Foods for the prevention or improvement of mild cognitive impairment

Abstract

Provided is a food for preventing or improving mild cognitive impairment in a subject who has received an evaluation report on the risk of mild cognitive impairment in a non-invasive and easy manner. The food for preventing or improving mild cognitive impairment controls, on the basis of gender difference, intestinal bacterial flora that contribute to the prevention or improvement of mild cognitive impairment. When a recipient is a man, the food for preventing or improving mild cognitive impairment comprises at least one ingredient selected from golden oyster mushroom, horseradish tree, natto powder, black ginger, resistant starch 2, brown rice, and rice bran. When a recipient is a woman, the food for preventing or improving mild cognitive impairment comprises at least one ingredient selected from golden oyster mushroom, horseradish tree, natto powder, black ginger, blueberry, pomegranate, brown rice, and rice bran.

Description

Technical Field

[0001] An embodiment of the present invention provides a food for preventing or improving mild cognitive impairment.

Background Art

[0002] Studies have been conducted on food compositions for maintaining brain health, particularly cognitive function. Patent Document 1 discloses a composition containing L-ergothioneine as an active ingredient for improving age-related attention decline based on simple attention and sustained attention.

[0003] Additionally, Non-Patent Document 1 is an English paper on the characteristics of intestinal microbiota of Japanese people suffering from mild cognitive impairment and a method for estimating the risk thereof. Non-Patent Document 2 is a Japanese press release regarding Non-Patent Document 1.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Non-Patent Documents

[0005]

Non-Patent Document 1

Non-Patent Document 2

[0006] However, Patent Document 1 did not mention that L-ergothioneine controls the gut microbiota, and no food product was known for preventing or improving mild cognitive impairment that controls the gut microbiota and contributes to the improvement of mild cognitive impairment.

[0007] This invention was developed through diligent research focusing on these issues, and its purpose is to provide a food product for preventing or improving mild cognitive impairment to subjects who have received an assessment report on their risk of mild cognitive impairment in a non-invasive and easy manner. [Means for solving the problem]

[0008] To solve the above problems, the first invention is a food for preventing or improving mild cognitive impairment that controls the gut microbiota, which contributes to the prevention or improvement of mild cognitive impairment, based on sex differences.

[0009] The second invention is the food described in the first invention, wherein the food is formulated based on the gut microbiota data of a subject who has received an assessment report regarding the risk of the mild cognitive impairment.

[0010] The third invention is a food product according to the second invention, wherein the intestinal microbiota data is formulated based on intestinal microbiota data derived from a stool sample of the subject.

[0011] The fourth invention is the food described in the first invention, which is applicable to a cognitive function improvement solution comprising an evaluation phase for evaluating the subject's risk of mild cognitive impairment, a prescription phase for prescribing the food to the subject, and a follow-up phase for confirming the increase or decrease in the risk after the subject has ingested the food.

[0012] The fifth invention is the food described in the first invention, wherein the intestinal microbiota is the intestinal microbiota of a man.

[0013] The sixth invention is the food described in the first invention, wherein the intestinal microbiota is the intestinal microbiota of a woman.

[0014] The seventh invention is a food for preventing or improving mild cognitive impairment, in which the ingestor is male and the food contains one or more of the following: Tamogitake mushroom, Moringa, Natto powder, Black turmeric, Resistant Starch 2, Brown rice, and Rice bran.

[0015] The eighth invention is a food for preventing or improving mild cognitive impairment, in which the ingestor is a woman, and the food contains one or more of the following: Tamogitake mushroom, Moringa, Natto powder, Black turmeric, Blueberry, Pomegranate, Brown rice, and Rice bran. [Effects of the Invention]

[0016] According to the present invention, it is possible to provide a food for preventing or improving mild cognitive impairment by controlling the gut microbiota, which contributes to the improvement of mild cognitive impairment. [Brief explanation of the drawing]

[0017] [Figure 1] This figure shows the results of a β-diversity analysis of the intestinal microbiota before and after a man ingests Tamogitake mushrooms, according to an embodiment of the present invention. [Figure 2] This figure shows the effect amount of intestinal microorganisms before and after a man ingests Tamogitake mushrooms, according to an embodiment of the present invention. [Figure 3] This figure shows the results of a β-diversity analysis of the gut microbiota before and after a woman ingests Tamogitake mushrooms, according to an embodiment of the present invention. [Figure 4] FIG. 1 is a diagram showing the effect sizes of intestinal microorganisms before and after women ingest *Pleurotus cornucopiae* according to an embodiment of the present invention. [Figure 5] FIG. 2 is a diagram showing the results of β-diversity analysis of intestinal microbiota before and after men ingest moringa according to an embodiment of the present invention. [Figure 6] FIG. 3 is a diagram showing the effect sizes of intestinal microorganisms before and after men ingest moringa according to an embodiment of the present invention. [Figure 7] FIG. 4 is a diagram showing the results of β-diversity analysis of intestinal microbiota before and after women ingest moringa according to an embodiment of the present invention. [Figure 8] FIG. 5 is a diagram showing the effect sizes of intestinal microorganisms before and after women ingest moringa according to an embodiment of the present invention. [Figure 9] FIG. 6 is a diagram showing the results of β-diversity analysis of intestinal microbiota before and after men ingest natto powder according to an embodiment of the present invention. [Figure 10] FIG. 7 is a diagram showing the effect sizes of intestinal microorganisms before and after men ingest natto powder according to an embodiment of the present invention. [Figure 11] FIG. 8 is a diagram showing the results of β-diversity analysis of intestinal microbiota before and after women ingest natto powder according to an embodiment of the present invention. [Figure 12] FIG. 9 is a diagram showing the effect sizes of intestinal microorganisms before and after women ingest natto powder according to an embodiment of the present invention. [Figure 13] FIG. 10 is a diagram showing the results of β-diversity analysis of intestinal microbiota before and after men ingest black turmeric according to an embodiment of the present invention. [Figure 14] FIG. 11 is a diagram showing the effect sizes of intestinal microorganisms before and after men ingest black turmeric according to an embodiment of the present invention. [Figure 15] FIG. 12 is a diagram showing the results of β-diversity analysis of intestinal microbiota before and after women ingest black turmeric according to an embodiment of the present invention. [Figure 16] FIG. 13 is a diagram showing the effect sizes of intestinal microorganisms before and after women ingest black turmeric according to an embodiment of the present invention. [Figure 17]This figure shows the results of a β-diversity analysis of the gut microbiota before and after a woman consumed blueberries, according to an embodiment of the present invention. [Figure 18] This figure shows the effect amount of intestinal microorganisms before and after a woman ingests blueberries, according to an embodiment of the present invention. [Figure 19] This figure shows the results of a β-diversity analysis of the gut microbiota before and after a man ingests resistant starch 2, according to an embodiment of the present invention. [Figure 20] This figure shows the effect amount of intestinal microorganisms before and after a man ingests resistant starch 2, according to an embodiment of the present invention. [Figure 21] This figure shows the results of a β-diversity analysis of the gut microbiota before and after a woman ingests pomegranate, according to an embodiment of the present invention. [Figure 22] This figure shows the effect amount of intestinal microorganisms before and after a woman ingests pomegranate, according to an embodiment of the present invention. [Figure 23] This figure shows the results of β-diversity analysis of the gut microbiota in a group of men consuming brown rice and a group of men with mild coagulation (MCI), according to an embodiment of the present invention. [Figure 24] This figure shows the effect size of intestinal microorganisms in a group of men consuming brown rice and a group of men with mild coagulation (MCI), according to an embodiment of the present invention. [Figure 25] This figure shows the results of a β-diversity analysis of the gut microbiota in a group of women consuming brown rice and a group of women with mild coagulation (MCI), according to an embodiment of the present invention. [Figure 26] This figure shows the effect size of intestinal microorganisms in a group of women consuming brown rice and a group of women with MCI, according to an embodiment of the present invention. [Figure 27] This figure shows the number of responders and non-responders in each group involved in the intervention trial. [Figure 28] This figure shows the results of cognitive testing for men in Group 1 who consumed Tamogitake mushrooms. [Figure 29] This figure shows the cognitive test results of men in Group 2 who consumed moringa. [Figure 30]This figure shows the results of the Cognitrax test for men in Group 3 who ingested rice bran. [Figure 31] This figure shows the cognitive test results of women in Group 4 who consumed Tamogitake mushrooms. [Figure 32] This figure shows the results of cognitive testing for women in Group 5 who consumed moringa. [Figure 33] This figure shows the results of cognitive testing for women in Group 6 who ingested rice bran. [Figure 34] This figure shows the cognitive domains in which the standardized score significantly improved in W4 or W8 compared to W0 in the Cognitrax test for responders and non-responders in each group. [Figure 35] This figure shows the changes in gut bacteria after consumption of the test product in male responders in Group 1 who ingested Tamogitake mushrooms. [Figure 36] This figure shows the changes in gut bacteria after taking the test product in male responders in Group 2 who consumed moringa. [Figure 37] This figure shows the changes in gut bacteria after ingesting the test product in male responders in Group 3 who consumed rice bran. [Figure 38] This figure shows the changes in gut bacteria after consumption of the test product in female responders in Group 4 who consumed Tamogitake mushrooms. [Figure 39] This figure shows the changes in gut bacteria after taking the test product in female responders in Group 5 who consumed moringa. [Figure 40] This figure shows the changes in gut bacteria after ingesting the test product in female responders from Group 6 who consumed rice bran. [Figure 41] This figure shows the changes in gut bacteria after consumption of the test product in non-responder men in Group 1 who ingested Tamogitake mushrooms. [Figure 42] This figure shows the changes in gut bacteria after consumption of the test product in non-responder men in Group 2 who consumed moringa. [Figure 43]This figure shows the changes in gut bacteria after consumption of the test product in non-responder men in Group 3 who ingested rice bran. [Figure 44] This figure shows the changes in gut bacteria after consumption of the test product in non-responder women in Group 4 who consumed Tamogitake mushrooms. [Figure 45] This figure shows the changes in gut bacteria after taking the test product in non-responder women in Group 5 who consumed moringa. [Figure 46] This figure shows the changes in gut bacteria after consumption of the test product in non-responder women in Group 6 who ingested rice bran. [Figure 47] This figure shows the NMDS plot of the gut microbiota of men immediately before ingestion (W0). [Figure 48] This figure shows the NMDS plot of the gut microbiota of women immediately before ingestion (W0). [Figure 49] This figure shows the number of responders in each group who showed improvement in MCI risk. [Figure 50] This figure shows an NMDS plot of the gut microbiota immediately before ingestion (W0) to explain male responders with improved MCI risk. [Figure 51] This figure shows an NMDS plot of the gut microbiota immediately before ingestion (W0) to explain female responders with improved MCI risk. [Modes for carrying out the invention]

[0018] Embodiments of the present invention will be described with reference to the drawings. Common parts in each drawing are denoted by the same reference numerals, and redundant explanations are omitted.

[0019] (Foods for the prevention or improvement of mild cognitive impairment) This embodiment relates to a food for the prevention or improvement of mild cognitive impairment. Hereinafter, it will simply be referred to as "this food." This food is a food for the prevention or improvement of mild cognitive impairment that controls the gut microbiota which contributes to the improvement of mild cognitive impairment.

[0020] When this food product is intended for oral intake (including beverages), it may contain other ingredients commonly used in food and beverages (such as vitamins and minerals, food ingredients, or food additives). Other ingredients that can be used include ethanol or water as a solvent, sweeteners, flavorings, seasonings, colorings, preservatives, bulking agents, thickeners, thickening stabilizers, antioxidants, bittering agents, acidulants, emulsifiers, fortifiers, processing agents, excipients, disintegrants, binders, lubricants, coating agents, and plasticizers.

[0021] Furthermore, this food can be in solid, semi-solid, or liquid form, and can be provided as, for example, confectionery (cookies, jelly, etc.), bread, processed fish products, processed meat products, noodles, soups, sauces, prepared foods, etc., or as beverages (dairy beverages, lactic acid bacteria beverages, soft drinks, vegetable beverages, powdered beverages, sports drinks, nutritional beverages, etc.). This food can also be provided as a health food, functional food, nutritional supplement, supplement, food for specified health uses, food for the sick / combined food for the sick, or food for the elderly. Furthermore, this food can be provided as a pharmaceutical or quasi-drug.

[0022] Furthermore, this food can be in various forms (dosage forms) such as solid, liquid, powder, granules, paste, mousse, gel, jelly, or tablet. It can also be packaged in bags, containers, or capsules. In the case of solid or tablet forms, the recommended intake amount can be contained in one serving. In the case of liquid, powder, granules, paste, mousse, gel, or jelly forms, the recommended intake amount can be contained in one package.

[0023] Mild cognitive impairment (MCI) is a disorder related to a decline in cognitive function in the brain. The risk of MCI refers to the probability of developing or already having MCI. The gut microbiota is a collection of intestinal microorganisms that inhabit the intestines, including not only intestinal bacteria (bacteria, archaea, etc.) but also fungi, yeasts, and other microorganisms. It is estimated that more than 1,000 species and approximately 10 to 100 trillion intestinal microorganisms coexist in the human intestines, weighing about 1.5 kg. Each intestinal microorganism lives in its own territory, and the whole collection is called the "gut microbiota."

[0024] This food product can be adapted as a cognitive function improvement solution for individuals (hereinafter referred to as subjects) who wish to have their risk of MCI assessed.

[0025] (Solutions for improving cognitive function) The cognitive function improvement solution aims to reduce the risk of MCI in subjects or to improve their cognitive function. This solution consists of an evaluation phase, a prescription phase, and a follow-up phase. In the evaluation phase, the subject's risk of MCI is assessed. In the prescription phase, the food is prescribed to the subject. In the follow-up phase, the increase or decrease in the subject's risk of MCI after they have consumed the food is monitored.

[0026] In the evaluation phase, subjects submit stool samples collected using a stool collection kit. The intestinal microbial DNA extraction device takes the stool sample (stool suspension) as input and outputs a DNA solution related to the subject's gut microbiota. The intestinal microbiota analysis device takes the DNA solution as input and outputs the subject's gut microbiota data. The gut microbiota database links the subject's ID (identification number) information with the gut microbiota data. Furthermore, subjects answer a questionnaire regarding their gut microbiota. A subject's gut microbiota may be influenced by their age, biological sex (hereinafter simply referred to as sex), and lifestyle factors such as the region where they lived during their childhood.

[0027] The questionnaire asks for basic information such as the subject's gender and age, as well as their background. Specifically, it asks about the subject's birth background, such as the method of delivery, which may be a factor in inheriting the mother's gut microbiota. It also asks about the subject's childhood background, specifically the prefecture where they primarily lived until the age of three. In this embodiment, it is assumed that all subjects are Japanese, so the subject's country of birth is not asked. However, the country of birth may be asked as a questionnaire item. The subject information extracted from the questionnaire response data in this way will be referred to as the subject's "attribute information" below.

[0028] Data on factors or gut microbiota suggested to be associated with MCI, extracted from the subjects' gut microbiota data, are input into a model that calculates the probability that a subject has MCI, thereby calculating the subject's risk of mild cognitive impairment. The model uses one or more gut microbiota data points as variables that show the differences between the gut microbiota of healthy individuals and those with MCI. The model is constructed from data from a large number of individuals who provide stool samples and questionnaire responses, as well as from the subjects. Hereafter, the provided stool samples and questionnaire responses, whether from subjects or a large number of individuals, will simply be referred to as "samples."

[0029] In this way, subjects can non-invasively and easily receive an assessment report on their risk of developing or already having MCI.

[0030] In the prescription phase, the evaluation report to the subject will describe the subject's risk of MCI and, based on gut microbiota data derived from the subject's stool sample, prescribe the food that will reduce the subject's risk of MCI or improve the subject's cognitive function. Specifically, the food will be prescribed to increase or decrease a particular bacterial species in the subject's gut microbiota.

[0031] In the follow-up phase, we will check for any increase or decrease in the subject's risk of MCI after they have consumed the food. Specifically, we will ask the subject to provide a sample again. If there are no changes in the questionnaire response data, only a stool sample will be required.

[0032] Furthermore, based on the results confirmed during the follow-up phase, it may be recommended to consume at least one of these foods simultaneously or at different times. Let's take the example of a woman who consumed moringa as this food. If the reduction in this woman's risk stagnates, it may be recommended that she consume tamogitake and moringa simultaneously, or replace moringa with tamogitake. As will be explained later, the gut microbiome affected by consuming tamogitake or moringa differs depending on the woman. Therefore, for individuals who do not see a risk reduction effect or whose risk reduction has stagnated with the consumption of one food, it may be recommended that they consume the other food, as this may reduce their risk.

[0033] (This food product) The food used in this embodiment is Tamogitake mushroom, Moringa, Natto powder, Black Turmeric, Blueberry, Resistant Starch 2, Pomegranate, and Brown Rice. The food used in this embodiment is as follows: For Tamogitake mushroom, we used "FULL MOON6" (dried Tamogitake granules, 1g per packet), sold by KJ Marrick Co., Ltd. For Moringa, we used Moringa powder, which is made from powdered Moringa leaves. For Natto powder, we used "Sonomono Natto" (freeze-dried natto powder, 380mg per capsule), sold by Sonomono Co., Ltd. For Black Turmeric, we used "Krachaidam Pure Capsule" (black ginger powder, 450mg per capsule), sold by Kyowa Shokken Co., Ltd. For Blueberry, we used "Minami Aso Plateau Blueberry 100% Granules" (blueberry powder, 2g per 4 granules), sold by Sky Food Co., Ltd. For the resistant starch 2, we used the product "Resista" (resistant starch made from moist heat-treated corn (high-amylose corn starch)) sold by Chonai Kankyo Co., Ltd. High-amylose corn starch is classified as RS2b, a type of resistant starch 2. For the pomegranate, we used the product "Zakuro no Shizuku (R) Stick Type" (20ml per stick, equivalent to about 2 pomegranates) sold by Tanaka Corporation. For the brown rice, we ate commercially available brown rice that had been cooked.

[0034] (Intervention study using this food product) In this embodiment, an intervention trial is conducted to determine whether the risk of MCI increases or decreases in subjects before and after they consume the food. In the intervention trial, the pre- and post-intervention state of the food intake is compared, taking into account the gender of the subjects. Furthermore, subjects participating in the intervention trial were selected from individuals whose gut microbiome was similar to that of individuals who already suffer from MCI (hereinafter referred to as MCI sufferers).

[0035] In this embodiment, first, the adult Japanese subject group is divided into male and female groups. The intervention group is the group that consumes one of the foods listed in the study. In the case of brown rice, the intervention group was selected from people who already practice macrobiotics and consume brown rice in their daily diet.

[0036] The intervention group will collect stool samples before and after consuming the food. Intestinal microbiota data extracted from the stool samples collected before and after the intervention will be analyzed. In this embodiment, β-diversity analysis will be performed, and the effect size will be calculated.

[0037] (Method for analyzing the gut microbiota before and after consuming this food) Generally, β diversity represents the degree of difference in diversity between two subject groups. This difference is expressed as a multidimensional distance between the two subject groups. The larger this distance, the more different the composition of the two subject groups is considered to be.

[0038] In the β diversity analysis of this embodiment, nonmetric multidimensional scaling (NMDS) is used. NMDS is a method that projects a high-dimensional (four or more dimensions) scatter plot onto a low-dimensional (two dimensions in this embodiment) plot while maintaining the positional relationships of the transformations in the original dimensions. This NMDS makes it possible to represent the high-dimensional distance between the intervention group and the MCI group in two-dimensional spatial (plane) coordinates. The MCI group is a group of people with MCI, consisting of 11 men in their 70s and 18 women in their 70s.

[0039] Generally, effect size is a measure of how much influence a particular variable has on a given phenomenon. In this embodiment, the effect size is calculated based on the influence of the intestinal microorganisms of interest—whether they are abundant or scarce in the MCI group—before and after the intervention group consumes the food. For example, after consuming the food, it becomes possible to confirm in a table that the effect size of the intestinal microorganisms abundant in the MCI group has changed.

[0040] In this embodiment, gut microbiota were selected in advance for each male and female population using the effect size between the healthy group and the MCI group as an indicator. Gut microbiota with an effect size greater than 0.20 were classified as being more abundant in the MCI group compared to the healthy group, and gut microbiota with an effect size less than -0.20 were classified as being less abundant in the MCI group. Here, the effect size values ​​were rounded to the third decimal place (the method for calculating effect sizes is the same hereafter).

[0041] Because the population was divided into males and females, the gut microbiota that are abundant and scarce in the MCI group differ between men and women. Here, the group of healthy individuals was selected based on criteria such as "no existing diseases" from the questionnaire items. Thus, gut microbiota with positive effect sizes are abundant in the gut microbiota of the MCI group, while gut microbiota with negative effect sizes are scarce in the gut microbiota of the MCI group.

[0042] (Analysis results before and after the subjects consumed this food) All figures showing the β diversity analysis results represent the multidimensional distance between the intervention group and the MCI group in planar coordinates. Therefore, please note that the values ​​on the two-dimensional coordinate axes are relative, (a) in each figure represents the state before each food was consumed, (b) in each figure represents the state after each food was consumed, and the coordinate axes in (b) are not necessarily the same as those in (a), hence the apostrophe.

[0043] Each figure showing the β-diversity analysis results, with the exception of the brown rice diet, shows (a) the β-diversity analysis results using stool samples collected before consuming the food, and (b) the β-diversity analysis results using stool samples collected after a predetermined period had elapsed since consuming the food. Among the samples, the cross symbol represents one person suffering from MCI and belongs to the MCI group. The black circle symbol represents one person with a gut microbiome similar to that of an MCI patient and belongs to the intervention group. The dotted ellipse represents the 95% confidence interval for the MCI group, and the solid ellipse represents the 95% confidence interval for the intervention group. Thus, since one person with a gut microbiome similar to that of an MCI patient was selected as the black circle symbol, please note that in the figures showing the β-diversity analysis results before consumption, most of the black circles fall within the dotted ellipse.

[0044] Furthermore, the figure showing the effect size of intestinal microorganisms before and after the intervention group ingested the food shows the intestinal microorganisms selected as described above. In this embodiment, as reported in Non-Patent Literature 1, when comparing the intestinal microbiota of a Japanese MCI group (11 men, 18 women) in their 70s with a control group without disease (17 men, 23 women), a total of 30 types of intestinal microorganisms were selected from the male population by performing a gender-separated analysis of 16S rRNA gene sequence data of intestinal microorganisms obtained from stool samples using a next-generation sequencer. Of these, 16 types were abundant in the MCI group and 14 types were less abundant in the MCI group. In addition, a total of 51 types of intestinal microorganisms were selected from the female population. Of these, 32 types were abundant in the MCI group and 19 types were less abundant in the MCI group.

[0045] Figure 1 shows the results of β-diversity analysis of the gut microbiota before and after ingestion of Tamogitake mushrooms in a male subject according to an embodiment of the present invention. All subjects were male, and the food in question was Tamogitake mushrooms. The intervention group consisted of 17 individuals. Figure (a) shows the β-diversity analysis results before the start of Tamogitake mushroom ingestion, and Figure (b) shows the β-diversity analysis results 28 days after ingestion of Tamogitake mushrooms. The dosage and method of ingestion of Tamogitake mushrooms were to take one packet (1g) three times a day with each meal, with lukewarm water or water, every day.

[0046] In Figure (a), there are no black dots outside the dotted ellipse representing the 95% confidence interval for the MCI group. In contrast, in Figure (b), there are three black dots in the same region. Therefore, there is a difference in the extent to which consuming Tamogitake mushrooms can control the male gut microbiota that contributes to the improvement of MCI.

[0047] Figure 2 shows the effect size of intestinal microorganisms before and after a man ingests Tamogitake mushrooms, according to an embodiment of the present invention. The leftmost column, based on information from Non-Patent Literature 1, indicates whether the intestinal microorganisms are abundant in the MCI group, sorted from largest to smallest absolute value of positive effect size before ingestion, or whether they are scarce in the MCI group, sorted from smallest to largest absolute value of negative effect size before ingestion. The second column is the name of the intestinal microorganism. The third column shows the effect size of the intestinal microorganisms comparing before and after ingestion. A positive effect size value means that the intestinal microorganisms increased after ingestion. On the other hand, a negative effect size value means that the intestinal microorganisms decreased after ingestion. The names of intestinal microorganisms that show the expected change and have an absolute effect size of 0.20 or more are underlined (hereinafter, in figures showing effect sizes, except for brown rice, names are similarly underlined). Here, the expected changes are, with the exception of the brown rice diet, a decrease in gut microbiota that are abundant in the MCI group after intake, i.e., a negative effect size, and an increase in gut microbiota that are scarce in the MCI group after intake, i.e., a positive effect size.

[0048] The fourth and fifth columns show the prevalence of gut microbiota (average value for subjects) before and after intake. The sixth and seventh columns show the prevalence of gut microbiota before and after intake. Items marked "NA" in the table mean "not applicable" (the same applies to the effect size figures below).

[0049] The effect size of the underlined Flavonifractor is -0.24. Please note that while the names of intestinal microorganisms are normally written in italics, they are written in a regular font due to the limitations of the character encoding available in the specification.

[0050] Therefore, calculations have shown that when men consume Tamogitake mushrooms, their Flavonifractor levels decrease. Considering the β-diversity and effect size before and after consumption, Tamogitake mushrooms can control the gut microbiota in men, contributing to the improvement of MCI (Mild Cognitive Impairment).

[0051] Figure 3 shows the results of β-diversity analysis of the gut microbiota before and after consumption of Tamogitake mushrooms by women according to an embodiment of the present invention. All subjects were women, and the food was Tamogitake mushrooms. The intervention group consisted of 20 people. Figure (a) shows the β-diversity analysis results before the start of Tamogitake consumption, and Figure (b) shows the β-diversity analysis results 28 days after Tamogitake consumption. The amount and method of Tamogitake consumption were the same as for men.

[0052] In Figure (a), there are two black dots outside the dotted ellipse representing the 95% confidence interval for the MCI group. In contrast, in Figure (b), there are six black dots in the same region. Therefore, there is a difference in the extent to which women who consume Tamogitake mushrooms can control the female gut microbiota that contributes to the improvement of MCI.

[0053] Figure 4 shows the effect sizes of intestinal microorganisms before and after a woman ingests Tamogitake mushrooms, according to an embodiment of the present invention. The effect size of Enterocloster, which is underlined, is -0.27. Similarly, the effect size of Ruthenibacterium is -0.35. The effect size of Ruminococcus2 is -0.30. The effect size of Romboutsia is -0.44. The effect size of Gordonibacter is -0.25. The effect size of Negativibacillus is -0.27. The effect size of Clostridium IV is -0.23. The effect size of Anaeromassilibacillus is -0.31.

[0054] Additionally, the effect size of Clostridium XIVb is +0.23, while the effect size of Sutterella is +0.20.

[0055] Therefore, calculations have shown that when women consume Tamogitake mushrooms, eight types of intestinal microorganisms—Enterocloster, Ruthenibacterium, Ruminococcus 2, Romboutsia, Gordonibacter, Negativibacillus, Clostridium IV, and Anaeromassilibacillus—decrease, while Clostridium XIVb and Sutterella increase. Considering the β-diversity and effect size before and after consumption, Tamogitake mushrooms can control the female gut microbiota, contributing to the improvement of MCI (Mild Cognitive Impairment).

[0056] Figure 5 shows the results of β-diversity analysis of the gut microbiota before and after ingestion of moringa in men, according to an embodiment of the present invention. All subjects were male, and the food was moringa. The intervention group consisted of 28 people. Figure (a) shows the β-diversity analysis results before the start of moringa ingestion, and Figure (b) shows the β-diversity analysis results 14 days after moringa ingestion. The amount and method of moringa intake was one packet (3g) once a day before dinner, dissolved in lukewarm water or water and taken daily. 3g was taken daily.

[0057] In Figure (a), there are no black dots outside the dotted ellipse representing the 95% confidence interval for the MCI group. In contrast, in Figure (b), there are four black dots in the same region. Therefore, there is a difference in the extent to which moringa intake by men can control the male gut microbiota that contributes to the improvement of MCI.

[0058] Figure 6 shows the effect size of intestinal microorganisms before and after a man ingests moringa, according to an embodiment of the present invention. In the second row of intestinal microorganisms, the underlined intestinal microorganisms are absent. Thus, the effect size calculation does not allow for the identification of the intestinal microorganisms that contribute to the improvement of MCI by a man ingesting moringa.

[0059] On the other hand, the fourth column from the left in the same figure shows the average percentage of intestinal microorganisms before consuming moringa, and the fifth column shows the average percentage of intestinal microorganisms after consuming moringa. The names of intestinal microorganisms that showed the expected changes are shown in bold (similarly, in figures showing effect sizes, if there is no underline, the name is also shown in bold). Comparing the percentage of intestinal microorganisms before and after consuming moringa, six types of intestinal microorganisms, shown in bold—Clostridium XVIII, Streptococcus, Intestinibacter, Erysipelatoclostridium, Anaerostipes, and Faecalicatena—decreased, while five types of intestinal microorganisms—Megasphaera, Prevotella, Coprobacillus, Catenibacterium, and Ruminococcus—increased. Therefore, based on a comprehensive assessment of the changes in the average values ​​of β-diversity and occupancy before and after intake, it is thought that moringa can control the gut microbiota in men, which contributes to the improvement of MCI.

[0060] Figure 7 shows the results of β-diversity analysis of the gut microbiota before and after women ingest moringa, according to an embodiment of the present invention. All subjects were women, and the food in question was moringa. The intervention group consisted of 19 participants. Figure (a) shows the β-diversity analysis results before the start of moringa intake, and Figure (b) shows the β-diversity analysis results 14 days after moringa intake. The amount and method of moringa intake were the same as for men.

[0061] In Figure (a), there are four black dots outside the dotted ellipse representing the 95% confidence interval for the MCI group. In contrast, in Figure (b), there are eight black dots in the same region. Therefore, there is a difference in the extent to which women who take moringa can control the female gut microbiota that contributes to the improvement of MCI.

[0062] Figure 8 shows the effect size of intestinal microorganisms before and after a woman ingests moringa, according to an embodiment of the present invention. The effect size of Anaerotruncus, which is underlined, is -0.27.

[0063] Therefore, there are calculations showing that when women consume moringa, the amount of Anaerotruncus decreases. When considering the β-diversity and effect size before and after consumption, moringa can control the gut microbiota of women, which contributes to the improvement of MCI.

[0064] Figure 9 shows the results of β-diversity analysis of the gut microbiota before and after ingestion of natto powder in men according to an embodiment of the present invention. All subjects were male, and the food was natto powder. The intervention group consisted of 25 people. Figure (a) shows the β-diversity analysis results before the start of natto powder ingestion, and Figure (b) shows the β-diversity analysis results 31 days after ingestion of natto powder. The dosage and method of natto powder intake was one capsule (380 mg) three times a day with each meal, taken daily with lukewarm water or water.

[0065] In Figure (a), there are no black dots outside the dotted ellipse representing the 95% confidence interval for the MCI group. In contrast, in Figure (b), there are two black dots in the same region. Therefore, there is a difference in the extent to which natto powder intake by men can control the male gut microbiota that contributes to the improvement of MCI.

[0066] Figure 10 shows the effect size of intestinal microorganisms before and after a man ingests natto powder, according to an embodiment of the present invention. In the second row of intestinal microorganisms, the underlined intestinal microorganisms are absent. Thus, effect size calculations cannot identify the names of intestinal microorganisms that contribute to the improvement of MCI by a man ingesting natto powder.

[0067] On the other hand, comparing the proportion of intestinal microorganisms before and after natto powder intake, eight types of intestinal microorganisms (shown in bold: Clostridium XVIII, Rothia, Streptococcus, Intestinibacter, Bifidobacterium, Flavonifractor, Faecalicatena, and Veillonella) decreased, while six types of intestinal microorganisms (Eisenbergiella, Megasphaera, Lawsonibacter, Akkermansia, Prevotella, and Dialister) increased. Therefore, considering the overall changes in β-diversity and average proportions before and after intake, it is thought that natto powder can control the intestinal microbiota of men, which contributes to the improvement of MCI.

[0068] Figure 11 shows the results of β-diversity analysis of the gut microbiota before and after ingestion of natto powder in women according to an embodiment of the present invention. All subjects were women, and the food was natto powder. The intervention group consisted of 13 people. Figure (a) shows the β-diversity analysis results before the start of natto powder ingestion, and Figure (b) shows the β-diversity analysis results 31 days after natto powder ingestion. The amount and method of natto powder ingestion were the same as in the case of men.

[0069] In Figure (a), there are no black dots outside the dotted ellipse representing the 95% confidence interval for the MCI group. In contrast, in Figure (b), there are two black dots in the same region. Therefore, there is a difference in the extent to which women who consume natto powder can control the female gut microbiota that contributes to the improvement of MCI.

[0070] Figure 12 shows the effect size of intestinal microorganisms before and after a woman ingests natto powder, according to an embodiment of the present invention. The effect size of Bacteroides, which is underlined, is -0.26. Similarly, the effect size of Neglecta is -0.21.

[0071] Furthermore, the effect size of Coprococcus is +0.31.

[0072] Therefore, calculations have shown that when women consume natto powder, two types of gut microbiota, Bacteroides and Neglecta, decrease, while Coprococcus increases. Considering the β-diversity and effect size before and after consumption, natto powder can control the gut microbiota of women, which contributes to the improvement of MCI (Mild Cognitive Impairment).

[0073] Figure 13 shows the results of β-diversity analysis of the gut microbiota before and after ingestion of black turmeric in men, according to an embodiment of the present invention. All subjects were male, and the food was black turmeric. The intervention group consisted of 24 people. Figure (a) shows the β-diversity analysis results before the start of black turmeric ingestion, and Figure (b) shows the β-diversity analysis results 14 days after black turmeric ingestion. The dosage and method of ingestion of black turmeric was to take one capsule (450 mg) twice a day, after breakfast and after dinner, with water every day.

[0074] In Figure (a), there are no black dots outside the dotted ellipse representing the 95% confidence interval for the MCI group. In contrast, in Figure (b), there are three black dots in the same region. Therefore, there is a difference in the extent to which men who consume black turmeric can control the male gut microbiota that contributes to the improvement of MCI.

[0075] Figure 14 shows the effect size of intestinal microorganisms before and after a man ingests black turmeric, according to an embodiment of the present invention. In the second row of intestinal microorganisms, the underlined intestinal microorganisms are absent. Thus, the effect size calculation does not allow for the identification of the intestinal microorganisms that contribute to the improvement of MCI by a man ingesting black turmeric.

[0076] On the other hand, comparing the occupancy rate of intestinal microorganisms before and after black turmeric intake, seven types of intestinal microorganisms (shown in bold: Clostridium XVIII, Rothia, Bifidobacterium, Anaerostipes, Faecalicatena, Veillonella, and Adlercreutzia) decreased, while eight types of intestinal microorganisms (Eisenbergiella, Megasphaera, Oscillibacter, Akkermansia, Prevotella, Catenibacterium, Roseburia, and Ruminococcus) increased. Therefore, considering the overall changes in β-diversity and average occupancy rates before and after intake, it is thought that black turmeric can control the intestinal microbiota of men, which contributes to the improvement of MCI.

[0077] Figure 15 shows the results of β-diversity analysis of the gut microbiota before and after ingestion of black turmeric in women, according to an embodiment of the present invention. All subjects were women, and the food in question was black turmeric. The intervention group consisted of 21 participants. Figure (a) shows the β-diversity analysis results before the start of black turmeric ingestion, and Figure (b) shows the β-diversity analysis results 28 days after black turmeric ingestion. The amount and method of black turmeric ingestion were the same as in the case of men.

[0078] In Figure (a), there are no black dots outside the dotted ellipse representing the 95% confidence interval for the MCI group. In contrast, in Figure (b), there are four black dots in the same region. Therefore, there is a difference in the extent to which women who consume black turmeric can control the female gut microbiota that contributes to the improvement of MCI.

[0079] Figure 16 shows the effect size of intestinal microorganisms before and after a woman ingests black turmeric, according to an embodiment of the present invention. The effect size of Bacteroides, which is underlined, is -0.20.

[0080] Therefore, there are calculations showing that Bacteroides decrease when women consume black turmeric. When considering the β-diversity and effect size before and after intake, black turmeric can control the gut microbiota of women, which contributes to the improvement of MCI.

[0081] Figure 17 shows the results of β-diversity analysis of the gut microbiota before and after women consumed blueberries, according to an embodiment of the present invention. All subjects were women, and the food was blueberries. The intervention group consisted of 23 people. Figure (a) shows the β-diversity analysis results before the start of blueberry consumption, and Figure (b) shows the β-diversity analysis results 14 days after blueberry consumption. The amount and method of consumption of blueberries was 4 berries (2g) per serving, taken twice a day after breakfast and after dinner, with water every day.

[0082] In Figure (a), there are no black dots outside the dotted ellipse representing the 95% confidence interval for the MCI group. In contrast, in Figure (b), there are six black dots in the same region. Therefore, there is a difference in the extent to which women can control the female gut microbiota that contributes to the improvement of MCI when they consume blueberries.

[0083] Figure 18 shows the effect size of intestinal microorganisms before and after a woman ingests blueberries, according to an embodiment of the present invention. The effect size of Erysipelatoclostridium, which is underlined, is -0.20. Similarly, the effect size of Flavonifractor is -0.24. The effect size of Intestinimonas is -0.20. The effect size of Bacteroides is -0.34. The effect size of Parabacteroides is -0.21. The effect size of Blautia is -0.23.

[0084] Therefore, calculations have shown that when women consume blueberries, the number of five types of gut microbiota decreases: Erysipelatoclostridium, Flavonifractor, Intestinimonas, Bacteroides, Parabacteroides, and Blautia. Considering the β-diversity and effect size before and after consumption, blueberries can control the female gut microbiota, which contributes to the improvement of MCI (Mild Cognitive Impairment).

[0085] Figure 19 shows the results of β-diversity analysis of the gut microbiota before and after intake of resistant starch 2 in men according to an embodiment of the present invention. All subjects were male, and the food was resistant starch 2. The intervention group consisted of 15 people. Figure (a) shows the β-diversity analysis results before the start of intake of resistant starch 2, and Figure (b) shows the β-diversity analysis results 14 days after intake of resistant starch 2. The intake amount and method of resistant starch 2 was 10g per serving, once a day after meals, dissolved in 100mL of water and taken daily.

[0086] In Figure (a), there are no black dots outside the dotted ellipse representing the 95% confidence interval for the MCI group. In contrast, in Figure (b), there are eight black dots in the same region. Therefore, there is a difference in the extent to which resistant starch 2 intake in men can control the male gut microbiota that contributes to the improvement of MCI.

[0087] Figure 20 shows the effect size of intestinal microbiota before and after a man ingests resistant starch 2, according to an embodiment of the present invention. In the second row of intestinal microbiota, the underlined intestinal microbiota is absent. Thus, the effect size calculation does not allow for the identification of the intestinal microbiota that contribute to the improvement of MCI by a man ingesting resistant starch 2.

[0088] On the other hand, comparing the occupancy rate of gut microbiota before and after resistant starch 2 intake, six types of gut microbiota (shown in bold) decreased, while five types of gut microbiota (shown in bold) increased: Eisenbergiella, Megasphaera, Oscillibacter, Coprobacillus, and Ruminococcus). Therefore, considering the overall changes in β-diversity and average occupancy rates before and after intake, it is thought that resistant starch 2 can control the gut microbiota in men, which contributes to the improvement of MCI.

[0089] Figure 21 shows the results of β-diversity analysis of the gut microbiota before and after women ingested pomegranates, according to an embodiment of the present invention. All subjects were women, and the food was pomegranate. The intervention group consisted of 25 people. Figure (a) shows the β-diversity analysis results before the start of pomegranate intake, and Figure (b) shows the β-diversity analysis results 14 days after pomegranate intake. The amount and method of intake of pomegranate was to dissolve one bottle (20 ml) in 100 ml of water and take it twice a day, after breakfast and after dinner.

[0090] In Figure (a), there are no black dots outside the dotted ellipse representing the 95% confidence interval for the MCI group. In contrast, in Figure (b), there are four black dots in the same region. Therefore, there is a difference in the extent to which pomegranate consumption by women can control the female gut microbiota that contributes to the improvement of MCI.

[0091] Figure 22 shows the effect size of intestinal microorganisms before and after a woman ingests pomegranate, according to an embodiment of the present invention. The effect size of underlined Flavonifractor is -0.25. Similarly, the effect size of Dysosmobacter is -0.24. The effect size of Eisenbergiella is -0.23. The effect size of Blautia is -0.22.

[0092] Therefore, calculations have shown that when women consume pomegranates, the number of four types of gut microbiota—Flavonifractor, Dysosmobacter, Eisenbergiella, and Blautia—decreases. Considering the β-diversity and effect size before and after consumption, pomegranates can control the female gut microbiota, which contributes to the improvement of MCI (Mild Cognitive Impairment).

[0093] Figure 23 shows the results of β-diversity analysis of the gut microbiota in a group of men consuming brown rice and a group of men with MCI, according to an embodiment of the present invention. All samples were male, and the food was brown rice. The intervention group consisted of 11 individuals. Since the people in the intervention group were already practicing macrobiotics, the method and amount of brown rice intake varied from person to person.

[0094] In this figure, there are no black dots outside the dotted ellipse representing the 95% confidence interval for the MCI group. Therefore, it cannot be concluded from this figure that consuming brown rice in men makes a difference in controlling the male gut microbiota that contributes to the improvement of MCI.

[0095] Figure 24 shows the effect size of intestinal microorganisms when comparing a group of men consuming brown rice with a group of men with mild cognitive impairment (MCI), according to an embodiment of the present invention. The leftmost column indicates whether the intestinal microorganisms are abundant or scarce in the MCI group. The second column is the name of the intestinal microorganism. The third column shows the effect size of intestinal microorganisms when comparing the group consuming brown rice with the MCI group. A positive effect size value means that the intestinal microorganisms are scarce in the group consuming brown rice. On the other hand, a negative effect size value means that the intestinal microorganisms are abundant in the group consuming brown rice. The names of intestinal microorganisms that show the expected change and have an absolute effect size of 0.2 or more are underlined (similarly, they are underlined in the figure showing the effect size for women, which will be described later). Here, the expected change is that the gut microbiota that are abundant in the MCI group are less abundant in the group consuming brown rice, meaning the effect size is positive, and conversely, the gut microbiota that are less abundant in the MCI group are more abundant in the group consuming brown rice, meaning the effect size is negative.

[0096] The effect size of Clostridium XVIII, which is underlined, is +0.44. Similarly, the effect size of Rothia is +0.35. The effect size of Intestinibacter is +0.49. Erysipelatoclostridium is +0.26. The effect size of Bifidobacterium is +0.30. The effect size of Fournierella is +0.21. The effect size of Eggerthella is +0.26. The effect size of Flavonifractor is +0.34. The effect size of Merdimonas is +0.33. The effect size of Faecalicatena is +0.20. The effect size of Veillonella is +0.23.

[0097] Furthermore, the effect size of Anaerotruncus is -0.20. The effect size of Oscillibacter is -0.30. The effect size of Prevotella is -0.44. The effect size of Turicibacter is -0.72. The effect size of Victivallis is -0.39. The effect size of Roseburia is -0.51. The effect size of Ruminococcus is -0.55.

[0098] Therefore, when men consume brown rice, effect size calculations show that 11 types of gut microbiota—Clostridium XVIII, Rothia, Intestinibacter, Erysipelatoclostridium, Bifidobacterium, Fournierella, Eggerthella, Flavonifractor, Merdimonas, Faecalicatena, and Veillonella—are less abundant in the group consuming brown rice, while 7 types of gut microbiota—Anaerotruncus, Oscillibacter, Prevotella, Turicibacter, Victivallis, Roseburia, and Ruminococcus—are more abundant in the group consuming brown rice. Judging from the effect size between the group consuming brown rice and the male MCI group, a brown rice diet can control the male gut microbiota that contributes to the improvement of MCI.

[0099] Figure 25 shows the results of β-diversity analysis of the gut microbiota in a group of women consuming brown rice and a group of women with MCI, according to an embodiment of the present invention. All subjects were female, and the food was brown rice. The intervention group consisted of 23 people. The method and amount of brown rice intake were the same as for men.

[0100] In the figure, there are 13 black dots outside the dotted ellipse representing the 95% confidence interval for the MCI group. Therefore, there is a difference in the extent to which women who consume brown rice can control the female gut microbiota that contributes to the improvement of MCI.

[0101] Figure 26 shows the effect size of intestinal microorganisms when comparing a group of women who consume brown rice with a group who do not, according to an embodiment of the present invention. The effect size of Enterocloster, which is underlined, is +0.91. Similarly, the effect size of Erysipelatoclostridium is +0.82. The effect size of Ruthenibacterium is +0.82. Flavonifractor is +0.83. The effect size of Anaerotignum is +0.97. The effect size of Ruminococcus2 is +0.42. The effect size of Dysomobacter is +0.81. The effect size of Turicibacter is +0.27. The effect size of Romboutsia is +0.41. The effect size of Eisenbergiella is +0.42. The effect size of Intestinimonas is +0.53. The effect size of Eggerthella is +0.87. The effect size of Clostridium XVIII is +0.45. The effect size of Sellimonas is +0.48. The effect size of Bacteroides is +0.54. The effect size of Frisingicoccus is +0.32. The effect size of Hungatella is +0.43. The effect size of Gordonibacter is +0.32. The effect size of Neglecta is +0.26. The effect size of Negativibacillus is +0.42. The effect size of Fusobacterium is +0.30. The effect size of Massilimicrobiota is +0.43. The effect size of Clostridium XIVa is +0.39. The effect size of Parabacteroides is +0.53. The effect size of Clostridium IV is +0.28. The effect size of Coprobacillus is +0.35. The effect size of Akkermansia is +0.25. The effect size of Anaerotruncus is +0.27. The effect size of Anaeromassilibacillus is +0.29. The effect size of Ihubacter is +0.20.

[0102] Furthermore, the effect size of Clostridium XIVb is -0.29. The effect size of Holdemanella is -0.29. The effect size of Lactococcus is -0.23. The effect size of Ligilactobacillus is -0.22. The effect size of Paraprevotella is -0.41. The effect size of Leuconostoc is -0.22. The effect size of Anaerostipes is -0.58. The effect size of Megasphaera is -0.22. The effect size of Slackia is -0.34. The effect size of Oscillibacter is -0.63. The effect size of Coprococcus is -0.52. The effect size of Sutterella is -0.27. The effect size of Roseburia is -0.28. The effect size of Veillonella is -0.26. The effect size of Prevotella is -0.58. The effect size of Agathobacter is -0.40.

[0103] Therefore, when women consume brown rice, 30 types of intestinal microorganisms—Enterocloster, Erysipelatoclostridium, Ruthenibacterium, Flavonifractor, Anaerotignum, Ruminococcus2, Dysomobacter, Turicibacter, Romboutsia, Eisenbergiella, Intestinimonas, Eggerthella, Clostridium XVIII, Sellimonas, Bacteroides, Frisingicoccus, Hungatella, Gordonibacter, Neglecta, Negativibacillus, Fusobacterium, Massilimicrobiota, Clostridium XIVa, Parabacteroides, Clostridium IV, Coprobacillus, Akkermansia, Anaerotruncus, Anaeromassilibacillu, and Ihubacter—are less abundant in the group consuming brown rice, and Clostridium Effect size calculations have shown that 16 types of gut microbiota—XIVb, Holdemanella, Lactococcus, Ligilactobacillus, Paraprevotella, Leuconostoc, Anaerostipes, Megasphaera, Slackia, Oscillibacter, Coprococcus, Sutterella, Roseburia, Veillonella, Prevotella, and Agathobacter—are more abundant in the group consuming brown rice. Considering the β-diversity and effect size between the brown rice group and the female MCI group, brown rice consumption can control the female gut microbiota that contributes to the improvement of MCI.

[0104] (effect) According to this embodiment, it is possible to provide subjects who have received an assessment report on their risk of MCI (mild cognitive impairment) in a non-invasive and easy manner with foods for preventing or improving mild cognitive impairment. Furthermore, it is possible to provide foods for preventing or improving mild cognitive impairment that control the gut microbiota according to the subject's gender.

[0105] The embodiments (including modifications) of the present invention have been described above, but two or more of these embodiments may be combined and implemented. Alternatively, one of these embodiments may be partially implemented. Furthermore, two or more of these embodiments may be partially combined and implemented. For example, men may consume at least one of the following as this food: Tamogitake mushroom, Moringa, Natto powder, Resistant Starch 2, and brown rice, either simultaneously or at different times. Women may consume at least one of the following as this food: Tamogitake mushroom, Moringa, Natto powder, Black Turmeric, Blueberry, Pomegranate, and Brown Rice, either simultaneously or at different times.

[0106] Furthermore, the present invention is not limited in any way to the examples described above. Various modifications are also included in this invention, provided they do not deviate from the scope of the claims and are easily conceivable by those skilled in the art. For example, it is not intended to limit the scope of this food and its uses. Specifically, it was explained that a brown rice diet can control the gut microbiota of men that contributes to the improvement of MCI, and that a total of 18 types of gut microbiota (11 types and 7 types) changed as expected. However, referring to the occupancy and possession rates in Figure 24, not all subjects possess all 18 types of gut microbiota mentioned above. Thus, if at least one of the 18 types of gut microbiota mentioned above shows the expected change in the gut microbiota of men consuming brown rice, the effects of this food can be achieved. In other words, it is sufficient if at least one type of gut microbiota shows the expected change in the gut microbiota of a person who has consumed this food according to any of the examples described above.

[0107] Furthermore, this food may also contain the following: 1-kestose, DHA, EPA, L-glutamine, MCT oil, alpha-linolenic acid, beta-carotene, beta-glucan, omega-3 fatty acids, almonds, arabinoxylan, Alpine bearberry, aronia, strawberries, inulin, turmeric, perilla oil, peas, oats, oatmeal, psyllium, horchata, oleic acid, oranges, caffeine, galactooligosaccharides, peanuts with skin, citrus fruits, Jerusalem artichoke, xylooligosaccharides, chitosan, beef, fish, guar gum, goji berries, kudzu, cloudberries, cranberries, curcumin Walnuts, quercetin, ginseng, chondroitin, konjac, pomegranate, salmon, sea buckthorn, shiitake mushrooms, cinnamon, ginger, spirulina, tart cherry, protein, chicory, cordyceps, tomato, chicken, natto, raw pu-erh tea, pineapple, fermented kimchi, beetroot, pistachios, vitamin B3, vitamin D, oyster mushrooms, sea cucumber, pork, grapes, fructooligosaccharides, flaxseed, black pepper, brindle cheese, blueberries, prunes, fructan, probiotics (L. kefiri LKF01 DSM32079), probiotics (Lactobacillus (Contains rhamnosus), pectin, whey protein, phosphatidylserine, hops, polydextrose, maitake mushroom, magnesium, mushroom, purple sweet potato, lion's mane mushroom, lychee, rye, unripe raspberry, green tea, apple, lingonberry, raisin, resistant starch 2, resistant starch 3, resistant starch 4, resistant starch 5, resveratrol, wine, Oysters, mulberries, brown rice, brown rice germ, fermented rice amazake, ancient wheat, yeast-derived protein, black plums, aged pu-erh tea, adzuki beans, wheat, wheat bran, wheat germ, plants, dietary fiber, hydrogen-rich water, red wine, whole grain barley, soybeans, barley, defatted rice bran, undefatted rice bran, tea flowers, Chinese pears, indigestible dextrin, rice, rice bran, matcha, wild blueberries, reishi mushrooms, and IgY antibodies targeting IgA protease produced by intestinal microorganisms.

[0108] (Other embodiments; intervention trials targeting individuals suspected of having MCI) In this embodiment, individuals suspected of having MCI (Mild Cognitive Impairment) are given this food (in this embodiment, the test products used are Tamogitake mushrooms, Moringa, and rice bran). An intervention study is then conducted to confirm that the ingestion of this food alters the ingestionees' gut microbiota based on sex differences, and that this alteration leads to an improvement in the ingestionees' cognitive function.

[0109] (Test subject) The test material used was dried Tamogitake mushroom granules (product name: KOJIRO F001), sold by KJ Marrick Co., Ltd. This is the same product as the one previously sold by the same company under the product name "FULL MOON6," which was renamed "KOJIRO F001." The test material used was Moringa leaf powder, a raw material for a product from Blow Up Co., Ltd. The test material used was rice bran (product name: Domestic Edible Rice Bran, equivalent to "Undefatted Rice Bran") sold by Nippon Garlic Co., Ltd.

[0110] (Method of taking the test product) Individuals suspected of having MCI (Mild Cognitive Impairment) consumed the assigned test product continuously for 8 weeks according to the specified administration method.

[0111] <How to consume Tamogitake mushrooms> The user should take the test product three times a day with each meal (morning, noon, and evening) with lukewarm water or water. The amount of the test product taken per serving is 1g.

[0112] <How to take moringa> The user should take the product once a day before dinner, dissolved in lukewarm water or water. The test dose is 3g per serving.

[0113] <How to consume rice bran> The user should take the product three times a day with each meal (morning, noon, and evening) with lukewarm water or water. The sample dose is 5g per serving.

[0114] (Selection of individuals suspected of having MCI) In selecting individuals suspected of having MCI, a screening survey was conducted targeting those who met all of the following eligibility criteria (1) to (5) and did not fall under any of the exclusion criteria (1) to (11). Those who met screening criterion (1) were selected. Screening tests were conducted on 1,229 individuals, and 214 individuals (134 men and 80 women) were selected as suspected of having MCI and participated in the study. Individuals suspected of having MCI were instructed to comply with management items (1) to (4).

[0115] <Eligibility Criteria> (1) Japanese men and women aged 60 to 79 years old at the time of obtaining consent for the intervention trial (2) Those who are concerned about their own forgetfulness (things they can't remember) (3) Persons who are able to have normal bowel movements and have bowel movements at least once every three days. (4) Persons who can ingest the test product every day during the trial period. (5) A person who is genetically Japanese and has lived in Japan since birth.

[0116] <Exclusion criteria> (1) Persons who may show allergic symptoms due to the test products (Tamogitake mushroom, Moringa, rice bran) (2) Persons participating in other clinical trials (3) Persons who are deemed by the examiner to have any problems (4) Persons who regularly consume the test products (Tamogitake mushrooms, Moringa mushrooms, rice bran) (5) Individuals who regularly consume health foods or supplements that are thought to potentially affect the test results (health foods or supplements that claim to contain lactic acid bacteria, oligosaccharides, or have intestinal regulating effects). (6) Persons suffering from a specific disease and receiving outpatient treatment, medication, etc. (7) Anyone who has used antibiotics or antimicrobial drugs within the past month (8) Those who plan to make significant changes to their diet or lifestyle (exercise, smoking, employment, living environment, etc.) during the examination period. (9) Those who plan to travel abroad during the examination period (10) Heavy drinkers (those who drink more than 2 go (approximately 360ml) of sake per day for more than half of the week) (11) Excessive smokers (those who smoke two packs (40 or more) of cigarettes per day)

[0117] <Screening Criteria> (1) Individuals with a total score of 24 to 27 on the MMSE (Mini Mental State Examination) (The MMSE is a cognitive function test with a maximum score of 30, and a score of 24 to 27 is considered a possible indication of MCI).

[0118] <Management matters> (1) During the trial period, take the test product daily as instructed. (2) During the examination period, maintain the same living environment (sleep, meals, and overall lifestyle) as before the start of the examination. (3) During the examination period, avoid taking any health foods (such as fiber-containing beverages), supplements (such as lactic acid bacteria and oligosaccharides), or medications (such as intestinal regulators) that may affect bowel function. (4) During the trial period, stool samples should be sent as soon as possible after collection.

[0119] 214 individuals suspected of having MCI (134 men, 80 women) were divided into three groups based on gender, each receiving one of the following test products: Tamogitake mushroom, Moringa, or rice bran. Participants were assigned to each group (groups 1 to 6 below) to ensure equal age and MMSE scores during screening. Group 1: Males - Tamogitake mushrooms (46 people) Group 2: Men - Moringa (45 people) Group 3: Men - Rice Bran (43 people) Group 4: Women - Tamogitake (26 people) Group 5: Women - Moringa (27 people) Group 6: Women - Rice Bran (27 people)

[0120] (Observation period and frequency, observation method) In the intervention trial, observations were made at four points: 4 weeks before ingestion of the test product (BW4: 28 days before ingestion), immediately before ingestion (W0: immediately before ingestion, considered baseline), 4 weeks after ingestion (W4: 28 days after ingestion), and 8 weeks after ingestion (W8: 56 days after ingestion), for a total of four observations. Cognitrax testing and gut microbiota testing were performed as observation items.

[0121] The Cognitrax test is a cognitive function testing service designed for Japan by Health Solution Co., Ltd., headquartered in Japan, based on cognitive function testing technology developed by CNS Vital Signs, Inc., headquartered in North Carolina, USA. In this observation, standardized scores were evaluated for 12 cognitive domains: Neurocognitive Index (NCI), overall memory, verbal memory, visual memory, cognitive speed, reaction time, overall attention, cognitive flexibility, processing speed, executive function, simple attention, and motor speed. These standardized scores are converted values ​​compared to peers, calculated with a mean of 100 and a standard deviation of 15. A standardized score of less than 70 is considered "potential impairment," 70 to 79 is considered "potential mild impairment," 80 to 89 is considered "slight impairment / problem," 90 to 110 is considered "standard," and over 110 is considered "high function."

[0122] The gut microbiota examination and analysis were performed in accordance with the method described in Japanese Patent No. 7,411,177 (and the corresponding PCT application: PCT / JP2024 / 019474). The gut microbiota analysis was performed to observe changes in the gut microbiota (limited to bacteria among microorganisms).

[0123] (Those analyzed) Nine individuals were excluded from the analysis from the 214 suspected MCI participants due to reasons such as meeting exclusion criteria, failure to submit gut microbiota samples, or significant data reliability issues arising from testing problems. Additionally, 35 individuals (26 males, 9 females) who were determined to have clearly high cognitive function (Cognitrax Neurocognitive Index (NCI) standardized score exceeding 110) at baseline immediately before ingestion (W0) were excluded from the analysis due to their high cognitive function and low likelihood of MCI. Ultimately, 170 individuals (101 males, 69 females) assigned to each test product were included in the analysis.

[0124] (Responders and non-responders) After 8 weeks of taking the test product, some participants showed improvement in cognitive function, while others showed little to no improvement. Therefore, participants who had a higher Neurocognitive Index (NCI) standardized score 8 weeks after intake (W8) compared to baseline immediately before intake (W0) were distinguished as responders whose cognitive function improved with the test product.

[0125] On the other hand, among the subjects analyzed, those whose Neurocognitive Index (NCI) standardized score 8 weeks after ingestion (W8) was the same as or lower than the baseline score immediately before ingestion (W0) were distinguished as non-responders, meaning their cognitive function did not improve with the intake of the test product. Figure 27 shows the number of responders and non-responders in each group involved in the intervention trial.

[0126] (Changes in cognitive function) Figures 28 to 33 show the cognitive track test results for responders and non-responders in each group. Figure 28 shows the cognitive track test results for men in Group 1 who ingested Tamogitake mushrooms. Figure 29 shows the cognitive track test results for men in Group 2 who ingested Moringa. Figure 30 shows the cognitive track test results for men in Group 3 who ingested rice bran. Figure 31 shows the cognitive track test results for women in Group 4 who ingested Tamogitake mushrooms. Figure 32 shows the cognitive track test results for women in Group 5 who ingested Moringa. Figure 33 shows the cognitive track test results for women in Group 6 who ingested rice bran.

[0127] The column names in Figures 28 to 33 represent 12 cognitive domains, and within each cognitive domain group, "Res" indicates a responder and "Non" indicates a non-responder. The row names in Figures 28 to 33 represent the standard score and Δ value. Standard score data is shown as mean ± (plus or minus) SD. BW4 represents 4 weeks before intake, W0 represents immediately before intake, W4 represents 4 weeks after intake, and W8 represents 8 weeks after intake. The Δ value shows the change in standard score from the baseline immediately before intake (W0). A paired t-test was performed for within-group comparisons (W4 and W8) from the baseline immediately before intake (W0), and a p-value less than 0.05 after Benjamini-Hochberg correction is indicated. For Δ values, an unpaired t-test was performed between responders and non-responders, and if the p-value is less than 0.05, it is indicated as † (called a dagger).

[0128] Figure 34 summarizes the cognitive domains in which standard scores significantly improved between baseline (immediately before ingestion) and 4 weeks (W4) or 8 weeks (W8) after ingestion, in the Cognitrax test for responders and non-responders in each group. The statistical method used was a paired t-test, and the significance level for the p-value (after Benjamini-Hochberg correction) was 0.05. Cognitive domains showing a significant increase in standard scores between the comparison periods are indicated by a circle (○).

[0129] Figures 28 and 34 show that in Group 1, male non-responders who consumed Tamogitake mushrooms did not show any significant improvement in standard scores in any cognitive domain. In contrast, in Group 1, male responders who consumed Tamogitake mushrooms showed significant improvements in standard scores for the Neurocognitive Index (NCI) (improvement observed at 4 and 8 weeks after ingestion), cognitive function speed (8 weeks after ingestion), overall attention (4 and 8 weeks after ingestion), cognitive flexibility (4 and 8 weeks after ingestion), processing speed (4 and 8 weeks after ingestion), and executive function (8 weeks after ingestion), indicating improvement in these cognitive domains.

[0130] Figures 29 and 34 show that in Group 2, male non-responders who consumed moringa did not show any significant improvement in standard scores in any cognitive domain. In contrast, in Group 2, male responders who consumed moringa showed significant improvements in standard scores for the following cognitive domains: Neurocognitive Index (NCI) (4 weeks and 8 weeks after consumption), verbal memory (8 weeks after consumption), cognitive function speed (8 weeks after consumption), reaction time (8 weeks after consumption), overall attention (4 weeks and 8 weeks after consumption), cognitive flexibility (4 weeks and 8 weeks after consumption), processing speed (8 weeks after consumption), and executive function (4 weeks and 8 weeks after consumption).

[0131] Figures 30 and 34 show that in Group 3, male non-responders who ingested rice bran did not show any significant improvement in standard scores in any cognitive domain. In contrast, in Group 3, male responders who ingested rice bran showed significant improvements in standard scores for the Neurocognitive Index (NCI) (4 weeks and 8 weeks after ingestion), overall memory (8 weeks after ingestion), verbal memory (8 weeks after ingestion), overall attention (8 weeks after ingestion), cognitive flexibility (4 weeks and 8 weeks after ingestion), processing speed (8 weeks after ingestion), and executive function (4 weeks and 8 weeks after ingestion), indicating improvement in these cognitive domains.

[0132] Figures 31 and 34 show that in female non-responders in Group 4 who consumed Tamogitake mushrooms, the standard score for executive function (8 weeks after consumption) significantly improved, indicating improvement in this cognitive domain. On the other hand, in female responders in Group 4 who consumed Tamogitake mushrooms, the standard scores for the Neurocognitive Index (NCI) (4 weeks and 8 weeks after consumption), cognitive flexibility (4 weeks and 8 weeks after consumption), processing speed (8 weeks after consumption), and executive function (4 weeks and 8 weeks after consumption) significantly improved, indicating improvement in these cognitive domains. It can be seen that responders showed improvement in more cognitive domains compared to non-responders.

[0133] Figures 32 and 34 show that in Group 5, female non-responders who consumed moringa did not show any significant improvement in standard scores in any cognitive domain. In contrast, female responders in Group 5 who consumed moringa showed significant improvements in standard scores for the Neurocognitive Index (NCI) (8 weeks after intake), overall memory (8 weeks after intake), verbal memory (8 weeks after intake), cognitive flexibility (8 weeks after intake), and executive function (8 weeks after intake), indicating improvement in these cognitive domains.

[0134] Figures 33 and 34 show that in Group 6, female non-responders who ingested rice bran did not show any significant improvement in standard scores in any cognitive domain. In contrast, female responders in Group 6 who ingested rice bran showed significant improvements in standard scores for the following cognitive domains: Neurocognitive Index (NCI) (4 weeks and 8 weeks after ingestion), overall memory (4 weeks and 8 weeks after ingestion), verbal memory (4 weeks and 8 weeks after ingestion), cognitive speed (4 weeks after ingestion), overall attention (8 weeks after ingestion), cognitive flexibility (4 weeks and 8 weeks after ingestion), processing speed (4 weeks after ingestion), and executive function (4 weeks and 8 weeks after ingestion).

[0135] The results shown in Figures 28 to 34 indicate that in each group of non-responders, cognitive function showed little improvement despite ingesting the test product.

[0136] The results in Figures 28 to 34 show that in each group of responders, some form of cognitive function improved after taking the test product. However, even among responders, there were differences in the cognitive domains that improved (at least at either 4 weeks or 8 weeks after ingestion) depending on gender and the test product used (overall memory, verbal memory, cognitive speed, reaction time, overall attention, and processing speed).

[0137] (Changes in gut microbiota between responders and non-responders) We analyzed the changes in the gut microbiota after ingestion of the test product for responders and non-responders in each group. Specifically, we performed a Friedman test (significance level: 0.05) on the relative abundance of gut bacteria (genera-level taxa) converted to centered log-ratios (CLR) immediately before ingestion (W0), 4 weeks after ingestion (W4), and 8 weeks after ingestion (W8). Taxa with significant changes were identified as the gut bacteria taxa that changed after ingestion of the test product.

[0138] Figures 35 to 40 show the classification groups of intestinal bacteria that changed after ingestion of the test product for responders in each group, along with their p-values, occupancy rates, and prevalence rates. The p-values ​​are those obtained from the Friedman test (with a significance level of 0.05) on the relative abundance of intestinal microorganisms converted to a heart-log ratio immediately before ingestion, 4 weeks after ingestion, and 8 weeks after ingestion. Intestinal bacteria (classification groups at the genus level) are those whose prevalence rate in responders of each group was 0.25 or higher immediately before ingestion (W0). Figure 35 shows the intestinal bacteria that changed after ingestion of the test product for male responders in Group 1 who ingested Tamogitake mushrooms. Figure 36 shows the intestinal bacteria that changed after ingestion of the test product for male responders in Group 2 who ingested Moringa mushrooms. Figure 37 shows the intestinal bacteria that changed after ingestion of the test product for male responders in Group 3 who ingested rice bran. Figure 38 shows the changes in gut bacteria after ingestion of the test product in female responders in Group 4 who ingested Tamogitake mushrooms. Figure 39 shows the changes in gut bacteria after ingestion of the test product in female responders in Group 5 who ingested Moringa mushrooms. Figure 40 shows the changes in gut bacteria after ingestion of the test product in female responders in Group 6 who ingested rice bran.

[0139] Figures 41 to 46 show the classification groups of intestinal bacteria that changed after ingestion of the test product, along with their p-values, occupancy rates, and prevalence rates for non-responders in each group. The p-values ​​are those obtained from the Friedman test (with a significance level of 0.05) on the relative abundance of intestinal microorganisms converted to a heart-log ratio immediately before ingestion, 4 weeks after ingestion, and 8 weeks after ingestion. Intestinal bacteria (classification groups at the genus level) are those whose prevalence rate in responders of each group was 0.25 or higher immediately before ingestion (W0). Figure 41 shows the intestinal bacteria that changed after ingestion of the test product for male non-responders in Group 1 who ingested Tamogitake mushrooms. Figure 42 shows the intestinal bacteria that changed after ingestion of the test product for male non-responders in Group 2 who ingested Moringa mushrooms. Figure 43 shows the intestinal bacteria that changed after ingestion of the test product for male non-responders in Group 3 who ingested rice bran. Figure 44 shows the changes in gut bacteria after ingestion of the test product in non-responder women in Group 4 who ingested Tamogitake mushrooms. Figure 45 shows the changes in gut bacteria after ingestion of the test product in non-responder women in Group 5 who ingested Moringa mushrooms. Figure 46 shows the changes in gut bacteria after ingestion of the test product in non-responder women in Group 6 who ingested rice bran.

[0140] (Comparison of changes in gut microbiota between responders and non-responders) Comparing male responders (Figure 35) and non-responders (Figure 41) who ingested Tamogitake mushrooms in Group 1, one group of gut bacteria (Ruminococcus 2) was common to both groups after ingestion of the test product, while the others differed. In other words, many of the gut bacteria that changed between responders and non-responders were different.

[0141] When comparing male responders (Figure 36) and non-responders (Figure 42) who ingested moringa in Group 2, all of the gut bacteria classifications that changed after ingesting the test product were different. In other words, the gut bacteria that changed differed between responders and non-responders.

[0142] Comparing male responders (Figure 37) and non-responders (Figure 43) who ingested rice bran in Group 3, one group of gut bacteria (Parabacteroides) was common to both groups after ingestion of the test product, while the others differed. In other words, many of the gut bacteria that changed between responders and non-responders were different.

[0143] Comparing female responders (Figure 38) and non-responders (Figure 44) who ingested the oyster mushroom in Group 4, all of the gut bacteria classifications that changed after ingesting the test product were different. In other words, the gut bacteria that changed differed between responders and non-responders.

[0144] When comparing female responders (Figure 39) and non-responders (Figure 45) who ingested moringa in Group 5, all of the gut bacteria classifications that changed after ingesting the test product were different. In other words, the gut bacteria that changed differed between responders and non-responders.

[0145] When comparing female responders (Figure 40) and non-responders (Figure 46) who ingested rice bran in Group 6, all of the gut bacteria classifications that changed after ingesting the test product were different. In other words, the gut bacteria that changed differed between responders and non-responders.

[0146] These findings indicate that the gut bacteria differ between responders and non-responders within the same group.

[0147] (Comparison of changes in gut microbiota between men and women in responders) When comparing male responders (Figure 35) and female responders (Figure 38) who ingested Tamogitake mushrooms, five taxonomic groups of intestinal bacteria (Agathobaculum, Blautia, Collinsella, Enterocloster, and Parabacteroides) were common to both groups, while all other groups differed.

[0148] When comparing male responders (Figure 36) and female responders (Figure 39) who ingested moringa, two taxonomic groups of intestinal bacteria (Agathobaculum and Intestinimonas) were common to both groups, while all other groups differed.

[0149] When comparing male responders (Figure 37) and female responders (Figure 40) who ingested rice bran, two groups of gut bacteria (Faecalibacterium and Parabacteroides) were common to both groups, while all other groups differed.

[0150] These findings suggest that there are some commonalities in the changing gut bacteria between male and female responders of the same test product, while other aspects differ.

[0151] (Comparison of changes in gut microbiota between men and women in non-responders) When comparing male non-responders (Figure 41) and female non-responders (Figure 44) who ingested Tamogitake mushrooms, all of the gut bacteria classifications that changed after ingesting the test product were different.

[0152] When comparing male non-responders (Figure 42) and female non-responders (Figure 45) who ingested moringa, two taxonomic groups of intestinal bacteria (Coprococcus and Mediterraneibacter) were common after ingestion of the test product, while other groups differed. However, these differed from the two taxonomic groups (Agathobaculum and Intestinimonas) that were common between male responders (Figure 36) and female responders (Figure 39) who ingested moringa.

[0153] When comparing male non-responders (Figure 43) and female non-responders (Figure 46) who ingested rice bran, the classification groups of intestinal bacteria that changed after ingesting the test product were all different.

[0154] These findings indicate that, in addition to moringa, there is no commonality in the gut bacteria that change between male and female non-responders of the same test product for tamogitake mushrooms and rice bran.

[0155] (Comparison of changes in gut microbiota among test products in male responders) In male responders of Tamogitake and Moringa (Figures 35 and 36), four taxonomic groups of intestinal bacteria that changed after ingestion of the test product were common (Agathobaculum, Anaerobutyricum, Enterocloster, and Phascolarctobacterium), while the others differed.

[0156] In male responders of Tamogitake mushrooms and rice bran (Figures 35 and 37), four taxonomic groups of intestinal bacteria (Anaerobutyricum, Blautia, Parabacteroides, and Ruminococcus2) were common to both groups that changed after ingestion of the test product, while the others differed.

[0157] In the male responders of moringa and rice bran (Figures 36 and 37), one group of gut bacteria (Anaerobutyricum) was common to both groups that underwent changes after ingesting the test product, while all other groups differed.

[0158] Among all male responders of the three test products (Figures 35 to 37), one gut microbiota (Anaerobutyricum) was common to all that changed after ingesting the test product.

[0159] These findings suggest that while there are some commonalities in the changing gut bacteria among male responders of different test products, there are differences in other areas.

[0160] (Comparison of changes in gut microbiota among test products in female responders) In the female responders of Tamogitake and Moringa (Figures 38 and 39), one group of intestinal bacteria (Collinsella) was common to both groups that changed after ingestion of the test product, while all other groups differed.

[0161] In the female responders of Tamogitake mushrooms and rice bran (Figures 38 and 40), one group of intestinal bacteria (Parabacteroides) was common to both groups after ingestion of the test product, while all other groups differed.

[0162] In the female responders of moringa and rice bran (Figures 39 and 40), one group of gut bacteria (Faecalibacterium) was common to both groups after ingestion of the test product, while all other groups differed.

[0163] These findings suggest that female responders share some commonalities in their gut bacteria, while differing in other areas.

[0164] (Comparison of changes in gut microbiota among test products in male non-responders) A comparison of male non-responders (Figures 41 to 43) for each of the three test products revealed no commonalities in the classification of intestinal bacteria that changed after ingesting the test product; all were different.

[0165] (Comparison of changes in gut microbiota among test products in female non-responders) In the female non-responders of Tamogitake and Moringa (Figures 44 and 45), one group of intestinal bacteria (Fusobacterium) was common to both groups that changed after ingestion of the test product, while all other groups differed.

[0166] In the female non-responders who consumed Tamogitake mushrooms and those who consumed rice bran (Figures 44 and 46), the taxonomic groups of intestinal bacteria that changed after ingesting the test products were all different.

[0167] In the female non-responders of moringa and rice bran (Figures 45 and 46), one group of intestinal bacteria (Mediterraneibacter) that changed after ingesting the test product was common, while all other groups differed.

[0168] These findings suggest that among female non-responders, there are some commonalities in the changing gut bacteria across the test products. However, these differ from the gut bacterial classifications that showed commonalities in the aforementioned "comparison of changes in the gut microbiota of female responders across test products."

[0169] (Summary of changes in gut microbiota between responders and non-responders) Based on the results of the aforementioned "comparison of gut microbiota changes between responders and non-responders," "comparison of gut microbiota changes between men and women in responders," "comparison of gut microbiota changes between men and women in non-responders," "comparison of gut microbiota changes among test products in male responders," "comparison of gut microbiota changes among test products in female responders," "comparison of gut microbiota changes among test products in male non-responders," and "comparison of gut microbiota changes among test products in female non-responders," the following (1) to (6) can be suggested.

[0170] (1) Improvement in cognitive function in individuals suspected of having MCI after ingesting the test product (Tamogitake mushroom, Moringa, or rice bran) is associated with changes in specific gut bacteria caused by ingesting the test product.

[0171] (2) Individuals who do not experience this specific change in gut bacteria after ingesting the test product are less likely to see improvement in cognitive function.

[0172] (3) Among men and women who consumed the same test product and showed improvement in cognitive function, there was a commonality in some of the gut bacteria that changed after consumption, which may be related to a commonality in some of the cognitive areas that improved.

[0173] (4) Among men and women who consumed the same test product and showed improvement in cognitive function, there were differences in some of the gut bacteria that changed after consumption, which may be related to differences in some of the cognitive areas that improved. Furthermore, these differences may be based on sex differences in the gut microbiota.

[0174] (5) Among same-sex individuals who consumed different test products and showed improvement in cognitive function, there may be commonalities in some of the gut bacteria that changed after ingestion, which may be related to the commonalities in some of the cognitive areas that improved.

[0175] (6) Among same-sex individuals who consumed different test products and showed improvements in cognitive function, differences were observed in some of the gut bacteria that changed after consumption, which may be related to differences in some of the cognitive areas that improved.

[0176] From (1) to (6), it can be seen that when individuals suspected of having MCI consume the test product, the test product contributes to the improvement of cognitive function through specific changes based on sex differences in the gut microbiota (sex-based control). Furthermore, it can be seen that individuals who do not experience these specific changes in gut bacteria after consuming the test product are less likely to experience improvement in cognitive function.

[0177] (Relationship between male responders and gut microbiota immediately before ingestion (W0)) As explained above, whether cognitive function improves (i.e., whether they become a responder or a non-responder) after ingesting the test product in individuals suspected of having MCI is thought to depend on whether a specific change in the gut microbiota occurs due to the test product's intake. Furthermore, whether this specific change in the gut microbiota occurs due to the test product's intake is thought to depend on the composition of the gut microbiota before the test product's intake. Therefore, for each test product, the relationship between the composition of the gut microbiota immediately before ingestion (W0) between responders and non-responders was visualized using NMDS plots. The NMDS plots show the results of the β-diversity analysis of the gut microbiota.

[0178] Figures 47(a)-(c) show NMDS plots of the gut microbiota of men immediately before ingestion (W0) for each test product: Tamogitake mushroom, Moringa, and rice bran. The position of the NMDS plots reflects the composition of the gut microbiota, with plots located close together indicating similar gut microbiota compositions. In the NMDS plots for each test product, the responder and non-responder plots showed a clustered positional relationship (Figures 47(a)-(c)). This suggests that responders and non-responders of each test product had similar gut microbiota compositions before ingestion.

[0179] Furthermore, by adding a new male sample's gut microbiota data to each of these NMDS plots and examining their relative positions, it is possible to estimate whether the provider of that new sample will be a responder or a non-responder.

[0180] Figure 47(d) shows NMDS plots of the gut microbiota of men immediately before ingestion (W0) for all three subjects: Tamogitake mushroom, Moringa, and rice bran. By adding a new male sample's gut microbiota data to this NMDS plot and observing its positional relationship, it is possible to estimate whether the provider of that new sample will be a responder or non-responder to each test product.

[0181] In other words, by using gut microbiota data, it is possible to estimate in advance the effect of the test product on improving cognitive function in male subjects. Furthermore, based on these results, it is possible to recommend the most suitable test product to the subjects.

[0182] (Relationship between female responders and gut microbiota immediately before ingestion (W0)) The relationship between the composition of the gut microbiota immediately before ingestion (W0) for each test product was visualized using NMDS plots. NMDS plots of the gut microbiota immediately before ingestion (W0) for each test product (Tamogitake, Moringa, and rice bran) are shown in Figures 48(a)-(c). In the NMDS plots for each test product, the plots for responders and non-responders showed a cohesive positional relationship (Figures 48(a)-(c)). This suggests that responders and non-responders for each test product had similar gut microbiota compositions before ingestion.

[0183] Furthermore, by adding a new female sample's gut microbiota data to each of these NMDS plots and examining their relative positions, it is possible to estimate whether the provider of that new sample will be a responder or a non-responder.

[0184] Figure 48(d) shows NMDS plots of the gut microbiota of women immediately before ingestion (W0) for all three subjects: Tamogitake mushroom, Moringa, and rice bran. By adding a new female sample's gut microbiota data to this NMDS plot and observing its positional relationship, it is possible to estimate whether the provider of that new sample will be a responder or non-responder for each test product.

[0185] In other words, by using gut microbiota data, it is possible to estimate in advance the effect of the test product on improving cognitive function in women (female test subjects). Furthermore, based on these results, it is possible to recommend the most suitable test product to the test subjects.

[0186] (Responders showing improvement in MCI risk) Japanese Patent No. 7,411,177 (and the corresponding PCT application: PCT / JP2024 / 019474) discloses a risk estimation model for MCI using gut microbiota data. This MCI risk estimation model was developed based on gut microbiota abnormalities (dysbiosis) characteristic of MCI, and takes gut microbiota data as input and outputs an MCI risk value (a value between 0 and 1). Japanese Patent No. 7,411,177 (and the corresponding PCT application: PCT / JP2024 / 019474) explains the hypothesis that the gut microbiota abnormalities characteristic of MCI cause dysregulation of the gut microbiota, increased intestinal barrier permeability, increased blood-brain barrier permeability, and increased chronic neuroinflammation, and that these abnormalities, if persistent over a long period, ultimately lead to cognitive decline. In other words, a reduction in the MCI risk value output by the MCI risk estimation model can be said to improve the gut microbiota abnormalities characteristic of MCI and lead to the prevention of MCI.

[0187] Following the method disclosed in Japanese Patent No. 7,411,177 (and the corresponding PCT application: PCT / JP2024 / 019474), gut microbiota data from each test product responder was input into an MCI risk estimation model, and an MCI risk value was output. Responders whose MCI risk value decreased by 0.05 or more 8 weeks after ingestion (W8) compared to the baseline immediately before ingestion (W0) were considered to have shown improvement in MCI risk. In other words, it can be said that responders who showed improvement in MCI risk were able to improve cognitive function and prevent MCI through the control of the gut microbiota by ingesting the test product.

[0188] The number of responders in each group who showed improvement in MCI risk is shown in Figure 49.

[0189] (Relationship between responders who show improvement in MCI risk in men and the gut microbiota immediately before intake (W0)) Figures 50(a)-(c) show the NMDS plots of the gut microbiota of men immediately before ingestion (W0) for each of the test products: Tamogitake mushroom, Moringa, and rice bran.

[0190] In the NMDS plots for each test product, the plots of responders showing improvement in MCI risk showed a clustered relationship (Figure 50(a)-(c)). This suggests that the responders showing improvement in MCI risk for each test product had similarities in the composition of their gut microbiota before taking the test product.

[0191] Furthermore, by adding a new male sample's gut microbiota data to each of these NMDS plots and examining their relative positions, it is possible to estimate whether the provider of that new sample will be a responder with improved MCI risk.

[0192] Figure 50(d) shows NMDS plots of the gut microbiota of men immediately before ingestion (W0) for all three subjects: Tamogitake mushroom, Moringa, and rice bran. By adding gut microbiota data from a new male sample to this NMDS plot and examining its positional relationship, it is possible to estimate which of the test products the provider of that new sample will be a responder with improved MCI risk.

[0193] In other words, using gut microbiota data, it is possible to estimate in advance the effects of both improving cognitive function and preventing mild cognitive impairment (MCI) in men (male subjects) who consume the test product. Furthermore, based on these results, it is possible to recommend the most suitable test product to the subjects.

[0194] (Relationship between responders who show improvement in MCI risk in women and gut microbiota immediately before intake (W0)) Figures 51(a)-(c) show the NMDS plots of the gut microbiota of women immediately before ingestion (W0) for each of the test products: Tamogitake mushroom, Moringa, and rice bran.

[0195] In the NMDS plots for each test product, the plots of responders showing improvement in MCI risk showed a clustered relationship (Figure 51(a)-(c)). This suggests that the responders showing improvement in MCI risk for each test product had similarities in the composition of their gut microbiota before taking the test product.

[0196] Furthermore, by adding a new female sample's gut microbiota data to each of these NMDS plots and examining their relative positions, it is possible to estimate whether the provider of that new sample will become a responder with improved MCI risk.

[0197] Figure 51(d) shows NMDS plots of the gut microbiota of women immediately before ingestion (W0) for all three subjects: Tamogitake mushroom, Moringa, and rice bran. By adding a new female sample's gut microbiota data to this NMDS plot and observing its positional relationship, it is possible to estimate which subject the provider of the new sample is likely to be a responder with improved MCI risk.

[0198] In other words, using gut microbiota data, it is possible to estimate in advance the effects of both improving cognitive function and preventing mild cognitive impairment (MCI) in women (female subjects) who consume the test product. Furthermore, based on these results, it is possible to recommend the most suitable test product to the subjects.

[0199] According to this embodiment, by inputting the gut microbiota data of a new subject into the positional relationship data of the NMDS plot (i.e., the calculation result data of the multivariate analysis), it is possible to estimate which test product the new subject will be a responder to. Furthermore, using the gut microbiota data, it is possible to estimate in advance the effect of the test product on improving the cognitive function of subjects who consume it.

[0200] Based on these estimated results regarding cognitive function improvement, a method can be provided to recommend the optimal test product (i.e., this food) to the subject. Furthermore, a report on how the food was consumed may be provided to the subject.

[0201] Furthermore, according to this embodiment, by inputting the gut microbiota data of a new subject into the positional relationship data of the NMDS plot (i.e., the calculation result data of the multivariate analysis), it is possible to estimate which test product the new subject will respond to, resulting in an improvement in MCI risk. Then, using the gut microbiota data, it is possible to estimate in advance both the effect of improving cognitive function and the effect of preventing MCI in subjects who consume the test product.

[0202] Based on these estimated results regarding cognitive function improvement and MCI prevention, a method can be provided to recommend the optimal test product (i.e., this food) to the subject. Furthermore, a report on how the food was consumed may be provided to the subject.

Claims

1. An estimation step in which, using attribute information of subjects who wish to have their risk for mild cognitive impairment assessed and data on their gut microbiota, the probability that the subject has mild cognitive impairment is calculated from a model, and the subject's risk is estimated as an MCI risk value. Based on the subject's attribute information and data on the gut microbiota, and the estimated risk of the subject, a recommendation step is made to recommend foods that reduce the subject's risk, specifically foods that reduce the MCI risk value by 0.05 or more eight weeks after ingestion compared to the baseline immediately before ingestion. Food recommendation method that includes the following.

2. The attribute information includes the gender of the subject, The food recommendation method according to claim 1, further comprising the step of creating an evaluation report on the risks of the subject.

3. The method for recommending food according to claim 1, wherein the data relating to the intestinal microbiota is based on data relating to intestinal microorganisms derived from the stool sample of the subject.

4. The food recommendation method according to claim 1, further comprising a follow-up step of confirming the increase or decrease of the risk after the subject has consumed the food.

5. The person who consumed the aforementioned food was male, 1) If the food is Tamogitake mushroom, The gut microbiota that contributes to the prevention or improvement of the aforementioned mild cognitive impairment is The intestinal microorganisms commonly associated with mild cognitive impairment are Rothia, Streptococcus, Intestinibacter, Bifidobacterium, Fournierella, Anaerostipes, Parasutterella, Faecalicatena, Veillonella, and Adlercreutzia. The intestinal microorganisms that are less common in the aforementioned mild cognitive impairment are Eisenbergiella, Anaerotruncus, Lawsonibacter, Akkermansia, Coprobacillus, Catenibacterium, Dialister, Turicibacter, and Ruminococcus. The gut microbes associated with improved cognitive function are Anaerobutyricum, Erysipelatoclostridium, Faecalibacillus, Megamonas, Phascolarctobacterium, and Ruminococcus 2. It includes at least one of the following: 2) If the food is moringa, The gut microbiota that contributes to the prevention or improvement of the aforementioned mild cognitive impairment is The intestinal microorganisms commonly associated with mild cognitive impairment are Rothia, Streptococcus, Intestinibacter, Bifidobacterium, Fournierella, Anaerostipes, Parasutterella, Faecalicatena, Veillonella, and Adlercreutzia. The intestinal microorganisms that are less common in the aforementioned mild cognitive impairment are Eisenbergiella, Anaerotruncus, Lawsonibacter, Akkermansia, Coprobacillus, Catenibacterium, Dialister, Turicibacter, and Ruminococcus. The gut microbes associated with improved cognitive function are Anaerobutyricum, Anaerostipes, Bacteroides, Butyricococcus, Dysosmobacter, Enterocloster, and Phascolarctobacterium. It includes at least one of the following: 3) If the food is natto powder, The gut microbiota that contributes to the prevention or improvement of the aforementioned mild cognitive impairment is The intestinal microorganisms commonly associated with mild cognitive impairment are Rothia, Streptococcus, Intestinibacter, Bifidobacterium, Fournierella, Anaerostipes, Parasutterella, Faecalicatena, Veillonella, and Adlercreutzia. The intestinal microorganisms that are less common in the aforementioned mild cognitive impairment are Eisenbergiella, Anaerotruncus, Lawsonibacter, Akkermansia, Coprobacillus, Catenibacterium, Dialister, Turicibacter, and Ruminococcus. It includes at least one of the following: 4) If the food is black turmeric, The gut microbiota that contributes to the prevention or improvement of the aforementioned mild cognitive impairment is The intestinal microorganisms commonly associated with mild cognitive impairment are Rothia, Streptococcus, Intestinibacter, Bifidobacterium, Fournierella, Anaerostipes, Parasutterella, Faecalicatena, Veillonella, and Adlercreutzia. The intestinal microorganisms that are less common in the aforementioned mild cognitive impairment are Eisenbergiella, Anaerotruncus, Lawsonibacter, Akkermansia, Coprobacillus, Catenibacterium, Dialister, and Ruminococcus. It includes at least one of the following: 5) If the food is brown rice, The gut microbiota that contributes to the prevention or improvement of the aforementioned mild cognitive impairment is The intestinal microorganisms commonly associated with mild cognitive impairment are Rothia, Streptococcus, Intestinibacter, Bifidobacterium, Fournierella, Anaerostipes, Parasutterella, Faecalicatena, Veillonella, and Adlercreutzia. The intestinal microorganisms that are less common in the aforementioned mild cognitive impairment are Eisenbergiella, Anaerotruncus, Lawsonibacter, Akkermansia, Coprobacillus, Catenibacterium, Dialister, Turicibacter, and Ruminococcus. It includes at least one of the following: 6) If the food is rice bran, The gut microbiota that contributes to the prevention or improvement of the aforementioned mild cognitive impairment is The gut microbiota associated with improved cognitive function are Adlercreutzia, Anaerobutyricum, Blautia, Holdemania, and Ruminococcus 2. A food recommendation method according to claim 2, comprising at least one of the following.

6. The person who consumed the aforementioned food was female, 1) If the food is Tamogitake mushroom, The gut microbiota that contributes to the prevention or improvement of the aforementioned mild cognitive impairment is The intestinal microorganisms commonly associated with mild cognitive impairment are Enterocloster, Ruthenibacterium, Anaerotignum, Dysosmobacter, Turicibacter, Romboutsia, Eisenbergiella, Intestinimonas, Sellimonas, Bacteroides, Frisingicoccus, Hungatella, Gordonibacter, Negregta, Negativibacillus, Fusobacterium, Massilimicrobiota, and Clostridium. XIVa, Parabacteroides, Blautia, Clostridium IV, Coprobacillus, Akkermansia, Anaerotruncus, Anaeromassilibacillus, and Ihubacter, The following intestinal microorganisms are less common in individuals with mild cognitive impairment: Megamonas, Clostridium XIVb, Holdemanella, Lactococcus, Ligilactobacillus, Paraprevotella, Leuconostoc, Anaerostipes, Slackia, Bifidobacterium, Coprococcus, Sutterella, Veillonella, and Agathobacter. Dorea, Lawsonibacter, and Massilimicrobiota are intestinal microorganisms associated with improved cognitive function. It includes at least one of the following: 2) If the food is moringa, The gut microbiota that contributes to the prevention or improvement of the aforementioned mild cognitive impairment is The intestinal microorganisms commonly associated with mild cognitive impairment are Enterocloster, Ruthenibacterium, Anaerotignum, Dysosmobacter, Turicibacter, Romboutsia, Eisenbergiella, Intestinimonas, Sellimonas, Bacteroides, Frisingicoccus, Hungatella, Gordonibacter, Negregta, Negativibacillus, Fusobacterium, Massilimicrobiota, and Clostridium. XIVa, Parabacteroides, Blautia, Clostridium IV, Coprobacillus, Akkermansia, Anaerotruncus, Anaeromassilibacillus, and Ihubacter, The following intestinal microorganisms are less common in individuals with mild cognitive impairment: Megamonas, Clostridium XIVb, Holdemanella, Lactococcus, Ligilactobacillus, Paraprevotella, Leuconostoc, Anaerostipes, Slackia, Bifidobacterium, Coprococcus, Sutterella, Veillonella, and Agathobacter. The gut microbiota associated with improved cognitive function are Adlercreutzia, Clostridium IV, Clostridium XVIII, Collinsella, Faecalibacterium, and Paraprevotella. It includes at least one of the following: 3) If the food is natto powder, The gut microbiota that contributes to the prevention or improvement of the aforementioned mild cognitive impairment is The intestinal microorganisms commonly associated with mild cognitive impairment are Enterocloster, Ruthenibacterium, Anaerotignum, Dysosmobacter, Turicibacter, Romboutsia, Eisenbergiella, Intestinimonas, Sellimonas, Bacteroides, Frisingicoccus, Hungatella, Gordonibacter, Negregta, Negativibacillus, Fusobacterium, Massilimicrobiota, and Clostridium. XIVa, Parabacteroides, Blautia, Clostridium IV, Coprobacillus, Akkermansia, Anaerotruncus, Anaeromassilibacillus, and Ihubacter, The following intestinal microorganisms are less common in individuals with mild cognitive impairment: Megamonas, Clostridium XIVb, Holdemanella, Lactococcus, Ligilactobacillus, Paraprevotella, Leuconostoc, Anaerostipes, Slackia, Bifidobacterium, Coprococcus, Sutterella, Veillonella, and Agathobacter. It includes at least one of the following: 4) If the food is black turmeric, The gut microbiota that contributes to the prevention or improvement of the aforementioned mild cognitive impairment is The intestinal microorganisms commonly associated with mild cognitive impairment are Enterocloster, Ruthenibacterium, Anaerotignum, Dysosmobacter, Turicibacter, Romboutsia, Eisenbergiella, Intestinimonas, Sellimonas, Bacteroides, Frisingicoccus, Hungatella, Gordonibacter, Negregta, Negativibacillus, Fusobacterium, Massilimicrobiota, and Clostridium. XIVa, Parabacteroides, Blautia, Clostridium IV, Coprobacillus, Akkermansia, Anaerotruncus, Anaeromassilibacillus, and Ihubacter, The following intestinal microorganisms are less common in individuals with mild cognitive impairment: Megamonas, Clostridium XIVb, Holdemanella, Lactococcus, Ligilactobacillus, Paraprevotella, Leuconostoc, Anaerostipes, Slackia, Bifidobacterium, Coprococcus, Sutterella, Veillonella, and Agathobacter. It includes at least one of the following: 5) If the food is brown rice, The gut microbiota that contributes to the prevention or improvement of the aforementioned mild cognitive impairment is The intestinal microorganisms commonly associated with mild cognitive impairment are Enterocloster, Ruthenibacterium, Anaerotignum, Dysosmobacter, Turicibacter, Romboutsia, Eisenbergiella, Intestinimonas, Sellimonas, Bacteroides, Frisingicoccus, Hungatella, Gordonibacter, Negregta, Negativibacillus, Fusobacterium, Massilimicrobiota, and Clostridium. XIVa, Parabacteroides, Blautia, Clostridium IV, Coprobacillus, Akkermansia, Anaerotruncus, Anaeromassilibacillus, and Ihubacter, The following intestinal microorganisms are less common in individuals with mild cognitive impairment: Megamonas, Clostridium XIVb, Holdemanella, Lactococcus, Ligilactobacillus, Paraprevotella, Leuconostoc, Anaerostipes, Slackia, Bifidobacterium, Coprococcus, Sutterella, Veillonella, and Agathobacter. It includes at least one of the following: 6) If the food is rice bran, The gut microbiota that contributes to the prevention or improvement of the aforementioned mild cognitive impairment is Bifidobacterium, an intestinal microorganism associated with improved cognitive function, A food recommendation method according to claim 2, comprising at least one of the following.

7. If the person consuming the aforementioned food is male, The food recommendation method according to claim 2, wherein the food is one or more of the following: Tamogitake mushroom, Moringa, Natto powder, Black turmeric, Resistant starch 2, Brown rice, and Rice bran.

8. If the person consuming the aforementioned food is female, The food recommendation method according to claim 2, wherein the food is one or more of the following: Tamogitake mushroom, Moringa, Natto powder, Black turmeric, Blueberry, Pomegranate, Brown rice, and Rice bran.

9. An estimation step in which, using attribute information of subjects who wish to have their risk for mild cognitive impairment assessed and data on their gut microbiota, the probability that the subject has mild cognitive impairment is calculated from a model, and the subject's risk is estimated as an MCI risk value. Based on the attribute information and data relating to the gut microbiota of the subject, and the estimated risk of the subject, the present invention provides a food that reduces the subject's risk, such that the MCI risk value eight weeks after ingestion decreases by 0.05 or more compared to the baseline value immediately before ingestion. A food serving method comprising the following features.

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