Method for relieving food allergy by fucosylated human milk oligosaccharide

By using fucoidylated human milk oligosaccharides, especially difucosylated lactose, the fucoidation of the intestinal mucosa is promoted, the intestinal barrier function is enhanced, and the immune response is regulated. This solves the problems of intestinal barrier damage and immune imbalance in food allergies and achieves effective relief of food allergies.

CN121817486APending Publication Date: 2026-04-10NORTHEAST AGRICULTURAL UNIVERSITY
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2026-01-13
Publication Date
2026-04-10

AI Technical Summary

Technical Problem

In the current technology, the pathogenesis of food allergies is complex, and it is difficult to effectively intervene in cases of impaired intestinal barrier function and immune imbalance. There is a lack of systematic research on the mechanism of action of fucoidylated human milk oligosaccharides in alleviating food allergies.

Method used

Human lactose oligosaccharides with different fucosylation structures, such as 2'-fucosylated lactose, 3-fucosylated lactose, or difucosylated lactose, can enhance intestinal barrier function and regulate immune responses associated with food allergies by promoting fucosylation of the intestinal mucosa.

Benefits of technology

By enhancing the intestinal barrier function, reducing the entry of allergens, regulating the immune response, improving the immune imbalance, and significantly alleviating food allergy symptoms.

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Abstract

The invention relates to the technical field of food nutrition and immune regulation, and provides a method for relieving food allergy. The method comprises providing an effective amount of a fucosylated human milk oligosaccharide to a subject in need of ameliorating food allergy. The fucosylated human milk oligosaccharide is a human milk oligosaccharide with a fucosylated structure, and is selected from 2 '-fucosyllactose, 3-fucosyllactose, difucosyllactose or a combination of the 2'-fucosyllactose, the 3-fucosyllactose and the difucosyllactose. According to the present invention, by promoting the improvement of the fucosylation level of the intestinal mucosa, the intestinal barrier function is enhanced, and the immune response associated with food allergy is regulated so as to prevent or alleviate the food allergy. A new technical scheme is provided for application of the fucosylated human milk oligosaccharide in the field of food allergy intervention, and the fucosylated human milk oligosaccharide has a good application prospect.
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Description

Technical Field

[0001] This invention relates to the field of food nutrition and immune regulation technology, specifically to the application of fucoidylated human milk oligosaccharides in alleviating food allergies, and more particularly to a method for alleviating food allergies by promoting intestinal fucoidylation, enhancing intestinal barrier function, and regulating immune responses. Background Technology

[0002] Food allergies are a type of abnormal immune response induced by specific food components. In recent years, their incidence has been rising globally, becoming a significant public health issue affecting the health of infants, young children, and some adults. Food allergies are usually related to the disruption of intestinal immune tolerance. Their main characteristic is that after allergens enter the body through the intestinal mucosa, they trigger a series of immune responses centered on the production of allergen-specific IgE, mast cell activation, and the release of inflammatory mediators, leading to symptoms in multiple systems, including the skin, digestive tract, and respiratory system.

[0003] Existing research indicates that the intestinal barrier function plays a crucial role in the occurrence and development of food allergies. Under normal circumstances, the intestinal mucosa, through the combined action of tight junctions of epithelial cells and the mucus layer, restricts the permeation of allergens and harmful substances. However, when the intestinal barrier is damaged or its permeability increases, allergens can more easily cross the intestinal barrier and come into contact with the immune system, thereby inducing abnormal immune responses. Therefore, enhancing intestinal barrier function is considered one of the important directions for intervening in and alleviating food allergies.

[0004] Fucosylation, as an important form of glycan modification in the intestinal mucosa, plays a crucial role in maintaining intestinal barrier integrity and regulating intestinal immune homeostasis. The intestinal mucus layer is rich in fucose-modified glycoproteins and glycolipids, which not only participate in building the physical barrier but also influence the composition of the intestinal microbiota and the function of immune cells. However, under inflammatory conditions such as allergies, the level of fucosylation in the intestinal mucosa may decrease, thereby weakening mucosal barrier function and exacerbating immune imbalance.

[0005] Human milk oligosaccharides, as important bioactive components in breast milk, have been shown to have potential roles in regulating the intestinal microenvironment and immune function. Among them, fucoidylated human milk oligosaccharides have attracted widespread attention due to their structural characteristics. However, in the current technology, there is a lack of systematic research on the differences in the effects of human milk oligosaccharides with different fucoidylation structures in alleviating food allergies and their relationship with the intestinal barrier and immune regulation, and the relevant mechanisms of action need to be further clarified.

[0006] Therefore, there is an urgent need for a technical solution that can effectively enhance intestinal barrier function and regulate immune response to alleviate food allergies, in order to meet the application needs of related fields. Summary of the Invention

[0007] To address the challenges of complex mechanisms, impaired intestinal barrier function, and difficulty in effectively intervening in immune imbalances associated with food allergies in existing technologies, this invention aims to provide a method for alleviating food allergies using fucoidylated human milk oligosaccharides. This invention utilizes human milk oligosaccharides with different fucoidylation structures to promote intestinal fucoidation levels, enhance intestinal barrier function, and regulate the immune response associated with food allergies, thereby alleviating food allergy symptoms.

[0008] In a first aspect, the present invention provides a fucoidylated human milk oligosaccharide for relieving food allergies, wherein the fucoidylated human milk oligosaccharide is selected from at least one of the following: 2'-fucosylated lactose (2'-FL), 3-fucosylated lactose (3-FL), or difucosylated lactose (DFL).

[0009] In one embodiment of the present invention, the fucoidylated human milk oligosaccharide enhances the intestinal barrier function by increasing the fucoidylation level of the intestinal mucosa, thereby reducing the entry of allergens into the body via the intestine.

[0010] In one embodiment of the present invention, the fucoidylated human milk oligosaccharide is difucosylated lactose.

[0011] In a second aspect, the present invention provides the use of the above-described fucoidylated human milk oligosaccharide in the preparation of formulations or food compositions for alleviating food allergies.

[0012] In one embodiment of the present invention, the formulation or food composition is used to reduce the occurrence of food allergy-related immune responses or alleviate food allergy symptoms.

[0013] A third aspect of the present invention provides a method for alleviating food allergies, comprising providing an effective amount of fucoidylated human lactose oligosaccharide to a person who needs to alleviate food allergies.

[0014] In one embodiment of the present invention, the method enhances intestinal barrier function by promoting fucosylation of the intestinal mucosa, thereby alleviating food allergies.

[0015] In one embodiment of the invention, the method further includes modulating the immune response associated with food allergies.

[0016] Compared with the prior art, the present invention has at least the following advantages and beneficial effects: This invention provides a new technical approach to alleviating food allergies from the perspective of regulating intestinal barrier function by employing fucoidylated human milk oligosaccharides. This invention can enhance the integrity of the intestinal mucosal barrier by promoting intestinal fucoidylation, thereby reducing the stimulation of the body's immune system by allergens; This invention helps to regulate immune responses associated with food allergies and improve immune imbalances. Human milk oligosaccharides with different fucoidylation structures have varying effects in alleviating food allergies, with difucosylated lactose showing better application potential. This invention provides a new technical approach and theoretical basis for the application of fucoidylated human milk oligosaccharides in the field of food allergy intervention. Attached Figure Description

[0017] Figure 1 This is a schematic diagram of the allergic reaction in mice under different fucoidylated human milk oligosaccharides interventions; where (a) is a schematic diagram of the changes in mouse body weight during the experiment, and (b) is the allergic symptom score of the mice; Figure 2 This is a schematic diagram showing the changes in the morphology of immune organs and intestines in experimental mice under different fucoidylated human milk oligosaccharides; where (a) is the spleen index of mice and (b) is the change in colon length of mice. Figure 3 A schematic diagram showing the changes in the number of mast cells in experimental mice under different fucoidylated human milk oligosaccharides intervention; Figure 4 This is a schematic diagram showing the detection results of biochemical indicators related to allergic reactions in experimental mice under different fucoidosylated human lactose interventions; where (a) is the level of β-lactoglobulin-specific IgE in mouse serum, (b) is the level of mast cell protease-1 in mouse serum, and (c) is the level of histamine in mouse plasma. Figure 5 This is a schematic diagram showing the detection results of immune balance-related indicators in experimental mice under different fucoidylated human milk oligosaccharides intervention; where (a) is the immunofluorescence staining of Th1 and Th2 cells in mouse spleen, and (b) is the level of cytokines in mouse serum. Figure 6 This is a schematic diagram showing the detection results of intestinal barrier function-related indicators in experimental mice under different fucosylated human milk oligosaccharides intervention; where (a) is the degree of fucosylation characterized by UEA-I staining of mouse colon, and (b) is the level of intestinal permeability markers in mouse serum. Detailed Implementation

[0018] To make the technical objectives, technical solutions, and beneficial effects of the present invention clearer, the present invention will be further described below in conjunction with specific embodiments and experimental examples. It should be understood that, unless otherwise specified, the technical features in the embodiments and experimental examples of the present invention can be combined with each other, and the scope of protection of the present invention is not limited by the following specific content.

[0019] Example

[0020] This embodiment provides a method for alleviating food allergies, including providing an effective amount of fucoidylated human lactose oligosaccharide to a person who needs to alleviate food allergies.

[0021] In this embodiment, the fucoidylated human milk oligosaccharide is a human milk oligosaccharide with a fucoidylated structure, and its source is not limited by a specific preparation method. For example, it can be obtained through human milk separation, chemical synthesis, biosynthesis, enzymatic synthesis, or other equivalent methods. The fucoidylated human milk oligosaccharide can be selected from 2'-fucosylvose, 3-fucosylvose, difucosylvose, or combinations thereof.

[0022] In some embodiments, the fucoidylated human milk oligosaccharide may be used alone or in combination with excipients acceptable in the food, nutrition or medical fields, and provided to the subject in a form suitable for ingestion or action on the intestine, such as oral, enteral administration or other methods acceptable to those skilled in the art.

[0023] In some embodiments, the method modulates intestinal mucosal function to promote increased intestinal fucosylation levels, thereby enhancing intestinal barrier function and reducing the likelihood of allergens entering the body via the intestine.

[0024] In some embodiments, the method further includes modulating the immune response associated with food allergies to improve immune imbalance, reduce the risk of food allergy reactions, or alleviate food allergy symptoms.

[0025] In some embodiments, the method can be used to prevent or alleviate food allergic reactions caused by a variety of food allergens, including but not limited to milk protein, eggs, nuts, grains, aquatic products and their products.

[0026] Example

[0027] A preferred embodiment of the method described in Example 1 Based on the method for alleviating food allergies described in Example 1, this example provides a preferred embodiment, wherein the fucoidylated human milk oligosaccharide is difucosylated lactose.

[0028] In this embodiment, the difucosyl lactose has at least two fucose residues, and its structural features enable it to participate more fully in intestinal mucosa-related biological processes, thereby showing better application potential in enhancing intestinal barrier function and regulating immune response.

[0029] In some embodiments, the method enhances the integrity of the intestinal barrier and reduces intestinal permeability by promoting increased fucosylation levels in the intestinal mucosa, thereby reducing the chances of allergens coming into contact with the body's immune system.

[0030] In some embodiments, the method also promotes the restoration of immune balance and inhibits the overactivation of allergy-related immune processes by modulating the immune response associated with food allergies.

[0031] In some embodiments, the fucosyl lactose may be used alone or in combination with the food, nutritional or medically acceptable excipients described in Example 1, and provided to the subject in a form suitable for ingestion or action on the intestine.

[0032] Experimental Example 1: Effects of different fucoidylated human milk oligosaccharides on the overall phenotype of food allergy To verify the effects of different fucoidosylated human milk oligosaccharides in alleviating food allergies, an animal model of food allergy was established using an allergen-induced method, and the overall phenotypic changes under different intervention conditions were compared and analyzed.

[0033] After acclimatization, the experimental animals were randomly divided into a blank control group, a model control group, and experimental groups treated with different fucoidosylated human milk oligosaccharides. During the experimental period, all groups of animals received routine feeding and appropriate treatment.

[0034] During the experiment, the weight of each group of animals was dynamically monitored to assess the impact of different intervention conditions on their overall physiological state. After allergen stimulation, the animals' behavioral performance was observed within a predetermined time period, and allergy symptoms were scored according to a pre-defined scoring standard.

[0035] After the experiment, the experimental animals were euthanized, the spleen was removed and weighed, and the spleen index was calculated to assess the status of the immune organs; at the same time, the colon tissue was removed and the length of the colon was measured in its naturally extended state to reflect changes in intestinal structure.

[0036] like Figure 1 and Figure 2 As shown, compared with the model control group, the animals' overall phenotypic indicators, such as body weight change trend, allergy symptom score, spleen index, and colon length, were all improved to varying degrees after intervention with fucoidylated human lactose. Among them, the fucosylated lactose intervention group showed more significant improvements in multiple indicators.

[0037] Experimental Example 2: Effects of different fucoidylated human milk oligosaccharides on mast cell activation and allergic effect indicators To further verify the effects of different fucoidylated human milk oligosaccharides on the allergic response process in alleviating food allergies, a food allergy animal model was used to detect and compare mast cell activation status and biochemical indicators related to allergic reactions.

[0038] During the experiment, relevant tissue and blood samples were collected from the experimental animals after allergen stimulation. Among them, some tissue samples were used for mast cell staining and observation. Mast cells were labeled using toluidine blue staining, and multiple fields of view were randomly selected under a microscope for observation and counting to evaluate the distribution and number changes of mast cells under different intervention conditions.

[0039] Simultaneously, blood samples were collected from experimental animals, and serum or plasma was separated. Immunological detection methods were used to detect biochemical indicators related to allergic reactions, including the levels of allergen-specific immunoglobulins, mast cell degranulation-related mediators, and mast cell activation-related proteins, to reflect the degree of activation of allergic reactions.

[0040] like Figure 3 and Figure 4 As shown, compared with the model control group, the number of mast cells in the experimental animal tissues and the levels of allergy-related biochemical indicators in the blood all showed a decreasing trend after intervention with fucoidylated human lactose. Among them, the difucosylated lactose intervention group showed a more significant improvement in inhibiting mast cell activation and reducing allergy effect indicators.

[0041] Experimental Example 3: The Regulatory Effects of Different Fucosylated Human Milk Oligosaccharides on Immune Homeostasis To verify the regulatory effect of different fucoidosylated human milk oligosaccharides on immune balance in alleviating food allergies, an animal model of food allergy was used to detect and compare the levels of immune-related cytokines and the differentiation status of immune cells.

[0042] During the experiment, blood samples were collected from experimental animals after allergen stimulation, and serum was obtained to detect the levels of cytokines related to immune homeostasis. The detection indicators included cytokines reflecting the functional status of Th1 cells and Th2 cells, to evaluate changes in Th1 / Th2 immune homeostasis under different intervention conditions. Simultaneously, immune-related tissue samples from the experimental animals were collected, and immunofluorescence staining was used to label and observe different T cell subsets to assess changes in immune cell differentiation and distribution under different intervention conditions.

[0043] like Figure 5 As shown, compared with the model control group, intervention with fucosylated human lactose oligosaccharides altered the levels of immune homeostasis-related cytokines in the serum of experimental animals, and improved the distribution of T cell subsets in immune tissues to varying degrees. Among them, the fucosylated lactose intervention group showed a more significant improvement in regulating immune homeostasis.

[0044] Experiment 4: Effects of different fucoidylated human milk oligosaccharides on intestinal barrier function To verify the effects of different fucoidylated human milk oligosaccharides on intestinal barrier function during the process of alleviating food allergies, a food allergy animal model was used to detect and compare the relevant structural features of the intestinal mucosa and intestinal permeability-related indicators.

[0045] During the experiment, colon tissue samples were collected from the experimental animals after the experiment. The degree of fucosylation in the colonic mucosa was detected using the lectin affinity fluorescent labeling method to evaluate the changes in the level of intestinal mucosal fucosylation under different intervention conditions. At the same time, blood samples were collected from the experimental animals, serum was obtained, and biochemical indicators related to intestinal permeability were detected to reflect changes in the state of intestinal barrier function.

[0046] like Figure 6 As shown, compared with the model control group, intervention with fucosylated human lactose oligosaccharides increased the degree of fucosylation in the colonic mucosa of experimental animals and altered the levels of serum intestinal permeability-related indicators, indicating varying degrees of improvement in intestinal barrier function. Among them, the fucosylated lactose intervention group showed a more significant improvement in enhancing intestinal barrier function.

Claims

1. A method for relieving food allergies, characterized in that, This includes providing effective amounts of fucoidoylated human milk oligosaccharides to individuals who need relief from food allergies.

2. The method according to claim 1, characterized in that, The fucoidylated human milk oligosaccharide is a human milk oligosaccharide with a fucoidylated structure.

3. The method according to claim 1 or 2, characterized in that, The fucosylated human milk oligosaccharide is selected from 2'-fucosylated lactose, 3-fucosylated lactose, difucosylated lactose, or combinations thereof.

4. The method according to claim 3, characterized in that, The fucosylated human milk oligosaccharide is difucosylated lactose.

5. The method according to any one of claims 1 to 4, characterized in that, The method enhances intestinal barrier function by promoting increased fucosylation levels in the intestinal mucosa.

6. The method according to any one of claims 1 to 5, characterized in that, The method is used to improve immune balance by modulating the immune response associated with food allergies.

7. The method according to any one of claims 1 to 6, characterized in that, The method described is used to prevent or alleviate food allergy reactions.

8. The method according to claim 7, characterized in that, The food allergy reaction is caused by one or more of the following food allergens: milk protein, eggs, nuts, grains, and seafood.

9. The method according to any one of claims 1 to 8, characterized in that, The fucoidylated human milk oligosaccharide is provided to the subject in a form suitable for ingestion or action in the intestine.

10. The method according to claim 9, characterized in that, The fucoidylated human milk oligosaccharide is used in conjunction with excipients acceptable in the food, nutrition, or medical fields.