Intestinal dysbiosis assessment system

Abstract

To provide a method for determining intestinal dysbiosis.SOLUTION: A method for determining intestinal dysbiosis includes the steps for: setting a determination criterion value and a determination score for intestinal dysbiosis with respect to at least one index selected from the group consisting of a diversity-related index, a short-chain fatty acid production index, an intestinal immunity-related index, an oral bacteria-related index, and a diarrhea constipation-related index, regarding the intestinal bacteria of a population for determining the criterion value; collating bacterial composition data obtained from an individual subject or a subject group (users) with the criterion value, and calculating a user value of the determination score for each of the indices; calculating an intestinal flora score by adding the calculated user value; and determining the intestinal dysbiosis of the user by using the intestinal flora score as an index.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a system for determining a non-specific and diverse condition called intestinal dysbiosis, and It relates to a determination method. [Background technology]

[0002] Approximately 1,000 types of intestinal bacteria live in the human intestine, and these bacteria act as a nutrient source. They play an important role in maintaining human health by providing nutrients and suppressing the growth of pathogens. However, for some reason, (i) the total number of intestinal bacteria is significantly reduced, or (ii) ) The composition ratio changes, and (iii) the bacterial species that are normally at low bacterial counts increase abnormally. This type of abnormality in the composition of the intestinal flora is called gut dysbiosis. The name of the system is Iosis (Non-Patent Document 1). However, the intestinal flora varies widely depending on the disease and lifestyle. The definition of intestinal dysbiosis is unclear, and there is a wide range of indicators and bacterial flora. There is no agreement between the two (Non-Patent Document 1).

[0003] On the other hand, when clinicians (healthcare professionals) provide feedback on the results of intestinal bacteria tests to patients, It is not possible to account for individual indicators or specific characteristics of bacteria. It is necessary to make it easy to explain whether a certain flora is "good" or "bad" in general. There is a need. Conventionally, technology related to disease prediction systems using intestinal bacteria has been known (Patent Document References 1-5) provide information on methods for determining intestinal dysbiosis, a non-specific and diverse condition. Research into intestinal dysbiosis has not yet progressed sufficiently, making it difficult to identify intestinal dysbiosis. I did. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Patent No. 5645761 [Patent Document 2] Patent Publication No. 2012-165716 [Patent Document 3] Special table number 2005-523695 [Patent Document 4] Patent Publication No. 2015-7985 [Patent Document 5] Special table number 2014-523589 [Non-patent literature]

[0005] [Non-Patent Document 1] Walker AD, Lavley TD. Pharmacological Research 69,(2013) 75-86. Summary of the Invention [Problem to be solved by the invention]

[0006] The present invention aims to provide a unified indicator and standard for the non-specific and diverse condition of intestinal dysbiosis. The present invention aims to provide a method for making it possible to judge the quality of a product based on a set of criteria. [Means for solving the problem]

[0007] As a result of intensive research to solve the above problems, the present inventors have discovered a method for controlling intestinal flora using indigenous intestinal bacteria. The present invention has been completed by discovering a method for easily evaluating the effect of oxidative stress using a unified index and standardized criteria. This led to... That is, the present invention is as follows. (1) A method for determining intestinal dysbiosis, comprising: Diversity-related indicators, short-chain fatty acid production indicators, and intestinal At least one selected from the group consisting of an intestinal immunity-related index, an oral bacteria-related index, and a diarrhea / constipation-related index. setting a criterion value for intestinal dysbiosis for at least one indicator; The bacterial composition data obtained from an individual subject or a group of subjects (users) is compared with the judgment criteria. A step of collating and calculating a judgment score for each of the indicators; A step of calculating an intestinal flora score by adding up the calculated judgment scores, and To A step of determining intestinal dysbiosis of the user using the intestinal flora score as an index. The method comprising:

[0008] (2) Diversity-related indices were diversity, FB ratio, number of bacterial species belonging to the Bacteroidetes phylum, and the most dominant genus. The method according to (1), further comprising at least one item selected from the group consisting of bacterial occupancy rate. (3) The short-chain fatty acid production indicators are bifidobacteria, lactic acid-producing bacteria, butyric acid-producing bacteria, and butyric acid-producing bacteria. The method according to claim 1, further comprising at least one item selected from the group consisting of: number of species of bacteria. . (4) Intestinal immunity-related indicators are Faecalibacterium spp., Akkermansia spp., and Chlamydia spp. A bacterium selected from the group consisting of the genus Stensenella, the genus Alistipes, and the genus Clostridium. The method according to (1), comprising at least one item: (5) Oral bacteria-related indicators: Fusobacterium spp., Streptococcus spp., oral At least one selected from the group consisting of bacterial occupancy rate and Gammaproteobacteria species number. The method according to (1), comprising one item. (6) The method according to (1), wherein the diarrhea / constipation related indicator is enterotype. (7) The reference values ​​are determined by examining the population for setting the reference values ​​for each item included in the index. The method according to any one of (1) to (6), which is set based on a comparison of value distributions. method.

[0009] (8) A system for determining intestinal dysbiosis, comprising: A means for storing bacterial composition data obtained from an individual subject or a group of subjects (users); Diversity-related indices, short-chain fatty acid production indices, and intestinal At least one selected from the group consisting of immune-related indicators, oral bacteria-related indicators, and diarrhea / constipation-related indicators A means for storing a standard value for intestinal dysbiosis for each indicator; The judgment criteria value is compared with the bacterial composition data to determine the judgment score for each of the indicators. A means for calculating the core; A means for calculating an intestinal flora score by adding up the calculated judgment scores; and A means for determining intestinal dysbiosis of the user using the intestinal flora score as an index. The system comprising: (9) Diversity-related indices include diversity, FB ratio, number of bacterial species belonging to the Bacteroidetes phylum, and the most dominant genus. The system according to (8), further comprising at least one item selected from the group consisting of: Hmm. (10) The short-chain fatty acid production indicator is bifidobacteria, lactic acid-producing bacteria, butyric acid-producing bacteria, and butyric acid-producing bacteria. The system according to (8), further comprising at least one item selected from the group consisting of the number of species of live bacteria. Tem.

[0010] (11) Intestinal immunity-related indicators are Faecalibacterium spp., Akkermansia spp., and Chlamydia spp. A bacterium selected from the group consisting of Listensenera, Alistipes and Clostridium. The system according to (8), further comprising at least one item to be (12) Oral bacteria-related indicators are Fusobacterium spp., Streptococcus spp., and oral At least one selected from the group consisting of enterobacteria occupancy rate and gammaproteobacteria species number The system according to (8), further comprising one more item. (13) The system described in (8), wherein the diarrhea / constipation related indicator is enterotype. (14) The judgment criteria are the results of a test of the population for setting judgment criteria for each item included in the indicator. The value is set based on a comparison of the distribution of the test values, as described in any one of (8) to (13). The system is as follows:

[0011] (15) A program for determining intestinal dysbiosis, comprising: Diversity-related indicators, short-chain fatty acid production indicators, and intestinal At least one selected from the group consisting of an intestinal immunity-related index, an oral bacteria-related index, and a diarrhea / constipation-related index. A means for storing a reference value for intestinal dysbiosis for at least one indicator; A means for storing bacterial composition data obtained from an individual subject or a group of subjects (users); The bacterial composition data is compared with the judgment criteria to obtain a judgment score for each of the indicators. A means for calculating the core; A means for calculating an intestinal flora score by adding up the calculated judgment scores; and A means for determining intestinal dysbiosis of the user using the intestinal flora score as an index. The program for causing the device to function as a (16) Diversity-related indices include diversity, FB ratio, number of species belonging to the Bacteroidetes phylum, and most dominant species. The process according to (15), further comprising at least one item selected from the group consisting of the occupancy rate of the genus Program. (17) The short-chain fatty acid production indicator is bifidobacteria, lactic acid-producing bacteria, butyric acid-producing bacteria, and butyric acid-producing bacteria. The process according to (15), further comprising at least one item selected from the group consisting of the number of species of live bacteria. Program. (18) Intestinal immunity-related indicators are Faecalibacterium spp., Akkermansia spp., and Chlamydia spp. A bacterium selected from the group consisting of Listensenera, Alistipes and Clostridium. The program according to (15), further comprising at least one item for determining whether or not a program is to be executed. (19) Oral bacteria-related indicators are Fusobacterium spp., Streptococcus spp., and oral At least one selected from the group consisting of enterobacteria occupancy rate and gammaproteobacteria species number The program according to (15), further comprising one more item. (20) The program according to (15), wherein the diarrhea / constipation related indicator is enterotype. (21) The judgment criteria are the results of a test of the population for setting judgment criteria for each item included in the indicator. The value is set based on a comparison of the distribution of the test values, and is any one of (16) to (20). The program described. Effect of the Invention

[0012] According to the present invention, there is provided a method and a system for determining intestinal dysbiosis. According to the study, it is now possible to determine intestinal dysbiosis non-specifically using various indicators. Ta. The present invention will be described in detail below. [Brief description of the drawings]

[0013] [Figure 1] FIG. 1 is a block diagram of a system of the present invention. [Diagram 2] 3 is a flowchart showing the operation of the system of the present invention. [Diagram 3]FIG. 1 shows the distribution of gut flora scores in healthy and diseased cohorts. [Figure 4] FIG. 1 shows the results of calculating the intestinal flora score. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] 1. Overview The method, system, and program of the present invention are directed to intestinal dysbiosis, which can occur in various forms. The non-specific condition of the intestinal flora is diagnosed by a unified indicator using intestinal flora or a standardized The present inventors have taken into consideration the medical history or medication of each subject and have made it possible to easily evaluate the We found that there were intestinal dysbiosis items that were specifically related to medication history. The flora score, which is the weighted sum of dysbiosis items, is nonspecifically associated with multiple diseases. The present invention was completed based on these findings.

[0015] In the present invention, in order to determine intestinal dysbiosis, the following items are used to score intestinal dysbiosis: The judgment criteria are set for each item. Diversity-related indicators, short-chain fatty acid production indicators, intestinal immunity-related indicators, and oral At least one index selected from the group consisting of a bacteria-related index and a diarrhea / constipation-related index is used as an index, Each indicator is assigned a unique value. The set of criteria for determining the judgment criteria includes: It includes either or both of a population of healthy individuals and a population of diseased individuals.

[0016] Next, the bacterial composition data (test values) of the individual subjects or subject groups who are the target users of the judgment The data is read and judged for the data that corresponds to the intestinal dysbiosis scoring items among the bacterial composition data. The judgement score is calculated by dividing the intestinal dysbiosis score items included in the above index into It means the value (score) assigned by comparing with the judgment reference value. The calculated scores are then added together to calculate the intestinal flora score. For example, the standard value is determined based on the distribution of test values ​​in the population for setting the standard value (a population of healthy subjects and a population of diseased subjects). Based on this intestinal flora score, intestinal dysb The intestinal flora score is calculated based on the number of intestinal flora detected. The "addition" in the calculation of includes the addition of a negative value, i.e., subtraction.

[0017] The intestinal flora score is a score used to determine the level of intestinal dysbiosis a user has. If the user is a group of multiple people, the overall trend of the gut flora score in that group (Intestinal flora score distribution) is extracted, and the position of each subject belonging to the group is determined. For example, the distribution of intestinal flora scores can be calculated based on statistical analysis. Or, plot it as a three-dimensional graph and judge the position on the graph to which the subject belongs. Perform stratified analysis within the value setting population. If there are differences in distribution as a result of stratified comparison, those differences will be The determined area or value can be used as a threshold for determining intestinal dysbiosis.

[0018] 2. How to determine intestinal dysbiosis (1) Setting the judgment criteria and judgment score In the present invention, first, a population for setting judgment reference values ​​(hereinafter also referred to as a "reference value population") is Obtain data on human resident bacteria and questionnaire data. The number of subjects can be two or more. There is no particular limitation on the number of subjects, but the number of subjects should be sufficient to show a statistically significant difference or trend. Preferably, the human resident bacteria is obtained, for example, from a fecal sample taken from a human. However, it can also be collected from the intestinal mucosa during colonoscopy. Bacteria data can be obtained by any known method, for example, a commercially available kit (Myki nso (registered trademark) can be used.

[0019] The questionnaire data consist of responses to questions from each subject in the reference population. The questionnaire included questions about the subjects' medical history and what they had done in the days prior to the collection of the stool sample. This includes questions about what foods the subjects ate and what they ate. The test should be conducted separately at a specified time (e.g., several weeks to several months) after the fecal sample is collected. You can also do it at the same time as other surveys. After that, all or part of the answers are converted into numbers while being weighted appropriately, and stored in a database. Let it be.

[0020] The intestinal dysbiosis scoring items are selected according to the following selection criteria (a) and (b). It is. (a) Bacterial composition data included in the Intestinal Bacteria Database (also referred to as the database) Based on the basic attributes and questionnaire information of the subjects that have been accumulated so far, the bacterial composition Select characteristic genera and indicators from the viewpoint of disturbance of the soil or stability of the balance of bacterial composition. did. (b) The publication contains literature comparing the indigenous bacteria of patients with diseases in which intestinal bacteria are involved with the pathology with those of healthy subjects. Based on the presence of findings consistent with previous studies in the database, intestinal dysb Select genera and indicators associated with iosis.

[0021] The indices that are selected in this way are diversity-related indices, short-chain fatty acid production indices, and intestinal These are immune-related indicators, oral bacteria-related indicators, and diarrhea / constipation-related indicators. The standard values ​​of the above scoring items are determined based on a population for setting the judgment standard values, such as a cohort of healthy subjects (database Among users listed on the website, those with a medical history, complaints of diarrhea or constipation, and age 60 or older The adult population excluding those who fall under the above category) and the affected cohort (those included in the database) Based on a comparison of the distribution of each test value of the adult population of users with a history of chronic illness Set according to the following.

[0022] (i) Diversity-related indicators The diversity-related index is an index that reflects the number of bacterial species and the uniformity of the occupancy rate of each bacterial species. The items included in the target were diversity, FB ratio, number of species belonging to the Bacteroidetes phylum, and the most dominant genus. Examples include: Diversity is a calculated value obtained by multiplying the number of bacterial species in a sample by the uniformity of the occupancy rate of each species. The diversity test value is converted into a predetermined numerical range based on the Shannon index. The diversity judgment score is, for example, 0 to 10, preferably 3 to 8. The diversity judgment score is the test value (converted value) in the range of -10 to 10, for example -10 to 10. Table 1 (Example) below is a list of the criteria and scores for each evaluation item. For example, for diversity, a judgment score is assigned in the range of -10 to 10 for test values ​​of 3 to 8. For other items, the test values, judgment criteria, and judgment scores are calculated in the same manner as for diversity. Set it up.

[0023] The FB ratio is the ratio of the major phyla of human intestinal bacteria, Firmicutes and Bacteroidetes. and includes both the Firmicutes / Bacteroidetes and Bacteroidetes / Firmicutes phyla. For example, the ratio of Firmicutes to Bacteroidetes is used. The FB ratio test value ranges from 0 to 0. The maximum numerical range is set (converted) to, for example, 0 to infinity. The judgment score is the test value (converted) of the FB ratio. value) in the range of -10 to 10, for example -10 to 3.

[0024] The number of bacterial species belonging to the phylum Bacteroidetes is set in the range of 0 to 100, for example, 0 to 20. The fixed score is a range of -10 to 10 for the test value (converted value) of the number of bacterial species belonging to the Bacteroidetes phylum. , for example, in the range of -5 to 3. The occupancy rate of the most dominant genus is the occupancy rate value of the bacterial species with the highest occupancy rate in a sample. The occupancy rate of the most dominant genus is set to 1 to 5 in the range of 0 to 1, for example, 2 as the standard value. For example, if two standard values ​​of occupancy rate, 0.35 and 0.4, are set, the judgment score will be 0. If it is 35 or more, the score is -1 to -5 (for example, -3), if it is 0.4 or more, the score is -2 to -10. (e.g., -5). Note that the occupancy rate of the most dominant genus is negatively affected (e.g., For example, a decrease in diversity, especially a decrease in the uniformity of the occupancy rate of each bacterium, can cause the test value to increase. The lower the value, the more negative the judgment score.

[0025] (ii) Short-chain fatty acid production index The short-chain fatty acid production indicator is an intestinal bacterium that is recognized to have the ability to produce short-chain fatty acids. The items that belong to this index are bifidobacteria, lactic acid-producing bacteria, and butyric acid-producing bacteria. and butyric acid-producing bacteria. Bifidobacteria represents the percentage of bifidobacteria in feces. Bifidobacteria ranges from 0 to 1. Set the numerical range, for example, 0 to 1. The judgment score is based on the test value (converted value) of bifidobacteria. and assign it in the range of -10 to 10, for example, -3 to 7.

[0026] The lactic acid-producing bacteria in feces were Lactobacillus, Pediococcus, Leucococcus, and This shows the percentage of bacteria selected from the genus Nostoc and the genus Lactococcus. The group is set to a numerical range of 0 to 1, for example, 0 to 1. The judgment score is the test value of the lactic acid-producing bacteria group ( The range of the lactic acid producing bacteria is set to -10 to 10, for example, -10 to 3. The group has a negative effect in the intestine (e.g., shows a positive correlation with diarrhea symptoms), so the test values The larger the value, the more negative the judgment score.

[0027] The butyric acid-producing bacteria were Butyricimonas spp., Coprococcus spp., and Rosebry spp. in feces. A plurality of bacteria selected from the genus Bacillus subtilis, the genus Butyricoccus, and the genus Faecalis bacterium. The occupancy rate of the butyric acid producing bacteria is set to a value in the range of 0 to 1, for example, 0 to 1. The judgment score is Divide the test value (converted value) of the butyric acid-producing bacteria group by a value in the range of -10 to 10, for example, -5 to 10. Hit. The number of species of butyric acid-producing bacteria means the number of species belonging to the above-mentioned group of butyric acid-producing bacteria. The number of species belonging to the group of butyric acid-producing bacteria is set in a numerical range of 0 to 5, for example 0 to 5. The score is calculated based on the test value (converted value) of the number of butyric acid-producing bacteria in the range of -10 to 10, for example - Assign in the range of 5-5.

[0028] (iii) Gut immunity-related indicators Intestinal immunity-related indicators are intestinal substances that are known to produce substances that modify intestinal immunity. The bacteria in this group are classified as Faecalis bacterium, Acanthopanax spp. -mansia, Christensenella, Alistipes and Clostridium Examples include: Faecalibacterium is a type of bacteria belonging to the genus Faecalibacterium present in feces. The genus Faecalis is set to a value range of 0 to 1, for example, 0 to 1. The judgement score is calculated on a scale of -10 to 10 for the test value (converted value) of Faecalibacterium spp. Assign a range, for example -5 to 5.

[0029] Akkermansia represents the proportion of Akkermansia bacteria in feces. The genus Akkermansia is set to a numerical range of 0 to 1, for example, 0 to 1. The test value (converted value) of Kermansia genus is divided into a range of -10 to 10, for example, a range of 0 to 3. Assign. Christensenella represents the proportion of bacteria belonging to the genus Christensenella in feces. The genus Christensenella is set to a numerical range of 0 to 1, for example, 0 to 1. The judgment score value is For the test value (converted value) of Christensenella spp., the range is -10 to 10, for example, 0 to 3. assign.

[0030] Alistipes bacteria indicates the occupancy rate of bacteria belonging to the genus Alistipes per feces. The genus Ristipes is set to a numerical range of 0 to 1, for example, 0 to 1. The test value (converted value) of Yersinia spp. is assigned in the range of -10 to 10, for example, 0 to 3. .

[0031] Clostridium indicates the percentage of Clostridium bacteria in feces. The genus Clostridium is set to a numerical range of 0 to 1, for example, 0 to 1. The test value (converted value) of Rostridium spp. is divided into a range of -10 to 10, for example, a range of -5 to 0. In addition, Clostridium bacteria have multiple types of substances that act on the intestinal immune system in the intestine. There are many different types of cytokines (for example, cytokines that promote inflammation and cytokines that suppress inflammation). Quality, etc.), negative judgment scores are set for both small and large test values.

[0032] (iv) Oral bacteria-related indicators Oral bacteria-related indicators are the intestinal bacteria groups that are recognized to be abundant in the oral cavity. The items belonging to this index are Fusobacterium spp., oral bacteria occupancy rate and gastrointestinal Examples include a number of species of the class Amphiproteobacteria. Fusobacterium indicates the percentage of bacteria belonging to the genus Fusobacterium in feces. The Fusobacterium genus is converted into a numerical range of 0 to 1, for example, 0 to 1. The judgment score is The range of -10 to 10 for the test value (converted value) of Fusobacterium spp., for example, the range of -10 to 0 In addition, Fusobacterium has a negative effect in the intestine (e.g., in patients with colon cancer). The higher the test value, the more negative the score. become.

[0033] Streptococcus genus: The percentage of bacteria belonging to the genus Streptococcus in feces The genus Streptococcus is set to a numerical range of 0 to 1, for example, 0 to 1. A is in the range of -10 to 10 for the test value (converted value) of Streptococcus genus, for example, -5 to 0 In addition, Streptococcus spp. has a negative effect in the intestine (e.g., ulcerative colitis). The higher the test value, the more negative the result. This is the judgement score.

[0034] The oral bacterial occupancy rate was Streptococcus, Fusobacterium, and Troublesome. The percentage of bacteria selected from the group consisting of the genus Gastrointestinalis, Gastrointestinal tract bacteria, and Klebsiella. The bacterial occupancy rate is set to a value ranging from 1 to 5 in the range of 0 to 1, for example, a value of 1 as the reference value. For example, if the standard value of the occupancy rate is set to 0.2 (one number), the score is 0.2 or more. In addition, oral bacteria have a negative effect on the intestines (e.g., Crohn's disease). The higher the test value, the more negative the judgment score. It becomes the core.

[0035] The number of Gammaproteobacteria species per feces The number of species belonging to the Gammaproteobacteria class is expressed as a number ranging from 0 to 100, e.g. For example, convert it to a value from 0 to 10. The judgment score is the test value of Gammaproteobacteria (converted value ) is assigned in the range of -10 to 10, for example, in the range of -7 to 0. The number of bacteria from the class Teriaria has a negative effect on the intestine (e.g., it is abundant in the intestines of patients with irritable bowel syndrome). etc.), the higher the test value, the more negative the judgment score.

[0036] (v) Diarrhea / constipation-related indicators The diarrhea / constipation-related index is a type of bacterial composition (enzyme) that shows a strong correlation with diarrhea and constipation symptoms. The items that belong to this index are diarrhea-predominant enterotype, constipation-predominant enterotype, and Enterotype and enterotype R.

[0037] Enterotype R represents a bacterial composition dominated by Ruminococcus spp. The score is calculated based on the value of the enterotype R. (conversion value), the range is assigned from -10 to 10, for example, from -5 to 5. The R type is a type of bacterial composition that shows a strong association with diarrhea and constipation symptoms and has a negative effect (e.g. For example, if the test result is negative, the more negative the score, the greater the negative effect. It becomes.

[0038] Diarrhea-type enterotypes represent bacterial composition types that show a strong association with diarrheal symptoms. The telotype is converted into a numerical range of 0 to 1, for example, 0 to 1. The judgment score is The type's inspection value (conversion value) is assigned in the range of -10 to 10, for example, -5 to 5. Constipation-type enterotypes represent bacterial composition types that show a strong association with constipation symptoms. The telotype is converted into a numerical range of 0 to 1, for example, 0 to 1. The judgment score is The type's inspection value (conversion value) is assigned in the range of -10 to 10, for example, -5 to 5.

[0039] (2) Calculation and assessment of intestinal flora score In this section, we will use the diversity-related indicators, short-chain fatty acid production indicators, intestinal immunity-related indicators, oral bacteria-related indicators, and diarrhea / constipation-related indicators At least one index is appropriately selected from the group consisting of the following: In the present invention, all of the items included in the related index are selected as appropriate. It is preferable to adopt a scoring item (18 items). Each test value is then compared to the criteria to determine a score for the item (i.e., the judgment score). ) is calculated using a method such as weighted addition.

[0040] After the calculation, the scores are added together to calculate the intestinal flora score. The Roller Score provides basic information for assessing intestinal dysbiosis. The gut flora score threshold for the evaluation of the gut flora was set based on the distribution of scores in healthy and diseased subjects. The threshold value of the intestinal flora score can be set appropriately within the range of 50 to 99. If the score was less than 50, the subject had intestinal dysbiosis or was at risk for intestinal dysbiosis. It is determined that.

[0041] In the present invention, a statistical analysis is performed on a predetermined number of subjects (primary population sample). Analyze and process the data to examine the correlation between the intestinal dysbiosis assessment items and user data. The results are stored in a database (DB). Therefore, the test results of each individual subject (one person) When making a judgment, the data from the above multiple subjects is used as a population sample, and the test data for the individual subject are Where is the subject's data located in the data of the population sample stored in the database? By examining whether the test applies to each individual, intestinal dysbiosis is determined. The data of the individual subjects can be incorporated into the values ​​of the population sample and subjected to statistical analysis again. After processing, it may be possible to determine where the individual subject is located in the population sample.

[0042] 3. Information processing device and program Next, an information processing device and a program according to an embodiment of the present invention will be described with reference to the drawings. The following is an explanation. FIG. 1 shows an overview of an intestinal dysbiosis determination system 1 including an information processing device 10 according to this embodiment. It is a schematic diagram. In the following, a group of subjects or an individual subject will be described as a "user." .

[0043] The information processing device 10 includes a CPU, a ROM, a RAM, and an input / output interface. The information processing device 10 is a server-type computer that is connected to the Internet or a LAN. Through which network 20, a plurality of user devices 30a to 30n (collectively referred to as “user devices”) The communication device 30 is connected to the communication device 30 so as to be capable of communicating with the communication device 30.

[0044] The information processing device 10 is configured to select a user who is the subject of a survey or is of interest (referred to as a “target user”). The intestinal dysbiosis scoring items of the subjects were compared with the intestinal dysbiosis scoring items of healthy subjects stored in the database. The information processing device 10 then performs a comparison and calculates a judgment score based on the comparison result. The resulting scores are added together to calculate the intestinal flora score. Based on the score, it is determined whether the target user has intestinal dysbiosis. The device 10 transmits the result of the determination of the user's intestinal dysbiosis to the user device 30. .

[0045] The user device 30 is a computer or a smart device equipped with an information input means and a display means. The device is a smartphone or tablet, and the device is connected to an information processing device via a network 20. The user device 30 is connected to the server 10 so as to be able to communicate with the server 10. The user device 30 is a browser or an application. Through the above, various information received from the information processing device 10 is displayed on the display, and information processing is It provides an interface for inputting information to be sent to the management device 10.

[0046] The information processing system 1 includes a device for testing multiple types of human intestinal bacteria collected from the feces of a user. The information processing device 10 may include an inspection agency 40 that provides the information. Information about the user's human intestinal bacteria associated with the user's identification information (human intestinal bacteria data) The information processing device 10 acquires the data from the inspection agency 40 via the network 20. The system is designed to directly obtain human intestinal bacteria data from laboratories 40 without going through the network 20. Also, human intestinal bacteria data may be sent from the testing institution 40 to the user device 30. In this case, the information processing device 10 is configured to acquire human intestinal bacteria data from the user device 30. Furthermore, the inspection organization 40 and the information processing device 10 may belong to the same organization. There may be one or more organizations, or they may belong to different organizations.

[0047] The human intestinal bacteria data includes diversity-related indicators, short-chain fatty acid production indicators, intestinal immunity-related indicators, and oral At least one index selected from the group consisting of an intraluminal bacteria-related index and an diarrhea / constipation-related index. The details of these indicators are as described above.

[0048] The information processing device 10 includes a program stored in a ROM or placed in a RAM, a CPU, and The functional units realized by the cooperation of the above include an information acquisition unit 101 and a scoring item extraction unit 102. , a judgment reference value setting unit 103, a comparison unit 104, an intestinal flora score calculation unit 105, and a judgment The information processing device 10 also includes a storage unit 106 provided in the ROM (or RAM). The storage unit 110 includes an intestinal bacteria database (DB) 111, a scoring item information database (SDB) 112, and a storage unit 113. The database includes a database (DB) 112 and a criteria database (DB) 113.

[0049] The information acquisition unit 101 receives the user device 30 and / or the inspection agency 4 via the network 20. 0 and stores various information in the storage unit 110. The information received from the contact 40 includes the user's intestinal bacteria data, questions for the user (questionnaires), etc. Information about responses to the questionnaire (survey data), and user identification information (user name, Date of birth, address, telephone number, email address used by the user, or the user's User identification information includes the user device 3 used by the user. The identifier 0 may be included.

[0050] When the information acquisition unit 101 receives the intestinal bacteria data of the user, it associates the data with the user identification information. The intestinal bacteria information DB 111 stores the information in this manner. The intestinal bacteria data collected from multiple users is stored in the intestinal bacteria information DB11. The information acquisition unit 101 includes user identification data and questionnaire information data. When the questionnaire data of the user is received, the questionnaire data is stored in the scoring item DB 112 in association with the user identification information. The evaluation item DB 112 stores the questionnaire data collected from the users in this manner. The judgment criteria DB 113 stores the judgment criteria value set by the judgment criteria value setting unit 104, which will be described later. The information obtained by the statistical analysis process to extract features from the data is stored. It depends on the members of the user population sample that are the subject of the analysis process and the number of members. Therefore, they are stored in association with information that identifies them.

[0051] The questions (survey) provided to the user include the user's name, age, height, weight, and BMI. value, family structure, type of work, living environment, exercise frequency, sleep satisfaction, eating habits, constitution, medical history, Even if information on the health condition at the time of collection, medication history at the time of collection, and mental state at the time of collection is included, good. The questionnaire data is generated by the information processing device 10 sending a question (questionnaire) to the user device 30. and obtains information regarding the answer to the question from the user device 30. The acquisition unit 101 may receive the questionnaire data, or the inspection institution 40 may handle the questionnaire data. In this case, the information acquisition unit 101 acquires questionnaire data from the inspection agency 40. Good too.

[0052] FIG. 2 is a flowchart showing a process performed by the information processing device 10 according to the present embodiment. In step S1, the information acquisition unit 101 of the information processing device 10 receives information on human intestinal cells from a user. Bacteria data and questionnaire data are acquired and stored in the intestinal bacteria information DB 111 . In step S2, the scoring item extraction unit 102 extracts the intestinal bacteria information stored in the intestinal bacteria information DB 111. From the information obtained, the following were identified: diversity-related index, short-chain fatty acid production index, intestinal immunity-related index, oral bacterial-related index At least one index selected from the group consisting of a diarrhea / constipation-related index, or the index The marking items included in the step S2 are extracted and stored in the marking item information DB 112. In the step S200, the judgment reference value setting unit 103 determines, from the information stored in the scoring item information DB 112, A judgment criterion value and a judgment score are set for each scoring item and stored in the judgment criterion DB.

[0053] In step S3, the comparison unit 104 compares the intestinal bacteria information DB 111 and the score item information D From B112, the population for setting the judgment reference value (healthy or diseased population) and the intestinal cells of the subjects The test values ​​for each indicator related to bacteria and the reference values ​​for the indicators were extracted, and the results were compared between the healthy control group and the subjects. The standard values ​​and test values ​​are compared and collated between the two.

[0054] In step S4, the intestinal flora score calculation unit 105 calculates the intestinal flora score assigned to the target user. The judgement scores are added together (including subtraction if the score is negative) to calculate the intestinal flora score. . In step S5, the determination unit 106 determines intestinal dysbiosis in the target user. The judgment by the judgment unit 106 is performed by changing the judgment reference value and the judgment score within a predetermined range (s Step S2) to extract the features of each of the multiple indices (steps S2 to S5 are repeated). ).

[0055] Here, the target user is the user used to extract the features by the scoring item extraction unit 102. It may be a person included in the population sample, or a new user (one) not included in the user population sample. In step S5, the determination unit 106 determines whether the target user is Depending on the result of the judgment as to whether the user has intestinal dysbiosis or is at risk, The result is generated and transmitted to the user device 30 of the target user.

[0056] The present invention will be described in more detail below with reference to examples. However, the present invention is not limited to these examples. Not limited to this. EXAMPLES

[0057] (1) Selection of intestinal dysbiosis scoring items <Selection criteria 1> Cykinso's doctors and researchers are using the bacterial composition data included in the intestinal bacteria database. The data and the basic attributes and questionnaire information of each of the subjects were reviewed to determine the disruption of the bacterial composition, From the perspective of balance stability, characteristic genera and indicators were selected. <Selection criteria 2> We checked whether there were any findings that matched previous studies included in overseas Disbiome databases. We selected genera and indicators associated with intestinal dysbiosis based on the criteria of whether they were related to intestinal dysbiosis or not.

[0058] The selected scoring items are as follows: 1. Diversity 2. FB ratio 3. Bifidobacteria 4. Lactic acid producing bacteria group 5. Butyric acid producing bacteria 6. Enterotype 7. Number of species in the phylum Bacteroidetes 8. Number of Gammaproteobacteria species 9. Faecalibacterium spp. 10. Akkermansia 11. Christensenella spp. 12. Alistipes spp. 13. Clostridium 14. Fusobacterium 15. Streptococcus spp. 16. Oral bacteria (Streptococcus, Fusobacterium, Trabulsiella, Klebsiella) occupancy rate 17. Occupancy rate of most dominant genus 18. Number of butyric acid-producing bacteria

[0059] Specific examples of the judgment criteria are shown in Table 1. [Table 1]

[0060] <Example of setting judgment criteria> In the case of bifidobacteria, the median value for healthy individuals is 5.75, so the following criteria and score are used: is set. If the test value is between 0 and less than 0.03, 3 points will be deducted. If the test value is between 0.03 and 0.06, add 3 points. If the test value is between 0.06 and 0.1, add 5 points. If the test value is 0.1 or more: 7 points added

[0061] (2) Calculation of Flora Score The criteria and scores for the intestinal dysbiosis scoring items were compared between healthy and diseased cohorts. The range was set based on a comparison of the distribution of test values. The healthy cohort is comprised of users who answered the questionnaire among those included in the database. The adult population was excluded if the following apply to the respondents: "Has a medical history," "Has complaints of diarrhea or constipation," "Age 60 or older"

[0062] (3) Flora score calculation algorithm In Step 1, the test values ​​for each user's bifidobacteria, butyric acid-producing bacteria, and lactic acid-producing bacteria were calculated. (i) Bifidobacteria = 0.013, (ii) Butyric acid-producing bacteria = 0.0643, (iii) Lactic acid-producing bacteria = 0.0001 In Step 2, the standard values ​​of bifidobacteria, butyric acid-producing bacteria, and lactic acid-producing bacteria in Table 1 are compared, and A score was calculated for each item. In this case, the more points subtracted, the more likely the patient is to have intestinal dysbiosis. (i) Bifidobacteria = -3, (ii) Butyric acid producing bacteria = 3, (iii) Lactic acid producing bacteria = -3 In Step 3, the intestinal flora is evaluated by weighting the scores of multiple scoring items. The core was calculated by adding up the scores for each item, with the base score being 60. Gut flora score = 58.5

[0063] (4) Results and Discussion The results are shown in Figure 3. A gut flora score of less than 50 points indicates a non-specific intestinal disorder common to multiple diseases. We found that this strongly reflects intracellular dysbiosis. The inventors found that approximately half of the intestinal dysbiosis items related to individual medical history and medication history were associated with multiple diseases. These results suggest that these bacteria and bacterial groups respond non-specifically to diseases. Therefore, many of the associations found in the selected gut dysbiosis items are not disease-specific. Instead, they are more likely to be biomarkers of non-specific, common responses to health and disease. stomach. EXAMPLES

[0064] In this example, in order to confirm disease-specific / non-specific characteristics for each item, Analyses were performed using generalized linear models and logistic regression analysis.

[0065] The results are shown in Figure 4. The first row of categories in Figure 4 shows the disease-specific / non-specific intestinal dysbiosis in the diversity-related index. Heatmap showing the intensity of sbiosis. In each panel, the areas showing a positive association with the disease The areas showing a negative association with the disease are shown in red, and the areas showing a negative association with the disease are shown in blue, with the intensity of the color indicating the strength of the association. In the cases of hypertension and ulcerative colitis, it can be seen that diversity overall is low.

[0066] The second row of the category in Figure 4 shows disease-specific / non-specific status in indicators related to short-chain fatty acid production. Heatmap showing the intensity of differential intestinal dysbiosis. In the case of diabetes (Figure 5), it can be seen that there are more lactic acid-producing bacteria and fewer butyric acid-producing bacteria.

[0067] The third row of the category in Figure 4 shows disease-specific / non-specific indices related to gut immunity. This is a heat map showing the intensity of intestinal dysbiosis. The genus Christensenella was found to be low in both diabetes and dyslipidemia.

[0068] The fourth row of the category in Figure 4 shows disease-specific / non-specific indicators related to oral bacteria. This is a heat map showing the intensity of intestinal dysbiosis. In cases of dyslipidemia, both Fusobacterium and Streptococcus are prevalent. I understand.

[0069] The fifth row of the category in Figure 4 shows disease-specific / non-specific indicators related to diarrhea and constipation. This is a heat map showing the intensity of intestinal dysbiosis. It was found that enterotype R was rare in three diseases: hypertension, dyslipidemia, and diabetes. [Explanation of symbols]

[0070] 1: System of the present invention, 10: Information processing device, 20: Network, 30: User device, 40: Inspection agency, 101: information acquisition unit, 102: scoring item extraction unit, 103: judgment criterion value setting unit, 104: comparison Comparison section, 105: intestinal flora score calculation section, 106: judgment section 110: memory unit, 111: intestinal bacteria information DB, 112: scoring item information DB, 113: judgment Standard DB

Claims

1. A method for calculating an intestinal flora score, comprising: A step of setting a judgment reference value for intestinal dysbiosis and assigning a judgment score for each of the scoring items included in the diversity-related index, the short-chain fatty acid production index, the intestinal immunity-related index, and the oral bacteria-related index regarding the intestinal bacteria of the judgment reference value setting population; A step of comparing the test values ​​of the scoring items obtained from an individual subject or a group of subjects (users) with the judgment reference values ​​and calculating a judgment score corresponding to the compared judgment reference value; A step of calculating an intestinal flora score by adding up the calculated judgment scores; The method comprising: The diversity-related index is an index reflecting the number of bacterial species and the evenness of the occupancy rate of each bacteria, and includes at least one item selected from the group consisting of diversity, FB ratio, the number of bacterial species belonging to the Bacteroidetes phylum, and the occupancy rate of the most dominant genus; The short-chain fatty acid production index includes at least one item selected from the group consisting of bifidobacteria, lactic acid-producing bacteria, butyric acid-producing bacteria, and the number of species of butyric acid-producing bacteria, which are intestinal bacteria recognized to have short-chain fatty acid production ability, The intestinal immunity-related index includes at least one item selected from the group consisting of intestinal bacteria recognized to produce a substance that modifies intestinal immunity, the group consisting of Faecalibacterium, Akkermansia, Christensenella, Alistipes, and Clostridium; The oral bacteria-related indicator includes at least one item selected from the group consisting of enterobacteria that are recognized to be abundant in the oral cavity, the genus Fusobacterium, the genus Streptococcus, the oral bacteria occupancy rate, and the number of species of Gammaproteobacteria. The method.

2. The method according to claim 1 , further comprising a step of displaying the calculated intestinal flora score.

3. The method of claim 1 , further comprising a step of storing the calculated intestinal flora score.

4. A system for calculating an intestinal flora score, comprising: A means for setting a judgment reference value for intestinal dysbiosis and assigning a judgment score for each of the scoring items included in the diversity-related index, the short-chain fatty acid production index, the intestinal immunity-related index, and the oral bacteria-related index regarding the intestinal bacteria of the judgment reference value setting population; A means for comparing the test values ​​of the scoring items obtained from an individual subject or a group of subjects (users) with the judgment reference values ​​and calculating a judgment score corresponding to the compared judgment reference value; and A means for calculating an intestinal flora score by adding up the calculated judgment scores; The system comprising: The diversity-related index is an index reflecting the number of bacterial species and the evenness of the occupancy rate of each bacteria, and includes at least one item selected from the group consisting of diversity, FB ratio, the number of bacterial species belonging to the Bacteroidetes phylum, and the occupancy rate of the most dominant genus; The short-chain fatty acid production index includes at least one item selected from the group consisting of bifidobacteria, lactic acid-producing bacteria, butyric acid-producing bacteria, and the number of species of butyric acid-producing bacteria, which are intestinal bacteria recognized to have short-chain fatty acid production ability, The intestinal immunity-related index includes at least one item selected from the group consisting of intestinal bacteria recognized to produce a substance that modifies intestinal immunity, the group consisting of Faecalibacterium, Akkermansia, Christensenella, Alistipes, and Clostridium; The oral bacteria-related indicator includes at least one item selected from the group consisting of enterobacteria that are recognized to be abundant in the oral cavity, the genus Fusobacterium, the genus Streptococcus, the oral bacteria occupancy rate, and the number of species of Gammaproteobacteria. The system.

5. The system according to claim 4, further comprising a means for displaying the calculated intestinal flora score.

6. The system according to claim 4, further comprising a means for storing the calculation result of the intestinal flora score.

7. A program for calculating an intestinal flora score, comprising: A means for setting a judgment reference value for intestinal dysbiosis and assigning a judgment score for each of the scoring items included in the diversity-related index, the short-chain fatty acid production index, the intestinal immunity-related index, and the oral bacteria-related index regarding the intestinal bacteria of the judgment reference value setting population; A means for comparing the test values ​​of the scoring items obtained from an individual subject or a group of subjects (users) with the judgment reference values ​​and calculating a judgment score corresponding to the compared judgment reference value; and A means for calculating an intestinal flora score by adding up the calculated judgment scores; The program for causing the program to function as The diversity-related index is an index reflecting the number of bacterial species and the evenness of the occupancy rate of each bacteria, and includes at least one item selected from the group consisting of diversity, FB ratio, the number of bacterial species belonging to the Bacteroidetes phylum, and the occupancy rate of the most dominant genus; The short-chain fatty acid production index includes at least one item selected from the group consisting of bifidobacteria, lactic acid-producing bacteria, butyric acid-producing bacteria, and the number of species of butyric acid-producing bacteria, which are intestinal bacteria recognized to have short-chain fatty acid production ability, The intestinal immunity-related index includes at least one item selected from the group consisting of intestinal bacteria recognized to produce a substance that modifies intestinal immunity, the group consisting of Faecalibacterium, Akkermansia, Christensenella, Alistipes, and Clostridium; The oral bacteria-related indicator includes at least one item selected from the group consisting of enterobacteria that are recognized to be abundant in the oral cavity, the genus Fusobacterium, the genus Streptococcus, the oral bacteria occupancy rate, and the number of species of Gammaproteobacteria. The said program.

8. The program according to claim 7, further comprising a means for displaying the calculation result of the intestinal flora score.

9. The program according to claim 7, further comprising a means for storing the calculation result of the intestinal flora score.

10. An information processing system including an information acquisition unit, a scoring item extraction unit, a judgment reference value setting unit, a comparison unit, an intestinal flora score calculation unit and a judgment unit, and a memory unit, The storage unit includes an intestinal bacteria information database (DB) that stores the intestinal bacteria data of the user in association with the user identification information from the intestinal bacteria data of the individual subject or group of subjects (user) and the user identification information received by the information acquisition unit; a scoring item information DB that stores the user questionnaire data received by the information acquisition unit in association with user identification information, and that stores each of the scoring items included in the diversity-related index, the short-chain fatty acid production index, the intestinal immunity-related index, and the oral bacteria-related index extracted by a scoring item extraction unit from the information stored in the intestinal bacteria information DB; a judgment criterion DB that stores judgment criterion values ​​and judgment scores for each of the scoring items set by a judgment criterion value setting unit from the information stored in the scoring item information DB, The comparison unit compares and collates the test value of the user with the reference value, The intestinal flora score calculation unit calculates a judgment score of the user assigned by the comparison and matching, The determination unit transmits the calculated Flora score to a user terminal. The information processing system.

11. The information processing system according to claim 10, wherein the calculation result of the intestinal flora score is displayed on a user terminal.

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