Method for evaluating amount of activity of autonomic nerve

Abstract

Provided is a method for determining the amount of activity of an autonomic nerve on the basis of skin gas in view of the relation between skin gas and the amount of activity of the autonomic nerve. Provided is a method for identifying autonomic nerve-related skin gases related to the amount of activity of an autonomic nerve and evaluating the amount of activity of the autonomic nerve on the basis of the amount of at least one of the autonomic nerve-related skin gases. Also provided are a device for evaluating the amount of activity of an autonomic nerve and a system for evaluating the amount of activity of an autonomic nerve.

Description

How to assess autonomic nervous activity

[0001] The present invention relates to a method for evaluating the activity of autonomic nerves based on the amount of autonomic nerve-related skin gas.

[0002] Volatile substances emitted from the human body surface are called skin gases, also known as skin volatile emissions. Skin gases contribute to body odor. However, sampling and quantifying skin gases have been difficult. However, recent advances in analytical technology have led to attempts to qualitatively analyze skin gas components. As a result, it has been discovered that skin gases contain over 600 compounds. Skin gases are composed of compounds such as aldehydes, acids, ketones, alcohols, hydrocarbons, and esters, with acetic acid, octanoic acid, nonanoic acid, geranylacetone, 6-methylhepten-2-one, nonanal, and decanal being known as major compounds. Skin gases can be classified by their emission pathway, broadly divided into those derived from surface reactions, skin glands (sweat glands, sebaceous glands), and blood. Surface-derived skin gas refers to skin gas that is produced when components secreted from skin glands are converted into volatile compounds and then dissipated on the skin surface by the action of skin resident bacteria, oxygen, ultraviolet rays, and the like. Skin gland-derived skin gas is skin gas emitted from sweat glands and sebaceous glands, and is known to increase due to sweating and sebaceous gland secretion. Blood-derived skin gas is a pathway in which components in the blood produced by metabolism and in vivo reactions volatilize and dissipate directly from the skin, and volatile components carried by blood are mainly dissipated via this pathway. Furthermore, since sweat is composed of plasma, volatile components in blood can also be dissipated from skin glands. Thus, skin gas can be classified into exogenous components based on skin surface reactions and endogenous components originating from the interior of the body. Endogenous components are caused by congenital genetics and chronological aging, and can be used as indicators of these, while exogenous components are caused by environmental and lifestyle factors, including ultraviolet light exposure, and can be used as indicators of these. By examining skin gases, it is expected that health monitoring and medical applications will be possible.Specifically, methods that have been developed include a method for estimating diabetes index values ​​using acetone (Patent Document 1: JP 2020-016448 A), a method for evaluating atopic dermatitis using the amount of acetone (Patent Document 2: JP 2019-219256 A), a method for determining fatigue levels based on the amount of nitrogen gas (Patent Document 3: JP 2019-78585 A), a method for predicting blood glucose levels based on skin gases (Patent Document 4: JP 2017-151063 A), a method for evaluating cancer based on skin gas patterns (Patent Document 5: JP 2021-148517 A), and a method for diagnosing Parkinson's disease based on components selected from medium- to long-chain acylcarnitines and secondary bile acids (Patent Document 6: JP 2017-138141 A).

[0003] Endogenous skin gases are further classified into components derived from metabolism in the body, components derived from ingested substances, and components derived from intestinal bacteria. Metabolic components include ammonia, amines, and acetone. Ingested components include ethanol and acetaldehyde resulting from alcohol consumption, cuminaldehyde resulting from eating curry, diallyl disulfide and allyl methyl sulfide resulting from eating garlic, and nicotine, methylfuran, and 2,5-methylfuran resulting from smoking. Intestinal bacteria-derived components include hydrogen, methane, ethane, and ethylene (Non-Patent Document 1: Journal of the Society on Odor and Fragrance Environment, Vol. 48, No. 6, pp. 410-417).

[0004] JP 2020-016448 A JP 2019-219256 A JP 2019-78585 A JP 2017-151063 A JP 2021-148517 A JP 2017-138141 A

[0005] Journal of Odor and Fragrance Environment, Vol. 48, No. 6, pp. 410-417

[0006] The object is to provide a method capable of determining the amount of autonomic nervous activity based on objective indicators.

[0007] The present inventors focused on the relationship between intestinal barrier function and autonomic nervous activity and conducted extensive research into an indicator that can simply determine intestinal barrier function and be used as an objective indicator for determining autonomic nervous activity. Surprisingly, they discovered that certain skin gases are associated with intestinal barrier function. Based on this finding and the relationship between intestinal barrier function and autonomic nervous activity, the present invention was completed. Specifically, the present invention provides a method for determining autonomic nervous activity based on the amount of skin gas associated with autonomic nervous activity. More specifically, the present invention relates to the following: [1] A method for assessing autonomic nervous activity, comprising: analyzing collected skin gases to detect an autonomic nervous-related skin gas; and evaluating autonomic nervous activity from the amount of at least one of the detected autonomic nervous-related skin gases using a predetermined correspondence relationship between the amount of the autonomic nervous-related skin gas and the autonomic nervous activity. [2] The method described in Item 1, wherein the autonomic nervous-related skin gas is selected from the group consisting of decane, ethylbenzene and / or xylene, nonanal, and decanal. [3] The method of Item 2, wherein the autonomic nerve-related skin gas serves as an index of intestinal barrier function. [4] The method of Item 1, wherein the correspondence relationship is a correspondence table showing the relationship between the range of the amount of the autonomic nerve-related skin gas and the amount of autonomic nerve activity, or the relationship between the threshold amount of the autonomic nerve-related skin gas and the amount of autonomic nerve activity. [5] An apparatus for evaluating autonomic nerve activity, comprising: an input unit to which analysis result data from a skin gas analyzer is input; a memory unit to store the correspondence relationship between at least one amount of autonomic nerve-related skin gas and the amount of autonomic nerve activity; a processing unit to determine the amount of autonomic nerve activity from the input analysis result data and the correspondence relationship stored in the memory unit; and an output unit to output the determined amount of autonomic nerve activity. [6] The apparatus for evaluating autonomic nerve activity according to Item 5, wherein the type of the autonomic nerve-related skin gas is selected from the group consisting of decane, ethylbenzene and / or xylene, nonanal, and decanal.[7] The device for evaluating an amount of autonomic nervous activity according to item 5, wherein the device provides a lifestyle improvement plan corresponding to the amount of autonomic nervous activity of the subject based on the determined amount of autonomic nervous activity, wherein: the memory unit further stores a correspondence relationship between the amount of autonomic nervous activity of the subject and lifestyle improvements corresponding to the amount of autonomic nervous activity; the processing unit determines the lifestyle improvement plan corresponding to the amount of autonomic nervous activity of the subject from the determined amount of autonomic nervous activity of the subject and the correspondence relationship stored in the memory unit; and the output unit outputs the determined lifestyle improvement plan. [8] The device for evaluating an amount of autonomic nervous activity according to item 7, wherein the lifestyle improvement plan is at least one selected from the group consisting of recommendations for stress reduction, consultation with a specialist, provision of supplements, recommended food (nutrient) intake, recommended exercise, sleep habits, quitting smoking, and drinking in moderation. [9] A system including the autonomic nervous activity evaluation device according to any one of items 5 to 8, wherein the autonomic nervous activity evaluation device is connected to a network, wherein the input unit receives data of analysis results from a skin gas analyzer via the network, and the output unit outputs the determined autonomic nervous activity or lifestyle improvement suggestions via the network.

[10] The system according to item 9, further including a network-connected skin gas analyzer, wherein the skin gas analyzer includes: a skin gas sampling unit; a skin gas analysis unit; and a network-connected output unit.

[11] The system according to item 9, further including a network-connected terminal device, wherein the terminal device includes: a network connection unit connected to the autonomic nervous activity evaluation device; and a terminal output unit that outputs, via the network connection unit, at least one selected from the group consisting of the autonomic nervous activity of the subject and / or the lifestyle improvement suggestions output from the output unit of the evaluation device.

[12] An apparatus for evaluating an amount of autonomic nervous activity, comprising: an input unit to which data of the analysis results from a skin gas analyzer is input; a learning unit that is pre-trained using teacher data including an amount of at least one autonomic nervous system-related skin gas and information on the amount of autonomic nervous activity, and that outputs the amount of autonomic nervous activity when input information including the amount of at least one autonomic nervous system-related skin gas is input; and an output unit that outputs the amount of autonomic nervous activity output from the learning unit.

[13] A system including the apparatus for evaluating an amount of autonomic nervous activity according to item 12, wherein the apparatus for evaluating an amount of autonomic nervous activity is connected to a network, and the system comprises: the input unit receives data of the analysis results from the skin gas analyzer via the network; and the output unit outputs the amount of autonomic nervous activity determined via the network.

[0008] By measuring the amount of autonomic nerve-related skin gas, the amount of autonomic nerve activity can be determined.

[0009] FIG. 1 shows a comparison of urinary lactulose / mannitol ratios before and after intestinal barrier damage treatment (Control and Barrier Disruption). FIG. 2 shows a comparison of intestinal barrier function and autonomic nervous activity (FIG. 2A: Total Power, FIG. 2B: CCVTP). FIG. 3 shows a configuration diagram of an autonomic nervous activity evaluation device 10 according to the present invention. The process for determining autonomic nervous activity is performed cooperatively by hardware resources including an input unit 11, a memory unit 12, a processing unit 13, an output unit 14, and a learning unit 15, all connected via a bus. FIG. 4 shows a configuration diagram of an autonomic nervous activity evaluation system 20 including an autonomic nervous activity evaluation device 10 according to the present invention, which is installed on the Internet.

[0010] The present invention relates to a method for evaluating autonomic nervous activity based on the amount of autonomic nervous-related skin gas among collected skin gases, and an apparatus and system for evaluating autonomic nervous activity. It also relates to a method for evaluating intestinal barrier function based on the amount of intestinal barrier function-related skin gas among collected skin gases, and an apparatus and system for evaluating intestinal barrier function.

[0011] [Method for Evaluating Autonomic Nerve Activity] The present invention relates to a method for evaluating autonomic nerve activity, comprising the steps of: analyzing collected skin gases to detect autonomic nerve-related skin gases; and evaluating autonomic nerve activity from the amount of at least one of the detected autonomic nerve-related skin gases using a predetermined correspondence relationship between the amount of autonomic nerve-related skin gas and autonomic nerve activity. By using a gas derived from a living body as an objective indicator of the autonomic nerve-related skin gas, autonomic nerve activity can be evaluated based on the amount. The evaluation of autonomic nerve activity may be a determination of whether or not a subject suffers from depression or chronic fatigue, or may determine the severity of depression or chronic fatigue in addition to whether or not the subject suffers from depression or chronic fatigue. The method for evaluating autonomic nerve activity may be referred to as a method for testing for depression or chronic fatigue, a method for determining or distinguishing the degree of depression or chronic fatigue, or a method for determining the possibility or risk of suffering from depression or chronic fatigue. The present invention may also relate to a method for determining the amount of autonomic nerve-related skin gas to evaluate depression or chronic fatigue. Such a method may include: analyzing the collected skin gases to detect autonomic-related skin gases; and determining the amount of at least one of the autonomic-related skin gases.

[0012] The autonomic nervous system, a collective term for nerves that function independently of our will, performs essential functions for maintaining life, such as controlling body temperature, breathing, and sweating. The autonomic nervous system is divided into the sympathetic and parasympathetic nervous systems. The sympathetic nervous system is dominant during daytime waking and stress, resulting in elevated body temperature, increased heart rate, and increased blood pressure. Meanwhile, the parasympathetic nervous system is dominant during relaxation and sleep, resulting in decreased body temperature, decreased heart rate, and decreased blood pressure. Disturbances in the autonomic nervous system can result in various physical symptoms, such as insomnia, fatigue, headaches, stiff shoulders, palpitations, dizziness, and tinnitus. They can also cause depression, chronic fatigue, and autonomic imbalance. Several methods are known for measuring autonomic nervous activity, including electrocardiograms (ECGs), heart rate variability tests, electrodermal activity tests, goosebump response tests, dermatological dysplasia, digital plethysmography (DP), and Schellong exercise. These tests are used by physicians to conduct interviews and make diagnoses by exclusion. For example, in electrocardiograms, a testing method is also used in which ccvTP is used as the amount of autonomic nervous activity. The amount of autonomic nervous activity may be expressed by the overall function of the autonomic nervous system, or total power (i.e., the sum of the activities of the sympathetic nervous system (LF) and the parasympathetic nervous system (HF)).

[0013] The present invention demonstrates the relationship between intestinal barrier function and autonomic nervous activity (Figure 2). Furthermore, a correlation between intestinal barrier function and autonomic nervous system-related skin gases has been demonstrated (Example 1). Furthermore, a correlation between autonomic nervous system-related skin gases and autonomic nervous activity and / or balance has been demonstrated (Example 3). This allows the amount of autonomic nervous system-related skin gas to be used to determine autonomic nervous activity, particularly total power (LF+HF), ccvTP, and balance (LF / HF). In cases where the amount of autonomic nervous system activity determined by the present invention is high, the symptom or condition actually suffered by the subject may be any symptom or condition of depression or chronic fatigue. More specifically, the higher the amount of autonomic nervous system-related skin gas, the greater the severity of depression or chronic fatigue. On the other hand, the lower the amount of autonomic nervous system-related skin gas, the less severe the severity of depression or chronic fatigue.

[0014] [Autonomic nerve-related skin gas] Autonomic nerve-related skin gas refers to skin gas emitted from the skin that is related to the activity of the autonomic nerve. Examples of autonomic nerve-related skin gas include decane, ethylbenzene and / or xylene, nonanal, and decanal. Without intending to be limited by theory, the results of the intestinal barrier challenge test have shown a relationship between the intestinal barrier function and the activity of the autonomic nerve (Figure 2), so it is thought that autonomic nerve-related skin gas is derived from the intestinal bacterial flora rather than the normal skin bacteria, but is not limited thereto and may be derived from any bacteria including normal skin bacteria. Therefore, the autonomic nerve-related skin gas according to the present invention can also be referred to as a skin gas related to the intestinal barrier function. Autonomic nerve-related skin gas / intestinal barrier function-related skin gas can be expressed by the following formula: Ethylbenzene and xylene have the same molecular weight and similar properties, which can make separation by gas chromatography difficult. Although o-xylene is described as xylene, p-xylene and m-xylene can also be difficult to separate. Therefore, in this invention, when ethylbenzene and / or xylene are referred to as autonomic nervous system-related skin gases, this also includes cases where the gas chromatography refers to a mixture of these compounds. The autonomic nervous system-related skin gas / intestinal barrier function-related skin gas is one selected from three compounds consisting of decane, nonanal, and decanal, and one mixture consisting of ethylbenzene and / or xylene. However, any combination of two, three, or all of these compounds may also be used. When a combination is used, the total amount may be used, or the contribution to autonomic nervous system activity may be taken into consideration.

[0015] Autonomic nerve-related skin gases may be collected and analyzed by any method. Skin gases can be collected by collecting gases emitted from the human body surface. Skin gas collection may be performed using contact sampling with cotton or a polymeric material (e.g., PDMS), or a wearable device (see JP 2023-99322 A). Furthermore, when collecting skin gases from the hand, the entire hand can be covered with a gas-impermeable bag (e.g., a vinyl bag) and sealed at the wrist. The bag preferably has an openable collection port through which gas can be introduced or removed from the bag. The gas in the bag is preferably air or replaced with an inert gas (e.g., nitrogen gas). After a predetermined time has elapsed, the gas in the bag can be transferred from the collection port to another container (e.g., a storage container). Skin-related skin gases contained in the storage container can be analyzed by methods well known in the art, such as chromatography and / or mass spectrometry. More preferably, analysis can be performed using gas chromatography-mass spectrometry (GC-MS). The amount of autonomic nerve-related skin gas may be calculated by using the Area% value of the chromatogram itself, by adjusting the skin gas sampling method, sampling time, and analysis method. Since skin gas sampling can be performed non-invasively and easily, it can be easily collected without placing a burden on the body.

[0016] [Method for Evaluating Intestinal Barrier Function] In yet another aspect, the present invention may relate to a method for evaluating intestinal barrier function. More specifically, the method may include the following steps: analyzing collected skin gases to detect intestinal barrier function-related skin gases; and evaluating intestinal barrier function using the amount of at least one of the intestinal barrier function-related skin gases and a predetermined correspondence between the intestinal barrier function-related skin gas and intestinal barrier function. The health of the intestinal tract can be determined through the evaluation of intestinal barrier function. Intestinal barrier function is based on the health of tight junctions in intestinal epithelial cells. Tight junctions are intercellular junctions between intestinal epithelial cells and are composed of constituent proteins such as occludin, claudin, and ZO-1. The formation of tight junctions acts as a physical barrier against foreign substances attempting to pass through intercellular spaces, thereby inhibiting the entry of foreign substances into the body. Digestive disorders such as inflammatory bowel disease and irritable bowel syndrome can reduce intestinal barrier function, allowing foreign substances to enter the body from the intestine. The method for evaluating intestinal barrier function can also be referred to as a method for determining intestinal barrier function. The present invention may further relate to a method for determining the amount of intestinal barrier function-related skin gases for the evaluation of intestinal barrier function, which may include the following steps: analyzing the collected skin gases to detect intestinal barrier function-related skin gases; and determining the amount of at least one of the intestinal barrier function-related skin gases.

[0017] Intestinal barrier function can generally be determined by a mannitol and lactulose challenge test. Mannitol, a small molecule, can pass through the intestinal barrier, while lactulose, a disaccharide, is only absorbed through sites of disrupted tight junctions. Intestinal barrier function can be determined by measuring the lactulose / mannitol ratio (L / M ratio) in blood or urine after ingesting mannitol and lactulose. An increase in the lactulose / mannitol ratio indicates a decrease in intestinal barrier function. Without intending to be limited by theory, a decrease in intestinal barrier function makes endogenous components originating from the inner surface of the body more likely to penetrate into the blood and be more likely to be released to the outside as skin gas.

[0018] In a study conducted by the present inventors, measurements of autonomic nervous activity and evaluation of intestinal barrier function were performed in healthy women, and it was found that a decline in intestinal barrier function was associated with a decline in autonomic nervous activity (Figure 2). This demonstrated a relationship between intestinal barrier function and autonomic nervous activity.

[0019] The method for assessing autonomic nervous activity according to the present invention can unambiguously determine autonomic nervous activity by using a predetermined correspondence relationship between the amount of autonomic nervous system-related skin gas and autonomic nervous activity. The correspondence relationship may be a correspondence relationship between the amount of at least one autonomic nervous system-related skin gas and autonomic nervous activity, or a correspondence relationship between the type and amount of autonomic nervous system-related skin gas and autonomic nervous activity. Using the correspondence relationship, autonomic nervous activity can be determined from the amount of at least one autonomic nervous system-related skin gas. Furthermore, it is also possible to pre-create a correspondence relationship between the amount of autonomic nervous system-related skin gas and the severity of depression or chronic fatigue, in addition to the amount of autonomic nervous system activity. Such a correspondence relationship may be a correspondence table, graph, or correlation equation, or a threshold value may be used. Since the determination of autonomic nervous activity can be unambiguously determined, it does not require a doctor's judgment and can be considered a so-called non-diagnostic method. The method of the present invention can be used by persons other than medical professionals, such as employees of cosmetics retailers, beauty salons, and other beauty service providers, or testing companies.

[0020] [Device for Evaluating Autonomic Nerve Activity] Another aspect of the present invention may relate to a device for evaluating autonomic nerve activity (hereinafter referred to as a device for evaluating autonomic nerve activity). Such a device for evaluating autonomic nerve activity can determine the amount of autonomic nerve activity based on the amount of autonomic nerve-related skin gas. Specifically, the device for evaluating autonomic nerve activity includes: an input unit 11 into which data on skin gas analysis results is input; a memory unit 12 that stores a correspondence relationship between the amount of at least one autonomic nerve-related skin gas and the amount of autonomic nerve activity; a processing unit 13 that determines the amount of autonomic nerve activity based on the amount of at least one autonomic nerve-related skin gas in the input data on skin gas analysis results and the correspondence relationship stored in the memory unit 12; and an output unit 14 that outputs the determined amount of autonomic nerve activity. For example, the correspondence relationship between the amount of at least one autonomic nerve-related skin gas and the amount of autonomic nerve activity stored in the memory unit 12 may be a correspondence table, graph, or correlation equation, or may be a relationship between one or more thresholds and the amount of autonomic nerve activity. The device for evaluating the amount of autonomic nervous activity can also be called a device for testing the amount of autonomic nervous activity.

[0021] The device for evaluating autonomic nervous activity may further include a processing unit 13 providing a lifestyle improvement plan corresponding to the determined autonomic nervous activity. In such a device for evaluating autonomic nervous activity, the memory unit 12 further stores a correspondence relationship between the subject's autonomic nervous activity and lifestyle improvements corresponding to the autonomic nervous activity; the processing unit 13 determines a lifestyle improvement plan corresponding to the autonomic nervous activity based on the determined subject's autonomic nervous activity and the correspondence relationship stored in the memory unit 12; and the output unit 14 outputs the determined lifestyle improvement plan. The lifestyle improvements may include recommendations for stress reduction, consultation with a specialist, provision of supplements, recommended food (nutrient) intake, recommended exercise, sleep habits, smoking cessation, and drinking moderation. More specifically, the lifestyle improvements may be at least one selected from the group consisting of recommendations for stress reduction, consultation with a specialist, provision of supplements, recommended food (nutrient) intake, recommended exercise, sleep habits, smoking cessation, and drinking moderation, or any combination thereof.

[0022] The processing unit 13 can determine the amount of autonomic nerve activity by reading a correspondence relationship between the amount of at least one autonomic nerve-related skin gas stored in the memory unit 12 and the amount of autonomic nerve activity, and then determining the amount of autonomic nerve activity from the amount of at least one autonomic nerve-related skin gas in the skin gas analysis result data input from the input unit 11 and the correspondence relationship. The processing unit 13 may extract the amount of autonomic nerve-related skin gas from the input skin gas analysis result data, or may input data on the amount of autonomic nerve-related skin gas in advance as the skin gas analysis result. The autonomic nerve-related skin gas may be one arbitrarily selected from three compounds consisting of decane, nonanal, and decanal, and one mixture consisting of ethylbenzene and / or xylene, or any combination thereof. If the correspondence relationship is a correspondence table, the amount of autonomic nerve activity corresponding to the amount of autonomic nerve-related skin gas in the analysis data can be read from the correspondence table to determine the amount of autonomic nerve activity. If the correspondence relationship is a correlation equation, the amount of autonomic nerve-related skin gas in the analysis data can be substituted into the correlation equation to determine a numerical value for the amount of autonomic nerve activity. When the correspondence relationship is between one or more thresholds and the amount of autonomic nerve activity, the amount of autonomic nerve activity can be determined by comparing with each threshold. The determined amount of autonomic nerve activity may be stored in the storage unit 12, or may be output from the storage unit 12 or directly from the processing unit 13 via the output unit 14.

[0023] In another embodiment, the device for evaluating autonomic nervous activity may use a learning unit 15 that has been pre-trained using information on the amount of at least one autonomic nervous system-related skin gas and information on the amount of autonomic nervous activity as training data when determining the amount of autonomic nervous activity. The learning unit 15 is pre-trained to output the amount of autonomic nervous activity when data including the amount of at least one autonomic nervous system-related skin gas is input. The information on the amount of at least one autonomic nervous system-related skin gas used when training the learning unit 15 may be information on the type and amount of the autonomic nervous system-related skin gas. In other words, a learning unit 15 that has been pre-trained using information on the type and amount of autonomic nervous system-related skin gas and information on the amount of autonomic nervous activity as training data may also be used. The learning unit 15 is pre-trained to output the amount of autonomic nervous activity when data including the type and amount of autonomic nervous system-related skin gas is input. Such an autonomic nervous activity evaluation device specifically includes the following: an input unit 11 that inputs data including the amount of at least one autonomic nervous system-related skin gas from a skin gas analyzer; a learning unit 15 that has been pre-trained using information regarding the amount of at least one autonomic nervous system-related skin gas and information regarding autonomic nervous activity as training data, and that outputs the amount of autonomic nervous activity when data including the amount of at least one autonomic nervous system-related skin gas input from input unit 11 is input; and an output unit 14 that outputs the output amount of autonomic nervous activity of the target. Such an autonomic nervous activity evaluation device may further include a processing unit 13 and a memory unit 12, and processing unit 13 may control input of data including the type and amount of autonomic nervous system-related skin gas input from input unit 11 to learning unit 15, and control output of the amount of autonomic nervous activity output by learning unit 15 from output unit 14. Processing unit 13 may also perform pre-adjustment of the input skin gas analysis result data. As an example, the data including the type and amount of autonomic nervous system-related skin gas input from the input unit 11 may be the data of the skin gas analysis results itself, in which case the processing unit 13 may perform a step of extracting the amount of autonomic nervous system-related skin gas from the input data of the skin gas analysis results.The memory unit 12 may temporarily store data including the type and amount of autonomic nerve-related skin gas input from the input unit 11 and the amount of autonomic nerve activity output by the learning unit 15.

[0024] The input unit 11 includes an interface. The interface may be connected to, for example, an operation unit such as a keyboard or mouse, a communication unit such as a LAN or port, or an external storage device such as a CD-ROM, DVD-ROM, BD-ROM, or memory stick. Data including the type and amount of autonomic nerve-related skin gas may be input via the operation unit. Furthermore, instructions for processing in the processing unit 13 can be given from the input unit 11 via the operation unit.

[0025] The storage unit 12 may include a memory device such as RAM, ROM, or flash memory, a fixed disk device such as a hard disk drive, or a portable storage device such as a flexible disk or optical disk. The storage unit 12 may store data and instructions input from the input unit 11. The storage unit 12 stores a correspondence between the type and amount of autonomic nerve-related skin gas and the amount of autonomic nerve activity. Specifically, the correspondence between the type and amount of skin gas and the amount of autonomic nerve activity is stored as a correspondence table, graph, correlation equation, or threshold. The storage unit 12 may store the results of the arithmetic processing performed by the processing unit 13, as well as programs and databases used for various computer processes, and may also store the program of the learning unit 15. The computer program may be installed, for example, from a computer-readable recording medium such as a CD-ROM or DVD-ROM, or via the Internet. The computer program is installed in the storage unit 12 using a known setup program or the like.

[0026] The processing unit 13 executes various types of arithmetic processing in accordance with the programs stored in the storage unit 12. The arithmetic processing is performed by a central processing unit (CPU) included in the processing unit 13. This CPU includes functional modules that control the input unit 11, the storage unit 12, the learning unit 15, and the output unit 14, and is capable of performing various types of control. Each of these units may be composed of an independent integrated circuit, microprocessor, firmware, or the like. Information generated after each process by the processing unit 13 may be temporarily stored in the storage unit 12, or may be used directly in the next process.

[0027] The output unit 14 is configured to output the amount of autonomic nerve activity generated by performing arithmetic processing in the processing unit 13. The output unit 14 may be a display device such as a liquid crystal display that directly displays the results of the arithmetic processing, or an output means such as a printer, or may be an interface unit for outputting to an external storage device or via a network.

[0028] The learning unit 15 uses a known machine learning technique, such as deep learning, to learn the relationship between input data containing the amount of at least one autonomic nerve-related skin gas and information about the amount of autonomic nerve activity at that time. Information about the amount of at least one autonomic nerve-related skin gas and information about the amount of autonomic nerve activity at that time are obtained for various subjects, and the learning unit 15 can be trained using this data. Deep learning is machine learning using a multilayer neural network consisting of an input layer, an intermediate layer, and an output layer. A feature vector of the detection information is input to each node in the input layer. Each node in the intermediate layer outputs the sum of values ​​obtained by multiplying each feature vector output from each node in the input layer by a weight, and the output layer outputs the sum of values ​​obtained by multiplying each feature vector output from each node in the intermediate layer by a weight. The learning unit 15 adjusts each weight while learning to reduce the difference between the output value from the output layer and the information about the amount of autonomic nerve activity. The input data input to learning unit 15 is input data relating to the amount of at least one autonomic nerve-related skin gas, preferably information relating to the type and amount of the autonomic nerve-related skin gas. The autonomic nerve-related skin gas may be any one selected from decane, ethylbenzene and / or xylene, nonanal, and decanal, or any combination thereof. In one example, the types and amounts of all four types may be input.

[0029] [Intestinal Barrier Function Evaluation Apparatus] Another aspect of the present invention may relate to an apparatus for evaluating intestinal barrier function (hereinafter referred to as an intestinal barrier function evaluation apparatus). Such an intestinal barrier function evaluation apparatus can determine intestinal barrier function based on the amount of intestinal barrier-related skin gas. This intestinal barrier function evaluation apparatus specifically includes the following: an input unit 11 into which data on skin gas analysis results is input; a memory unit 12 that stores a correspondence relationship between the amount of intestinal barrier function-related skin gas and intestinal barrier function; a processing unit 13 that determines intestinal barrier function based on the amount of intestinal barrier function-related skin gas in the skin gas analysis data and the correspondence relationship between the amount of intestinal barrier function-related skin gas and intestinal barrier function stored in the memory unit 12; and an output unit 14 that outputs the determined intestinal barrier function. As an example, the correspondence relationship between the type and amount of intestinal barrier function-related skin gas stored in the memory unit 12 and intestinal barrier function may be a correspondence table, graph, or correlation equation, or may be a relationship between one or more thresholds and intestinal barrier function. The intestinal barrier function evaluation device can also be called an intestinal barrier function determination device.

[0030] [System for Evaluating Autonomic Nervous Activity] The autonomic nervous activity evaluation device 10 of the present invention may exist on a network and constitute an autonomic nervous activity evaluation system 20 including the autonomic nervous activity evaluation device 10. The autonomic nervous activity evaluation system 20 is configured such that data on the results of a skin gas analysis is input to the input unit 11 of the autonomic nervous activity evaluation device 10 via the network; and the determined autonomic nervous activity level is output from the output unit 14 via the network. The autonomic nervous activity evaluation system 20 may further include a terminal device 30 and / or a skin gas analyzer 40 connected via the network. That is, the autonomic nervous activity evaluation device 10 may exist on a server, and the input unit 11 and the output unit 14 may each be connected to the network via an interface unit. Furthermore, the learning unit 15 used by the autonomic nervous activity evaluation device 10 may also be externally located via a server, etc., and the autonomic nervous activity level may be evaluated via communication.

[0031] The skin gas analyzer 40 includes the following components: a skin gas sampling unit; a skin gas analysis unit; and a skin gas analyzer output unit. Data on the results of the skin gas analysis can be output via the skin gas analyzer output unit. The output skin gas analysis data may be provided to the autonomic nervous activity evaluation device via a network or directly. The skin gas analyzer 40 may be any device capable of analyzing skin gas samples, and a chromatography device, particularly a gas chromatography mass spectrometry (GC / MS) device, may be used.

[0032] The network-connected terminal device 30 may include the following: a network connection unit connected to the autonomic nervous activity evaluation device 10; and a terminal output unit that outputs, via the network connection unit, at least one selected from the group consisting of the subject's autonomic nervous activity output from the output unit 14 of the autonomic nervous activity evaluation device and lifestyle improvement suggestions according to severity. Data on the results of skin gas analysis may be input to the autonomic nervous activity evaluation device 10 via the network connection unit.

[0033] Another aspect of the present invention may relate to a program for causing the above-described processing to be performed by the autonomic nervous activity evaluation device 10. Such a program includes the following instructions to the processing unit 13: read input data including an amount of at least one autonomic nervous system-related skin gas input from the input unit 11, read a correspondence relationship between the amount of at least one autonomic nervous system-related skin gas and the amount of autonomic nervous activity stored in the memory unit 12, determine the amount of autonomic nervous activity from the input data and the correspondence relationship, and output the determined amount of autonomic nervous activity to the output unit 14. Instead of having the processing unit 13 determine the amount of autonomic nervous activity from the correspondence relationship, the input data may be input to a learning unit 15 that has been pre-trained to output the amount of autonomic nervous activity when input data regarding the amount of at least one autonomic nervous system-related skin gas is input, thereby determining the amount of autonomic nervous activity.

[0034] All documents mentioned herein are incorporated by reference in their entirety.

[0035] The following examples of the present invention are for illustrative purposes only and do not limit the technical scope of the present invention. The technical scope of the present invention is limited only by the claims. The present invention may be modified, for example, by adding, deleting, or substituting components of the present invention, provided that the modifications do not depart from the spirit of the present invention.

[0036] Example 1: Relationship between Intestinal Barrier Function and Skin Gases To study the relationship between the intestinal barrier and skin gases, four healthy men in their 40s and 50s were subjected to intestinal barrier injury treatment before and after skin gas collection and assessment of intestinal barrier function. On the day before skin gas collection, the subjects ate a designated dinner and fasted for breakfast (only water was allowed). After waking, they urinated and ingested a lactulose (L) / mannitol (M) (5 g / 1 g) mixture. Urine samples were collected 2.5 to 5 hours after lactulose (L) / mannitol (M) ingestion, and the L / M ratio was determined by LC / MS / MS. After lactulose (L) / mannitol (M) ingestion, a skin gas collection bag made of a highly gas-barrier material was attached to the subject's hand and sealed. The skin gas collection bag had a connector, through which suction was applied and then filled with approximately 0.5 L of nitrogen gas. After wearing, the device was left in place for 2.5 hours, and skin gas samples were collected before intestinal barrier injury treatment. To collect skin gas samples after intestinal barrier injury treatment, the subjects were instructed to take a nonsteroidal anti-inflammatory drug after a designated dinner as intestinal barrier injury treatment. The following day, subjects fasted for breakfast. After waking up, the L / M ratio was determined and skin gas samples were collected according to the same schedule as on day 1. The changes in the L / M ratio before and after intestinal challenge are shown in Figure 1.

[0037] The collected skin gas samples were transferred from the connecting part to a skin gas storage bag made of a highly gas-barrier material and stored there. The skin gas in the storage bag was analyzed using gas chromatography-mass spectrometry. Of the skin gas components that showed significant changes before and after the intestinal barrier injury treatment, the following five compounds were focused on: The ratio of skin gases before and after the change of the above compounds was calculated using the following formula: The results are shown in Table 1.

[0038] Example 2: Relationship between intestinal barrier function and autonomic nervous system indices Healthy women (25 to 39 years old, n = 33) were tested for autonomic nervous system function (total power and ccvTP) using a fatigue stress meter MF-100 (Murata Manufacturing Co., Ltd.), and intestinal barrier function was measured using the lactulose (L) / mannitol (M) test described below.

[0039] Measurement of intestinal barrier function Intestinal barrier function was measured using the following method. Subjects were fasted for breakfast (only water was allowed). After waking up, they urinated and ingested lactulose (L) / mannitol (M) (5 g / 1 g). Urine was collected 2.5 to 5 hours after ingestion of lactulose (L) / mannitol (M), and the amounts of lactulose and mannitol were measured using LC / MS / MS to calculate the L / M ratio.

[0040] The relationship between the measured L / M ratio and autonomic nervous function is shown in Figure 2 (Figure 2(A) total power, (B) ccvTP). A correlation was observed between intestinal barrier function and autonomic nervous function.

[0041] Example 3: Relationship between autonomic nervous index and skin gases Healthy women (25 to 45 years old, n=57) were tested for autonomic nervous function (total power and LH / HF) using a fatigue stress meter MF-100 (Murata Manufacturing Co., Ltd.), and intestinal barrier function was also measured.

[0042] Skin gas analysis: A skin gas sampling bag made of a highly gas-barrier material was attached to the palm of the subject's hand and its seal was confirmed. The skin gas sampling bag was equipped with a connecting part, and suction was performed through the connecting part, followed by filling with approximately 0.5 L of nitrogen gas. After attachment, the bag was left stationary for 45 minutes to collect skin gas.

[0043] The collected skin gas samples were transferred from the connecting part to a skin gas storage bag made of a highly gas-barrier material and stored there. The skin gas in the storage bag was analyzed using gas chromatography-mass spectrometry. The amounts of nonanal and decanal in the skin gas were determined.

[0044] The correlations of the amounts of nonanal and decanal with total power and LH / HF, respectively, were determined by Spearman correlation analysis. The results are shown below.

[0045] Nonanal and decanal correlate with total autonomic nervous activity (total power) and autonomic nervous balance (LF / HF), respectively, and thus, by measuring the amounts of nonanal and decanal, it is possible to determine total autonomic nervous activity (total power) and autonomic nervous balance (LF / HF), respectively.

Claims

1. A method for evaluating autonomic nervous activity, comprising: analyzing collected skin gases and detecting autonomic nervous system-related skin gases; and evaluating the autonomic nervous system activity from the amount of at least one of the detected autonomic nervous system-related skin gases using a predetermined correspondence between the amount of autonomic nervous system-related skin gas and the autonomic nervous system activity.

2. The method of claim 1, wherein the autonomic nerve-related skin gas is selected from the group consisting of decane, ethylbenzene and / or xylene, nonanal, and decanal.

3. The method according to claim 2, wherein the autonomic nervous system-related skin gas is an indicator of intestinal barrier function.

4. The method described in claim 1, wherein the correspondence relationship is a correspondence table showing the relationship between the range of the amount of the autonomic nervous system-related skin gas and the activity level of the autonomic nervous system, or the relationship between the threshold amount of the autonomic nervous system-related skin gas and the activity level of the autonomic nervous system.

5. An apparatus for evaluating autonomic nervous activity, comprising: an input unit into which analysis result data from a skin gas analyzer is input; a memory unit that stores a correspondence between the amount of at least one autonomic nervous-related skin gas and the amount of autonomic nervous activity; a processing unit that determines the amount of autonomic nervous activity from the input analysis result data and the correspondence stored in the memory unit; and an output unit that outputs the determined amount of autonomic nervous activity.

6. The device for evaluating the activity of the autonomic nerves according to claim 5, wherein the type of the autonomic nerve-related skin gas is selected from the group consisting of decane, ethylbenzene and / or xylene, nonanal, and decanal.

7. The autonomic nervous activity evaluation device of claim 5, wherein the autonomic nervous activity evaluation device provides lifestyle improvement suggestions corresponding to the autonomic nervous activity level based on the determined autonomic nervous activity level of the subject, wherein: the memory unit further stores a correspondence relationship between the autonomic nervous activity level of the subject and lifestyle improvements corresponding to the autonomic nervous activity level; the processing unit determines a lifestyle improvement suggestion corresponding to the autonomic nervous activity level from the determined autonomic nervous activity level of the subject and the correspondence relationship stored in the memory unit; and the output unit outputs the determined lifestyle improvement suggestion.

8. The device for evaluating autonomic nervous activity described in claim 7, wherein the lifestyle improvement suggestions are at least one selected from the group consisting of recommendations for stress relief, consultation with a specialist, provision of supplements, recommendations for food (nutrient) intake, recommendations for exercise, sleep habits, smoking cessation, and drinking in moderation.

9. A system including the autonomic nervous activity evaluation device according to any one of claims 5 to 8, wherein the autonomic nervous activity evaluation device is connected to a network, and wherein the input unit receives analysis result data from a skin gas analyzer via the network; and the output unit outputs the determined autonomic nervous activity or lifestyle improvement proposal via the network.

10. The system of claim 9, further comprising a network-connected skin gas analyzer, the skin gas analyzer comprising: a skin gas sampling unit; a skin gas analysis unit; and a network-connected output unit.

11. The system according to claim 9, further comprising a network-connected terminal device, the terminal device comprising: a network connection unit connected to the evaluation device for the amount of autonomic nervous activity; and a terminal output unit that outputs, via the network connection unit, at least one selected from the group consisting of the amount of autonomic nervous activity of the subject output from the output unit of the evaluation device and / or lifestyle improvement suggestions.

12. An apparatus for evaluating autonomic nervous activity, comprising: an input unit to which data on the analysis results from a skin gas analyzer is input; a learning unit that has been pre-trained using teacher data including the amount of at least one autonomic nervous-related skin gas and information on the amount of autonomic nervous activity, and that outputs the amount of autonomic nervous activity when input information including the amount of at least one autonomic nervous-related skin gas is input; and an output unit that outputs the amount of autonomic nervous activity output from the learning unit.

13. A system including the autonomic nervous activity evaluation device according to claim 12, wherein the autonomic nervous activity evaluation device is connected to a network, and the system comprises: data on the analysis results from a skin gas analyzer is input via the network to the input unit; and the determined autonomic nervous activity is output via the network from the output unit.

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