Bifidobacterium animalis and application thereof

Abstract

The invention provides bifidobacterium animalis (Bifidobacterium animalis) and an application of the bifidobacterium animalis (Bifidobacterium animalis). According to the present invention, the Bifidobacterium animalis provided by the present invention can express the oleic acid hydratase so as to regulate the oleic acid metabolism level in the intestinal tract, such that the positive regulation effect of the application of the Bifidobacterium animalis on the development process of the chronic stress-related colorectal cancer metastasis is disclosed, and a foundation is provided for the actual clinical application of the bifidobacterium animalis and the preparation of the medicine of the bifidobacterium animalis. Meanwhile, by improving the abundance of Bifidobacterium animalis in the intestinal tract, enrichment of beneficial bacteria is promoted, proinflammatory bacteria are reduced, and the flora environment in the intestinal tract is adjusted; by promoting oleic acid in the intestinal tract to be metabolized into 10-hydroxystearic acid, the oleic acid metabolism level in the intestinal tract is directionally adjusted, a good intestinal tract microenvironment is constructed, and the treatment effect of Bifidobacterium aniis in prevention and treatment of colorectal cancer metastasis is achieved.

Description

Technical Field

[0001] The present invention relates to the field of biomedical technologies, and more particularly, to a Bifidobacterium animalis and its application. Background Art

[0002] Colorectal cancer is one of the most common malignant tumors of the digestive tract. Its incidence rate ranks the 3rd among male malignant tumors and the 2nd among female malignant tumors. Compared with other types of tumors, colorectal cancer is characterized by a long onset period, high concealment, a short treatment window period, and a high mortality rate. Moreover, since the liver is the main target organ for hematogenous metastasis of colorectal cancer, among newly diagnosed colorectal cancer cases, 20% - 25% have liver metastases, and among colorectal cancer cases treated by surgical resection, 40% - 50% will eventually develop liver metastases. The proportion of liver metastases among patients with postoperative recurrence is also as high as 70%. In the autopsy of patients who died of colorectal cancer, it was found that about 70% had liver metastases. That is to say, liver metastasis is the main cause of death from colorectal cancer. Therefore, studying the key factors affecting the metastasis of colorectal cancer and designing targeted diagnosis and treatment plans have important implications for improving the survival rate of patients and the prognosis of the disease.

[0003] The occurrence of colorectal cancer metastasis is affected by various factors, including genetic and immune environmental factors. At the same time, more and more evidence also shows that mental factors play a role in all stages of the disease, including as a predictive factor, a marker for undiagnosed pathology, or a trigger for clinical events in subclinical disease individuals. Among them, chronic stress, which is a common phenomenon in cancer patients, continuously activates the hypothalamic - pituitary - adrenal (HPA) axis and the sympathetic nervous system (SNS) in patients. It has been proven that it can trigger the depressive mood of patients, weaken psychological and physical health, and promote the deterioration of the disease, especially having a serious adverse impact on the progression of malignant tumors and the remodeling of the tumor microenvironment. Existing studies have shown that chronic stress is involved in multiple processes including tumorigenesis, progression, and metastasis, and has a certain promoting effect on the growth or metastasis of tumors such as ovarian cancer, gastric cancer, breast cancer, etc., and also has an important impact on the metastasis of colorectal cancer.

[0004] The gut microbiota is known as the "second genome of the human body" and has a huge impact on the enteric nervous system. Dysbiosis of the microbiota affects the normal function of the enteric nervous system. Existing studies have shown that in patients with depression and anxiety, the composition of the gut microbiota undergoes characteristic changes, specifically manifested as the enrichment of pro-inflammatory bacteria and the reduction of short-chain fatty acid-producing bacteria. Moreover, transplanting the gut microbiota of patients with depression into rats can cause depressive-like behaviors in the rats; at the same time, existing research data also prove that probiotic intervention therapy can improve the depressive-like behaviors of animals and the mood of patients with depression. Therefore, by studying the dysregulation characteristics and their mechanisms of action of the gut microbiota in patients with colorectal cancer under chronic stress conditions, and by establishing the relationship between the characteristic dysbiotic microbiota in the intestine and tumor metastasis, it is possible to improve the distant metastasis of tumors in clinical colorectal cancer patients by targeting and improving stress-related dysbiotic microbiota (or microbiota metabolism). Summary of the Invention

[0005] The present invention aims to overcome at least one of the above-mentioned deficiencies of the prior art and provides a Bifidobacterium animalis and its application. By using Bifidobacterium animalis to specifically regulate the function of the gut microbiota, the use of preventing and treating stress-related colorectal cancer metastasis can be achieved, which helps to improve the treatment effect of colorectal cancer.

[0006] One object of the present invention is to provide a Bifidobacterium animalis that expresses oleic acid hydratase in the intestine. Bifidobacterium animalis is a strain of Bifidobacterium isolated from animals. Generally, an increase in pro-inflammatory bacterial species and a decrease in beneficial bacterial genera are easily observed in the intestinal flora of colorectal cancer patients. In recent years, Bifidobacterium animalis has achieved good therapeutic effects in murine colitis models and murine colon cancer models, suggesting that Bifidobacterium animalis has good cytoprotective and anti-inflammatory properties in the intestine and has thus received increasing attention. However, without understanding the treatment mechanism of Bifidobacterium animalis, both clinical applications and improving the therapeutic effect of Bifidobacterium animalis will be limited. A series of experimental studies on a stress-related colorectal cancer metastasis model constructed based on mice have shown that the microbial composition in the intestines of mice with colorectal cancer metastasis developed under chronic stress conditions has changed, and the decreasing trend of the abundance of Bifidobacterium animalis is proportional to the development process and malignancy of colorectal cancer metastasis; at the same time, characteristic changes in the oleic acid metabolism level have also occurred along with the change in the abundance of Bifidobacterium animalis, suggesting that the intestinal microenvironment created by the decrease in the abundance of Bifidobacterium animalis and abnormal oleic acid metabolism is strongly correlated with the progression of stress-related colorectal cancer metastasis. Therefore, the Bifidobacterium animalis provided in this technical solution regulates the oleic acid metabolism level in the intestine by promoting the expression of oleic acid hydratase in the intestine, and then positively regulates the development process of colorectal cancer metastasis related to chronic stress, thereby achieving preventive and therapeutic effects.

[0007] Furthermore, Bifidobacterium animalis can be applied to the preparation of a preparation for preventing or treating stress-related colorectal cancer metastasis. Bifidobacterium animalis colonizes in the intestine, increasing the abundance of Bifidobacterium animalis in the intestine. At the same time, the targeted introduction of Bifidobacterium animalis can increase the expression of oleic acid hydratase in the intestine, thereby directionally regulating the metabolic level of the intestinal flora, promoting the metabolism of oleic acid in the intestine into 10-hydroxy stearic acid, and then protecting the integrity and functionality of intestinal mucosal cells, regulating the activities and functions of immune cells, and reducing the damage caused by stress response to the body, thus achieving the corresponding effects of preventing and treating colorectal cancer metastasis, which also corresponds to the research on the importance of intestinal flora in preventing and treating stress-related colorectal cancer metastasis in the prior art.

[0008] Furthermore, the stress-related colorectal cancer includes primary colorectal cancer. In one embodiment of the present invention, the disease condition treated by Bifidobacterium animalis regulating the intestinal flora is the spontaneous liver metastasis after orthotopic injection of colorectal cancer in the cecum of mice.

[0009] Furthermore, there is also provided an application of Bifidobacterium animalis in the preparation of a preparation for regulating the intestinal flora. Specifically, it includes increasing the abundance of Bifidobacterium animalis in the intestine. In addition to the direct application in preventing stress-related colorectal cancer metastasis, increasing the abundance of Bifidobacterium animalis in the intestine can promote the enrichment of beneficial bacteria in the intestine through functions such as biological oxygen deprivation, reduce the abundance of pro-inflammatory bacteria, and regulate the intestinal flora environment, achieving the therapeutic effect in preventing and treating colorectal cancer metastasis. Preferably, other substances for regulating the intestinal flora can also be used in combination with live Bifidobacterium animalis to improve the therapeutic effect and prepare corresponding drugs with significant preventive and therapeutic effects.

[0010] Furthermore, there is also provided an application of Bifidobacterium animalis in the preparation of a preparation for regulating intestinal flora metabolic disorders. Specifically, it includes promoting the metabolism of oleic acid in the intestine into 10-hydroxy stearic acid. In the mechanism described in the present invention, Bifidobacterium animalis promotes the expression of oleic acid hydratase in the intestine, thereby directionally regulating the oleic acid metabolism level in the intestine. By promoting the metabolism of oleic acid in the intestine into 10-hydroxy stearic acid, the physiological function of 10-hydroxy stearic acid is exerted, the metabolic level of the flora in the intestine is positively regulated, a good intestinal microenvironment is constructed, and the activities and functions of normal cells and immune cells in the intestine are protected and stimulated, thereby reducing the damage caused by the stress response to the body.

[0011] Furthermore, the preparation is a drug or a probiotic agent; the preparation includes an active ingredient and excipients acceptable in drugs or foods, and the active ingredient includes viable bacteria of Bifidobacterium animalis described in this technical solution. Combining the results of the examples of the present invention, it can be seen that oral administration of Bifidobacterium animalis can increase the intestinal colonization of Bifidobacterium animalis. Based on the mechanism described in the present invention, increasing the intestinal colonization of Bifidobacterium animalis is beneficial for Bifidobacterium animalis to achieve its therapeutic function.

[0012] Preferably, the active ingredient further includes other ingredients that increase the abundance of Bifidobacterium animalis in the intestine. Combining with a reagent that increases the abundance of Bifidobacterium animalis in the intestine helps to increase the abundance of Bifidobacterium animalis to further promote its positive effect on reducing colorectal cancer metastasis. Preferably, based on the therapy of Bifidobacterium animalis inhibiting colorectal cancer metastasis, it is beneficial to adopt a more effective treatment strategy, such as avoiding using other drugs that kill probiotics including Bifidobacterium animalis while using a live Bifidobacterium animalis preparation. In an embodiment of the present invention, after clearing the flora including Bifidobacterium animalis with antibiotics, Bifidobacterium animalis loses its role in protecting against stress-related colorectal cancer metastasis.

[0013] In this technical solution, it is also possible to prepare an appropriate dose based on the anti-tumor metastasis function of Bifidobacterium animalis, so as to achieve effective and safe prevention and treatment of colorectal cancer metastasis. Preferably, the number of live Bifidobacterium animalis in the active ingredient is not less than 1.0×10 7 CFU.

[0014] Preferably, the dosage form of the preparation is aqueous solution, powder, capsule, granule, tablet, suppository and / or sustained-release agent.

[0015] In addition to revealing that Bifidobacterium animalis prevents stress-related colorectal cancer metastasis through pathways including oleic acid degradation, etc., the present invention further reveals the positive regulatory role of Bifidobacterium animalis in the development of colorectal cancer. In addition to applying Bifidobacterium animalis to the preparation of drugs for preventing or treating stress-related colorectal cancer metastasis, Bifidobacterium animalis can also be applied to related drugs whose mechanism acts directly on the target, such as the preparation of drugs for regulating the intestinal flora. Existing studies have shown that the intestinal flora is closely related to the occurrence of various diseases, and adjusting the intestinal flora is also one of the strategies for relieving or treating some diseases. Therefore, in addition to being applied to the treatment of preventing colorectal cancer metastasis, Bifidobacterium animalis can also prepare corresponding drugs for adjusting the intestinal flora by using its mechanism of adjusting the intestinal flora and be applied to other diseases or fields.

[0016] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0017] 1. It reveals the mechanism of action of Bifidobacterium animalis in preventing and treating stress-related colorectal cancer metastasis by regulating the oleic acid metabolism level in the intestine through the expression of oleic acid hydratase, and reveals the positive regulatory role of applying Bifidobacterium animalis in slowing down the development process of stress-related colorectal cancer metastasis, providing a basis for the actual clinical application and drug preparation of Bifidobacterium animalis.

[0018] 2. By using Bifidobacterium animalis to regulate the intestinal flora structure to prevent and treat stress-related colorectal cancer metastasis, by increasing the abundance of Bifidobacterium animalis to promote the enrichment of beneficial bacteria and the reduction of pro-inflammatory bacteria in the intestine, and regulating the intestinal flora environment, the therapeutic effect in preventing and treating colorectal cancer metastasis is achieved.

[0019] 3. Application of Bifidobacterium animalis in the preparation of a preparation for regulating intestinal flora metabolic disorders. By promoting the metabolism of oleic acid in the intestine into 10-hydroxy stearic acid, the metabolic level of oleic acid in the intestine is directionally regulated, and then the physiological function of 10-hydroxy stearic acid is exerted to construct a good intestinal microenvironment, protect and stimulate the activity and function of normal cells and immune cells in the intestine, thereby reducing the damage caused by stress response to the body and achieving the therapeutic effect in the prevention and treatment of colorectal cancer metastasis.

[0020] 4. Using viable bacteria of Bifidobacterium animalis as an active ingredient to promote its colonization in the intestine, thereby avoiding components that may be adverse to the efficacy of Bifidobacterium animalis as part of a drug, enabling the finished drug to achieve a better therapeutic effect, and providing a treatment strategy for preventing colorectal cancer metastasis using Bifidobacterium animalis. It fills the gap in the existing technology for preventing or treating stress-related colorectal cancer metastasis and improves the current situation of the existing technology for preventing or treating stress-related colorectal cancer metastasis. Brief Description of the Drawings

[0021] Figure 1 Showing that chronic stress in Example 1 can promote the metastasis of colorectal cancer.

[0022] Figure 2 Showing that fecal microbiota transplantation in mice in the chronic stress group in Example 2 can promote the metastasis of colorectal cancer.

[0023] Figure 3 Showing that chronic stress in Example 3 can significantly change the intestinal flora structure and play a role in promoting the metastasis of colorectal cancer.

[0024] Figure 4 Showing that Bifidobacterium animalis inhibits stress-related colorectal cancer metastasis in Example 5. Figure 5 Showing the relative abundances of Bifidobacterium animalis in CRC patients with metastasis, CRC patients without metastasis, and normal populations in Example 6. Detailed Description of the Specific Embodiments

[0025] It should be noted that the following detailed description is illustrative and is intended to provide further explanation of the present application. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the technical field to which the present application belongs.

[0026] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit the exemplary embodiments according to the present application. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. In addition, it should also be understood that when the terms "comprise" and / or "include" are used in this specification, they specify the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0027] The present invention will be further described in conjunction with specific examples below. The following examples are only for explaining the present invention and do not constitute a limitation to the present invention. The test samples and test procedures used in the following examples include the following content (if the specific experimental conditions are not specified in the examples, they are usually in accordance with conventional conditions or the conditions recommended by the reagent company; the reagents, consumables, etc. used in the following examples, unless otherwise specified, can be obtained from commercial channels).

[0028] Specifically, the quadruple antibiotic water formulation involved in the following examples is shown in Table 1, and the qPCR primer sequences are shown in Table 2.

[0029] Table 1 Quadruple antibiotic water formulation

[0030] Antibiotic Concentration Vancomycin Hydrochloride 100mg / L Metronidazole 200mg / L Ampicillin 200mg / L Neomycin Sulfate 200mg / L

[0031] Table 2 qPCR primer sequences

[0032]

[0033] Example 1

[0034] This example provides the process of the effect of chronic stress on colorectal cancer metastasis.

[0035] By injecting 1×10 4 CT26 (MC38) cells stably expressing luciferase protein per 100 μl into the cecum to establish a liver metastasis model of orthotopic cecal tumor of colorectal cancer in mice. 6-8-week-old SPF mice were randomly divided into a control group (Control group) and a stress group (stress group). The control group drank normal water every day, and the treatment group fixed the mice in a centrifuge tube for 8 hours every day, allowing the mice to move only back and forth. The mice were continuously restrained for 14 days to make the mice in a state of chronic stress. On the 30th day, the tumor metastasis in the liver was observed, and the metastasis rate, mouse survival time, number of metastatic tumor nodules in the liver, and liver weight were recorded.

[0036] The results showed that chronic stress could promote the metastasis of colorectal cancer. The results are as Figure 1 shown. Compared with the control group, the number of liver metastasis foci in the chronic stress group increased (P<0.05), suggesting that chronic stress could promote the metastasis of colorectal cancer.

[0037] Example 2

[0038] This example provides the process of the effect of fecal microbiota transplantation in chronically stressed mice on colorectal cancer metastasis.

[0039] A liver metastasis model of cecal in situ tumor of colorectal cancer in mice was established by injecting 1×10 4 CT26 (MC38) cells stably expressing luciferase protein into the cecum at a dose of 100 μl. SPF-grade C57BL / 6 mice aged 4 - 6 weeks were randomly divided into a control group (control group) and a stress group (stress group). Mice in the control group drank normal water every day, while mice in the treatment group were fixed in a centrifuge tube for 8 hours every day, allowing the mice to move only back and forth. The mice were continuously restrained for 14 days to make them in a state of chronic stress. From the second week, the feces of chronically stressed mice were collected every day and transplanted into the corresponding mice in the FMT-stress group and the FMT-control group. On the 30th day, the liver tumor metastasis in the mice of the FMT-stress group receiving the chronically stressed microbiota was observed, and the metastasis rate, mouse survival time, the number of metastatic tumor nodules in the liver, and the liver weight were recorded.

[0040] As Figure 2 shown, compared with the control group, the number of liver metastases in the mice receiving the chronically stressed microbiota increased (P < 0.05). The results indicate that the transplantation of the intestinal microbiota of chronically stressed mice can promote the metastasis of colorectal cancer, suggesting that chronic stress can promote the metastasis of colorectal cancer by changing the intestinal microbiota structure.

[0041] Example 3

[0042] This example provides the process of the effect of chronic stress on the intestinal microbiota structure in mice.

[0043] The genomic DNA of feces from the control mice and the stress group mice in Example 2 was extracted using the DNeasy Blood&Tissue Kit (QIAGEN, Germantown, MD), and 16S rRNA gene sequencing was performed. The V4 variable region was amplified by PCR using dual-barcode primers, and the amplicons were purified using AMPure XP (Beckman Coulter) and quantified using the Quantum-iT PicoGreen ds DNA Assay Kit (Thermo Fisher Scientific). The amplicons were further identified and quantified on a Bioanalyzer 2100 using the High Sensitivity DNA Kit (Agilent) and the KAPA Library Quantification Kit for Illumina (KAPA Biosystems). The denatured amplicons were mixed with 20% PhiX Control v.3 and sequenced on a HiSeq (Illumina, 2×250-bp paired-end reads). The data of each sample was split from the downloaded data according to the Barcode sequence and the PCR amplification primer sequence. After truncating the Barcode and primer sequences, FLASH (V1.2.7, http: / / ccb.jhu.edu / software / FLASH / ) was used to splice the reads of each sample, and the spliced sequences were the original Tags data (Raw Tags); the Raw Tags obtained by splicing needed to be strictly filtered to obtain high-quality Tags data (Clean Tags). The Clean Tags needed to be processed to remove chimeric sequences. The Tags sequences were compared with the species annotation database through (https: / / github.com / torognes / vsearch / ) to detect chimeric sequences, and finally the chimeric sequences among them were removed to obtain the final effective data (Effective Tags). All the Effective Tags of all samples were clustered, and the Quantitative Insights into Microbial Ecology (Qiime) software was used to perform multiplexing and quality filtering with recommended parameters, and the 16S V4 sequences with a similarity of >97% were clustered into OTUs. The UCLUST3 algorithm based on the GreenGene database was used to classify the OTU taxonomic units. Finally, the data of each sample was normalized, and the normalization was performed based on the sample with the least amount of data. The subsequent Alpha diversity analysis and Beta diversity analysis were both based on the normalized data.

[0044] The Chao1 and Shannon indices were calculated using Qiime software (Version 1.9.1), and the inter-group differences in the Alpha diversity index were analyzed using R software (Version 2.15.3). The inter-group differences in the Alpha diversity index were analyzed by parametric test and non-parametric test respectively, and the statistical methods used were Tukey test and wilcox test of the agricolae package. The Unifrac distance was calculated using Qiime software, and the UPGMA sample clustering tree was constructed. The PCA plot was drawn using R software, and the PCA analysis was performed using the ade4 package and ggplot2 package of R software. The inter-group differences in the Beta diversity index were analyzed using R software, with parametric test and non-parametric test respectively, and the statistical analysis was performed using Tukey test and wilcox test of the agricolae package.

[0045] The results are as Figure 3 shown. The results of principal component analysis showed that there were significant differences in the intestinal flora structure between the chronic stress group and the control group after chronic stress treatment, indicating that chronic stress could significantly change the intestinal flora structure. Through the genus-level analysis, it was found that the abundance of the Bifidobacterium genus in the chronic stress mice decreased significantly in the chronic stress group, suggesting that the decrease in the abundance of the Bifidobacterium genus was strongly correlated with the development of stress-related colorectal cancer metastasis.

[0046] Example 4

[0047] This example provides a verification process for the inhibition of stress-related colorectal cancer metastasis by Bifidobacterium animalis.

[0048] The acquisition method of the Bifidobacterium animalis used was as follows: The fecal bacteria of commercially available C57 mice were collected and cultured on Brucella blood agar plates, and then the Bifidobacterium animalis with the gene fragments shown in Table 2 was screened by culturomics and purified.

[0049] Six- to eight-week-old SPF mice were randomly divided into a control group (Control group), a stress group (stress group), a control + Bifidobacterium animalis gavage group (Control + B.a group), a stress + Bifidobacterium animalis gavage group (stress + B.a group), and a stress + heat-killed Bifidobacterium animalis gavage group (stress + HK-B.a group). The control group drank normal water every day. In the treatment groups, mice were fixed in centrifuge tubes for 8 hours every day, allowing them to move only back and forth, and the mice were continuously restrained for 14 days. In this example and the following examples, CT26 (MC38) cells stably expressing luciferase protein were injected into the cecum at a dose of 1×10 4 cells / 100 μl to establish a mouse model of orthotopic liver metastasis of colorectal cancer in the cecum. On the 30th day, the liver metastasis situation was observed, and the metastasis rate, mouse survival time, number of metastatic tumor nodules in the liver, and liver weight were recorded, etc.

[0050] The results are as Figure 4 shown. Chronic stress can promote the metastasis of colorectal cancer. Compared with the control group, the number of liver metastasis foci in mice of the chronic stress group was significantly reduced (P<0.05) when gavaged with live Bifidobacterium animalis, suggesting that live Bifidobacterium animalis can inhibit the process of colorectal cancer metastasis induced by chronic stress.

[0051] Example 5

[0052] This example provides the relative abundances of Bifidobacterium animalis in CRC patients with metastasis, CRC patients without metastasis, and normal populations.

[0053] The fecal 16S data of CRC patients with metastasis, CRC patients without metastasis, and normal populations were downloaded from NCBI, and the relative abundances of Bifidobacterium animalis in different samples were analyzed.

[0054] The results are as Figure 5 shown. Compared with normal populations and CRC patients without metastasis, the relative abundance of Bifidobacterium animalis in CRC patients with metastasis was significantly reduced, suggesting a strong correlation between Bifidobacterium animalis and the development of colorectal cancer metastasis.

[0055] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the technical solutions of the present invention, rather than limitations on the specific implementation manners of the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the claims of the present invention shall be included within the protection scope of the claims of the present invention.

Claims

1. An animal Bifidobacterium, characterized in that It has the gene fragment listed in Attached Table 2 and can express oleate hydratase.

2. Use of the animal bifidobacterium according to claim 1 in the preparation of a preparation for preventing or treating stress-related colorectal cancer metastasis.

3. The use according to claim 2, wherein the stress-related colorectal cancer comprises primary colorectal cancer.

4. Use of the animal bifidobacterium according to claim 1 in the preparation of a preparation for regulating intestinal flora.

5. The use according to claim 4, comprising increasing the abundance of animal Bifidobacterium in the intestine.

6. Use of the animal bifidobacterium according to claim 1 in the preparation of a preparation for regulating metabolic disorders of intestinal flora.

7. The use according to claim 6, comprising promoting the metabolism of oleic acid in the intestine into 10-hydroxystearic acid.

8. The use according to any one of claims 2 to 7, wherein the preparation is a medicine or a probiotic agent; the preparation comprises an active ingredient and an adjuvant acceptable in medicine or food, and the active ingredient comprises the live bacteria of animal Bifidobacterium according to claim 1.

9. The use according to claim 8, wherein the active ingredients further comprise other ingredients that increase the abundance of animal Bifidobacterium in the intestine.

10. The use according to claim 8, characterized in that: The number of live animal Bifidobacterium in the active ingredient is not less than 1.0×10 7 CFU.

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