A probiotic having an effect of preventing and treating allergic diseases caused by casein

Abstract

The application discloses a postbiotic with the effect of preventing and treating allergic diseases caused by casein, and belongs to the technical field of microorganisms. The postbiotic is prepared by the following method: fermenting Lactobacillus muciadegradus bacterial liquid in MRS culture medium, culturing at 30-40 DEG C for 12-48 h, until the bacterial liquid concentration is at least 1x10 9 CFU / mL; then sterilizing, centrifuging, collecting supernatant, and obtaining the postbiotic of the fermented Lactobacillus muciadegradus. The postbiotic can relieve allergic reactions caused by casein, thereby having good application prospect and value in preventing and treating cow milk allergy.

Description

Technical Field

[0001] This invention belongs to the field of microbial technology, specifically relating to a metabiotic that has the effect of preventing and treating allergic diseases caused by casein. Background Technology

[0002] Milk allergy is one of the most common food allergies in infants and young children, with a continuously rising global incidence rate, making it a global public health issue. Casein is one of the main allergens in cow's milk, and the allergic reactions it induces mainly manifest as diarrhea, eczema, vomiting, and splenomegaly. In severe cases, it can lead to anaphylactic shock and endanger life. Currently, the core clinical approach to the prevention and treatment of milk casein allergy is strict allergen avoidance. However, this method easily leads to malnutrition and growth retardation in infants and young children, and cannot fundamentally correct the body's immune imbalance. While specific immunotherapy is a causal treatment, it suffers from a high incidence of adverse reactions and difficulty in maintaining long-term immune tolerance. Symptomatic treatments such as antihistamines and corticosteroids can only relieve symptoms and cannot cure the allergy; long-term use also has side effects, limiting their application in infants and young children. Therefore, developing a mild, side-effect-free, and highly effective anti-allergy agent is of significant value for the prevention and treatment of milk allergy in infants and young children. Summary of the Invention

[0003] This invention provides a postbiotic derived from fermented *Lactobacillus mucilaginosus*, prepared by the following method: Inoculate the *Lactobacillus fermentans* culture into MRS medium and incubate at 30–40°C for 12–48 h until the bacterial concentration reaches at least 1 × 10⁻⁶. 9 CFU / mL; then sterilize, centrifuge, collect the supernatant to obtain fermented Lactobacillus mucinus postbiotic.

[0004] In the above technical solution, the fermenting Lactobacillus mucinus is deposited at the China General Microbiological Culture Collection Center, with accession number CGMCC No. 39247.

[0005] In the above technical solution, the bacterial content in the fermented *Lactobacillus mucinus* bacterial solution is at least 1×10⁻⁶. 9 CFU / mL; the inoculum size is 1-5%, V / V.

[0006] This invention provides the application of the above-mentioned metabiotic in the preparation of formulations that correct Th1 / Th2 immune imbalance.

[0007] This invention provides the application of the above-mentioned metagenics in the preparation of formulations that repair damaged intestinal mucosa, reduce intestinal inflammatory response, or improve intestinal barrier structure disruption; the intestinal mucosal damage, intestinal inflammation, and intestinal barrier disruption are caused by casein allergic reactions.

[0008] This invention provides the application of the above-mentioned metabiotics in the preparation of formulations for repairing the intestinal microbiota.

[0009] This invention provides the application of the above-mentioned metagenic agent in the preparation of formulations for preventing and treating allergic reactions caused by casein.

[0010] This invention provides the application of the above-mentioned post-biotic in the preparation of formulations for preventing and treating bovine milk allergy.

[0011] This invention provides a milk allergy reliever containing the aforementioned fermented Lactobacillus mucinus postbiotic; the reliever may also contain other biologically acceptable excipients.

[0012] The beneficial effects of this invention are as follows: This invention develops an epigenetic agent prepared from fermented Lactobacillus mucilaginosus. This epigenetic agent can alleviate allergic reactions caused by casein, thus showing good application prospects and value in the prevention and treatment of cow's milk allergy.

[0013] This post-biotic can significantly increase the expression levels of the protective Th1 cytokine IFN-γ and the intestinal anti-inflammatory factor IL-10, while simultaneously downregulating the secretion of pro-allergic Th2 cytokines IL-4 and IL-13, increasing the IFN-γ / IL-4 ratio. It can also significantly reduce the levels of serum IgE, mast cell protease MMCP-1, histamine, and intestinal inflammatory IgG in sensitized individuals, inhibit the mast cell degranulation process, and block the amplification of the allergic inflammatory cascade.

[0014] This metabiotic can also significantly upregulate the expression levels of intestinal tight junction proteins Claudin1 and Occludin, reduce intestinal permeability, repair colonic tissue pathological damage caused by casein stimulation, restore the intact morphology of intestinal villi and normal crypt structure, reduce inflammatory cell infiltration in the intestinal lamina propria, alleviate intestinal edema, damage and local inflammation, and can also reduce the water content of feces in allergic animals to improve diarrhea symptoms associated with allergies, and downregulate the spleen index to alleviate splenomegaly and excessive activation of the systemic immune system induced by allergies.

[0015] Furthermore, this postbiotic can effectively reshape the disordered gut microbiota under allergic conditions. At the phylum level, it upregulates Firmicutes abundance and downregulates Bacteroidetes abundance, restoring the normal Firmicutes / Bacteroidetes ratio. At the genus level, it inhibits the abnormal proliferation of pro-inflammatory and sensitizing bacteria such as Bacteroidetes, Mucor, and Duncanella, and enriches beneficial bacteria such as Akkermansia, Rosette, Broutbacter, Eubacterium, and Odorbacterium, which have both anti-inflammatory and intestinal barrier protection functions. The results of microbiota correlation analysis show that pro-inflammatory bacteria are significantly positively correlated with various allergy mediators, and beneficial bacteria are significantly positively correlated with protective cytokines and intestinal tight junction proteins, confirming that this postbiotic can achieve long-term anti-allergy regulation based on the "microbiota-gut-immune axis". Attached Figure Description

[0016] Figure 1 The colony morphology of strain CSProbio-K2 is shown.

[0017] Figure 2 The image shows the microscopic morphology of strain CSProbio-K2.

[0018] Figure 3 The effect of post-genetic agents on mouse spleen cytokines; where A is IFN-γ, B is IL-4, and C is IFN-γIL-4 / .

[0019] Figure 4 The effect of postbiotics on fecal water content in mice.

[0020] Figure 5 The effect of post-biotics on the spleen index in mice.

[0021] Figure 6 The effect of postbiotics on factors in mouse serum; where A is IgE, B is MMCP-1, C is Histamine, D is IFN-γ, E is IL-4, and F is IFN-γIL-4 / .

[0022] Figure 7 The effect of postbiotics on allergy-related factors in mouse ileum tissue; where A is IL-10, B is IL-13, and C is IgG.

[0023] Figure 8 The effect of metabiotics on tight junction proteins in the mouse intestine; where A is Claudin1 and B is Occludin.

[0024] Figure 9 The effect of postbiotics on the intestinal structure of mice was investigated; where A was the blank group (Normal), B was the casein sensitization group (Allergy), and C was the postbiotic group (Postbio-M2).

[0025] Figure 10 The effect of metabiotics on the composition of the gut microbiota in mice; where A represents the phylum level and B represents the genus level.

[0026] Figure 11 Spearman correlation analysis of mouse gut microbiota and allergy-related factors. Detailed Implementation

[0027] Strains Isolation and Identification 1. Strains Isolation On July 7, 2023, samples were collected from the intestines of a 96-year-old male at a nursing home in Weihai City. The samples were placed in sterile MRS liquid culture medium and incubated for 1-2 days with shaking. Then, the medium was serially diluted with physiological saline, with 200 μL of each diluted medium being transferred to solid culture medium and spread. The medium was then incubated upside down for 2-3 days. Colonies with different morphologies were picked and streaked, and after isolation and purification, a bacterial strain was obtained and named CSProbio-K2.

[0028] 2. Strain identification Morphological characteristics: Colony morphology of strain CSProbio-K2 on MRS agar medium (aerobic incubation at 37°C for 24 h), such as... Figure 1 and Figure 2 As shown, the colonies are round, gray, small, with a smooth, moist, slightly raised, and opaque surface.

[0029] Biological characteristics: Gram staining is purple, indicating that the bacterium is a Gram-positive bacterium.

[0030] Genetic characterization: 16S rRNA gene analysis was performed. Genomic DNA was extracted from strain CSProbio-K2, and PCR amplification was performed using universal primers for the 16S rRNA gene. Sequencing yielded a 1493 bp gene sequence, as shown below: Based on the sequence homology comparison of standard strains in the EZBioCloud database, the 16S rRNA gene of strain CSProbio-K2 showed 99.80% homology with the 16S rRNA gene of the standard strain *Limosilactobacillus fermentum* strain NBRC 15885. Based on morphological characteristics, biological, physiological, and biochemical characteristics, and gene sequence characteristics, strain CSProbio-K2 was identified as *Lentilactobacillus fermentum*. This bacterium was deposited on June 15, 2026, at the China General Microbiological Culture Collection Center (CGMCC, address: No. 3, Courtyard 1, Beichen West Road, Chaoyang District, Beijing, Institute of Microbiology, Chinese Academy of Sciences, 100101, China), with accession number CGMCC No. 39247.

[0031] Lactobacillus fermentum is a widely used probiotic strain in the Lactobacillus genus. This strain is widely found in the human gut, fermented foods and the natural environment. It has a good ability to colonize the gut. Its live bacteria and metabolites have a variety of probiotic functions, such as regulating the body's immune balance, repairing the intestinal mucosal barrier and regulating the structure of the gut microbiota. It has shown excellent effects in maintaining intestinal health and inhibiting inflammatory responses.

[0032] Other materials used in this invention, unless otherwise stated, are commercially available. Other terms used in this invention, unless otherwise specified, generally have the meanings commonly understood by those skilled in the art. The invention is further described in detail below with reference to specific embodiments and data. The following embodiments are merely illustrative and not intended to limit the scope of the invention in any way.

[0033] Example 1

[0034] The steps for preparing Postbio-M2 are as follows: The *Lactobacillus fermentata* was removed from a -80 °C freezer and inoculated (2% inoculum) into MRS medium. It was then incubated at 37 °C for 24 h, and continuously activated up to the third generation using a 2% (v / v) inoculum. The cultured bacterial solution was centrifuged at 4 °C and 4000 r / min for 10 min, the supernatant was discarded, and the culture was reconstituted with 5 mL of physiological saline. The total bacterial count was determined using a hemocytocyte count. The bacterial solution was diluted with physiological saline to obtain the desired concentration: *Lactobacillus fermentata* (1 × 10⁻⁶) 9 (CFU / mL).

[0035] Inoculate the *Lactobacillus fermentata* culture at a volume fraction of 2% (V / V) into MRS medium and incubate at 37 °C for 24 h until the bacterial concentration reaches at least 1 × 10⁻⁶. 9 CFU / mL, autoclave at 121 ℃ for 15 min, centrifuge at 4600×g at 4 ℃ for 10 min, and collect the supernatant, which is Postbio-M2.

[0036] I. Effects of metagenerogen on spleen cells of casein-sensitized mice Isolation of mouse spleen cells Female Balb / c mice approximately six weeks old were selected and euthanized by cervical dislocation. The mice were then immersed in 75% ethanol for 5 minutes, dissected, and the spleen was removed. The spleen was placed in a sterile culture dish, and 5 mL of RPMI-1640 incomplete culture medium was added. Excess fat and tissue were removed using scissors and forceps. The spleen was homogenized to obtain a tissue homogenate. The homogenate was poured into a 70 μm cell filter, and the filter was washed with 2 mL of incomplete culture medium. The cells were centrifuged to obtain a cell pellet, and then an appropriate amount of erythrocyte lysis buffer was added and reacted for 5 minutes to remove erythrocytes. The pellet was centrifuged again, washed twice with incomplete culture medium, and then resuspended in 5 mL of complete culture medium to obtain a spleen cell suspension. After counting, the cells were ready for subsequent experiments.

[0037] Postbiotics alleviate casein allergy in mouse spleen cells The experiment was divided into three groups: a normal group, a casein-sensitized group, and a postbiotic (Postbio-M2) group. The postbiotic was diluted with RPMI-1640 complete medium to a concentration of 4% (v / v) (this concentration has no toxic effect on mouse spleen cells). The concentration of mouse spleen cells was adjusted to 5 × 10⁶ cells / year using the aforementioned RPMI-1640 complete medium containing postbiotic. 6 Cells / mL: 180 μL was pipetted into 96-well plates, and 20 μL of 200 μg / mL casein solution was added to each well to sensitize mouse spleen cells. The concentration of mouse spleen cells in the normal group and the sensitized group was adjusted to 5 × 10⁶ cells / mL using RPMI-1640 complete medium without post-biotics. 6 Cells / mL, 180 μL was pipetted into a 96-well plate. For the sensitized group, 20 μL of 200 μg / mL casein solution was added; for the normal group, an equal volume of PBS solution was added. The plates were incubated at 37℃ and 5% CO2 for 72 h, and the supernatant was collected. The levels of IFN-γ and IL-4 in the supernatant were determined according to the ELISA kit manufacturer's instructions.

[0038] The test results are as follows Figure 3 As shown: The levels and ratios of IFN-γ and IL-4 in different treatment groups are as follows: Figure 3As shown, the results demonstrate that the post-genetic group can upregulate the level of Th1 cytokine IFN-γ and downregulate the level of Th2 cytokine IL-4, thereby effectively restoring the Th1 / Th2 balance and effectively alleviating casein allergy in mouse spleen cells.

[0039] II. Effects of post-biotics on casein-sensitized mice Establishment of a casein-sensitized BALB / c mouse model Five-week-old female BALB / c mice were selected and placed in an animal facility for one week for acclimatization. The animal facility temperature was maintained at 20–25 °C, with a 12-hour day-night cycle and good ventilation. Standard mouse food and purified water were provided daily. The mice were randomly divided into three groups: a control group (Normal), a casein-sensitized group (Allergy), and a postbiotic group (Postbio-M2), with eight mice in each group. Except for the control group, all mice were administered 200 μL of casein (2 mg / kg, supplemented with aluminum hydroxide) by gavage on days 0, 7, 14, 21, 28, and 35, and were orally sensitized.

[0040] Casein sensitization group: The Allergy group was administered 0.2 mL of sterile PBS solution by gavage daily, and 2 mg / kg casein was orally administered by gavage on days 0, 7, 14, 21, 28, and 35, supplemented with aluminum hydroxide. On day 42, after fasting overnight, mice were induced to develop allergy with 10 mg / kg casein. Postbiotic group: 0.2 mL of Postbio-M2 was administered by gavage daily, and 2 mg / kg casein was orally administered by gavage on days 0, 7, 14, 21, 28, and 35, supplemented with aluminum hydroxide. On day 42, after fasting overnight, mice were induced to develop allergy with 10 mg / kg casein. Normal group: 0.2 mL of sterile PBS solution was administered by gavage daily, and sterile PBS was orally administered by gavage on days 0, 7, 14, 21, 28, and 35. On day 42, after fasting overnight, mice were induced to develop allergy with the same volume of sterile PBS.

[0041] After the experiment, mouse feces were collected. After anesthetizing the mice, blood was collected from their eyeballs, and the mice were euthanized by cervical dislocation. The mice were then dissected under aseptic conditions, and their spleen and intestinal tissue were collected.

[0042] 1. Detection of water content in mouse feces Feces from each mouse were collected into a 1.5 mL dry, sterile EP tube (weighing, W1). The total weight of feces plus tube weight was recorded as (W2). Wet weight = W2 - W1. The feces were dried in an oven at 105℃ until constant weight, and the total weight of feces plus tube weight was recorded as (W3). Moisture content = W2 - W3. Fecal moisture content = Moisture weight / Wet weight × 100%.

[0043] The test results are as follows Figure 4 As shown: The fecal water content of normal mice was approximately 59%, while that of sensitized mice was 67%, indicating that the sensitized mice experienced diarrhea. The fecal water content of the post-biotic group was 60%, significantly lower than that of the sensitized group (P < 0.05), and there was no statistically significant difference compared to the normal group. This suggests that fermented Lactobacillus mucinus post-biotic can effectively improve diarrhea in allergic mice.

[0044] 2. Spleen index test The spleen was dissected and separated, then rinsed in PBS for two seconds to remove excess adipose tissue. It was weighed, and the spleen index was calculated. Spleen index = spleen weight / (mouse body weight × 10).

[0045] The results are as follows Figure 5 As shown: The spleen index of the sensitized group mice was significantly higher than that of the normal group (P < 0.05), indicating that the spleen of the sensitized group was swollen, suggesting an allergic reaction. Postbiotics could alleviate the spleen swelling and restore it to normal levels.

[0046] 3. Detection of allergy-related factors in serum The levels of IgE, histamine, mast cell proteinase-1 (MMCP-1), IFN-γ, and IL-4 in the serum of mice in each group were detected using an ELISA kit.

[0047] The test results are as follows Figure 6 As shown: The results are as follows Figure 6 As shown in Figures A, B, and C, the serum levels of IgE, MMCP-1, and Histamine in the allergic group were significantly higher than those in the normal group (P < 0.05), indicating an allergic reaction in the mice. The post-biotic group showed decreased levels of IgE, MMCP-1, and Histamine, indicating that post-biotics can inhibit allergic reactions in mice. Figure 6 The results of D, E, and F were consistent with the in vitro cell experiments, indicating that the post-genetic group could upregulate the level of Th1 cytokine IFN-γ and downregulate the level of Th2 cytokine IL-4, effectively restoring the Th1 / Th2 balance and alleviating casein allergy in mouse spleen cells.

[0048] 4. Detection of allergy-related factors in ileal tissue The levels of IL-10, IL-13, and IgG in ileal tissue were detected by ELISA.

[0049] The test results are as follows Figure 7 As shown: The sensitized group had significantly lower IL-10 levels than the normal group, while IL-13 and IgG levels were significantly higher (P < 0.05). In contrast, the ileum tissue of the metabiotic group showed significantly upregulated Th1 factor IL-10 levels and significantly downregulated Th2 factors IL-13 and pathogenic IgG levels (P < 0.05), indicating that metabiotics can inhibit Th2 responses in the ileum tissue and suppress excessive inflammatory responses mediated by pathogenic IgG antibodies.

[0050] 5. Effects of metabiotics on intestinal tight junction proteins and intestinal structure The expression levels of tight junction protein 1 (Claudin1) and ocludin in mouse ileum tissue were detected by Western blotting (WB).

[0051] The test results are as follows Figure 8 As shown: The expression levels of Claudin1 and Occludin in the sensitized group were significantly lower than those in the normal group (P < 0.05), suggesting that allergic reactions lead to increased intestinal permeability. Metabiotics significantly upregulated the expression of Claudin1 and Occludin (P < 0.05), indicating that metabiotics can effectively upregulate the expression of tight junction proteins and reduce intestinal permeability.

[0052] The pathological morphological changes in mouse colon tissue were observed using hematoxylin-eosin (HE) staining. The results are as follows: Figure 9 As shown.

[0053] In the normal group of mice, the colonic mucosa structure was intact, with intestinal villi arranged neatly, regularly shaped, and without breakage. The crypt structure was clear and intact, and there was no inflammatory cell infiltration in the lamina propria, indicating that the intestinal mucosal barrier structure was in a normal physiological state. In the casein-sensitized group of mice, the colonic mucosa showed significant pathological damage, with broken, edematous, and disordered intestinal villi. The crypt structure was deformed and its integrity was disrupted, and a large number of inflammatory cells were infiltrated in the lamina propria, suggesting that bovine casein sensitization triggered an inflammatory response in the intestinal mucosa, causing severe damage to the intestinal structure. After metagenic intervention, the pathological damage to the colonic mucosa of mice was significantly improved. The intestinal villi arrangement returned to neatness, edema and breakage disappeared, the crypt structure basically returned to normal morphology, the number of inflammatory cells infiltrating the lamina propria was greatly reduced, and the overall structure of the intestinal mucosa tended to be intact.

[0054] The above results corroborate the results of intestinal tight junction protein detection, confirming that fermented Lactobacillus mucinus postbiotic can repair damaged intestinal mucosal structure, reduce intestinal inflammatory response, improve sensitization-induced intestinal barrier structure damage, reduce intestinal permeability, and block allergens from entering the body's circulatory system through the intestine at the structural level, thereby alleviating a series of pathological reactions caused by bovine casein allergy.

[0055] 6. Effects of postbiotics on the gut microbiota of mice Metagenomic high-throughput sequencing technology was used to sequence and analyze mouse fecal samples to evaluate the regulatory effect of postbiotics on the composition of gut microbiota and homeostasis in bovine casein-allergic mice.

[0056] (1) Analysis of gut microbiota composition like Figure 10 As shown in Figure A, at the phylum level, the dominant phyla in the gut microbiota of the three groups of mice were Bacteroides and Bacillota. Compared with the normal group, the relative abundance of Firmicutes was significantly reduced and the relative abundance of Bacteroides was significantly increased in the sensitized group, resulting in an imbalance in the Firmicutes / Bacteroides ratio. This imbalance is a typical biological characteristic of intestinal inflammation and allergic states. After metabiotic intervention, the relative abundance of Firmicutes in the mice significantly recovered and the relative abundance of Bacteroides significantly decreased. The F / B ratio recovered compared with the sensitized group, effectively correcting the phylum-level microbiota imbalance induced by sensitization and improving the intestinal inflammatory microenvironment.

[0057] like Figure 10 As shown in Figure B, at the genus level, compared with the normal group, the relative abundance of pro-inflammatory and allergy-related genera such as *Bacteroides*, *Duncaniella*, and *Paramuribaculum* was higher in the gut of sensitized mice. Conversely, the relative abundance of genera such as *Odoribacter*, *Roseburia*, *Blautia*, and *Eubacterium* was higher in the normal group but decreased in the sensitized group. This change is a key marker of intestinal flora imbalance under allergic conditions. In the metagenic group, the abnormal proliferation of the aforementioned pro-inflammatory genera was inhibited, while the relative abundance of beneficial genera was significantly enriched. In addition, beneficial genera such as *Akkermansia*, which have anti-inflammatory activity and intestinal barrier protection function, were enriched, achieving a remodeling of the intestinal flora structure and blocking the environmental basis for allergy at the microecological level.

[0058] (2) Correlation analysis between gut microbiota and immune / barrier function The results of the Spearman correlation analysis are as follows: Figure 11As shown, pro-inflammatory bacteria genera such as *Paramuribaculum*, *Duncaniella*, and *Bacteroides* are positively correlated with allergy-related inflammatory markers such as histamine, MMCP-1, IL-4, IL-13, and IgE. Among them, *Paramuribaculum* showed a highly significant positive correlation with IL-13 (p<0.01). At the same time, *Paramuribaculum* showed a highly significant negative correlation with IFN-γ (p<0.01) and a significant negative correlation with the expression levels of tight junction proteins Claudin1 and Occludin (p<0.05). Beneficial bacteria genera such as Akkermansia and Kineothrix showed a negative correlation with allergic inflammatory markers such as Histamine, MMCP-1, and IL-13, and a positive correlation with the expression levels of Th1 cytokines IFN-γ, tight junction proteins Claudin1, and Occludin. In addition, short-chain fatty acid-producing bacteria such as Roseburia and Eubacterium also showed a positive correlation with IFN-γ, Claudin1, and Occludin, and a negative correlation with pro-inflammatory markers.

[0059] The results confirm that Postbio-M2, a fermenting Lactobacillus mucinus, precisely regulates the microbial community structure by inhibiting pro-inflammatory bacteria and enriching beneficial bacteria, thereby correcting Th1 / Th2 immune imbalance and repairing the intestinal mucosal barrier. Through the synergistic blocking of the cascade reaction of bovine casein allergy via the "microbiome-gut-immune axis," it provides direct mechanistic support for its anti-allergic effect.

[0060] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention in any other way. Any person skilled in the art may make changes or modifications to the above-disclosed technical content to create equivalent embodiments. However, any simple modifications, equivalent changes, and modifications made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the protection scope of the present invention.

Claims

1. A fermented *Lactobacillus mucinus* postbiotic, characterized in that, It is prepared by the following method: Inoculate the *Lactobacillus fermentans* culture into MRS medium and incubate at 30–40°C for 12–48 h until the bacterial concentration reaches at least 1 × 10⁻⁶. 9 CFU / mL; then sterilize, centrifuge, collect the supernatant to obtain fermented Lactobacillus mucinus postbiotic.

2. The postbiotic of fermented *Lactobacillus mucinus* according to claim 1, characterized in that, The fermenting Lactobacillus mucinus is deposited at the China General Microbiological Culture Collection Center (CGMCC) with accession number CGMCC No. 39247.

3. The postbiotic of fermented *Lactobacillus mucinus* according to claim 1, characterized in that, The bacterial content of the fermented *Lactobacillus mucinus* culture is at least 1 × 10⁻⁶. 9 CFU / mL; the inoculum size is 1-5%, V / V.

4. The use of the fermented Lactobacillus mucinus postbiotic of claim 1 in the preparation of a formulation for correcting Th1 / Th2 immune imbalance.

5. The use of the fermented Lactobacillus mucinus postbiotic of claim 1 in the preparation of formulations for repairing damaged intestinal mucosa, reducing intestinal inflammatory response, or improving intestinal barrier structure damage.

6. The application according to claim 5, characterized in that, The intestinal mucosal damage, intestinal inflammation, and intestinal barrier disruption are caused by casein allergic reactions.

7. The use of the fermented Lactobacillus mucinus postbiotic of claim 1 in the preparation of a formulation for repairing the intestinal microecology.

8. The use of the fermented Lactobacillus mucinus postbiotic of claim 1 in the preparation of a formulation for preventing and treating allergic reactions caused by casein.

9. The use of the fermented Lactobacillus mucinus postbiotic of claim 1 in the preparation of a formulation for preventing and treating bovine milk allergy.

10. A milk allergy reliever, characterized in that, The allergen contains the fermented Lactobacillus mucinus postbiotic as described in claim 1.

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