Application of bifidobacterium breve i1088 or afterbiogen of bifidobacterium breve i1088 to improvement of cognition

Abstract

The invention relates to an application of bifidobacterium breve i1088 or a postbiotic thereof in improvement of cognition. The bifidobacterium breve i1088 or the afterbiogen of the bifidobacterium breve i1088 is used for preparing a product for enhancing the oxidative stress capacity of mammalian cells, improving the in-vitro free radical scavenging level of mammals and changing at least one of the expression levels of mammalian cells Nrf2 and anti-oxidation related genes. The invention aims to explore the potential of the bifidobacterium breve in the aspect of improving the Alzheimer's disease and provide a safer and more effective nutritional supplement scheme for middle-aged and elderly people.

Description

Technical Field

[0001] The present invention relates to the field of microbial engineering technology, and more particularly to the application of Bifidobacterium breve, specifically the application of Bifidobacterium breve i1088 in improving and preventing Alzheimer's disease, and the application of the strain in formula milk powder, yogurt and health food for the middle-aged and elderly. Background Art

[0002] With the aging of the global population, the health status of the middle-aged and elderly people has received more and more attention. In particular, cognitive decline has become an important factor affecting the quality of life of the elderly. Cognitive function includes memory, attention, spatial learning ability and other aspects. Its decline not only affects personal life, but also brings a heavy burden to society. At present, there are many ways to improve cognitive function, including drug therapy, cognitive training, lifestyle adjustment, etc. However, these methods often have certain limitations. For example, drugs may bring side effects, and cognitive training requires long-term persistence and the effect varies from person to person. Therefore, finding safer and more effective methods to improve cognitive function has important social significance. In recent years, probiotics, as a microecological regulator, have received increasing attention for their role in maintaining and improving human health. In particular, Bifidobacterium breve (B.breve), as a common probiotic, has been shown to have a positive effect on intestinal health. However, the application of Bifidobacterium breve in improving cognitive function has not been widely studied and applied.

[0003] China has rapidly entered a deeply aging society, with a population of about 280 million people aged 60 and above, accounting for 19.84% of the total population. Age-related disabilities and diseases brought about by aging are increasing rapidly. Alzheimer's disease is one of the common diseases that causes the elderly to lose their ability to live daily lives, with about 9.83 million patients at present. Alzheimer's disease also brings a huge economic burden to society. In China, the average annual socioeconomic cost per patient in 2015 was 119,269.36 yuan, and the national total annual cost was 1,045.02 billion yuan. It is estimated that by 2030, the total annual social cost will exceed 3 trillion yuan.

[0004] Alzheimer's disease (AD) is an age-related neurodegenerative disease with characteristic pathological changes including the aggregation of amyloid β-peptide, hyperphosphorylated tauprotein (p-tau) levels, and redox homeostasis imbalance. Oxidative stress is a redox imbalance caused by excessive accumulation of reactive oxygen species (ROS) and damage to the antioxidant system. Oxidative stress plays a key role in the pathogenesis of AD. It not only causes irreversible damage to cells and interferes with neurological function, but also triggers proinflammatory signaling, cell apoptosis and necrosis (see Bhatt S, Puli L, Patil CR. Role of reactive oxygen species in the progression of Alzheimer's disease [J]. Drug discovery today, 2021, 26 (3): 794-803). Nrf2 (Nuclear factor erythroid 2-related factor 2) is a transcription factor that plays a key role in maintaining cellular redox homeostasis and regulating inflammatory responses. Studies have found that the expression of Nrf2 and its driver genes (NQO1, HO-1, and GCLC) is decreased in the brains of AD patients. Activating Nrf2 gene expression can provide cellular protection for AD against a variety of pathological changes including neurodegeneration (see Osama A, Zhang J, Yao J, et al. Nrf2: a dark horse in Alzheimer's disease treatment [J]. Ageing research reviews, 2020, 64: 101206). Summary of the invention

[0005] The following is a summary of the subject matter described in detail herein. This summary is not intended to limit the scope of the claims.

[0006] In order to solve the above deficiencies in the prior art, the present application aims to explore the potential of Bifidobacterium breve in improving Alzheimer's disease and provide a safer and more effective nutritional supplement for the elderly. In addition, the present application also applies Bifidobacterium breve i1088 or its postbiotics that have improved cognitive function to middle-aged and elderly formula milk powder, yogurt and health foods, in order to provide support for the cognitive health of the elderly through the adjustment of daily diet. The present application provides an application of Bifidobacterium breve i1088 in improving cognition. The bacteria and its postbiotics or bacterial agents can significantly increase the proportion of the residence time of APP / PS1 mice with congenital cognitive impairment in the original platform position area in the water maze experiment test, and increase the number of times the original platform position area is crossed.

[0007] To achieve the above objectives, the technical solutions adopted in this application are as follows:

[0008] On the one hand, the present application provides an application of Bifidobacterium breve i1088 or its postbiotics in the preparation of a product that enhances the oxidative stress capacity of mammalian cells, improves the level of free radical scavenging in vitro in mammals, and changes the expression level of Nrf2 and antioxidant-related genes in mammalian cells. Among them, the Bifidobacterium breve i1088, the strain has been deposited in the General Microbiological Culture Collection Center of the China Microbiological Culture Collection Administration on May 8, 2023, with a deposit number of CGMCCNO.27281, and the Latin name is Bifidobacterium breve.

[0009] In an exemplary embodiment, the mammal comprises a human.

[0010] In an exemplary embodiment, in the product, the viable count of Bifidobacterium breve i1088 is 1×10 5 CFU / g~5×10 11 CFU / g or 1×10 5 CFU / ml~5×10 11 CFU / ml; for example, 1×10 5 CFU / g or CFU / ml, 5×10 5 CFU / g or CFU / ml, 1×10 6 CFU / g or CFU / ml, 5×10 6 CFU / g or CFU / ml, 1×10 7 CFU / g or CFU / ml, 5×10 7 CFU / g or CFU / ml, 1×10 8 CFU / g or CFU / ml, 5×10 8 CFU / g or CFU / ml, 1×10 9CFU / g or CFU / ml, 5×10 9 CFU / g or CFU / ml, 1×10 10 CFU / g or CFU / ml, 5×10 10 CFU / g or CFU / ml, 1×10 11 CFU / g or CFU / ml, 5×10 11 CFU / g or CFU / ml or any two of them are used as range values ​​between endpoint values, but are not limited to the listed values. Other unlisted values ​​within the numerical range are also applicable.

[0011] In an exemplary embodiment, in the product, the viable count of Bifidobacterium breve i1088 is 2×10 6 CFU / g or CFU / ml~5×10 10 CFU / g or CFU / ml.

[0012] In an exemplary embodiment, in the product, the viable count of Bifidobacterium breve i1088 is 1×10 5 CFU / g or CFU / ml.

[0013] In an exemplary embodiment, in the product, the viable count of Bifidobacterium breve i1088 is 5×10 9 CFU / g or CFU / ml.

[0014] In an exemplary embodiment, in the product, the viable count of Bifidobacterium breve i1088 is 2×10 10 CFU / g or CFU / ml.

[0015] In an exemplary embodiment, in the product, the added amount of Bifidobacterium breve i1088 is 0.07% to 2% by weight.

[0016] In an exemplary embodiment, the daily intake of Bifidobacterium breve i1088 is 2×10 6 ~5×10 11 CFU;

[0017] Preferably, the daily intake of Bifidobacterium breve i1088 is 5×10 9 CFU.

[0018] In an exemplary embodiment, the application is the application of the Bifidobacterium breve i1088 or its postbiotics in the preparation of a product for improving cognition.

[0019] In an exemplary embodiment, the product is at least one of a food, a health product, a probiotic, a medicine, and a pharmaceutical composition.

[0020] In an exemplary embodiment, the product is a food or a health product.

[0021] In an exemplary embodiment, the product is at least one of formula milk powder and liquid milk;

[0022] Optionally, the liquid milk is a lactic acid bacteria beverage or low-temperature yogurt;

[0023] Optionally, the formula milk powder is a middle-aged and elderly formula milk powder.

[0024] In an exemplary embodiment, the product is a probiotic, optionally a probiotic powder.

[0025] In an exemplary embodiment, the product is a medicine or a pharmaceutical composition.

[0026] In an exemplary embodiment, the application is the application of the Bifidobacterium breve i1088 or its postbiotics in the preparation of a product for preventing, alleviating or improving Alzheimer's disease or mixed cognitive impairment.

[0027] Compared with the existing related technologies, this application has the following technical effects:

[0028] This application applies Bifidobacterium breve i1088 or its postbiotics that improve cognitive function to middle-aged and elderly formula milk powder, yogurt and health foods, in order to provide support for the cognitive health of middle-aged and elderly people through the adjustment of daily diet. The bacteria and its postbiotics or bacterial agents can significantly increase the proportion of the stay time of APP / PS1 congenital cognitive impairment mice in the original platform position area in the water maze experiment test, and increase the number of times they cross the original platform position area.

[0029] Other features and advantages of the present application will be described in the following description, and partly become apparent from the description, or be understood by implementing the present application. Other advantages of the present application can be realized and obtained by the schemes described in the description and the drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] The accompanying drawings are used to provide an understanding of the technical solution of the present application and constitute a part of the specification. Together with the embodiments of the present application, they are used to explain the technical solution of the present application and do not constitute a limitation on the technical solution of the present application.

[0031] Figure 1 To compare the effects of Bifidobacterium breve i1088, Bifidobacterium breve JMCC0794 and Bifidobacterium breve JMCC1106 in improving the anti-oxidative stress capacity of cells;

[0032] Figure 2To compare the effects of Bifidobacterium breve i1088, Bifidobacterium breve JMCC0794 and Bifidobacterium breve JMCC1106 on the expression of SOD mRNA gene in Caco-2 cells under LPS stress;

[0033] Figure 3 To compare the effects of Bifidobacterium breve i1088, Bifidobacterium breve JMCC0794 and Bifidobacterium breve JMCC1106 on the expression of NRF2 mRNA in Caco-2 cells under LPS stress;

[0034] Figure 4 It is the proportion of time each group of mice stayed in the original platform location area in the water maze test;

[0035] Figure 5 It is the number of times each group of mice crossed the original platform location area in the water maze test. DETAILED DESCRIPTION

[0036] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0037] The raw materials used in this application are all conventional products on the market.

[0038] Unless otherwise specified, the materials and reagents used in the examples of the present invention can be obtained from commercial sources. Experimental methods without specific conditions in the examples are usually carried out under conventional conditions or under conditions recommended by the manufacturer.

[0039] In the embodiment:

[0040] Bifidobacterium breve i1088, the strain was deposited in the China General Microbiological Culture Collection Center on May 8, 2023, with the deposit number CGMCC NO.27281, and the Latin name is Bifidobacterium breve;

[0041] The commercial Bifidobacterium breve strains JMCC0794 and JMCC1106 were provided by Junlebao Microbiologiccal Culture Collection (JMCC) and were derived from the intestines of healthy infants.

[0042] Example 1 Bifidobacterium breve i1088 enhances cellular oxidative stress capacity

[0043] Experimental cells: Human colorectal adenocarcinoma cells (Caco-2)

[0044] 1) Experimental reagents, instruments and consumables

[0045] DMEM cell culture medium, penicillin-streptomycin mixture (100X), cell culture plate (6-well plate), cell scraper, CCK-8 kit (Cell Counting Kit-8), cell workbench, constant temperature incubator (5% CO2), microplate reader (450nm filter), 96-well plate, 3% hydrogen peroxide, pipette (10μL\100μL\1000μL), Bifidobacterium breve i1088, Bifidobacterium breve JMCC0794, Bifidobacterium breve JMCC1106.

[0046] 2) Experimental methods:

[0047] 1. Culture the cells to a confluence of more than 95% and plate them evenly in a 96-well plate, with a fixed cell volume of 5×10 4 Around, culture overnight until adherent;

[0048] 2. Add 8 mM hydrogen peroxide and 1×10 5 CFU strains, co-intervention for 6 h;

[0049] 3. Add 10 μL of CCK-8 reagent to each well, mix well, incubate at 37°C in the dark for 0.5 h, and then immediately measure the absorbance at 450 nm;

[0050] 4. Experimental groups: blank group (containing cells, culture medium and CCK-8), model group (containing cells, culture medium, hydrogen peroxide and CCK-8), experimental group 1 (containing i1088, cells, culture medium, hydrogen peroxide and CCK-8), experimental group 2 (containing JMCC0794, cells, culture medium, hydrogen peroxide and CCK-8), experimental group 3 (containing JMCC1106, cells, culture medium, hydrogen peroxide and CCK-8);

[0051] 5. Analysis method: The absorbance at 450 nm is used to indirectly react to the cell activity index for evaluation. The closer the cell activity is to the blank group, the better the effect of the cells after intervention on anti-oxidative stress is.

[0052] 3) Result analysis:

[0053] Compared with the model group, Bifidobacterium breve i1088 (experimental group 1), Bifidobacterium breve JMCC0794 (experimental group 2) and Bifidobacterium breve JMCC1106 (experimental group 3) can all enhance the anti-oxidative stress capacity of cells, which is manifested in that the cell activity is significantly different from that of the model group. Intra-group comparison shows that Bifidobacterium breve i1088 has a better effect in enhancing the anti-oxidative stress of cells (see Figure 1 , where ###: compared with the model group, P<0.001; **: compared with the experimental group 1, P<0.01; ***: compared with the experimental group 1, P<0.001).

[0054] Example 2 In vitro free radical scavenging effect of Bifidobacterium breve i1088

[0055] 1) DPPH free radical scavenging effect

[0056] Method: Take 300 μL bacterial cell solution (same concentration: 2×10 10 CFU / mL) was mixed with an equal volume of 2mM DPPH ethanol solution and incubated in the dark at room temperature for 30 minutes. Centrifuged at 3000g for 5 minutes, the supernatant was taken to measure the absorbance A at 517nm, and physiological saline was used as a negative control. The results are shown in Table 1. The formula for free radical scavenging rate is as follows.

[0057] Clearance rate (%) = (1-A sample / A control )×100%

[0058] Table 1

[0059] strain i1088 JMCC0794 JMCC1106 DPPH free radical scavenging rate <![CDATA[72.4%±5.1% a ]]> <![CDATA[60.9%±4.5% c ]]> <![CDATA[64.3%±3.8% b ]]>

[0060] 2) Oxygen ion free radicals (O 2- ) Clear effect

[0061] Method: Take 200 μL bacterial cell solution (same concentration: 2×10 10 CFU / mL) and 520μL 50mM Tris-HCl solution (pH 8.5, containing 10mM EDTA) were added to a 1.5mL Ep tube, reacted at room temperature for 20min, 80μL 25mM pyrogallol solution prepared with 0.1M HCl was added, incubated at room temperature for 10min, and 100μL 1M HCl was quickly added to terminate the reaction. Centrifuged at 3000g for 5min, the supernatant was taken to determine its absorbance value A at 325nm, and an equal volume of physiological saline was used as a control. The results are shown in Table 2. The scavenging rate of oxygen ion free radicals is calculated as follows.

[0062] Clearance rate (%) = (1-A sample / A control )×100%

[0063] Table 2

[0064] strain i1088 JMCC0794 JMCC1106 Oxygen ion free radical scavenging rate <![CDATA[17.5%±2.2% a ]]> <![CDATA[16.9%±3.5% b ]]> <![CDATA[17.3%±2.3% a ]]>

[0065] 3) Hydroxyl radical (·OH) scavenging effect

[0066] Method: Take 200 μL bacterial cell solution (same concentration: 2×10 10 CFU / mL), 200μL 5mM salicylic acid ethanol solution, 200μL 5mM ferrous sulfate solution and 200μL 3mM H2O2 solution in a 1.5mL Eppendorf tube, mix well and react at room temperature for 30min, centrifuge at 3000g for 5min, take the supernatant and measure the absorbance A at 510nm, and use an equal volume of physiological saline as a control. The results are shown in Table 3. The scavenging rate of hydroxyl radicals is calculated as follows.

[0067] Clearance rate (%) = (1-A sample / A control )×100%

[0068] Table 3

[0069] strain i1088 JMCC0794 JMCC1106 Hydroxyl radical scavenging rate <![CDATA[54.4%±4.9% a ]]> <![CDATA[46.7%±4.6% b ]]> <![CDATA[48.8%±6.1% b ]]>

[0070] In Tables 1 to 3, abc indicates that the results are significantly different from each other. The comparison within the group showed that Bifidobacterium breve i1088 had a better effect in scavenging free radicals.

[0071] Example 3 Bifidobacterium breve i1088 changes the expression levels of Nrf2 and antioxidant-related genes in CaCo-2 cells

[0072] Nrf2 (Nuclear factor erythroid 2-related factor 2) is an important intracellular anti-oxidative stress transcription factor that plays a key role in maintaining cellular redox balance, metabolism and protein homeostasis.

[0073] 1) Experimental method: CaCo-2 cells were inoculated in 6-well plates, with approximately 2×10 cells per well. 6 The experimental group and the positive control group were treated with 10 μg / mL lipopolysaccharide (LPS) for 24 hours to complete the modeling. 7 The cfu of Bifidobacterium breve (i1088, JMCC0794, JMCC1106) was different, and the bacteria were eluted for 12 hours. The total RNA of the cells was extracted and reverse transcribed into cDNA using a kit. After the synthesized cDNA was diluted a certain multiple, 10 μL of cDNA was added to the total system, 0.5 μL of upstream and downstream primers, 3 μL of ddH2O, and 5 μL of SYBR Green were added, and real-time PCR analysis was performed using a CFX 96TMReal-timeSystem instrument. 2 -△△Ct The relative expression of mRNA was calculated by the method. Figures 2 to 3, among which, compared with the model group, *P<0.05, **P<0.01, ***P<0.001. The primer sequences used in this study are shown in Table 4.

[0074] Table 4

[0075]

[0076] Intra-group comparison showed that Bifidobacterium breve i1088 had a better ability to increase the expression levels of Nrf2 and antioxidant-related genes in CaCo-2 cells.

[0077] Example 4 Bifidobacterium breve i1088 with the ability to improve Alzheimer's disease

[0078] 1) Experimental animals:

[0079] C57BL / 6 mice, male, 14 weeks old.

[0080] APP / PS1 mice, male, 14 weeks old.

[0081] 2) Experimental reagents, instruments and consumables

[0082] Disposable 5 ml syringe (Shanghai Kangdeli, China), electronic analytical balance (Precisa12A, Precisa, Switzerland), depyrogenation ultrapure water system (Millipo3150, Millipore, USA), mouse gavage needle (Zhongke Life Science, China), electric constant temperature water bath (HW-SY11-K P2, Beijing Changfeng Instrument Co., Ltd., China), centrifuge tube (1.5 ml, Wuxi Nice Life Science Co., Ltd., China), water maze apparatus (ACT-200A, Beijing Youcheng Biotechnology Co., Ltd., China).

[0083] Positive control drug: Edaravone (M70800-5G, Sigma-Aldrich, USA).

[0084] 3) Experimental methods:

[0085] Animal grouping and oral administration

[0086] 1. After 7 days of adaptive feeding, 60 mice were divided into 6 groups: blank group, model group, positive drug group, i1088 group, short bifidobacterium A (No. JMCC0794), short bifidobacterium B (No. JMCC1106), with 10 mice in each group. The blank group used C57BL / 6 male mice without any treatment, and the other groups used APP / PS1 congenital cognitive impairment male mice.

[0087] 2. The mice in each group were gavaged daily. The mice in the blank group and the model group were given an equal volume of saline daily. The mice in the positive drug group were given 3 mg / kg of edaravone daily. The mice in the i1088 group were gavaged daily with Bifidobacterium breve i1088, which is equivalent to 5×10 9 CFU; mice in group A were given the same dose of Bifidobacterium breve JMCC0794 by oral gavage daily; mice in group B were given the same dose of Bifidobacterium breve JMCC1106 by oral gavage daily, and the solvent was normal saline, once a day for 42 consecutive days.

[0088] Water maze experimental training and testing

[0089] 1. 24 hours after the last gavage, each group began water maze training: 4 training sessions per day, each mouse entered the swimming pool from a different quadrant of the water maze, and a training session was terminated when the mouse found the underwater platform or lasted for 60 seconds. Each training session was separated by 15 minutes, and the training was continued for 4 days.

[0090] 2. After 4 days of training, the water maze test began on the 5th day: each mouse entered the swimming pool (without platform) 4 times, starting from a different quadrant of the water maze each time, and recorded the movement trajectory of the mice within 120 seconds. The proportion of the time each group of mice stayed in the original platform position area during the 120-second test time, as well as the number of times they crossed the original platform position area, were analyzed.

[0091] 4) Result analysis:

[0092] Bifidobacterium breve i1088 has the effect of improving cognitive impairment. Specifically, it can increase the proportion of time that APP / PS1 mice with congenital cognitive impairment stay in the original platform position area in the water maze test (p<0.01), and increase the number of times that they cross the original platform position area (p<0.01). In addition, the improvement effect of this strain is better than that of Bifidobacterium breve A and Bifidobacterium breve B of the same genus, see Figures 4 to 5 ;in: Figure 4 Compared with the blank control group, **p<0.01; compared with the model control group, #p<0.05, ##p<0.01; Figure 5 Compared with the blank control group, **p<0.01; compared with the model control group, #p<0.05, ##p<0.01.

[0093] Example 5 Bifidobacterium breve i1088 for improving cognitive function in middle-aged and elderly formula milk powder

[0094] Bifidobacterium breve i1088 is added to the middle-aged and elderly formula milk powder, wherein the viable count of Bifidobacterium breve i1088 is 2×10 6 ~5×10 7 CFU / g.

[0095] Example 6 Bifidobacterium breve i1088 for improving cognitive function in low-temperature yogurt

[0096] Add Bifidobacterium breve i1088 into low-temperature yogurt, wherein the viable cell count of Bifidobacterium breve i1088 is 1×10 6 ~1×10 8 CFU / g.

[0097] Example 7 Bifidobacterium breve i1088 in lactic acid bacteria beverage for improving cognitive function

[0098] Bifidobacterium breve i1088 is added to a lactic acid bacteria beverage, wherein the number of viable bacteria of Bifidobacterium breve i1088 is 2×10 6 ~5×10 7 CFU / g.

[0099] Example 8 Bifidobacterium breve i1088 in probiotic powder for improving cognitive function

[0100] The probiotic powder was prepared by freeze-drying Bifidobacterium breve i1088, wherein the viable bacterial count of Bifidobacterium breve i1088 was 5×10 7 ~8×10 10 CFU / g.

[0101] Conclusion: In this application, Bifidobacterium breve i1088 or its postbiotics can enhance the oxidative stress capacity of mammalian cells, improve the level of free radical scavenging in mammals in vitro or change the expression level of Nrf2 and antioxidant-related genes in mammalian cells, and can significantly increase the proportion of the residence time of APP / PS1 mice with congenital cognitive impairment in the original platform position area in the water maze test, and increase the number of crossing the original platform position area. Therefore, this application applies Bifidobacterium breve i1088 or its postbiotics that have improved cognitive function to middle-aged and elderly formula milk powder, yogurt and health foods, in order to provide support for the cognitive health of the middle-aged and elderly population through the adjustment of daily diet, and prevent, alleviate or improve Alzheimer's disease or mixed cognitive impairment.

[0102] Although the embodiments of the present application have been shown and described above, it can be understood that the above embodiments are exemplary and cannot be understood as limitations on the present application. Ordinary technicians in this field can change, modify, replace and modify the above embodiments within the scope of the present application.

Claims

1. A use of Bifidobacterium breve i1088 or its postbiotics in the preparation of a product that enhances the oxidative stress capacity of mammalian cells, improves the free radical scavenging level of mammals in vitro, and changes the expression level of Nrf2 and antioxidant-related genes in mammalian cells; wherein: The Bifidobacterium breve i1088 was deposited in the China General Microbiological Culture Collection Center on May 8, 2023, with the collection number CGMCC NO.27281, and the Latin name is Bifidobacterium breve.

2. The use according to claim 1, characterized in that: The mammals include humans.

3. The use according to claim 2, characterized in that: In the product, the viable count of Bifidobacterium breve i1088 is 1×10 5 CFU / g~5×10 11 CFU / g or 1×10 5 CFU / ml~5×10 11 CFU / ml.

4. The use according to claim 3, characterized in that: In the product, the viable count of Bifidobacterium breve i1088 is 2×10 6 CFU / g or CFU / ml~5×10 10 CFU / g or CFU / ml.

5. The use according to any one of claims 1 to 4, characterized in that The application is the application of the Bifidobacterium breve i1088 or its postbiotics in the preparation of a product for improving cognition.

6. The use according to claim 5, characterized in that: The product is at least one of food, health care product, probiotic, medicine and pharmaceutical composition.

7. The use according to claim 6, characterized in that: The product is at least one of formula milk powder and liquid milk.

8. The use according to claim 7, characterized in that: The liquid milk is a lactic acid bacteria beverage or low-temperature yogurt; and / or The formula milk powder is formula milk powder for middle-aged and elderly people.

9. The use according to claim 6, characterized in that: The product is probiotic powder.

10. The use according to claim 6, characterized in that: The application is the application of the Bifidobacterium breve i1088 or its postbiotics in the preparation of a product for preventing, alleviating or improving Alzheimer's disease or mixed cognitive impairment.

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