Bifidobacterium animalis subsp. lactis C-2 with the efficacy of improving inflammatory bowel disease and its application

Abstract

The present invention relates to Bifidobacterium animalis subsp. lactis C-2 with the efficacy of improving inflammatory bowel disease and its application. The taxonomic nomenclature of Bifidobacterium animalis subsp. lactis C-2 is Bifidobacterium animalis subsp. lactis , and the preservation number is GDMCC No: 65455. This strain can inhibit the colonization of harmful bacteria and promote the colonization of beneficial bacteria, optimize the composition of intestinal microbiota, and thus induce an anti-inflammatory response and improve intestinal barrier function through mechanisms such as regulating the intestinal microecology, repairing the intestinal mechanical barrier, improving the intestinal immune response, and inhibiting the oxidative stress response. Therefore, this Bifidobacterium animalis subsp. lactis C-2 strain is suitable for preparing drugs with the efficacy of preventing, improving or treating inflammatory bowel disease.

Description

Technical Field

[0001] The present invention belongs to the technical field of microbial culture, and relates to a Bifidobacterium animalis subsp. lactis C-2 with the efficacy of improving inflammatory bowel disease and its application. Background Art

[0002] Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory disease involving the ileum, rectum, and colon, including ulcerative colitis (UC) and Crohn's disease (CD). Their clinical manifestations usually include abdominal pain, diarrhea, and bloody stools, and in severe cases, they can lead to complications such as digestive tract perforation and bleeding. The pathogenesis of IBD has not been fully elucidated, but existing studies have revealed that multiple factors may play important roles in its occurrence and progression. Modern third-generation sequencing technologies have revealed that the diversity and richness of the gut microbiota in IBD patients are lower, and the number of beneficial bacteria decreases while the number of pathogenic bacteria increases. These microbial imbalances trigger the overproduction of lipopolysaccharides, which in turn activate the inflammatory signaling pathways in the gut, promoting the development of the inflammatory response. The disruption of the gut barrier function is also an important link in the pathogenesis of IBD. Under normal circumstances, the gut barrier can effectively isolate harmful substances and pathogenic microorganisms in the gut, but IBD patients often experience disruption of the gut barrier function, leading to an overactive immune response in the gut. Metabolites of the gut microbiota, such as short-chain fatty acids, can maintain the integrity of the gut barrier and support the balance of the immune system. The reduction of these beneficial metabolites in IBD patients results in insufficient nutrient supply and abnormal immune function of intestinal epithelial cells, further exacerbating intestinal inflammation.

[0003] Current IBD treatment mainly relies on drug treatment, mainly including aminosalicylate drugs, corticosteroids, immunosuppressants, and biological agents, etc. Aminosalicylate drugs (such as mesalazine) are effective in controlling mild to moderate active diseases, but the effect is average and can only relieve related symptoms; corticosteroid drugs can be used to control acute attacks, but long-term use may cause side effects such as osteoporosis and diabetes; immunosuppressants (such as azathioprine, cyclophosphamide) also increase the risk of infection with long-term use; biological agents, especially tumor necrosis factor (TNF)-specific inhibitors (such as infliximab, adalimumab), have become an important means of treating IBD, but some patients develop resistance or non-responsiveness to biological agents. Therefore, exploring new treatment strategies has become an urgent need.

[0004] Probiotics are defined as "live microorganisms" that, when ingested in sufficient amounts, have a health effect on the host. The intestine, as the most important organ for the digestion and absorption of nutrients, determines the overall health of the body. Probiotics can play a potential role in the prevention and treatment of ulcerative colitis by improving intestinal barrier function, regulating the structure of the intestinal flora, and inhibiting the growth of harmful bacteria. Therefore, how to provide an efficient probiotic-containing microbial preparation for improving inflammatory bowel disease and promoting intestinal health has become an urgent technical problem to be solved. Summary of the Invention

[0005] Aiming at the deficiencies of the prior art, the purpose of the present invention is to provide a Bifidobacterium animalis subsp. lactis C-2 with the efficacy of improving inflammatory bowel disease and its application.

[0006] To achieve the purpose of this invention, the following technical solutions are adopted:

[0007] In the first aspect, the present invention provides a Bifidobacterium animalis subsp. lactis C-2 with the efficacy of improving inflammatory bowel disease, and the taxonomic nomenclature of the Bifidobacterium animalis subsp. lactis C-2 is Bifidobacterium animalis subsp. lactis , and the preservation number is GDMCC No: 65455, and the preservation date is November 8, 2024.

[0008] The present invention isolated and preserved a new Bifidobacterium animalis subsp. lactis with the efficacy of improving inflammatory bowel disease from milk-based media, named Bifidobacterium animalis subsp. lactis C-2 strain. This strain can regulate the intestinal environment, inhibit the colonization of harmful bacteria and promote the colonization of beneficial bacteria, optimize the composition of intestinal microorganisms, thereby inducing an anti-inflammatory response and improving intestinal barrier function. Therefore, this Bifidobacterium animalis subsp. lactis C-2 strain can be used to prepare drugs with the efficacy of preventing, improving or treating inflammatory bowel disease.

[0009] In the second aspect, the present invention provides a culture of Bifidobacterium animalis subsp. lactis C-2 as described in the first aspect, and the culture is prepared by the following method: inoculating Bifidobacterium animalis subsp. lactis C-2 into a culture medium and culturing at 35-38 °C for 22-26 h.

[0010] Among them, the above "35-38 °C" can be, for example, 35 °C, 35.5 °C, 36 °C, 36.5 °C, 37 °C, 37.5 °C, 38 °C, etc. Other specific point values within this numerical range can be selected and will not be elaborated here one by one.

[0011] The above "22-26 h" can be, for example, 22 h, 22.5 h, 23 h, 23.5 h, 24 h, 24.5 h, 25 h, 25.5 h, 26 h, etc. Other specific point values within this numerical range can be selected and will not be elaborated here one by one.

[0012] Thirdly, the present invention provides a probiotic agent with the efficacy of improving inflammatory bowel disease, and the strains in the probiotic agent with the efficacy of improving inflammatory bowel disease include the Bifidobacterium animalis subsp. lactis C-2 strain described in the first aspect.

[0013] Preferably, in the probiotic agent, the viable count of the Bifidobacterium animalis subsp. lactis C-2 is not less than 1×10 9 CFU / mL or 1×10 9 CFU / g, such as 1×10 9 CFU / mL (CFU / g), 2×10 9 CFU / mL (CFU / g), 5×10 9 CFU / mL (CFU / g), 8×10 9 CFU / mL (CFU / g), 1×10 10 CFU / mL (CFU / g), 5×10 10 CFU / mL (CFU / g), 1×10 11 CFU / mL (CFU / g), etc. Other specific point values within this numerical range can be selected and will not be elaborated one by one here.

[0014] Preferably, the strains in the probiotic agent with the efficacy of improving inflammatory bowel disease further include Lactobacillus gasseri Lactobacillus gasseri CKCC 1913, with the preservation number of CGMCC No. 23175 and the preservation date of August 23, 2021.

[0015] The present invention also creatively discovers that the above-mentioned Lactobacillus gasseri Lactobacillus gasseri CKCC 1913 strain can be compounded with the Bifidobacterium animalis subsp. lactis Bifidobacterium animalis subsp. lactis C-2 strain for the prevention, improvement or treatment of inflammatory bowel disease, and has more excellent effects than a single bacterial agent or other compounding methods, indicating that the CKCC 1913 strain and the C-2 strain have a synergistic effect in regulating the balance of intestinal flora and inducing anti-inflammatory responses to improve intestinal barrier function.

[0016] Preferably, the ratio of the viable counts of the Bifidobacterium animalis subsp. lactis C-2 and the Lactobacillus gasseri CKCC 1913 is 1:10 - 10:1, such as 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 5:1, 6:1, 8:1, 10:1, etc. Other specific point values within this numerical range can be selected and will not be elaborated one by one here.

[0017] Preferably, the dosage form of the probiotic agent includes freeze-dried powder, capsules, tablets or granules.

[0018] Preferably, the probiotic agent further includes a protective agent.

[0019] Preferably, the protective agent includes any one or a combination of at least two of skim milk, gelatin, dextrin, gum arabic, dextran, sodium alginate, polyvinylpyrrolidone, sucrose, lactose, trehalose, sorbitol or xylitol.

[0020] Fourthly, the present invention provides an application of the Bifidobacterium animalis subsp. lactis C-2 as described in the first aspect, or the culture as described in the second aspect, or the probiotic agent as described in the third aspect in the preparation of a product for regulating the intestinal microecological environment.

[0021] Fifthly, the present invention provides an application of the Bifidobacterium animalis subsp. lactis C-2 as described in the first aspect, or the culture as described in the second aspect, or the probiotic agent as described in the third aspect in the preparation of a preparation with the efficacy of preventing, improving or treating inflammatory bowel disease.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] A novel Bifidobacterium animalis subsp. lactis with the efficacy of improving inflammatory bowel disease was isolated and preserved from milk-based substrates in the present invention, named Bifidobacterium animalis subsp. lactis C-2 strain. This strain can regulate the intestinal environment, inhibit the colonization of harmful bacteria and promote the colonization of beneficial bacteria, optimize the composition of intestinal microorganisms, thereby inducing an anti-inflammatory response and improving intestinal barrier function. Therefore, this Bifidobacterium animalis subsp. lactis C-2 strain can be used to prepare a drug with the efficacy of preventing, improving or treating inflammatory bowel disease.

[0024] The taxonomic nomenclature of the C-2 strain involved in the present invention is Bifidobacterium animalis subsp. lactis , the preservation unit is the Guangdong Provincial Microbial Culture Collection Center, the preservation number is GDMCC No: 65455, the preservation date is November 8, 2024, and the preservation address is the 5th floor, Building 59, No. 100, Xianlie Middle Road, Guangzhou;

[0025] The taxonomic nomenclature of the CKCC 1913 strain involved in the present invention is Lactobacillus formatum Lactobacillus gasseri , the preservation unit is the China General Microbiological Culture Collection Center of the China Committee for Culture Collection of Microorganisms, the preservation number is CGMCC No. 23175, the preservation date is August 23, 2021, and the preservation address is No. 3, Yard 1, Beichen West Road, Chaoyang District, Beijing. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1It is a statistical result graph of the weight change rate of each group of mouse tests;

[0027] Figure 2 It is a statistical result graph of the content levels of various cytokines in the colon samples of each group of mice;

[0028] Figure 3 It is a statistical result graph of the content levels of various cytokines in the serum samples of each group of mice;

[0029] Figure 4 It is a statistical result graph of the content levels of various key mucinous proteins in the colon samples of each group of mice;

[0030] Figure 5 It is a statistical result graph of the concentration levels of various immunoglobulins in the serum samples of each group of mice. Detailed implementation manners

[0031] The technical solutions of the present invention will be further described below through specific implementation manners. Those skilled in the art should understand that the described embodiments are only for helping to understand the present invention and should not be regarded as specific limitations on the present invention.

[0032] The following are the information on the bacterial strains involved:

[0033] ① The taxonomic name of the C-2 strain involved in the following embodiments is Bifidobacterium animalis subsp. lactis , and the preservation number is GDMCC No: 65455;

[0034] ② The taxonomic name of the CKCC 1913 strain involved in the following embodiments is Lactobacillus gasseri Lactobacillus gasseri , and the preservation number is CGMCC No. 23175;

[0035] ③ The ATCC 700541 involved in the following embodiments is the strain of Bifidobacterium animalis subsp. lactis ATCC 700541.

[0036] The following are the media and their formulations involved:

[0037] ① MRS liquid medium: Beef extract 10.0 g, Glucose 20.0 g, Peptone 10.0 g, Yeast extract 5.0 g, Sodium chloride 5.0 g, Diammonium hydrogen citrate 2.0 g, Dipotassium hydrogen phosphate 2.0 g, Magnesium sulfate 0.2 g, Manganese sulfate 0.05 g, Tween-80 1.0 g, Made up to 1000 mL with distilled water, pH 6.2 - 6.4.

[0038] MRS solid medium: 10.0 g of beef extract, 20.0 g of glucose, 10.0 g of peptone, 5.0 g of yeast extract, 5.0 g of sodium chloride, 2.0 g of diammonium hydrogen citrate, 2.0 g of dipotassium hydrogen phosphate, 0.2 g of magnesium sulfate, 0.05 g of manganese sulfate, 1.0 g of Tween-80, 2% agar powder, made up to 1000 mL with distilled water, pH 6.2 - 6.4.

[0039] ② TPY liquid medium: Weigh 26.4 g of commercially available TPY medium powder, made up to 1000 mL with distilled water,

[0040] TPY solid medium: Weigh 26.4 g of commercially available TPY medium powder, made up to 1000 mL with distilled water, 2% agar powder.

[0041] The simulated gastric juice (pH 3.0) involved in the following examples: Prepare 0.85% normal saline, adjust the pH to 3.0 with dilute hydrochloric acid, then add 0.3% pepsin, and after fully dissolving, filter and sterilize with a microporous membrane to obtain it.

[0042] The preparation methods of the bacterial suspension and bacterial powder involved in the following are: After activating the strain, inoculate it into the medium for culture to obtain the culture solution; centrifuge the culture solution, resuspend the bacterial cells to obtain the bacterial suspension, or further add a cryoprotectant for freeze-drying to prepare the freeze-dried bacterial powder product. Example 1

[0043] In this example, a strain of Bifidobacterium animalis subsp. lactis with the effect of improving inflammatory bowel disease was isolated and screened, and the steps are as follows:

[0044] (1) Select the sample isolated from milk base, perform 10-fold serial dilutions with 0.9% normal saline for 3 times, spread on the solid medium, after culturing at 37°C for 48 h, pick out colonies with different morphologies and then streak and purify on the surface of the modified MRS solid medium, pick out single colonies and expand the culture with the liquid medium at 37°C, and then preserve with 35% glycerol by mass concentration. Example 2

[0045] In this example, morphological identification and 16S rRNA molecular biology identification were carried out on the strain screened in Example 1, and the steps are as follows:

[0046] (1) Morphological identification:

[0047] The strain was inoculated into TPY medium and anaerobically cultured at 37°C for 48 h, and then observed under a microscope. After smear and Gram staining, microscopic examination showed that: the Gram stain was positive, and the strain had a polymorphic, milky white colony with a diameter of 0.1 - 0.2 cm, smooth, moist, raised surface, and neat edges.

[0048] (2)16S rRNA molecular biological identification:

[0049] The strain stored at -80°C was taken out and inoculated into a centrifuge tube containing 20 mL of TPY liquid medium at a ratio of 2% (v / v). After culturing at 37°C for 24 h, centrifugation separation was carried out at 8000 rpm for 10 min. The supernatant was removed, and the bacterial cells were collected. The genomic DNA of the strain was extracted, and universal bacterial primers were added for PCR amplification. The amplified product was sent to a sequencing company for sequencing and identification. After sequencing and analysis of the strain, its 16S rRNA sequence was as shown in SEQ ID No:1. The sequenced sequence was aligned with the nucleic acid sequences in GeneBank, and the results showed that the strain was Bifidobacterium animalis subsp. lactis.

[0050] SEQ ID No:1:

[0051] CCGCGATTACTAGCGACTCCGCCTTCACGCAGTCGAGTTGCAGACTGCGATCCGAACTGAGACCGGTTTTCAGCGATCCGCCCCACGTCACCGTGTCGCACCGCGTTGTACCGGCCATTGTAGCATGCGTGAAGCCCTGGACGTAAGGGGCATGATGATCTGACGTCATCCCCACCTTCCTCCGAGTTGACCCCGGCGGTCCCACATGAGTTCCCGGCATCACCCGCTGGCAACATGCGGCGAGGGTTGCGCTCGTTGCGGGACTTAACCCAACATCTCACGACACGAGCTGACGACGACCATGCACCACCTGTGAACCGGCCCCGAAGGGAAACCGTGTCTCCACGGCGATCCGGCACATGTCAAGCCCAGGTAAGGTTCTTCGCGTTGCATCGAATTAATCCGCATGCTCCGCCGCTTGTGCGGGCCCCCGTCAATTTCTTTGAGTTTTAGCCTTGCGGCCGTACTCCCCAGGCGGGATGCTTAACGCGTTGGCTCCGACACGGGACCCGTGGAAAGGGCCCCACATCCAGCATCCACCGTTTACGGCGTGGACTACCAGGGTATCTAATCCTGTTCGCTCCCCACGCTTTCGCTCCTCAGCGTCAGTGACGGCCCAGAGACCTGCCTTCGCCATTGGTGTTCTTCCCGATATCTACACATTCCACCGTTACACCGGGAATTCCAGTCTCCCCTACCGCACTCCAGCCCGCCCGTACCCGGCGCAGATCCACCGTT。

[0052] Based on the results of 16S rRNA molecular biological identification and morphological identification in Example 2, it was confirmed that the strain belongs to Bifidobacterium animalis subsp. lactis, and was named Bifidobacterium animalis subsp. lactis Bifidobacterium animalis subsp. lactis Strain C-2.

[0053] Test Example 1

[0054] This test example explored the effects of strain C-2 on various symptom indicators of mice with enteritis. The specific steps are as follows:

[0055] (1)Test animals: 6-week-old SPF male Balb / C mice. Breeding environment: temperature 25°C, humidity: 50%, lighting 12 h. Feed the mice with basic diet for one week for adaptation (free access to food and water).

[0056] (2)Grouping: After the adaptation test, randomly divide the mice into 9 groups: Group S1 (C-2 bacterial suspension), Group S2 (CKCC 1913 bacterial suspension), Group S3 (C-2 bacterial suspension + CKCC 1913 bacterial suspension, viable bacteria ratio 10:1), Group S4 (C-2 bacterial suspension + CKCC 1913 bacterial suspension, viable bacteria ratio 1:1), Group S5 (C-2 bacterial suspension + CKCC 1913 bacterial suspension, viable bacteria ratio 1:10), Group S6 (ATCC700541 bacterial suspension + CKCC 1913 bacterial suspension, viable bacteria ratio 10:1), Group S7 is the positive control group (0.01 g / ml 5-ASA solution), Group S8 is the model group, and Group S9 is the blank group. There are 12 mice in each group. The total viable bacteria in each of Groups S1 - S6 is 1×10 9 CFU / mL.

[0057] (3)Intervention method:

[0058] During the experiment, all mice in each group were allowed free access to food and water.

[0059] From day 0 to day 14, Groups S1 - S6 were respectively gavaged with 200 μL of the corresponding bacterial suspension, Group S7 was gavaged with 200 μL of 5-ASA solution, and Groups S8 - S9 were respectively gavaged with an equal volume of normal saline, once a day, 200 μL each time;

[0060] From day 8 to day 14, the drinking water of the mice in Groups S1 - S8 was changed to 2.5% DSS aqueous solution;

[0061] On day 15, the mice were sacrificed, blood was collected from the eye socket, and the blood samples were allowed to stand for 30 min and then centrifuged to collect the serum samples. At the same time, colon tissue and intestinal content samples were collected for detection and analysis of relevant indicators.

[0062] (a)Body weight change

[0063] On the 14th day of the experiment, the mice in each group were weighed respectively. The body weight change rate of the mice was calculated by the following formula, and the calculation results were averaged, as Figure 1 shown.

[0064] Body weight change rate = [(body weight of mice on day N - body weight of mice on day 0) / body weight of mice on day 0] × 100%

[0065] As can be seen from the statistical results in the figure, both C-2 and CKCC 1913 strains can delay and weaken the weight loss in mice with enteritis, and the effect of the C-2 bacterial suspension is the best. In addition, it was unexpectedly found that when C-2 and CKCC 1913 strains are used in combination, the effect of delaying and weakening the weight loss in mice with enteritis is better.

[0066] (b)Change in disease activity index (DAI)

[0067] The defecation of mice in each group was observed, and the DAI scores of mice in each group were evaluated according to the scoring criteria in Table 1. The scoring results are shown in Table 2.

[0068] Table 1

[0069]

[0070] Table 2

[0071]

[0072] As can be seen from the data in the table, compared with the mice in the S9 control group, the DAI scores of the mice in the S8 model group were significantly increased. Both C-2 and CKCC 1913 strains have a relieving effect on symptoms such as weight loss, diarrhea, and bloody stools caused by colitis, and the effect of the C-2 bacterial suspension is the best. In addition, it was unexpectedly found that when C-2 and CKCC 1913 strains are used in combination, the related effect is better.

[0073] (c)Effect of inhibiting inflammatory response

[0074] The colon homogenates of mice in each group were centrifuged, the supernatants were collected, and the sera of the mice were collected. The colon homogenates and serum samples were detected according to the steps in the ELISA kit instructions. The contents of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and interleukin-10 (IL-10) in the collected cell supernatants and sera were detected respectively. The experimental results were analyzed by data processing software. The statistical results of the content levels of various cytokines in the colon samples are as Figure 2 shown, and the statistical results of the content levels of various cytokines in the serum samples are as Figure 3 shown.

[0075] As can be seen from the results in the figure, compared with the mice in the S9 control group, the mRNA expression levels of the pro-inflammatory cytokines TNF-α and IL-1β in the colon tissues and sera of the mice in the S8 model group were significantly increased, the expression level of the pro-inflammatory cytokine IL-6 was also increased, and the mRNA expression level of the anti-inflammatory factor IL-10 was decreased. Both the C-2 and CKCC 1913 strains had anti-inflammatory effects, and the effect of the C-2 bacterial suspension was the best. In addition, it was unexpectedly found that when the C-2 and CKCC 1913 strains were used in combination, the related effects were better.

[0076] (d)Changes in key colonic mucin proteins

[0077] The mouse colon homogenate supernatant was analyzed by immunohistochemistry using qRT-PCR to detect the mRNA expression changes of four proteins, Claudin, Occludin, zonula occludens protein-1 (ZO-1), and mucin-2 (MUC2). The results are as Figure 4 shown.

[0078] As can be seen from the results in the figure, compared with the mice in the S9 control group, the mRNA expression levels of the four key colonic mucin proteins, Claudin, Occludin, ZO-1, and MUC2, in the colon tissues of the mice in the S8 model group were all significantly decreased. Both the C-2 and CKCC 1913 strains could promote the expression of related colonic key mucin proteins, and the effect of the C-2 bacterial suspension was the best. In addition, it was unexpectedly found that when the C-2 and CKCC 1913 strains were used in combination, the related effects were better.

[0079] (e)Changes in serum immunoglobulin expression levels

[0080] ELISA kits were used to detect the levels of three immunoglobulins, immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG), in the sera of mice in each group. The detection results are as Figure 5 shown.

[0081] As can be seen from the results in the figure, compared with the mice in the S9 control group, the expression levels of the three immunoglobulins, Ig A, Ig G, and Ig M, in the sera of the mice in the S8 model group were all significantly decreased. Both the C-2 and CKCC 1913 strains could promote the expression of related immunoglobulins, and the effect of the C-2 bacterial suspension was the best. In addition, it was unexpectedly found that when the C-2 and CKCC 1913 strains were used in combination, the related effects were better.

[0082] In summary, a new strain of Bifidobacterium animalis with the efficacy of improving inflammatory bowel disease was isolated, obtained and preserved in the present invention, and named Bifidobacterium animalis subsp. lactis C-2 strain. This strain can regulate the intestinal environment, inhibit the colonization of harmful bacteria and promote the colonization of beneficial bacteria, optimize the composition of intestinal microbiota, thereby inducing an anti-inflammatory response and improving intestinal barrier function. Therefore, this Bifidobacterium animalis subsp. lactis C-2 strain can be used to prepare a drug with the efficacy of preventing, improving or treating inflammatory bowel disease.

[0083] The applicant declares that the technical solution of the present invention is illustrated by the above embodiments, but the present invention is not limited to the above embodiments, that is, it does not mean that the present invention must rely on the above embodiments to be implemented. Those skilled in the art should understand that any improvement of the present invention, the equivalent substitution of each raw material of the product of the present invention, the addition of auxiliary components, the selection of specific methods, etc., all fall within the protection scope and the disclosure scope of the present invention.

[0084] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

[0085] In addition, it should be noted that, in the case of no contradiction, the various specific technical features described in the above specific embodiments can be combined in any appropriate way. To avoid unnecessary repetition, the present invention will not separately describe various possible combination methods.

Claims

1. A probiotic agent with the efficacy of improving inflammatory bowel disease, characterized in that, The strains in the probiotic agent are composed of Bifidobacterium animalis subspecies lactis C-2 strain and Lactobacillus gasseri CKCC 1913 with a live bacterial count ratio of 1:10-10:1; The taxonomic name of Bifidobacterium animalis subsp. lactis C-2 is Bifidobacterium animalis subsp. lactis , with the preservation number of GDMCC No: 65455 and the preservation date of November 8, 2024; The classification name of Lactobacillus gasseri CKCC 1913 is Lactobacillus formatum Lactobacillus gasseri , with the preservation number of CGMCC No. 23175 and the preservation date of August 23, 2021.

2. The probiotic agent with the efficacy of improving inflammatory bowel disease according to claim 1, wherein In the probiotic agent, the viable count of Bifidobacterium animalis subsp. lactis C-2 is not less than 1×10 9 CFU / mL or 1×10 9 CFU / g.

3. The probiotic agent with the efficacy of improving inflammatory bowel disease according to claim 1, characterized in that, The dosage form of the probiotics includes freeze-dried powder, capsules, tablets or granules.

4. The probiotic agent with the efficacy of improving inflammatory bowel disease as described in claim 1, characterized in that, The probiotics also include a protective agent; The protective agent includes any one of skim milk, gelatin, dextrin, gum arabic, dextran, sodium alginate, polyvinyl pyrrolidone, sucrose, lactose, trehalose, sorbitol or xylitol, or a combination of at least two thereof.

5. Use of the probiotic according to any one of claims 1 to 4 in the preparation of a product for regulating intestinal microecological environment.

6. Use of the probiotic according to any one of claims 1 to 4 in the preparation of a preparation having the efficacy of preventing, improving or treating inflammatory bowel disease.

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