CN116004416B - Application of bifidobacterium bifidum from infant intestinal tract - Google Patents

Application of bifidobacterium bifidum from infant intestinal tract Download PDF

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CN116004416B
CN116004416B CN202210821655.XA CN202210821655A CN116004416B CN 116004416 B CN116004416 B CN 116004416B CN 202210821655 A CN202210821655 A CN 202210821655A CN 116004416 B CN116004416 B CN 116004416B
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bifidobacterium bifidum
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沈曦
程如越
何方
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Sichuan University
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Abstract

The invention discloses application of bifidobacterium bifidum from infant intestinal tracts, belongs to the field of biotechnology, and solves the problem that in the prior art, the construction of intestinal flora in early life is promoted by bifidobacterium from infant intestinal tracts so as to relieve symptoms of long-term inflammatory bowel diseases. The invention provides application of bifidobacterium bifidum BD-1 from infant intestinal tracts, which has the preservation number of CGMCCNO.24517 and is applied to preparation of medicines or foods with the effect of promoting construction of intestinal flora in early life. Animal experiments show that the bifidobacterium BD-1 is used in early life, so that the construction of intestinal flora of a newborn mouse can be promoted, long-term influence is generated, and long-term colonitis of the mouse is prevented.

Description

Application of bifidobacterium bifidum from infant intestinal tract
Technical Field
The invention belongs to the technical field of biology, and particularly relates to application of bifidobacterium bifidum from infant intestinal tracts with a preservation number of CGMCC NO. 24517.
Background
Inflammatory bowel disease (Inflammatory bowel disease, IBD), a chronic, non-specific inflammatory disease of the intestinal tract whose etiology is not yet well understood, mainly comprises ulcerative colitis (Ulcerative colitis, UC) and Crohn's Disease (CD). IBD occurs mainly in the colon, often affecting all the colon, limited to the colonic mucosa, and is mainly ulcers and erosions. The pathogenesis of IBD is currently not completely defined, but there may be some key contributors. There is evidence that genetic factors, defective mucosal barrier function, innate and adaptive immunity, and altered microbial composition contribute to the development and progression of IBD. In recent years, the incidence of IBD has been high in European and American countries, with the incidence of UC being about 8/10 ten thousand and the incidence of CD being about 7.8/10 ten thousand. The incidence of IBD in Asia is about 1.37/10 ten thousand, with the incidence in China being about 3.44/10 ten thousand. IBD can be seen as a further important chronic disease that afflicts human health.
IBD patients have been investigated to focus mainly on the young population, with children in western countries and IBD patients in the teenagers increasing year by year, with about 20% -30% of IBD patients diagnosed during childhood or adolescence. Young patients are found to develop chronic inflammatory bowel disease more readily than adult patients, and childhood IBD patients may be at risk for extra-intestinal symptoms such as growth retardation, anemia, joint symptoms, and delayed puberty. Early prevention of IBD is therefore particularly important.
Early life refers to the period of time from the beginning of fetal life to two years after birth. Human intestinal microorganisms begin to colonize from postnatal and gradually develop into adult flora structures, with increased flora diversity. The applicant finds that in the research of allergic diseases, in the construction process of intestinal flora in early life, the change of factors such as environment and the like easily affects the structure and diversity of early intestinal microorganisms, and long-term effect on health conditions and immune functions is generated, so that adult allergic diseases are prevented. The applicant has surprisingly found that the onset of IBD with a certain immune mechanism, like allergic diseases, is also affected by the construction of intestinal flora early in life.
Bifidobacteria are the major components of the human intestinal microbiota and are one of the most important dominant microbiota in the infant intestinal tract. The first week after birth, bifidobacteria begin to colonise the neonatal gut, forming a protective barrier against potential pathogens and stimulating the immune system. Bifidobacterium bifidum (Bifidobacterium bifidum, b.bifidum) is one of the representative species of bifidobacteria in the infant intestinal tract. The study shows that b.bifidum can prevent infantile diarrhea caused by rotavirus and significantly reduce stress-related behavior, and is likely to treat stress-related diseases. There are studies indicating that bifidobacteria promote the development of thymus in infants, thereby enhancing their response to oral administration and injection of vaccines. However, in the prior art, there is no report of improving the construction of early life intestinal flora by bifidobacteria derived from infant intestinal tracts to relieve symptoms of long-term inflammatory bowel disease.
Therefore, the provision of bifidobacteria derived from infant intestinal tracts, which promote the construction of intestinal flora in early life and relieve the symptoms of long-term inflammatory bowel disease, is a problem to be solved urgently by those skilled in the art.
Disclosure of Invention
The invention aims to provide an application of bifidobacterium bifidum from infant intestinal tracts, which solves the problem that bifidobacterium from infant intestinal tracts does not exist in the prior art so as to promote the construction of early-life intestinal flora and relieve symptoms of long-term inflammatory bowel diseases.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:
The invention provides application of bifidobacterium bifidum BD-1 from infant intestinal tracts, which has the preservation number of CGMCC NO.24517 and is applied to preparation of medicines or foods with the effect of promoting construction of intestinal flora in early life.
The preservation units of the bifidobacterium bifidum are as follows: the China general microbiological culture Collection center (China Committee for culture Collection of microorganisms) has a collection unit address of: the preservation date of the Gao district North Star West Liu 1,3 in Beijing city is: 2022, 03, 11.
In some embodiments of the invention, the use is in the manufacture of a medicament or food having the effect of promoting the establishment of intestinal flora early in life and preventing/alleviating long-term inflammatory bowel disease.
In some embodiments of the present invention, the pharmaceutical or food product comprises bifidobacterium bifidum with a collection number of CGMCC No.24517, and one or more pharmaceutically acceptable carriers.
By "pharmaceutically acceptable carrier" as used herein is meant a diluent, adjuvant, excipient or vehicle with which the therapeutic agent is administered, and which is suitable for contacting the tissues of humans and/or other animals without undue toxicity, irritation, allergic response, or other problem or complication commensurate with a reasonable benefit/risk ratio, within the scope of sound medical judgment.
In some embodiments of the invention, the pharmaceutical or food product is an oral formulation.
In some embodiments of the invention, the oral formulation comprises a solid oral formulation or a liquid oral formulation.
The bifidobacterium bifidum BD-1 of the present invention was isolated from the intestinal tract of a healthy infant of one year old and identified as bifidobacterium bifidum. Animal experiments show that the bifidobacterium BD-1 is used in early life, so that the construction of intestinal flora of a newborn mouse can be promoted, long-term influence is generated, and long-term colonitis of the mouse is prevented.
Compared with the prior art, the invention has the following beneficial effects:
The invention creatively separates bifidobacteria from intestinal tracts of healthy infants aged one year to obtain bifidobacteria BD-1. Animal experiments show that the bifidobacterium BD-1 is used in early life, so that the construction of intestinal flora of a newborn mouse can be promoted, long-term influence is generated, and long-term colonitis of the mouse is prevented.
Drawings
FIG. 1 is a view of strain BD-1 under a microscope (1000X).
FIG. 2 shows a colony morphology plate of strain BD-1.
FIG. 3 is a phylogenetic tree of strain BD-1.
FIG. 4 is a graph showing the results of inflammatory pathology scoring of mice with DSS-induced colitis, wherein "ns" indicates that p >0.05; ". Times" means p <0.05; "x" means p <0.01; ", denotes p <0.001, n=6-8/group.
FIG. 5 is a graph of colon tissue HE staining of colitis mice, wherein A is the physiological saline-water group and B is the physiological saline-DSS group; c is BD-1-water group; d is BD-1-DSS group.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention more clear, the technical solutions of the embodiments of the present invention will be clearly and completely described below. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
Example 1
This example discloses a method for separating and screening bifidobacterium bifidum BD-1 of the present invention.
1. Isolation of strains from crowd sources
Normal term newborns born at the child-producing hospital at the university Hua Xifu of Sichuan university between 3 and 4 of 2013 were selected as subjects. Inclusion criteria: residing in five urban areas of Chengdu city; the birth weight is 2500-4000 g after 37-42 weeks, and the infant has no congenital abnormality or birth defect. Exclusion criteria: the mother used antibiotics within one month before birth; parents have infectious diseases such as AIDS, tuberculosis, hepatitis B and the like; the neonate cannot collect the feces due to severe diseases such as neonatal pneumonia. The study followed Helsink principles and infants incorporated into the study were given informed consent by their father or mother on their behalf. The collection of faeces from a follow-up infant aged 1 facilitates a sterilized faeces cassette. Immediately after sampling, the sample was stored at 4℃and sent to a laboratory at low temperature by a researcher for dilution culture of the stool sample, and if the sample could not be immediately handled, the sample was stored at 4℃anaerobically and cultured on the same day.
2. Separation of dominant bifidobacteria in specimens
0.5G of excrement is weighed, 4.5mL of excrement diluent is added, and the mixture is stirred and mixed uniformly for serial 10-time dilution. 100 mu L of fecal mixed solution with proper concentration is respectively and evenly coated on a BL plate containing 5% horse blood by an L-shaped glass rod, and cultured for 48-72 h under anaerobic condition at 37 ℃. The total number of anaerobes was counted and suspicious colonies with bifidobacteria characteristics were picked from the high dilution BL plates and inoculated on selective medium TOS plates and placed in anaerobic conditions at 37℃for 48h, based on the remarkable characteristics of bifidobacteria growth on BL plates (brownish in central brown or marginal portion, smooth and moist surface, rounded, bulging, clean edge, diameter about 3-5 mm). The bacteria growing well on TOS plate are selected for gram staining, the form of the bacteria is observed under microscope, microscopic examination is gram positive bacillus, the staining is uneven, one end or two ends are enlarged or forked, no spore exists, and the bacteria are inoculated on MRS plate, after aerobic culture for 48 hours at 37 ℃, the bacteria are completely free of growing, the bacteria are primarily judged to be bifidobacterium, and the bacteria are preserved at-80 ℃ by taking skimmed milk powder as solvent.
Example 2
The bifidobacterium bifidum BD-1 of the invention is sent to China center for identification,
1. The strain is shown in figure 1 and figure 2.
2. 16S rRNA identification is carried out, and the 16S rRNA identification sequence of the strain is shown as SEQ ID NO. 1.
3. The results of BLAST for the 16S rRNA gene sequencing of this strain are shown in Table 1:
TABLE 1
4. The Neighbor-training phylogenetic tree constructed by using Scardovia inopinata DSM10107 (D89332) as an outer branch based on the 16S rRNA gene sequence comparison result is shown in figure 3.
5. The strain of the invention is subjected to physiological and biochemical characteristic detection, the enzyme activity detection result is shown in table 2, and the acid production result by using a carbon source is shown in table 3.
TABLE 2 physiological and biochemical Properties of strain BD-1-enzyme Activity
+: A positive reaction; -: a negative reaction; w: weak positive reaction
TABLE 3 physiological and biochemical characteristics of strain BD-1-acid production Using carbon sources
+: A positive reaction; -: a negative reaction;
Based on the above-described detection results, the strain BD-1 of the present invention was identified as Bifidobacterium bifidum (bifidobacterium bifidum, great name: bacillus bifidus).
Test example 1
The test example discloses an influence test of bifidobacterium bifidum BD-1 of the present invention on the composition of intestinal flora and on the symptoms of colitis.
1 Data and method
1.1 Laboratory animals and reagents
BALB/C mice were purchased from Liaoning Changsheng biotechnology Co., ltd (animal license number: SCXK (Liao) 2020-0001), bred in the animal center of the university of Sichuan China, china public health college (laboratory license number: SYXK (Sichuan) 2018-011), and had an environmental relative humidity of 40% -60%, a room temperature of (22+ -1) deg.C, and a 12-hour day-night cycle, and were free of ordinary drinking water. The feeding conditions were grade without specific pathogen (specific pathogen free, SPF).
The probiotic is Bifidobacterium bifidum BD-1 (Bifidobacterium bifidum BD-1). Each gram of the bacterial powder contains 1250 hundred million live bacteria (the counting unit is CFU).
1.2 Animal Experimental groups
The sex of the obtained novel BALB/C mice is distributed naturally according to birth, and the sex is randomly divided into 4 groups including physiological saline-water group, physiological saline-DSS group, BD-1-water group and BD-1-DSS group, wherein the total number of the groups is about 16. Mice were stopped from postnatal groups, normal saline-water and normal saline-DSS groups were perfused with normal saline (lavage amount 0.2 mL/day) to 3 weeks of age, BD-1-water and BD-1-DSS groups were perfused with BD-1 (absolute bacterial load 10 9 CFU/day, lavage amount 0.2 mL/day) for 3 weeks of age, and half of the mice were sacrificed at each group at 3 weeks of age. When the rest mice continue to be fed with the common feed until the age of 6 weeks, the drinking water of the normal saline-water group and the BD-1-water group is still pure water, and the mice are free to drink for 4 days; the drinking water of the physiological saline-DSS group and BD-1-DSS group is added with 3% dextran sulfate sodium salt (DSS) (molecular weight is 30-50 kDa) to induce colonitis model, and the colonitis model is drunk freely for 4 days. At week 6 for 4 days, the remaining mice were sacrificed and the trial ended. Weekly weight changes were recorded in the experiments, fecal samples were taken from the mice at 3 weeks and 6 weeks for 4 days (end of the experiment), and after animal sacrifice, all the intestinal tissue was collected.
1.3 Method for evaluating pathological section and inflammation condition of colon tissue
Colon tissue samples were collected for 3 weeks and at the end of the experiment. Firstly 10% neutral formalin is soaked and fixed for 2 days, then 60% -70% alcohol is used for soaking, then tissue dehydration and paraffin embedding are carried out, longitudinal slicing is carried out according to intestinal morphology, and finally HE staining is carried out. The pathologist was asked to score the tissue according to pathology scoring criteria. Specific scoring criteria are as follows, and the degree of inflammatory injury [0 points (no injury); 1min (mild); 2 minutes (middle); 3 minutes (severe) ], inflammatory injury depth [0 minutes (intact); score 1 (mucosal layer); score 2 (submucosa); 3 minutes (full layer) ], the area range of the mucosa of inflammatory destruction [1 minute (0-25%); 2 minutes (26% -50%); 3 minutes (51% -75%); 4 points (76% -100%) ], crypt damage degree [0 points (no damage); score 1 (1/3 of the base layer); 2 minutes (2/3 of the base layer); 3 minutes (only intestinal surface epithelium intact); 4 minutes (intestinal epithelium and basal layer are both destroyed) ], the mucosa area range of crypt destruction [1 minute (0-25%); 2 minutes (26% -50%); 3 minutes (51% -75%); score of 4 (76% -100%). And adding the scores of the individual items to obtain a final pathology score, wherein the score range is 1 to 18 points.
1.4 Fecal microorganism sequencing methods
1.4.1 Fecal genomic DNA extraction
Fecal genomic DNA was extracted according to TIANamp Stool DNAKit (cat# DP 328) instructions
1.4.2 Amplicon Generation
Bacterial 16S rRNAV3-V4 region universal primers were selected for PCR amplification of fecal genomic DNA, and the region fragments contained rich bacterial classification information. The universal primers for the 16S rRNAV3-V4 region are 341FCCTAYGGGRBGCASCAG and 806R GGACTACNNGGGTATCTAAT.
1.4.3 Clone sequencing
According toInstructions for DNAPCR-Free sample preparation kit (Illumina, usa) a sample DNA sequencing library was generated, which was sequenced on the IlluminaNovaSeq platform.
1.5 Intestinal microbiota analysis
1.5.1Alpha diversity analysis
The Alpha diversity index may reflect the richness and uniformity of the microbiota composition, and the Shannon index and Simpson index represent uniformity indicators in the sample microbiota diversity.
1.6 Statistical treatment
Statistical analysis was performed using SPSS26.0 software. Metering data conforming to normal distributionAnd (3) representing. The data obey normal distribution and are uniformly distributed, the comparison between two groups adopts t-test, and the comparison between multiple groups adopts one-way analysis of variance (ANOVA). The data do not obey normal distribution or variance disorder, and a t' test or a nonparametric test is adopted. P <0.05 is statistically significant for the differences.
2 Results
2.1 Cases of colitis inflammation in groups of mice at the end of the experiment
After the end of the experiment (4 days at 6 weeks) mice were sacrificed, colon tissues of the mice were HE stained and pathologically scored for inflammation. The results are shown in fig. 4 and table 4: after DSS induction, the mean score for inflammatory pathology in the saline-DSS group was 17.1 score higher than the mean score for saline-water group by 5.3 score, and the mean score for inflammatory pathology in the BD-1-DSS group was 12.3 score higher than the mean score for BD-1-water group by 3.6 score, with the differences all statistically significant (p < 0.05). As shown in FIG. 5, HE stained sections of intestinal tissue from both model groups showed abnormal colonic glandular patterns, with structural damage being more severe, similar to the symptoms of colitis in IBD patients, in the saline-DSS group compared to the saline-water group and in the BD-1-DSS group compared to the BD-1-water group. Indicating successful modeling.
As shown in fig. 4 and table 4, the inflammatory pathological score was significantly reduced in the BD-1-DSS group compared to the saline-DSS group, and the difference was statistically significant (p < 0.05). The HE staining slice result is shown in figure 5, wherein A is physiological saline-water group, and colonic mucosa is normal in morphology and regular in structure; b is a normal saline-DSS group, obvious damage to the crypt structure, gland atrophy, epithelial morphology change and inflammatory infiltration abnormality; c is BD-1-water group, the crypt structure is complete, the gland development is normal, and the structure is regular; d is BD-1-DSS, and shows different degrees of inflammatory response, but crypt destruction and inflammatory infiltration are smaller than those of the saline-water group. Compared with the physiological saline-DSS group, the BD-1-DSS group has less damage to colon crypt structure, lower inflammatory infiltration degree and more complete epithelial structure. The probiotic effect possibly generated by using the bifidobacterium bifidum BD-1 in early life still exists in a period of time after the bacteria are stopped, the intestinal mucosa structure of a long-term mouse can be protected within a certain limit, and the pathological inflammation symptoms of colonitis can be effectively relieved.
Table 4 inflammatory pathology score
Note that: ". Times." indicates p <0.05 compared to saline group; ". Times." means p <0.01 compared to saline group; ", denotes p <0.001 compared to saline group. "#" indicates p <0.05 compared to saline-DSS group; "#" indicates p <0.01 compared to saline-DSS group; "# #" indicates p <0.001 compared to saline-DSS group. n=6-8/group
2.2 Immediate and long-term effects on intestinal flora with BD-1 before 3 weeks
Intestinal flora composition data as in tables 5 and 6 show: at 3 weeks, at the portal level, there was no statistical significance for differences in relative abundance (p > 0.05) between the phylum bacteroides/firmicutes (Bacteroidetes/Firmicutes, B/F) in the group BD-1, but the relative abundance of actinomycota (Actinobacteria) in the group BD-1 was higher than that in the group saline, and the differences were statistically significant (p < 0.05); at the genus level, the relative abundance of bifidobacteria (bifidobacteria) in the BD-1 group was increased compared to the normal saline group, the difference was statistically significant (p < 0.05), the relative abundance of Lactobacillus (Lactobacillus) showed a trend of increasing, the difference was not statistically significant (p > 0.05), but the relative abundance of Enterococcus (Enterococcus) and Staphylococcus (Staphylococcus) were significantly decreased, and the difference was statistically significant (p < 0.05). At the end of the experiment, at the portal level, the difference in relative abundance of B/F was statistically insignificant (p > 0.05) compared to that of BD-1-DSS, but the relative abundance of Proteus (Proteus) was decreased in BD-1, and the difference was statistically significant (p < 0.05); at the genus level, the relative abundance of Lactobacillus in the BD-1-DSS group was increased compared to the saline-DSS group, but the relative abundance of Staphylococcus, ruminococcus (Ruminococcus) and Escherichia/Shigella was decreased, and the differences were statistically significant (p < 0.05).
Table 53 average relative abundance of species at levels of mice intestinal flora at week 53 and end of experiment
Note that: ". Times." indicates p <0.05 compared to saline group; ". Times." means p <0.01 compared to saline group; ", denotes p <0.001 compared to saline group. "#" indicates p <0.05 compared to saline-DSS group; "#" indicates p <0.01 compared to saline-DSS group; "# #" indicates p <0.001 compared to saline-DSS group. n=5/group
Table 6 3 average relative abundance of species at mouse intestinal flora level at week and end of experiment
Note that: ". Times." indicates p <0.05 compared to saline group; ". Times." means p <0.01 compared to saline group; ", denotes p <0.001 compared to saline group. "#" indicates p <0.05 compared to saline-DSS group; "#" indicates p <0.01 compared to saline-DSS group; "# #" indicates p <0.001 compared to saline-DSS group. n=5/group
As shown in table 7, the intestinal flora Alpha diversity data showed that both Shannon index and Simpson index were decreased in BD-1 group compared to saline group at 3 weeks, and the difference was statistically significant (p < 0.05); similarly, at the end of the experiment, the Shannon index and Simpson index were also lower for the BD-1-DSS group than for the saline-DSS group, the differences were statistically significant (p < 0.05).
TABLE 7 intestinal flora Alpha diversity
Note that: ". Times." indicates p <0.05 compared to saline group; ". Times." means p <0.01 compared to saline group; ", denotes p <0.001 compared to saline group. "#" indicates p <0.05 compared to saline-DSS group; "#" indicates p <0.01 compared to saline-DSS group; "# #" indicates p <0.001 compared to saline-DSS group. n=5/group
From the above test results, it is apparent that the BD-1 group used 3 weeks before the present invention had higher relative abundance of beneficial bacteria (e.g., bifidobacterium, lactobacillus) and lower relative abundance of harmful bacteria (e.g., enterococcus and Staphylococcus) than the physiological saline group. After stopping the intervention in the adult period of mice, after inducing colitis with DSS, the BD-1-DSS group still has higher beneficial bacteria (such as Lactobacillus) and lower harmful bacteria (such as Staphylococcus) than the physiological saline-DSS group. In addition, when colitis occurs, BD-1-used neonatal mice have lower ruminococcus in adulthood and Escherichia/Shigella. While ruminococci and adhesion-invasiveness escherichia are closely related to IBD and intestinal inflammation.
The data for gut flora diversity show that both Shannon and Simpson indices were lower in the gut flora of BD-1-interfered mice than in the non-interfered mice at 3 weeks and at the end of the experiment. The Shannon index and Simpson index are indicators representing uniformity in flora diversity, suggesting that BD-1 may relatively increase non-dominant bacteria (e.g., bifidobacteria) in the intestinal tract of neonatal and adult mice, resulting in decreased flora uniformity, similar to the results of intestinal flora composition data.
In conclusion, the possible probiotics effect generated by using BD-1 in early life still exists after bacteria are stopped until the experiment is finished, so that the intestinal mucosa structure of a long-term mouse can be protected within a certain limit, and the pathological inflammation symptoms of colonitis can be effectively relieved. BD-1 can promote the construction of intestinal flora of newborn mice to a certain extent in early stage, so that the relative abundance of beneficial bacteria is increased, and the relative abundance of harmful bacteria is reduced. After the BD-1 is deactivated, the early establishment of a good flora structure can also be sustained until adulthood. When colonitis occurs in the adult stage, the intestinal flora still maintains a state in which there are relatively more beneficial bacteria, relatively fewer harmful bacteria, and fewer inflammation-related flora. Thus, promoting early intestinal flora establishment still has some intestinal anti-inflammatory effect at the end of the adult phase of the probiotic dry prognosis.
Finally, it should be noted that: the above embodiments are merely preferred embodiments of the present invention for illustrating the technical solution of the present invention, but not limiting the scope of the present invention; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some or all of the technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit of the corresponding technical solutions; that is, even though the main design concept and spirit of the present invention is modified or finished in an insubstantial manner, the technical problem solved by the present invention is still consistent with the present invention, and all the technical problems are included in the protection scope of the present invention; in addition, the technical scheme of the invention is directly or indirectly applied to other related technical fields, and the technical scheme is included in the scope of the invention.

Claims (5)

1. The application of bifidobacterium bifidum (Bifidobacterium bifidum) from infant intestinal tracts is characterized in that the preservation number of the bifidobacterium bifidum is CGMCC No. 24517, and the application is the application in preparing medicines or foods with the effect of promoting the construction of intestinal flora in early life.
2. The use according to claim 1, characterized in that it is the use in the preparation of a medicament having the effect of promoting the establishment of intestinal flora early in life and preventing/alleviating inflammatory bowel disease in the long term.
3. The use according to claim 1 or 2, wherein the medicament comprises bifidobacterium bifidum with a collection number of CGMCC No. 24517, and one or more pharmaceutically acceptable carriers.
4. The use according to claim 1 or 2, wherein the medicament is an oral formulation.
5. The use according to claim 4, wherein the oral formulation comprises a solid oral formulation or a liquid oral formulation.
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