Composite probiotics, synbiotics and application of composite probiotics and synbiotics

Abstract

The invention discloses compound probiotics, synbiotics and application thereof, and relates to the technical field of probiotics. The invention develops a brand new compound probiotic, the compound probiotic comprises lactobacillus helveticus R0052, bifidobacterium longum R0175 and lactobacillus paracasei R0215, and the compound probiotic can effectively regulate intestinal inflammation and has a certain effect in the aspects of anxiety and depression resistance. The invention develops a brand new synbiotics, the synbiotics comprise 2 '-fucosyllactose, lactobacillus helveticus R0052, bifidobacterium longum R0175 and lactobacillus paracasei R215, and the synbiotics can effectively regulate anxiety and depression mood.

Description

Technical Field

[0001] The present invention relates to the technical field of probiotics, and in particular to a composite probiotic, a synbiotic and applications thereof. Background Art

[0002] The World Health Organization and the Food and Agriculture Organization of the United Nations define probiotics as "live microorganisms that contribute to the health of the host (human or other organisms) when properly ingested". Probiotics have a symbiotic relationship with the human body, so they can be considered a type of symbiotic bacteria. Their functions include assisting our metabolism, helping the small intestine to move and digest food, preventing the immune system from being allergic, and acting as a barrier to the intestine to prevent harmful bacteria or allergic substances from passing through the intestinal wall.

[0003] Prebiotics refer to organic substances that are not digested and absorbed by the host but can selectively promote the metabolism and proliferation of beneficial bacteria in the body, thereby improving the health of the host. A successful prebiotic should be mostly undigested when passing through the upper digestive tract and can be fermented by intestinal flora. The most important thing is that it can only stimulate the growth of beneficial bacteria, but not harmful bacteria with potential pathogenicity or spoilage activity. The most basic prebiotic is carbohydrate, but the definition does not exclude non-carbohydrate substances from being used as prebiotics. In theory, any antibiotic that can reduce harmful bacteria and benefit healthy bacteria or activities can be called a prebiotic.

[0004] Prior art CN117887646A discloses a composite probiotic for anti-anxiety and depression and its application. The composition is composed of Bacillus coagulans BC99 strain and Bifidobacterium bifidum BBi32 strain. The two strains can cooperate with each other, promote each other, and synergize in the effects of anti-anxiety and depression. The application only examines whether probiotics have a positive effect on anxiety and depression, and does not examine whether prebiotics have a positive effect on anxiety and depression, and whether probiotics and prebiotics have a synergistic effect on anxiety and depression.

[0005] Prior art CN110799045A discloses a composition containing human milk oligosaccharides (HMO) for improving short-term memory and other cognitive benefits. The nutritional composition includes probiotics and prebiotics, and the composition has an effect on promoting, enhancing or improving the short-term memory of infants and / or young children. The application only examines whether the combination of prebiotics and probiotics can enhance the short-term memory of infants and young children, and does not examine whether the combination of probiotics and prebiotics has a positive effect on anxiety and depression.

[0006] In view of this, in order to solve the deficiencies of the prior art, the present invention provides a composite probiotic, synbiotic and application thereof. There are few existing composite probiotic and synbiotic products that can effectively regulate intestinal inflammation and improve anxiety and depression. It is very necessary to develop a composite probiotic and synbiotic preparation that can effectively regulate intestinal inflammation and improve anxiety and depression. Summary of the invention

[0007] The purpose of the present invention is to provide a composite probiotic, a synbiotic and an application thereof, expand the application scope of Lactobacillus paracasei R0215, and develop a new strategy for effectively regulating intestinal inflammation and improving anxiety and depression.

[0008] To achieve the above-mentioned purpose of the invention, the technical solution of the present invention is as follows:

[0009] In one aspect, the present invention provides a composite probiotic, comprising Lactobacillus helveticus R0052 (R0052), Bifidobacterium longum R0175 (R0175) and Lactobacillus paracasei R0215 (R0215).

[0010] Preferably, the ratio of the viable counts of Lactobacillus helveticus R0052, Bifidobacterium longum R0175, and Lactobacillus paracasei R0215 is 1-10: 1-10: 1-10.

[0011] More preferably, the ratio of the viable counts of Lactobacillus helveticus R0052, Bifidobacterium longum R0175, and Lactobacillus paracasei R0215 is 9:1:10.

[0012] In another aspect, the present invention provides use of the composite probiotics in producing probiotic products.

[0013] In yet another aspect, the present invention provides a synbiotic comprising 2'-fucosyllactose, Lactobacillus helveticus R0052, Bifidobacterium longum R0175 and Lactobacillus paracasei R0215.

[0014] Preferably, the ratio of 2'-fucosyllactose, Lactobacillus helveticus R0052, Bifidobacterium longum R0175, and Lactobacillus paracasei R0215 is: 1-10 mg: 1×10 7 -1×10 8 CFU: 1×10 7 -1×10 8 CFU: 1×10 7 -1×10 8 CFU.

[0015] More preferably, the ratio of 2'-fucosyllactose, Lactobacillus helveticus R0052, Bifidobacterium longum R0175, and Lactobacillus paracasei R0215 is: 1 mg: 9×10 7 CFU: 1×10 7 CFU: 1×10 8 CFU.

[0016] In yet another aspect, the present invention provides use of the above synbiotics in producing synbiotic products.

[0017] In yet another aspect, the present invention provides a product comprising the above-mentioned composite probiotics and any one of the above-mentioned synbiotics.

[0018] Preferably, the products include foods, nutritional supplements and medicines.

[0019] Finally, the present invention provides the use of the above product in preparing products for relieving intestinal inflammation and stabilizing emotions.

[0020] Preferably, the mood stabilization is the prevention, improvement or treatment of depression and / or anxiety.

[0021] The beneficial effects of the present invention are:

[0022] (1) The present invention develops a new composite probiotic, which includes Lactobacillus helveticus R0052, Bifidobacterium longum R0175 and Lactobacillus paracasei R0215. The composite probiotic can effectively regulate intestinal inflammation and has certain effects in anti-anxiety and anti-depression.

[0023] (2) The present invention has developed a new synbiotic, which includes 2'-fucosyllactose, Lactobacillus helveticus R0052, Bifidobacterium longum R0175 and Lactobacillus paracasei R0215. The synbiotic can effectively regulate anxiety and depression. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 It is the time that the mouse stays in the middle area of ​​the open field.

[0025] Figure 2 The distance the mouse moves in the open field.

[0026] Figure 3 It is the number of times the mouse enters the middle area of ​​the open field.

[0027] Figure 4 It is the time that mice stay in the open arm.

[0028] Figure 5 The time that mice remain motionless in the elevated maze.

[0029] Figure 6 It is the time that mice stay in the light box.

[0030] Figure 7 It is the time when the mouse first enters the dark chamber from the light chamber.

[0031] Figure 8 The number of times the mouse crossed the light-dark box.

[0032] Fig. 9 It is the immobility time of the mouse during the tail suspension process. DETAILED DESCRIPTION

[0033] The following non-limiting examples can enable those skilled in the art to more fully understand the present invention, but do not limit the present invention in any way. The following content is only an exemplary description of the scope of the present invention, and those skilled in the art can make various changes and modifications to the invention of the present invention based on the disclosed content, and they should also fall within the scope of the present application.

[0034] 2'-fucosyllactose (2'-FL): DSM, the Netherlands;

[0035] Lactobacillus helveticus R0052: French Raman

[0036] Bifidobacterium longum R0175: French Raman

[0037] Lactobacillus paracasei R0215: French Raman

[0038] Bifidobacterium animalis HN019: International Flavors & Fragrances IFF, USA;

[0039] Lactobacillus rhamnosus HN001: International Flavors & Fragrances IFF, USA;

[0040] Lactobacillus reuteri DSM17938: BioGaia, Bio, Sweden.

[0041] Example 1

[0042] Cell line HT-29: Beijing Zhongyuan Heju Biotechnology Co., Ltd., ATCC HTB38;

[0043] Live / Dead Bacterial Viability Kit: Thermofisher.

[0044] 1. Cell test

[0045] 1.1. Establishment of small intestinal epithelial cell model

[0046] This example uses human colon cancer cell line HT-29, and provides the cells with the necessary nutrients and a suitable culture environment for growth: culture medium: RPMI1640 basal culture medium + 10% fetal bovine serum + 1% NEAA and 1% penicillin / streptomycin; culture conditions: constant temperature and humidity incubator (37°C, 5% CO 2 HT-29 cells were cultured at 2.5×10 6 cells / 5mL inoculated in T25-cm 2 After 48 h of culture, the cell density reached 5×10 6 If a cell model with characteristics similar to those of the human small intestine is successfully constructed, subsequent inflammation induction and probiotic intervention experiments can be carried out.

[0047] 1.2 Protective effects of probiotics and prebiotics on inflamed intestinal cells

[0048] Based on previous studies showing that a variety of probiotics and 2'-fucosylated lactose (2'-FL) have the effect of regulating mood, 6 specific strains were selected for cell intervention experiments, as shown in Table 1. After all strains were resuscitated using MRS solid medium supplemented with 0.05% cysteine ​​hydrochloride, single colonies were picked and inoculated in MRS broth medium containing 0.05% cysteine ​​hydrochloride for overnight culture, and the bacterial liquid was centrifuged to remove the supernatant to obtain the bacterial cells, which were washed three times with PBS and resuspended in RPMI-1640 basal medium. Finally, the number of live bacteria was determined using the Live / Dead bacterial viability kit.

[0049] Table 1. List of experimental strains

[0050] Chinese name Latin name Strain No. Lactobacillus helveticus Lactobacillus helveticus R0052 Bifidobacterium longum subsp. longum Bifidobacterium longum subsp.longum R0175 Lactobacillus paracasei Lacticaseibacillus paracasei R0215 Bifidobacterium animalis subsp. lactis Bifidobacterium animalis subsp.lactis HN019 Lactobacillus rhamnosus Lacticaseibacillus rhamnosus HN001 Lactobacillus reuteri Limosilactobacillus reuteri DSM17938

[0051] Based on previous studies showing that R0052 and R0175 mainly work in combination, we fixed R0052 and R0175 in a 9:1 ratio to prepare 10 9 CFU / mL of R0052 and R0175 mixed bacterial solution. The mixed bacterial solution was then mixed with the remaining probiotics in a 1:1 ratio. The specific intervention plan is as follows:

[0052] Experiment 1: PBS buffer solution;

[0053] Experiment 2: 9×10 8 CFU / mL of R0052+1×10 8 CFU / mL of R0175;

[0054] Experiment 3:10 9 CFU / mL of R0215;

[0055] Experiment 4:10 9 CFU / mL of HN019;

[0056] Experiment 5:10 9 CFU / mL of HN001;

[0057] Experiment 6:10 9 CFU / mL of DSM17938;

[0058] Experiment 7: 9×10 8 CFU / mL of R0052+1×10 8 CFU / mL of R0175+10 9 CFU / mL of R0215;

[0059] Experiment 8: 9×10 8 CFU / mL of R0052+1×10 8 CFU / mL of R0175+10 9 CFU / mL of HN019;

[0060] Experiment 9: 9×10 8 CFU / mL of R0052+1×10 8 CFU / mL of R0175+10 9 CFU / mL of HN001;

[0061] Experiment 10: 9×10 8 CFU / mL of R0052+1×10 8 CFU / mL of R0175+10 9 CFU / mL of DSM17938.

[0062] For cell intervention, the use of T25-cm 2 The total volume of the intervention solution was 5 mL, and the probiotics and cells were added at a ratio of 100:1 for 6 h, that is, the total amount of probiotics added to all groups was 5 × 10 8 CFU; at the same time, the pro-inflammatory factor poly(I:C) was added at 10 μg / mL to induce intestinal cell inflammation. After the culture, the TEER value was detected, and the cell culture supernatant was collected and centrifuged for 10 minutes (600×g, 4°C), and then the concentrations of inflammatory factors TNF-α and IL-8 in the supernatant were analyzed according to the method of the ELISA kit manufacturer.

[0063] 1.3 Results

[0064] Table 2. Effects of different intervention groups on pro-inflammatory factors secreted by inflamed intestinal cells

[0065]

[0066]

[0067] *Note: The same letters in the same column indicate no significant difference (p>0.05), while different letters indicate significant difference (p<0.05).

[0068] As shown in Table 2, the results of experimental group 1 showed that under the intervention of poly(I:C), HT-29 cells secreted a large amount of proinflammatory factors IL-8 and TNF-α, and under the intervention of probiotics (experimental groups 2-10), the secretion of IL-8 and TNF-α was significantly reduced (p<0.05).

[0069] Compared with single strains (experimental groups 3-6), the secretion of IL-8 protein in experimental group 2 was only significantly lower than that in experimental group 4 (p<0.05), which was comparable to the other groups; for the three-strain combination groups, the secretion of IL-8 protein in experimental groups 8, 9 and 10 was significantly lower than that in experimental groups 4 and 6, while that in experimental group 7 was significantly lower than that in all single strain or two-strain experimental groups (p<0.05).

[0070] In terms of TNF-α secretion, the secretions of experimental groups 8, 9 and 10 in the three-strain combination group were significantly lower than those of experimental groups 4, 5 and 6, but still comparable to those of experimental group 2, while that of experimental group 7 was significantly lower than all other groups (p<0.05). The above results show that the combination of R0052, R0175 and R0215 has a significant synergistic effect in regulating intestinal inflammation, and the regulation of intestinal inflammation is also one of the important ways to regulate neuroinflammation and brain health.

[0071] Example 2

[0072] 1. Experimental ethics

[0073] This experiment was reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of the Institute of Brain Cognition and Brain Disorders (BCBDI), Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, with the ethics number SIAT-IACUC-20211222-NS-NTPZX-WLP-A2090-01.

[0074] 2. Materials

[0075] 2.1 Experimental Animals

[0076] 7-week-old male C57BL / 6 mice (50, purchased from Zhejiang Weitong Lihua) with an average body weight of (20±2) g were used. These mice were housed in a controlled environment with room temperature maintained at 22±2°C, humidity at 55%±5%, and a 12h light / dark cycle. They had free access to food and water, and all experimental procedures involving mice were in accordance with the ethical review guidelines for experimental animal welfare.

[0077] 2.2 Animal grouping: After one week of adaptive feeding, 50 mice were randomly divided into five groups (10 mice in each group): blank control group, model group, intervention 1 + model group, intervention 2 + model group, and intervention 3 + model group.

[0078] 2.3 Experimental process: 50 adult male mice in each batch were given samples of single component or different formulations by long-term oral gavage for 5 weeks. Then, in the fourth week of intervention, the mice were subjected to 1 week of stress induction. The blank control group was not intervened, and then their fecal samples were collected; finally, behavioral tests were performed, and the mice were continuously sampled during the above evaluation experiment. After the behavioral test, all animals will be handled and samples will be collected, including brain organs, blood samples, cecal colon tissues and bone samples. The collected samples will be further analyzed.

[0079] The components or compositions involved in each group in the experiment are as follows:

[0080] Blank control group: intragastric administration of normal saline;

[0081] Model group: intragastric administration of normal saline;

[0082] Intervention 1 + model group: intragastric administration of 500 mg / kg / d 2'-fucosyllactose;

[0083] Intervention 2+ model group: oral administration of three probiotics, including 9×10 8 CFU / d R0052, 10 8 CFU / dR0175, and 10 9 CFU / d R0215;

[0084] Intervention 3+ model group: intragastrically administered 500 mg / kg / d 2'-FL and three probiotics (9×10 8 CFU / dR0052, 10 8 CFU / d R0175, 10 9 CFU / d R0215).

[0085] The stress response program is as follows:

[0086] Plantar stimulation 10 times (current 0.5 mA, each lasting 2 seconds, with an interval of 10 seconds);

[0087] Tail suspension for 30 min;

[0088] Restraint 1h.

[0089] 2.4 Anxiety-like behavior test

[0090] 2.4.1 Open field test

[0091] The open field consists of a square box (35cm*35cm*30cm), which is divided into 16 areas (8.75cm*8.75cm), and the 4 areas in the middle will be defined as the middle area (17.5cm*17.5cm). Mice will be randomly placed in the middle area of ​​the open field. After 10 minutes of exploration, the time the mice stay in the middle area will be recorded and used as an indicator of anxiety. The longer the mice stay in the middle area, the lower their anxiety level.

[0092] 2.4.2 Elevated Maze

[0093] The elevated maze device is a cross-shaped maze with two open arms (35cm*5cm*15cm) and two closed arms (35cm*5cm). The middle area of ​​the cross maze is a fully open area (5cm*5cm). The entire cross maze is 50cm above the ground. At the beginning of the experiment, the mice were placed in the middle area of ​​the maze, facing the open arms. Then, the number of times the mice entered the open arms and closed arms within 7 minutes, the time they stayed in the open arms and closed arms, and the time they were still were automatically monitored. The time the mice stayed in the open arms was used as an anxiety indicator. The longer the mice stayed in the open arms, the lower their anxiety level.

[0094] 2.4.3 Light and dark box

[0095] The size of the light-dark box device is 50cm*25cm*25cm. It contains two spaces, a light box and a dark box. The partition wall between the two boxes has a 7.5cm*7.5cm door hole for mice to shuttle through. The test time for each mouse is 5 minutes. At the beginning of the test, the mouse is placed in the light box and allowed to explore freely in the device. Monitor the time the mouse stays in the light box, the number of times the light and dark boxes shuttle, and the time of the first entry into the dark room. The time spent in the light box is used as an anxiety indicator. The longer the mouse stays in the light box, the lower the anxiety level.

[0096] 2.5. Depression-like behavior test (tail suspension test)

[0097] The tail suspension test is widely used to assess despair behavior in rodents. Briefly, mice are suspended by tape about 1 cm from the tip of the tail 30 cm above the ground. The duration of the experiment is 6 min, and the immobility time (no struggling, little body movement) during the suspension process is automatically monitored during the last 5 min. The duration of immobility of mice will be used as an indicator of depression, and the longer the immobility time, the higher the degree of depression of the mice.

[0098] 2.6 Statistical Analysis

[0099] Prism software was used for statistical analysis. In the behavioral experimental results, each group was first checked for outliers, and then a significance analysis was performed after elimination. The blank control group and the model group used an unpaired t-test, while the model group and the three intervention groups used a one-way anova. In order to more accurately compare the significance between different experimental groups, the Z-score method was used to normalize the behavioral results and then compare them, and finally the efficacy of each intervention group was ranked. Taking the open field experiment as an example, the Z-score calculation formula is as follows:

[0100]

[0101] in,

[0102] X: observed values ​​of behavioral indices of mice in the intervention group;

[0103] μ: mean values ​​of behavioral indicators of mice in the model group;

[0104] σ: standard deviation of behavioral indicators of mice in the model group;

[0105] TC: time mice stayed in the open area in the open field test;

[0106] DR: The ratio of the exploration distance of mice in the middle area to the total exploration distance in the open field test.

[0107] Then the elevated maze behavior Z EPM Scoring, light-dark box behavior Z LDB Scoring and tail suspension test Z TST score, due to the anxiety-like behavior Z score (such as Z OF , Z EPM , Z LDB ) indicates that the individual has a lower risk of anxiety; in addition, a higher Z score for depression-like behavior indicates that the individual has a higher risk of depression. A The score is the weighted average of the Z scores of each behavior, that is, Z A =(Z OF +Z EPM +Z LDB) / 3. The overall anxiety and depression behavior is Z T The score is the mean of the sum of the anxiety behavior Z score minus the depression behavior Z score, that is, Z T =(Z OF +Z EPM +Z LDB -Z TST ) / 4.

[0108] 2.7 Results

[0109] 2.7.1 Effects of different nutritional components on anxiety-like behaviors in stressed mice

[0110] 2.7.1.1 Open field test

[0111] The open field test showed that compared with the blank group, the time that the mice stayed in the middle area of ​​the open field after stress induction showed a trend of decreasing, but there was no significant difference ( Figure 1 ); however, after intervention with intervention 1 (2'-FL), intervention 2 (probiotic combination) and intervention 3 (2'-FL combined with probiotic combination), the time mice stayed in the middle area of ​​the open field was significantly higher than that of the model group, indicating that the probiotic combination and its combination with 2'-FL can significantly improve the anxiety-like behavior of mice in the open field ( Figure 1 ).

[0112] 2.7.1.2 Elevated maze test

[0113] like Figure 4 As shown, the results of the elevated maze experiment showed that compared with the blank control group, the time mice stayed in the open arm after stress induction was significantly reduced, indicating that mice showed anxiety-like behavior in the elevated maze after stress induction; compared with the model group, the time mice in the intervention 1 (2'-FL) and intervention 3 (2'-FL combined with probiotic combination) groups stayed in the open arm increased, and were comparable to the blank control group, but not significant; the above results indicate that intervention 1 and intervention 3 may alleviate the anxiety-like behavior of mice in the elevated maze.

[0114] 2.7.1.3 Light and dark box experiment

[0115] like Figure 6 As shown, in the light-dark box experiment, compared with the blank group, the time that mice stayed in the light box after stress induction was significantly reduced, indicating that mice showed anxiety-like behavior in the light-dark box after stress induction; compared with the model group, the time that mice in the intervention 1 (2'-FL) and intervention 2 (probiotic combination) groups stayed in the light box was significantly increased, and was comparable to the blank control group; the above results indicate that intervention 1 and intervention 2 significantly alleviated the anxiety-like behavior of mice in the light-dark box.

[0116] 2.7.2 Effects of different nutritional components on depressive-like behavior of stressed mice (tail suspension test)

[0117] like Fig. 9 As shown, the results of the mouse tail suspension experiment showed that compared with the blank control group, the immobility time of mice in the stress-induced model group was significantly increased, indicating that the mice showed depressive-like behavior after stress induction; compared with the model group, intervention 1 (2'-FL), intervention 2 (probiotic combination) and intervention 3 (2'-FL combined with probiotic combination) could significantly reduce the immobility time of mice, and were close to the blank control group; the above results indicate that intervention 1, intervention 2 and intervention 3 can significantly improve the depressive-like behavior of mice during tail suspension.

[0118] 2.7.3 Behavioral Z-score

[0119] The behavioral Z scores of each intervention group are shown in Table 3. The score table shows that the Z scores of intervention group 1 and intervention group 3 A Rating and Z T The scores were similar and higher than those of the intervention group 2. In addition, based on Z A The percentage of individuals with scores above the mean of this experiment was counted. The results showed that intervention 1 group had 33.3% (3 / 9), intervention 2 had 37.5% (3 / 8), and intervention 3 had 44.4% (4 / 9). This indicates that intervention 3 performed best in the anxiety-like behavior Z score, followed by intervention 1, and finally intervention 2. T The scores were the mean of this experiment, and the percentage of individuals with scores above the mean was statistically analyzed. The results showed that intervention 1 had 55.6% (5 / 9) in the group with intervention 1, 25% (2 / 8) in the group with intervention 2, and 55.6% (5 / 9) in the group with intervention 3. This shows that intervention 1 and intervention 3 performed similarly in the overall behavioral Z score, and were better than intervention 2.

[0120] Table 3. Behavioral Z score table of each intervention group

[0121]

[0122]

[0123] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A composite probiotic, characterized in that: Including Lactobacillus helveticus R0052, Bifidobacterium longum R0175 and Lactobacillus paracasei R0215.

2. The composite probiotic according to claim 1, characterized in that The live cell count ratio of Lactobacillus helveticus R0052, Bifidobacterium longum R0175 and Lactobacillus paracasei R0215 is 1-10: 1-10: 1-10.

3. The composite probiotic according to claim 2, characterized in that The live cell count ratio of Lactobacillus helveticus R0052, Bifidobacterium longum R0175 and Lactobacillus paracasei R0215 is 9:1:

10.

4. A synbiotic, characterized in that: Including 2'-fucosyllactose, Lactobacillus helveticus R0052, Bifidobacterium longum R0175 and Lactobacillus paracasei R0215.

5. The synbiotic according to claim 4, characterized in that The ratio of 2'-fucosyllactose, Lactobacillus helveticus R0052, Bifidobacterium longum R0175, and Lactobacillus paracasei R0215 is: 1-10 mg: 1×10 7 -1×10 8 CFU: 1×10 7 -1×10 8 CFU: 1×10 7 -1×10 8 CFU.

6. Use of the composite probiotic according to any one of claims 1 to 3 in the production of probiotic products.

7. Use of the synbiotic according to any one of claims 4 to 5 in producing synbiotic products.

8. A product, characterized in that Contains any one of the composite probiotics described in any one of claims 1-3 and the synbiotics described in any one of claims 4-5.

9. The product according to claim 8, characterized in that Includes food, nutritional supplements and medicines.

10. Use of the product according to any one of claims 8 to 9 in the preparation of products for relieving intestinal inflammation and stabilizing mood.

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