredient adjustment support unit 111 calculates the ingredients that make up a meal based on the registered meal contents. Also, for example, the ingredient adjustment support unit 111 calculates the ingredients that make up a meal based on the user's basic information, each nutritional component of the registered meal, and, if necessary, the contents of the completed task. The calculated ingredients that make up a meal can also be said to be estimated values ​​or predicted values.

[0120] The components constituting the diet include, for example, essential nutrients (proteins, lipids, carbohydrates), vitamins, minerals, etc., as well as components that modify epigenetics and / or suppress energy metabolism, and / or amino acids or fats, or components related to these metabolisms, which are the subject of the present disclosure. Among these, in addition to the basal metabolic rate and calorie consumption, the amount of required nutrients, the amount of components that modify epigenetics and / or suppress energy metabolism, and / or amino acids or fats, or components related to these metabolisms, are calculated based on the user's basic information (physical information, lifestyle, etc.).

[0121] In addition, the ingredient adjustment support unit 111 is configured to present information other than food, such as additional medicine or supplements to be taken. For example, the ingredient adjustment support unit 111 transmits screen data of the screen, control data, etc. to the user terminal 30.

[0122] In this way, the component adjustment support server 10 of the present embodiment calculates or determines the components that modify epigenetics and / or suppress energy metabolism and / or amino acids or fats or those related to the metabolism, and presents a screen on which nutritional component objects having an appearance based on the calculation or determination are displayed to the user, so that the user can intuitively know through the object whether or not epigenetics is modified and / or energy metabolism is suppressed, and / or amino acids or fats or those related to the metabolism need to be increased or decreased. In other words, the component adjustment support server 10 supports easy management of the components that modify epigenetics and / or suppress energy metabolism, and / or amino acids or fats or those related to the metabolism.

[0123] In this embodiment, the object relating to epigenetics modified and / or energy metabolism suppressed and / or amino acids or fats or components related to these metabolisms may be displayed in various manners. For example, the object may be configured to be displayed in a first manner when epigenetics modified and / or energy metabolism suppressed and / or amino acids or fats or components related to these metabolisms are in excess, while being displayed in a second manner when epigenetics modified and / or energy metabolism suppressed and / or amino acids or fats or components related to these metabolisms are insufficient. The first and second manners may differ, for example, in at least one of shape, size, color, and visual effect (including animation effect). Such a configuration allows the user to know the magnitude relationship of epigenetics modified and / or energy metabolism suppressed and / or amino acids or fats or components related to these metabolisms through the display manner of the object.

[0124] Furthermore, the object of epigenetics modification and / or energy metabolism suppression and / or amino acids or fats or components related to these metabolisms may be configured to have a size corresponding to the amount or level of epigenetics modification and / or energy metabolism suppression and / or amino acids or fats or components related to these metabolisms in a predetermined period. For example, the object has a larger area as the display is larger, and a smaller area as the display is smaller. This configuration allows the user to know the size of epigenetics modification and / or energy metabolism suppression and / or amino acids or fats or components related to these metabolisms through this object.

[0125] Also, the object of epigenetics modification, and / or energy metabolism suppression, and / or amino acids or fats, or components related to these metabolisms, may be configured so that at least a part of the object is displayed in association with each of one or more registered tasks. For example, the object of epigenetics modification, and / or energy metabolism suppression, and / or amino acids or fats, or components related to these metabolisms, may have a size corresponding to the amount and necessity of epigenetics modification, and / or energy metabolism suppression, and / or amino acids or fats, or components related to these metabolisms in a predetermined period, and the part associated with the task may have a size corresponding to the corresponding calorie consumption (calorie consumption of the associated task). Also, for example, the object of epigenetics modification, and / or energy metabolism suppression, and / or amino acids or fats, or components related to these metabolisms, may be configured so that the part associated with the task is divided by task. For example, when the calorie intake is greater than the calorie expenditure, one or more tasks set to consume at least a portion of the surplus of the calorie intake are displayed in association with a portion of the calorie difference object corresponding to the surplus (e.g., information identifying the task is added). Such a configuration helps the user intuitively understand the correspondence between the task and the difference (e.g., the surplus of the intake) in which epigenetics is modified and / or energy metabolism is suppressed and / or amino acids or fats or components related to these metabolisms are modified and / or the task is associated with the difference (e.g., the surplus of the intake).

[0126] In this embodiment, the task registration unit 113 can be configured to manage the achievement of the registered task, in which case the object of modifying epigenetics and / or suppressing energy metabolism and / or the object of amino acids or fats or components related to these metabolisms can be configured to change a portion associated with the task in response to the achievement of the task. For example, the task registration unit 113 can be configured to accept an input of the achievement of the task via a screen displayed on the user terminal 30, and the calorie difference object can change a portion associated with the accomplished task in response to the acceptance of the input of the achievement of the task (for example, disappear with an animation effect). Such a configuration can provide the user with fun in response to the achievement of the task, and as a result, can promote continuous use of the component adjustment support service.

[0127] In this embodiment, the predetermined period for which epigenetics is modified and / or energy metabolism is suppressed, and / or amino acids or fats or components related to these metabolisms are calculated or determined may be set as various periods. For example, the predetermined period may be configured as a period from a predetermined start point to a current time. The predetermined start point includes, for example, a start point (e.g., a start point of use of the service) for modifying epigenetics and / or energy metabolism is suppressed, and / or management of amino acids or fats or components related to these metabolisms, and a timing when the difference is cleared (initialized) thereafter (for example, it may be cleared in a cycle of one day, one week, one month, one year, etc.). Such a configuration makes it possible to inform the user of information based on the modification of epigenetics and / or energy metabolism is suppressed, and / or the intake amount of amino acids or fats or components related to these metabolisms from a predetermined start point to a current time.

[0128] In this embodiment, various timings can be set as the timing for modifying epigenetics, and / or suppressing energy metabolism, and / or calculating or determining amino acids, fats, or components related to these metabolisms. For example, the component adjustment support unit 111 can be configured to modify epigenetics corresponding to the meal, and / or suppress energy metabolism, and / or reflect the amount of amino acids, fats, or components related to these metabolisms, etc., in the recommended amount for a predetermined period in response to the registration of the contents of the meal by the meal registration unit 112. This configuration makes it possible to update the amount or necessity of epigenetics modified, and / or energy metabolism suppressed, and / or amino acids, fats, or components related to these metabolisms, each time the contents of the meal are registered.

[0129] The epigenetics corresponding to the meal are modified, and / or energy metabolism is suppressed, and / or amino acids or fats or components related to these metabolisms can be, for example, a value obtained by allocating the reference value of the epigenetics corresponding to the meal, and / or energy metabolism is suppressed, and / or amino acids or fats or components related to these metabolisms for one day to three meals. In this case, it can also be said that the epigenetics corresponding to the meal are modified, and / or energy metabolism is suppressed, and / or amino acids or fats or components related to these metabolisms, and the epigenetics in one meal are modified, and / or energy metabolism is suppressed, and / or amino acids or fats or components related to these metabolisms, which are set based on the reference value for one day. For example, the total value of the basal metabolic rate and the calorie consumption in daily life can be set as the reference value of the epigenetics corresponding to the meal, and / or energy metabolism is suppressed, and / or amino acids or fats or components related to these metabolisms for one day. In addition, the ratio to be allocated to each meal may be set arbitrarily by the user. In addition, the amount of epigenetics corresponding to a meal that is modified and / or energy metabolism that is suppressed, and / or the amount of amino acids or fats or components related to these metabolisms is calculated, for example, by adding up the components of each menu that makes up the content of the meal (e.g., managed in the meal information table 152).

[0130] Furthermore, the task registration unit 113 may be configured to suggest to the user a task for consuming calories in response to the registration of the meal contents by the meal registration unit 112. For example, a task to be suggested to the user is specified based at least on various information associated with the user (for example, the purpose of ingredient adjustment, physical information, and physical condition information, etc.). In this case, for example, a task for a predetermined mode may be suggested to a user who is set to the predetermined mode. The predetermined mode is set, for example, as a mode corresponding to various conditions that may affect the physical condition or health of the user, and includes, for example, a physiological mode. Such a configuration promotes the registration of an appropriate task by the user.

[0131] Next, a specific example of the ingredient adjustment support server 10 of the present embodiment having such functions will be described. The server 10 of this example provides a diet support service that supports dieting by users, and supports ingredient adjustment by users in the service. First, the information managed by each table in this example will be described.

[0132] In this specification, "or" is used when "at least one or more" of the items listed in the sentence can be employed. The same applies to "alternative." In this specification, when it is specified that "within the range of" "two values", the range includes the two values ​​themselves.

[0133] All references cited herein, including scientific literature, patents, patent applications, and the like, are hereby incorporated by reference in their entirety to the same extent as if each was specifically set forth.

[0134] The present disclosure has been described above by showing preferred embodiments for ease of understanding. The present disclosure will be described below based on examples, but the above description and the following examples are provided for illustrative purposes only and are not provided for the purpose of limiting the present disclosure. Therefore, the scope of the present disclosure is not limited to the embodiments or examples specifically described in this specification, but is limited only by the scope of the claims. EXAMPLES

[0135] In the examples, for ease of description, the abbreviations shown above and the abbreviations shown below may be used.

[0136] <About food> Regular diet (Regulated diet): Oriental Yeast Co., Ltd.'s MFG (diet name) laboratory animal diet (for mice, rats, and hamsters) was used. The deficiency diet was custom-made by Dyets. The ingredients are as follows (units are grams per kg of diet):

[0137] [Table 2]

[0138] (Example 1: Example of component deficiency via DSS) In Example 1, dextran sodium sulfate (DSS), which induces inflammatory bowel disease (IBD), was given free drinking from the 18th day (DSS was not used in Examples 2 and 3).

[0139] This example was carried out as shown in FIG.

[0140] BALB / c mice were randomly divided into 5 mice per cage and started to be fed Reg, 1K, 2K, or 3K diets. Dextran sodium sulfate (DSS), an IBD inducer, was provided in the cages as a 2% solution for free drinking from day 18. On day 28, the deficient diet in all cages was changed to Reg diet. Feces and mouse intestines were collected on days 28 and 33, and feces were used for 16S rRNA analysis and intestines for gene expression analysis by RNA-seq.

[0141] (conditions) Fecal samples on day 28 were R, 1K, 2K, and 3K. Fecal samples on day 33 were RR-A, RR-B, 1KR-A, 1KR-B, 2KR, 3KR, and C. C is a control mouse that did not drink DSS water.

[0142] (result) The results are shown in Figure 3.

[0143] Figure 3 shows the results of 16S rRNA analysis using fecal samples from mice drinking dextran sulfate sodium (DSS). Changes in the intestinal flora were observed when mice were fed 1K, 2K, or 3K deficient diets compared to regular diet, and when these diets were returned to regular diet, the proportion of lactic acid bacteria increased to approximately 75% in 1KR, approximately 95% in 2KR, and approximately 50% in 3KR. This suggests that temporary deficiencies of methionine, tryptophan, and niacin bring about changes in the intestinal environment.

[0144] Figure 4 shows the results of examining body weight on the 14th day after feeding the deficient diet. Compared to the regular diet, the deficient diet showed a decrease in body weight.

[0145] (Results and Discussion) This example indicates that in IBD model mice, changes in the intestinal environment and weight loss occurred due to epigenetic gene expression control and changes in energy metabolism caused by methionine, tryptophan, and niacin deficiency.

[0146] (Example 2: Example 2 without DSS) This example was carried out as shown in FIG.

[0147] As shown in Figure 5, BALB / c mice were randomly divided into 5 mice per cage and C57BL / 6J mice were randomly divided into 3-5 mice per cage and started to be fed Reg, 1K, 2K, or 3K diets, respectively. On day 13, the deficient diet in all cages was changed to Reg diet. Feces and mouse intestines were collected on days 13 and 15, and feces were used for 16S rRNA analysis and intestines for gene expression analysis by RNA-seq.

[0148] Figure 6 shows the results of 16S rRNA analysis using each fecal sample. Changes in the intestinal flora were observed when the animals were fed 1K, 2K, or 3K deficient diets compared to the regular diet, and when these diets were returned to the regular diet, the proportion of lactic acid bacteria increased. This suggests that temporary deficiencies of methionine, tryptophan, and niacin can cause changes in the intestinal environment.

[0149] (Results and Discussion) This example indicates that deficiencies of methionine, tryptophan, and niacin also cause changes in the intestinal environment in mice that do not drink DSS.

[0150] Figure 7 shows the graph of changes in body weight. Up until the 13th day of feeding the deficient diet, the mice fed the deficient diet continued to lose weight compared to the mice fed the regular diet. This suggests that deficiencies in methionine, tryptophan, and niacin suppress the intake of nutrients necessary for maintaining body weight.

[0151] (Results and Discussion) From this example, it can be said that the change in the intestinal environment and weight loss occurred due to epigenetic gene expression control and changes in energy metabolism caused by deficiencies of methionine, tryptophan, and niacin.

[0152] (Example 3: Administration Example 3) This example was carried out as shown in FIG.

[0153] As shown in Figure 8, BALB / c mice were randomly assigned to one per cage and fed each diet according to the schedule shown above. Feces were collected on days 14 and 19 and subjected to 16S rRNA analysis.

[0154] (result) The results are shown in Figure 9.

[0155] Figure 9 shows the results of 16S rRNA analysis of fecal samples taken 5 days after the diet was returned to regular feed and before the diet was returned to regular feed after the deprivation period was set to 2, 9, and 14 days. A significant increase in lactic acid bacteria was observed in the 2K and 3K diets.

[0156] (Results and Discussion) From this example, based on the results of the intestinal flora analysis, it can be said that it is preferable to ensure a deprivation period of 2 days or more in mice.

[0157] Figure 10 shows a graph of the weight of mice under each condition. Since weight loss was observed during the deficiency period, it can be said that deficiencies of methionine, tryptophan, and niacin suppress the intake of nutrients necessary for maintaining body weight.

[0158] (Results and Discussion) This example shows that epigenetic gene expression regulation and energy metabolism changes caused by methionine, tryptophan, and niacin deficiency lead to changes in the intestinal environment and weight loss. It is preferable to perform the deficiency period for more than two days in mice, and it is presumed that it is necessary to ensure the deficiency period in humans.

[0159] (Example 4: Example of lack of tryptophan only) A composition that lacks only tryptophan is created, and an experiment similar to that in Example 1-3 is carried out. That is, mice are fed the tryptophan-deficient diet for more than two days, then the normal diet is returned, and feces are collected within five days. Body weight changes are recorded during this period. The intestinal flora is examined by 16S rRNA analysis.

[0160] (Example 5: Example of niacin deficiency only) A composition lacking only niacin is prepared, and an experiment similar to that of Example 1-3 is carried out. Mice are fed a diet lacking only niacin for at least two days, then fed a normal diet again, and feces are collected within five days. Body weight changes are recorded during this period. The intestinal microbiota is examined by 16S rRNA analysis.

[0161] (Example 6: Application for realizing a calculation program) The mass percentage of the ingredients in the feed used in this study is compared with the mass percentage of the nutrients actually ingested, and a score is generated based on how similar the mass percentage of the nutrients is to the mass percentage of the feed used in this study. The closer the mass percentage of the ingredients in the feed used in this study is to the mass percentage of the nutrients actually ingested, the greater the effect of increasing lactic acid bacteria and reducing body weight obtained in this study will be, and the results are output.

[0162] (Example 7: Examples of epigenetic modification and energy metabolism modification) In this example, we clarify "epigenetic modification and energy metabolism modification."

[0163] For this purpose, experiments using enzyme inhibitors involved in histone modification are performed. As such enzyme inhibitors, inhibitors of histone H3K9 demethylase and the like can be used. For example, it can be understood that inhibitors of JHDM2A, a histone H3K9 demethylase, induce obesity (Inagaki T, Tachibana M, Magoori K, Kudo H, Tanaka T, Okamura M, Naito M, Kodama T, Shinkai Y, Sakai J. Obesity and metabolic syndrome in histone demethylase JHDM2a-deficient mice. Genes Cells. 2009 Aug;14(8):991-1001. https: / / www.u-tokyo.ac.jp / focus / ja / press / p01_210907.html), and for example, epigenetic control important for the onset of lifestyle-related diseases (genetic modification leading to obesity) can be elucidated.

[0164] (Example 8: Target to be deleted) A customized diet can be achieved by recording the daily diet of a target subject and consuming the diet with ingredients omitted that correspond to the ingredients of the present disclosure.

[0165] Example 9: Characteristics of the administration method This example demonstrates the versatility of the administration method.

[0166] One approach involves administering the drug in combination with fasting. The specific methods are as follows: For example, it is possible to assume that fasting and administration are repeated every day. For example, although it has not been tested on humans, administration and non-administration can be continued every day for three weeks, and in the case of fasting, for example, even every day is effective. For continuous administration, 2 to 4 days is an example.

[0167] (Example 10: The range of the period to be omitted should be clearly specified) In this embodiment, the identification of the period of deficiency is demonstrated. That is, data that can be extrapolated to humans is carried out. And the period of the regular diet. Various varieties are assumed. And the schedule of step A can be adjusted. For example, administration and non-administration are continued for three weeks on each day. In the case of fasting, the effect can be confirmed even on a daily basis. It is understood that two or more days in mice corresponds to roughly one or more days in humans, but is not limited to this.

[0168] (Example 11: What happens if you delete multiple elements?) In the above example, all 3Ks are missing, but an experiment can be performed with any two of the three as 2Ks.

[0169] Example 12: Longest Range Experiments similar to those in Examples 1 to 3 can be performed for humans over a period of 14 days. In addition, in mice, a period of 14 days or more can be set by feeding normal food for one day in between.

[0170] Example 13: Analysis of Essentiality In Example 1 and the like, experiments can be performed in which, in addition to methionine and tryptophan, other promising substances are lacking: homocysteine, nicotinamide riboside, nicotinamide mononucleotide, N'-formylkynurenine, kynurenine, 3-hydroxy-L-kynurenine, 3-hydroxyanthranilic acid, 2-amino-3-carboxymuconic acid semialdehyde, and quinolinic acid.

[0171] Example 14: Inflammatory Diseases Using the composition of the present disclosure, it has been confirmed that when polyhydroxybutyrate is administered to DSS-drinking water IBD model mice, Lactobacillus johnsonii increases and the expression of inflammatory cytokines IL-1β, IL-6, and TNF-α decreases, and this disclosure can also confirm such markers (Ma N, Guo P, Chen J, Qi Z, Liu C, Shen J, Sun Y, Chen X, Chen GQ, Ma X. Poly-β-hydroxybutyrate alleviated diarrhea and colitis via Lactobacillus johnsonii biofilm-mediated maturation of sulfomucin. Sci China Life Sci. 2023 Jul;66(7):1569-1588.).

[0172] Example 15: Autoimmune Disease When the composition of the present disclosure is used and Lactobacillus johnsonii is orally administered to atopic dermatitis model mice exposed to mite antigens, it has been confirmed that the expression of proinflammatory cytokines IL-8, IL-12, and IL-23, as well as CTLA4, one of the genes associated with atopic dermatitis in infants, is reduced (Inoue R, Otsuka M, Nishio A, Ushida K. Primary administration of Lactobacillus johnsonii NCC533 in weaning period suppresses the elevation of proinflammatory cytokines and CD86 gene expressions in skin lesions in NC / Nga mice. FEMS Immunol Med Microbiol. 2007 Jun;50(1):67-76.).

[0173] (Example 16: Analysis results for identifying the uses of intestinal bacteria) In this example, it has been shown in mice that Lactobacillus johnsonii enhances the effects of immune checkpoint inhibitors (CTLA-4) in cancer treatment (Mager LF, Burkhard R, Pett N, Cooke NCA, Brown K, Ramay H, Paik S, Stagg J, Groves RA, Gallo M, Lewis IA, Geuking MB, McCoy KD. Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy. Science. 2020 Sep 18;369(6510):1481-1489.). Therefore, an increase in Lactobacillus johnsonii can be expected to be applied to cancer treatment.

[0174] (Example 17: Degree of deficiency: amount) The amount of half deficiency and 30% deficiency can be calculated and configured in Examples 1 to 3 and the like, and similar Examples can be implemented, allowing these effects to be confirmed.

[0175] (Example 18: Degree of deficiency: time (duration)) The amount of half deficiency and 30% deficiency can be calculated and configured in Examples 1 to 3, and similar Examples can be implemented, and the long-term effects of these periods can be confirmed for 2 weeks, 4 weeks, 8 weeks, 12 weeks, etc.

[0176] (Example 19: Degree of deficiency: Frequency (2 times, 3 times)) The amount of half deficiency and 30% deficiency can be calculated and configured in Examples 1 to 3 and the like, and similar Examples can be carried out, and the effects of repeating these two or three times can be confirmed.

[0177] (Note) Although the present disclosure has been illustrated using the preferred embodiments thereof, it is understood that the present disclosure should be interpreted in scope only by the claims. It is understood that the patents, patent applications and other documents cited in this specification are incorporated by reference into this specification in the same manner as if the contents themselves were specifically set forth herein. [Industrial Applicability]

[0178] The present disclosure is effective in improving the intestinal environment and is useful in the pharmaceutical and food industries.

Claims

1. A method for improving intestinal environment or for preventing or treating intestinal environment-related diseases, comprising modifying epigenetics and / or suppressing energy metabolism.

2. The method according to claim 1, wherein the modification / suppression comprises ingesting a substance related to epigenetics and / or energy metabolism in an amount less than that normally required.

3. 3. The method according to claim 1 or 2, wherein the alteration or suppression comprises providing at least one of methionine, tryptophan, and / or niacin in an amount less than that normally required.

4. The method according to any one of claims 1 to 3, wherein the modification or suppression comprises ingesting a total amount of methionine, tryptophan, and niacin, and equivalent amounts of substances related thereto, that is less than the amount normally required.

5. The method according to any one of claims 1 to 4, wherein the alteration or suppression comprises providing a lower amount of methionine than normally required, or providing a lower amount of tryptophan and niacin than normally required.

6. The method according to any one of claims 1 to 5, wherein the intake amount is less than half the amount required.

7. The method according to any one of claims 1 to 6, wherein the intake is substantially zero.

8. The method according to any one of claims 1 to 7, wherein, except for step A), the subject is provided with a normal diet free of the deficiency.

9. The method according to any one of claims 1 to 8, wherein step A) is carried out for a period of between 14 and 33 days.

10. The method of any one of claims 1 to 9, wherein said lack means less than the amount normally required.

11. The method according to any one of claims 1 to 10, wherein said lack means less than half the amount normally required.

12. The method according to any one of claims 1 to 11, wherein said lack means complete absence of ingestion.

13. The method according to any one of claims 1 to 12, wherein the improvement of the intestinal environment comprises an increase in lactic acid bacteria.

14. The method according to any one of claims 1 to 13, wherein the intestinal environment-related disease includes at least one selected from an autoimmune disease and an inflammatory disease.

15. The method according to any one of claims 1 to 14, wherein the intestinal environment-related disease includes at least one selected from inflammatory bowel disease (IBD), obesity, cancer, fatty liver, and dyslipidemia.

16. A diet, medicine or composition for improving the intestinal environment or for preventing or treating intestinal environment-related diseases, characterized in that it is configured to modify epigenetics and / or suppress energy metabolism in a diet that provides normal nutrition.

17. 17. The food, medicine or composition of claim 16, characterized in that it is configured to provide a total amount of methionine, tryptophan and niacin, and the equivalent amounts of related substances, in an amount less than that normally required in a diet providing normal nutrition.

18. 18. A diet, medicine or composition as described in 16 or 17, characterized in that it is configured to provide at least one of methionine, tryptophan and / or niacin in an amount less than that normally required in a diet providing normal nutrition.

19. A diet, medicament or composition according to any one of claims 16 to 18, wherein the intake amount is less than half the amount required.

20. A diet, medicine or composition according to any one of claims 16 to 19, wherein the intake is substantially zero.

21. A method for designing a diet, medicine or composition for improving the intestinal environment or for preventing or treating an intestinal environment-related disease, the method comprising calculating a diet, medicine or composition configured to modify epigenetics and / or suppress energy metabolism in a diet that provides normal nutrition.

22. A program for causing a computer to implement a method for designing a diet, medicine or composition for improving the intestinal environment or for preventing or treating an intestinal environment-related disease, the method comprising: calculating a diet configured to modify epigenetics and / or suppress energy metabolism in a diet, medicine or composition that provides normal nutrition; and displaying the calculated diet.

23. A device for designing a diet for improving an intestinal environment or for preventing or treating an intestinal environment-related disease, the device including: a calculation unit that calculates a diet configured to modify epigenetics and / or suppress energy metabolism in a diet, medicine, or composition that provides normal nutrition; and a display unit that displays the calculated diet, medicine, or composition.

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