Compositions comprising lactobionic acid

Abstract

An object of the present disclosure is to effectively suppress a decrease in body temperature and symptoms associated therewith, or to modify the intestinal flora so as to be effective in suppressing these symptoms.SOLUTION: The present disclosure provides a composition for suppressing a decrease in body temperature comprising lactobionic acid or a salt thereof, a composition for alleviating a symptom associated with an allergic reaction comprising lactobionic acid or a salt thereof, a composition for modifying a relative abundance of bacteria in intestinal flora comprising lactobionic acid or a salt thereof, and the like.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present disclosure relates to compositions comprising lactobionic acid or a salt thereof. [Background technology]

[0002] For example, in an allergic reaction involving anaphylaxis, an individual's body temperature may drop. A drop in an individual's body temperature can have various adverse effects on the individual. For example, a drop in body temperature can cause symptoms such as shivering. A further drop in body temperature can cause symptoms such as cessation of shivering, slowed and clumsy movements, increased reaction times, clouded thinking, and impaired judgment. A further drop in body temperature can lead to coma, slowed and weakened heartbeats and breathing, and ultimately cardiac arrest. Therefore, when an individual's body temperature drops, or when there is a possibility that an individual's body temperature may drop, it is important to effectively prevent the drop in the individual's body temperature.

[0003] In order to suppress the drop in body temperature that accompanies allergic reactions, drugs with antihistamine action, such as ortho-vanillic acid (Non-Patent Document 1) and coumarin (Non-Patent Document 2), are used. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] Kim et al., Acta Pharmacologica Sinica, 2017, Vol. 38, pp. 90-99 [Non-patent document 2] Liu et al., Food & Functaion, 2019, Volume 10, Issue 10, pp. 6767-6778 Summary of the Invention [Problem to be solved by the invention]

[0005] An object of the present disclosure is to effectively suppress a decrease in body temperature and symptoms associated therewith, or to modify the intestinal flora so as to be effective in suppressing these symptoms. [Means for solving the problem]

[0006] The present inventors have discovered that compositions containing lactobionic acid have excellent physiological effects, and have completed the present invention. The present disclosure provides, for example, a composition for suppressing a decrease in body temperature, which comprises lactobionic acid or a salt thereof. [Effects of the Invention]

[0007] According to the present disclosure, it is possible to effectively suppress a drop in body temperature and associated symptoms, or to modify the intestinal flora so as to be effective in suppressing these symptoms. [Brief explanation of the drawings]

[0008] [Figure 1] Figure 1 shows an example of an experimental schedule for verifying the effects of lactobionic acid using mice as a model organism. [Figure 2] Figure 2 shows the effect of lactobionic acid on lowering body temperature. The horizontal axis of the graph represents the time (minutes) after the addition of ovalbumin (OVA), and the vertical axis represents the change in body temperature. Circles represent the plots for the control group, and squares represent the plots for the lactobionic acid-treated group. [Figure 3] Figure 3 shows the effect of lactobionic acid on serum total IgG concentration (A) and MCPT1 concentration (B). In each graph, the plot on the left (-) is the plot for the control group, and the plot on the right (+) is the plot for the lactobionic acid-administered group. [Figure 4]Figure 4 shows a principal coordinate analysis (PcoA) plot based on the UniFrac distances of lactobionic acid-treated and control individuals. Pco1 and Pco2 indicate the contribution of the principal components, with plots that are close to each other indicating similar bacterial compositions in the intestinal flora, and plots that are far from each other indicating similar bacterial compositions in the intestinal flora. [Figure 5] Figure 5 shows the relative abundance of Lactobacillus (A), Alistipes (B), Parabacteroides (C), and Lachnospiraceae UCG-006 (D) in the intestinal flora of individuals or control individuals on days 0 and 21 after lactobionic acid administration. In each graph, the plot on the left (-) is the plot for the control group, and the plot on the right (+) is the plot for the lactobionic acid-administered group. [Figure 6] FIG. 6 shows an example of an experimental schedule for verifying the effects of lactobionic acid and / or antibiotics using mice as a model organism. [Figure 7] FIG. 7 shows the effect of lactobionic acid and / or antibiotics on reducing body temperature. [Figure 8] 8 shows the total bacterial counts in the intestinal flora of individuals administered lactobionic acid and / or antibiotics or control individuals. From left to right, the graph shows the total bacterial counts in the intestinal flora on days 1 and 21 for individuals administered water, lactobionic acid, water + antibiotics, and lactobionic acid + antibiotics, respectively. [Figure 9] 9 shows the relative abundance of bacteria of the Bacteroidaceae family in the intestinal flora of individuals 21 days after administration of lactobionic acid and / or antibiotics or control individuals. From left to right, the graph shows the relative abundance of bacteria of the Bacteroidaceae family in individuals administered water, lactobionic acid, water + antibiotics, and lactobionic acid + antibiotics, respectively. [Figure 10]Figure 10 shows the correlation between the relative abundance of bacteria in the intestinal flora and body temperature in individuals administered lactobionic acid and antibiotics. The Pearson product-moment correlation coefficient was calculated using the analytical software Rstudio for each mouse's body temperature change and the relative abundance of each bacterium in the intestinal flora. The numerical values ​​indicate the correlation coefficient, and *, **, and *** indicate false positive rates of 0.05 or less, 0.01 or less, and 0.001 or less, respectively. DETAILED DESCRIPTION OF THE INVENTION

[0009] An embodiment of the present disclosure will be described in detail below. However, the scope of the present disclosure is not limited to the embodiment described herein, and various modifications can be made without departing from the spirit of the present disclosure. Each aspect disclosed in this specification can be combined with any other feature disclosed in this specification. Furthermore, when multiple upper and lower limit values ​​are described for a specific parameter, any of these upper and lower limit values ​​can be combined to form a suitable numerical range. Furthermore, the lower and / or upper limit values ​​of a numerical range described in this disclosure are numerical values ​​within that numerical range and may be replaced with numerical values ​​shown in the examples. The expression "X to Y" indicating a numerical range means "X or more and Y or less." If a specific description described for one embodiment also applies to other embodiments, that description may be omitted in other embodiments.

[0010] <Composition> In one embodiment, a composition for suppressing a decrease in body temperature, comprising lactobionic acid or a salt thereof, is disclosed, which can effectively suppress a decrease in body temperature in an individual when the individual's body temperature has decreased or when the individual's body temperature is likely to decrease.

[0011] In one embodiment, a composition for alleviating symptoms associated with allergic reactions is disclosed, comprising lactobionic acid or a salt thereof, which can effectively alleviate symptoms associated with allergic reactions.

[0012] In one embodiment, a composition for modifying the relative abundance of bacteria in intestinal flora is disclosed, comprising lactobionic acid or a salt thereof, which can effectively modify the relative abundance of bacteria in intestinal flora.

[0013] [Lactobionic acid or its salts] Lactobionic acid is a disaccharide and sugar acid consisting of gluconic acid and galactose. Lactobionic acid is also known as 4-O-β-galactopyranosyl-D-gluconic acid. The salt of lactobionic acid may be a salt of lactobionic acid with an inorganic cation or an organic cation. Non-limiting examples of inorganic cations include calcium, potassium, sodium, zinc, etc. Non-limiting examples of organic cations include antibiotics such as erythromycin. Lactobionic acid or its salts can be produced by known methods. For example, lactobionic acid or its salts can be produced by oxidizing lactose contained in milk or dairy products. Alternatively, commercially available lactobionic acid or its salts can be used as lactobionic acid or its salts.

[0014] <Decrease in body temperature> The composition of the present disclosure may be a composition that suppresses a decrease in body temperature. Hypothermia is when an individual's body temperature drops below normal. This can cause symptoms such as shivering. If the body temperature drops further, the shivering may stop and symptoms such as slow, clumsy movements, increased reaction times, clouded thinking, and impaired judgment may occur. If the body temperature drops even further, the individual may fall into a coma, with a slow and weakened heartbeat and breathing, and eventually, the heart may stop. In the case of a human, a body temperature of 35°C or below may be considered to be a hypothermic state. A hypothermic state is sometimes called hypothermia. Hypothermia with core temperatures of 32-35°C, 28-32°C, and 20-28°C can be classified as mild, moderate, and severe hypothermia, respectively.

[0015] An individual to whom a composition of the present disclosure has been administered may have a reduced body temperature, preferably by 0.5°C or more, 1°C or more, 2°C or more, 3°C or more, 4°C or more, or 5°C or more, or by 0.5 to 5°C, 1 to 5°C, 2 to 5°C, 3 to 5°C, or 4 to 5°C, compared to an individual to whom a composition of the present disclosure has not been administered. An individual to whom a composition of the present disclosure has been administered may experience suppressed decline in body temperature for 10 minutes or more, 20 minutes or more, 30 minutes or more, 40 minutes or more, 50 minutes or more, 60 minutes or more, 90 minutes or more, or 120 minutes or more, or 10 to 120 minutes, 20 to 120 minutes, 30 to 120 minutes, 40 to 120 minutes, 50 to 120 minutes, 60 to 120 minutes, or 90 to 120 minutes after administration of the composition.

[0016] The decrease in body temperature is preferably a decrease in body temperature associated with an allergic reaction, as described below. However, the decrease in body temperature in the present disclosure is not limited to this. For example, the decrease in body temperature may be caused or aggravated by exposure to a cold environment, may be caused by a disease or symptom, or may be caused by stress.

[0017] When the composition of the present disclosure inhibits a decrease in body temperature, non-limiting examples of the mechanism of action of the composition include the following. Directly inhibits mast cell degranulation. Induce regulatory T cells to suppress antigen responses and inhibit mast cell degranulation. · Cells of the innate immune system suppress the differentiation of Th2 cells without the intervention of regulatory T cells.

[0018] <Allergic reactions> The compositions of the present disclosure may be compositions that alleviate symptoms associated with an allergic reaction. An allergic reaction is a condition in which an individual's immune system reacts abnormally to a specific substance (allergen). Non-limiting examples of allergic reactions include seasonal allergies such as hay fever, drug allergies, food allergies, and perennial allergies caused by house dust and the like. Allergic reactions can be induced in mice as a model organism by administering, for example, ovalbumin as an allergen.

[0019] The allergic reaction may be accompanied by anaphylaxis, a particularly severe allergic reaction that is a dangerous condition in which allergic symptoms appear in multiple organs.

[0020] Allergic reactions are typically accompanied by symptoms in an individual, including, but not limited to, the aforementioned decreased body temperature, decreased blood pressure, skin symptoms such as hives, mucosal symptoms such as swelling of the mucous membranes, and respiratory symptoms such as difficulty breathing.

[0021] When a composition of the present disclosure relieves symptoms associated with an allergic reaction, non-limiting examples of the mechanism of action of the composition include the following: Directly inhibits mast cell degranulation. Induce regulatory T cells to suppress antigen responses and inhibit mast cell degranulation. · Cells of the innate immune system suppress the differentiation of Th2 cells without the intervention of regulatory T cells.

[0022] <Intestinal flora> The compositions of the present disclosure may be compositions that alter the relative abundance of bacteria in the intestinal flora. The intestinal flora is a general term for the diverse intestinal bacteria that normally reside in the intestinal tract. The intestinal flora is also called the intestinal bacterial flora or the intestinal resident microflora. Bacteria in the gut flora not only coexist with each other but also with the host organism, and the relative abundance of bacteria in the gut flora affects the health of the individual. The compositions of the present disclosure are preferably capable of modifying the relative abundance of bacteria in the intestinal flora so as to be effective in reducing body temperature and suppressing symptoms associated with allergic reactions.

[0023] The bacteria in the intestinal flora are diverse, but non-limiting examples include the following bacteria and their closely related bacteria: Bacteroides Lactobacillus ·[Closrtidium] innocuum group Akkemansia Dubosiella Blautia Parabacterioides Citrobacter Muribaculaceae Faecalibaculum ·[Ruminococcus] torques group Romboutsia Alistos Entetococcus Rikenellaceae RC9 gut group Ruminococcaceae Oscillospiraceae Clostridioides Bifidobacterium Erysipelatoclostridium Roseburia Closrtidium sensu stricto 1 Lactococcus Helicobacter

[0024] Bacteria closely related to a certain bacterium preferably include bacteria that are taxonomically closely related to the certain bacterium. For example, closely related bacteria of a certain genus include bacteria of another genus in the same family as the bacterium. For example, Bacteroides and related bacteria include bacteria of the family Bacteroidaceae. Lactobacillus and related bacteria include bacteria belonging to the family Lactobacillaceae. Alistipes and related bacteria include bacteria belonging to the family Rikenellaceae. Parabacteroides and related bacteria include bacteria belonging to the family Tannerellaceae. Lachnospiraceae UCG-006 and its closely related bacteria include bacteria belonging to the family Lachnospiraceae. Akkermansia and related bacteria include bacteria of the family Akkermansiaceae. Dubisiella and its related bacteria include bacteria of the Erysipelotrichaceae family.

[0025] When a composition of the present disclosure alters the relative abundance of bacteria in the intestinal flora, the composition of the present disclosure may increase the relative abundance of one or more bacteria in the intestinal flora (e.g., one or more of the bacteria listed in Table 1 and their closely related bacteria).

[0026] The composition of the present disclosure increasing the relative abundance of one or more bacteria may be an increase, preferably statistically significant increase, in the relative abundance of one or more bacteria in an individual to whom the composition of the present disclosure has been administered, compared to the relative abundance of the one or more bacteria in an individual to whom the composition of the present disclosure has not been administered or in an individual before the composition of the present disclosure was administered. An increase in the relative abundance of one or more bacteria by a composition of the present disclosure may be an increase in the percentage of relative abundance of one or more bacteria in an individual to which a composition of the present disclosure has been administered by 3 points or more, 5 points or more, or 10 points or more, or 3 to 50 points, 5 to 50 points, or 10 to 50 points, compared to the percentage of relative abundance of one or more bacteria in an individual to which a composition of the present disclosure has not been administered or in an individual before administration of a composition of the present disclosure. Furthermore, an increase in the relative abundance of one or more bacteria by the composition of the present disclosure may mean an increase in the percentage of relative abundance of one or more bacteria in an individual to which the composition of the present disclosure has been administered by 1.5 times or more, 2 times or more, or 3 times or more, or 1.5 to 1000 times, 2 to 500 times, or 3 to 400 times the percentage of relative abundance of one or more bacteria in an individual to which the composition of the present disclosure has not been administered or in an individual before the composition of the present disclosure has been administered. When the composition of the present disclosure is administered in combination with an antibiotic as described below, increasing the relative abundance of one or more bacteria may be preferably a statistically significant increase in the relative abundance of one or more bacteria compared to an individual who has not been administered the composition of the present disclosure, an individual before being administered the composition of the present disclosure, or an individual who has been administered an antibiotic and not administered lactobionic acid. When a composition of the present disclosure is administered in combination with an antibiotic, an increase in the relative abundance of one or more bacteria by the composition of the present disclosure may be an increase in the percentage of relative abundance of one or more bacteria in an individual to which the composition of the present disclosure is administered by 10 points or more, 15 points or more, 20 points or more, or 30 points or more, or 10 to 80 points, 15 to 80 points, 20 to 80 points, or 30 to 20 points, compared to the percentage of relative abundance of one or more bacteria in an individual not administered the composition of the present disclosure, the individual before the composition of the present disclosure is administered, or an individual administered an antibiotic and not administered lactobionic acid. Furthermore, when the composition of the present disclosure is administered in combination with an antibiotic, increasing the relative abundance of one or more bacteria may mean increasing the percentage of relative abundance of one or more bacteria in an individual to which the composition of the present disclosure has been administered by 1.5 times or more, 2 times or more, 3 times or more, or 5 times or more, or by 1.5 to 1000 times, 2 to 500 times, 3 to 400 times, or 5 to 10 times the percentage of relative abundance of one or more bacteria in an individual to which the composition of the present disclosure has not been administered, an individual before the composition of the present disclosure has been administered, or an individual to which an antibiotic has been administered but lactobionic acid has not been administered.

[0027] Increasing the relative abundance of one or more bacteria may mean increasing the relative abundance of one or more bacteria preferably after 7 days or more, more preferably 14 days or more, and particularly preferably 21 days or more from the start of administration of lactobionic acid.

[0028] Increasing the relative abundance of one or more bacteria in the intestinal flora may include increasing the relative abundance of one or more bacteria selected from the group consisting of bacteria of the Lactobacillaceae family, bacteria of the Rikenellaceae family, bacteria of the Tannerellaceae family, and bacteria of the Lachnospiraceae family, in which case the intestinal flora may be that of an individual not receiving antibiotics. The compositions of the present disclosure can inhibit a drop in body temperature and alleviate symptoms associated with allergic reactions by modifying the relative abundance of bacteria in the intestinal flora.

[0029] Increasing the relative abundance of one or more bacteria in the gut flora may include increasing the relative abundance of bacteria of the family Bacteroidaceae in the gut flora, where the gut flora may be the gut flora of an individual to whom an antibiotic has been administered.

[0030] Increasing the relative abundance of one or more bacteria in the intestinal flora may involve decreasing the relative abundance of one or more other bacteria in the intestinal flora. In this case, decreasing the relative abundance of one or more other bacteria in the intestinal flora may include decreasing the relative abundance of Lactobacillaceae bacteria in the intestinal flora. The intestinal flora may be that of an individual to whom an antibiotic has been administered.

[0031] When a composition of the present disclosure alters the relative abundance of bacteria in the intestinal flora, non-limiting examples of the mechanism of action of the composition include the following: Directly inhibits mast cell degranulation. Induce regulatory T cells to suppress antigen responses and inhibit mast cell degranulation. · Cells of the innate immune system suppress the differentiation of Th2 cells without the intervention of regulatory T cells.

[0032] <Antibiotics> The composition of the present disclosure may be administered to an individual in combination with an antibiotic. In this case, the composition of the present disclosure and the antibiotic may be administered to an individual at the same time or at different times. The composition of the present disclosure and the antibiotic may be formulated as a formulation containing both, or may be formulated as separate formulations. When administered in combination with an antibiotic, the compositions of the present disclosure tend to be more effective at preventing a drop in body temperature, more effective at alleviating symptoms associated with allergic reactions, and more effective at altering the relative abundance of bacteria in the intestinal flora.

[0033] An antibiotic is a substance that has antibacterial activity. Any antibiotic can be used as the antibiotic as long as the effects of the present invention can be obtained. The antibiotic is preferably a glycopeptide antibiotic such as vancomycin, an aminoglycoside antibiotic such as streptomycin, or a β-lactam antibiotic such as ampicillin, or a cocktail comprising any combination thereof. The dosage regimen of the antibiotic to be administered can be appropriately determined by those skilled in the art.

[0034] When the compositions of the present disclosure are administered in combination with antibiotics, the compositions of the present disclosure may inhibit the reduction in the total number of bacteria in the intestinal flora caused by the administration of antibiotics.

[0035] <Individual> The individual is preferably an animal. The animal may be human or non-human. Non-limiting examples of individuals include humans, monkeys, dogs, cats, horses, cows, pigs, sheep, goats, rabbits, guinea pigs, hamsters, mice, rats, etc. The animal may also be a livestock animal, a pet animal, a laboratory animal, etc.

[0036] <Ingredients and condition of the composition> The composition of the present disclosure contains lactobionic acid or a salt thereof at any concentration within the range in which the effects of the present invention are obtained. For example, the composition of the present disclosure may contain lactobionic acid or a salt thereof in an amount of preferably 0.001 to 50 wt %, more preferably 0.01 to 20 wt %, and even more preferably 0.1 to 10 wt %, based on the total weight of the composition. Furthermore, the composition of the present disclosure may contain lactobionic acid or a salt thereof as a main component.

[0037] The composition of the present disclosure may contain any additives as long as the effects of the present invention are achieved. Non-limiting examples of additives include excipients, binders, fillers, disintegrants, surfactants, lubricants, dispersants, buffers, diluents, preservatives, flavoring agents, fragrances, etc.

[0038] The compositions of the present disclosure may be in a liquid or solid state.

[0039] <Pharmaceutical Composition> The composition of the present disclosure may be a pharmaceutical composition. The pharmaceutical composition may be a composition that is a medicine itself, or may be a composition used as a material for medicines. The pharmaceutical composition may be a prescription drug, an over-the-counter drug, or a quasi-drug.

[0040] The pharmaceutical compositions may be formulated into one or more dosage forms. The pharmaceutical composition can be administered to an individual systemically or locally at any administration frequency or interval as long as the effects of the present invention are achieved. Non-limiting examples of administration routes include oral administration, intravenous administration, intramuscular administration, intrathecal administration, sublingual administration, rectal administration, ocular administration, otic administration, transauricular administration, and transdermal administration.

[0041] The pharmaceutical composition may take any form as long as the effects of the present invention can be obtained. For example, the pharmaceutical composition may take the form of tablets, granules, powders, capsules, emulsions, suspensions, syrups, injections or drip infusions (sterile solutions, suspensions, etc.), etc.

[0042] <Food composition> The composition of the present disclosure may be a food composition. The food composition may be a composition that is a food in itself, or a composition that is used as a food ingredient. The food composition may be a general food, a health food (including a nutrient-functional food, a food for specified health uses, or a food with functional claims), a health food, a functional food, a nutritional supplement, a food for patients, or a food additive. The food composition may take any form as long as the effects of the invention can be obtained, for example, a drink, powder, paste, jelly, capsule, tablet, or the like. The food composition may be ingested alone or mixed with other foods and beverages. Non-limiting examples of other foods and beverages include oil-containing products such as edible oils, dressings, mayonnaise, and margarine; liquid foods such as soups, dairy drinks, soft drinks, tea drinks, alcoholic drinks, energy drinks, jelly drinks, and functional drinks; carbohydrate-containing foods such as rice dishes, noodles, and bread; processed livestock foods such as ham and sausage; processed seafood foods such as kamaboko, dried fish, and salted fish; processed vegetable foods such as pickles; semi-solid foods such as jelly and yogurt; fermented foods such as miso and fermented drinks; various confectioneries such as Western confectioneries, Japanese confectioneries, candies, chewing gum, gummy candies, frozen desserts, and frozen desserts; retort pouch products such as curry, thickened sweets, and Chinese soup; instant foods such as instant soup and instant miso soup, and microwaveable foods.

[0043] The food composition may be prepared as one or more food products. The food composition can be ingested by an individual at any frequency or interval as long as the effects of the invention are achieved.

[0044] <Evaluation of the effect of the composition> The effects of the compositions of the present disclosure can be evaluated using mice as a model organism. For example, the effects of the compositions of the present disclosure can be evaluated by analyzing the effects of administering lactobionic acid or a salt thereof (and, if an antibiotic is added, the antibiotic) on a decrease in body temperature and changes in the relative abundance of bacteria that constitute the intestinal flora in mice in which an allergic reaction has been induced by administering an allergen (e.g., ovalbumin). These evaluations can be appropriately performed by those skilled in the art using known methods.

[0045] <Other embodiments> In one embodiment, a method for inhibiting a decrease in body temperature is disclosed, comprising administering an effective amount of lactobionic acid or a salt thereof to an individual in need thereof.

[0046] In one embodiment, lactobionic acid or a salt thereof is disclosed for use in inhibiting a decrease in body temperature.

[0047] In one embodiment, the use of lactobionic acid or a salt thereof in suppressing a decrease in body temperature is disclosed.

[0048] In one embodiment, a method for altering the relative abundance of bacteria in the intestinal flora is disclosed, comprising administering an effective amount of lactobionic acid or a salt thereof to an individual in need thereof.

[0049] In one embodiment, lactobionic acid or a salt thereof is disclosed for use in modifying the relative abundance of bacteria in the intestinal flora.

[0050] In one embodiment, the use of lactobionic acid or a salt thereof to modify the relative abundance of bacteria in the intestinal flora is disclosed.

[0051] In one embodiment, a method for alleviating symptoms associated with an allergic reaction is disclosed, comprising administering to an individual in need thereof an effective amount of lactobionic acid or a salt thereof.

[0052] In one embodiment, lactobionic acid or a salt thereof is disclosed for use in alleviating symptoms associated with allergic reactions.

[0053] In one embodiment, the use of lactobionic acid or a salt thereof in alleviating symptoms associated with allergic reactions is disclosed.

[0054] In one embodiment, the use of lactobionic acid or a salt thereof in the preparation of the above composition is disclosed.

[0055] A non-limiting list of exemplary embodiments and combinations of exemplary embodiments of the present disclosure are disclosed below. [1] A composition for suppressing a decrease in body temperature, comprising lactobionic acid or a salt thereof. [2] The composition described in [1], wherein the decrease in body temperature is a decrease in body temperature associated with an allergic reaction. [3] The composition described in [2], wherein the allergic reaction is accompanied by anaphylaxis. [4] A composition according to any one of [1] to [3], which modifies the relative abundance of bacteria in the intestinal flora. [5] A composition described in any of [1] to [4], which increases the relative abundance in the intestinal flora of one or more bacteria selected from the group consisting of bacteria of the Lactobacillaceae family, bacteria of the Rikenellaceae family, bacteria of the Tannerellaceae family, and bacteria of the Lachnospiraceae family. [6] A composition described in any of [1] to [5], which increases the relative abundance of bacteria of the Bacteroidaceae family in the intestinal flora of an individual to whom an antibiotic has been administered. [7] A composition for alleviating symptoms associated with allergic reactions, comprising lactobionic acid or a salt thereof. [8] The composition described in [7], wherein the allergic reaction is accompanied by anaphylaxis. [9] A composition for modifying the relative abundance of bacteria in intestinal flora, comprising lactobionic acid or a salt thereof.

[10] The composition described in [9], which increases the relative abundance of one or more bacteria selected from the group consisting of bacteria of the Lactobacillaceae family, bacteria of the Rikenellaceae family, bacteria of the Tannerellaceae family, and bacteria of the Lachnospiraceae family in the intestinal flora.

[11] The composition described in [9] or

[10] , which increases the relative abundance of bacteria of the Bacteroidaceae family in the intestinal flora of an individual to whom an antibiotic has been administered.

[12] The composition according to any one of [1] to

[11] , which is administered to an individual in combination with an antibiotic.

[13] The composition according to any one of [1] to

[12] , which is a pharmaceutical composition.

[14] The composition according to any one of [1] to

[12] , which is a food composition. The configurations and combinations thereof in each embodiment are merely examples, and additions, omissions, substitutions, and other modifications of the configurations are possible as appropriate within the scope that does not deviate from the gist of this disclosure. [Example]

[0056] The present disclosure will be explained in more detail below by showing examples, but interpretation of the present disclosure is not limited to these examples.

[0057] [Example 1] As a model, BALB / cAJcl mice (4 weeks old, female, manufactured by CLEA Japan, n=7) were used to examine the effects of lactobionic acid according to the schedule shown in FIG. That is, after the 7-day acclimation period, administration of the aqueous lactobionic acid solution or water was started on day 1. A 1 wt % aqueous solution of lactobionic acid or water was administered to the mice by allowing them to drink water ad libitum for 21 days. On day 7, 10 μg / mouse of ovalbumin (OVA) was intraperitoneally administered as the first sensitization. On day 14, 10 μg of ovalbumin (OVA) was intraperitoneally administered to the mice as the second sensitization. On day 21, the mice were sacrificed by intraperitoneal administration of 200 μg of ovalbumin (OVA) per mouse.

[0058] As shown in Figure 2, the decrease in body temperature after the administration of ovalbumin (OVA) was suppressed by the administration of an aqueous lactobionic acid solution. Furthermore, the effect of the administration of an aqueous lactobionic acid solution in suppressing the decrease in body temperature continued for more than 120 minutes after administration. The decrease in body temperature was evaluated by placing a temperature sensor subcutaneously in the mice and measuring their body temperature every 10 minutes. This result indicates that lactobionic acid effectively suppresses the decrease in body temperature.

[0059] As shown in Figure 3, the concentrations of total IgE and mast cell protease (MCPT) 1 in serum each tended to decrease after administration of the lactobionic acid solution. These concentrations were measured using a commercially available ELISA kit (BioLegend) for serum collected within 30 minutes after the final sensitization. This result suggests that lactobionic acid may inhibit mast cell degranulation.

[0060] As shown in Figure 4, the relative abundance of bacteria in the intestinal flora of individuals administered lactobionic acid was significantly different from that of control individuals. Furthermore, the difference became more pronounced over time. The q value for the relative abundance of bacteria in the intestinal flora of individuals administered lactobionic acid and that of control individuals on day 21 was 0.025.

[0061] Furthermore, as shown in Table 1, the relative abundance of bacteria in the intestinal flora of individuals administered lactobionic acid was significantly different from the relative abundance of bacteria in the intestinal flora of individuals administered water. For example, the relative abundance of Lactobacillus (family Lactobacillaceae), Alistipes (family Rikenellaceae), Parabacteroides (family Tannerellaceae), and Lachnospiraceae UCG-006 (family Lachnospiraceae) increased, while the relative abundance of Bacteroides (family Bacteroidaceae), Akkermansia (family Akkermansiaceae), Dubosiella (family Erysipelotrichaceae), etc. decreased in individuals administered lactobionic acid.

[0062] [Table 1]

[0063] Table 1 shows the relative abundance (%) of bacteria in the intestinal flora of individuals 21 days after administration of water or lactobionic acid. Bacterial DNA was extracted from feces, and the DNA samples were amplified by PCR using primers specific to the variable region of the 16S rRNA gene and sequenced. The relative abundance of bacteria was determined by determining the proportion of sequences derived from each bacterium among the 8,000 to 10,000 sequence reads.

[0064] These results indicate that lactobionic acid effectively modifies the relative abundance of bacteria in the intestinal flora.

[0065] As shown in Figure 5, in the individuals on day 21, the relative abundance of Lactobacillus (Lactobacillaceae family bacteria), Alistipes (Rikenellaceae family bacteria), Parabacteroides (Tannerellaceae family bacteria), and Lachnospiraceae UCG-006 (Lachnospiraceae family bacteria) was significantly increased in the intestinal flora of individuals administered lactobionic acid compared to the intestinal flora of control individuals. This result indicates that lactobionic acid increases the relative abundance of these bacteria in the intestinal flora.

[0066] [Example 2] BALB / cAJcl mice (4-week-old, female, manufactured by CLEA Japan, n=7 or 8) were used as a model to examine the effects of lactobionic acid and / or antibiotics according to the schedule shown in Figure 6. A cocktail of vancomycin, streptomycin, and ampicillin was used as the antibiotics. After a 7-day acclimation period, which was designated Day 1, mice were given a 1 wt% lactobionic acid solution or water by allowing them to drink freely from Day 1 onwards. From Day 1 onwards, 200 μL of an antibiotic solution (0.25 g / L vancomycin, 5.0 g / L streptomycin, 1.0 g / L ampicillin) was orally administered to the mice by force every two days. On day 7, 10 μg / animal of ovalbumin (OVA) was intraperitoneally administered as the first sensitization. On the 14th day, 10 μg / animal of ovalbumin (OVA) was intraperitoneally administered as the second sensitization. On day 21, the mice were sacrificed by intraperitoneal administration of 200 μg / mouse of ovalbumin (OVA).

[0067] As shown in Figure 7, the decrease in body temperature of individuals administered with the lactobionic acid aqueous solution or the antibiotic aqueous solution was suppressed compared to the decrease in body temperature of individuals administered with water. Furthermore, the decrease in body temperature in the individuals administered with lactobionic acid and antibiotics was more significantly suppressed than the decrease in body temperature in the individuals administered with water or an aqueous antibiotic solution. This result indicates that the combined use of lactobionic acid and antibiotics synergistically inhibits the decrease in body temperature.

[0068] As shown in Table 2A, the relative abundance of bacteria in the intestinal flora of mice administered an aqueous solution containing lactobionic acid and antibiotics on day 21 was significantly different from that of mice administered an aqueous solution of lactobionic acid, an aqueous solution of antibiotics, or water. For example, the relative abundance of Bacteroides (Bacteroidaceae bacteria) was increased. Table 2B shows the relative abundance of bacteria in mice on day 0.

[0069] [Table 2A]

[0070] [Table 2B]

[0071] Tables 2A and 2B show the relative abundance (%) of bacteria in the intestinal flora of individuals on days 21 and 0 after administration of water, lactobionic acid, antibiotics, or both. Bacterial DNA was extracted from feces, and the DNA samples were amplified by PCR using primers specific to the variable region of the 16S rRNA gene and sequenced. The relative abundance of bacteria was determined by determining the proportion of sequences derived from each bacterium among the 8,000 to 10,000 sequence reads.

[0072] The results indicate that the combination of lactobionic acid and antibiotics effectively alters the relative abundance of bacteria in the intestinal flora.

[0073] As shown in Figure 8, the administration of lactobionic acid and / or antibiotics did not change the total number of bacteria in the intestinal flora. The total number of bacteria in the intestinal flora was measured by extracting DNA from feces and quantifying it by real-time PCR using primers specific to the variable region of the 16S rRNA gene, with the genome of Escherichia coli, of which the bacterial count is known, as a standard. Antibiotics are known to reduce the total number of bacteria in the intestinal flora, and therefore, the results indicate that lactobionic acid inhibits the reduction in the total number of bacteria in the intestinal flora caused by antibiotics.

[0074] As shown in Figure 9, in individuals on day 21, the relative abundance of Bacteroides (Bacteroidaceae bacteria) was increased in the intestinal flora of individuals administered lactobionic acid and antibiotics compared to the intestinal flora of control individuals or individuals administered an aqueous lactobionic acid solution or an aqueous antibiotic solution. These results indicate that the combined use of lactobionic acid and antibiotics synergistically increases the relative abundance of bacteria of the Bacteroidaceae family in the intestinal flora.

[0075] As shown in Figure 10, when the correlation between the relative abundance of bacteria in the intestinal flora and body temperature in individuals administered lactobionic acid and antibiotics was analyzed, a negative correlation was found between the relative abundance of bacteria of the Bacteroidaceae family and body temperature. On the other hand, a positive correlation was found between the relative abundance of bacteria other than bacteria of the Bacteroidaceae family and body temperature for all bacteria. These results indicate that in individuals administered lactobionic acid and antibiotics, the increase in the relative abundance of bacteria of the Bacteroidaceae family in the intestinal flora is involved in the suppression of body temperature reduction.

Claims

1. A composition for suppressing a decrease in body temperature, comprising lactobionic acid or a salt thereof.

2. The composition according to claim 1, wherein the decrease in body temperature is a decrease in body temperature associated with an allergic reaction.

3. The composition of claim 2, wherein the allergic reaction involves anaphylaxis.

4. The composition of claim 1, which alters the relative abundance of bacteria in the intestinal flora.

5. 2. The composition of claim 1, which increases the relative abundance in intestinal flora of one or more bacteria selected from the group consisting of bacteria of the Lactobacillaceae family, bacteria of the Rykenellaceae family, bacteria of the Tannerellaceae family, and bacteria of the Lachnospiraceae family.

6. 2. The composition of claim 1, which increases the relative abundance of bacteria of the Bacteroidaceae family in the intestinal flora of an individual receiving an antibiotic.

7. A composition for alleviating symptoms associated with allergic reactions, comprising lactobionic acid or a salt thereof.

8. The composition of claim 7, wherein the allergic reaction involves anaphylaxis.

9. A composition for modifying the relative abundance of bacteria in the intestinal flora, comprising lactobionic acid or a salt thereof.

10. 10. The composition of claim 9, which increases the relative abundance of one or more bacteria selected from the group consisting of bacteria of the Lactobacillaceae family, bacteria of the Rykenellaceae family, bacteria of the Tannerellaceae family, and bacteria of the Lachnospiraceae family in intestinal flora.

11. 10. The composition of claim 9, which increases the relative abundance of bacteria of the Bacteroidaceae family in the intestinal flora of an individual receiving an antibiotic.

12. 12. The composition of any one of claims 1 to 11, administered to an individual in combination with an antibiotic.

13. 12. The composition of any one of claims 1 to 11, which is a pharmaceutical composition.

14. 12. The composition of any one of claims 1 to 11, which is a food composition.

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