A synbiotic composition for promoting the proliferation of intestinal flora, and a preparation method and application thereof

Abstract

The application provides a probiotic composition capable of promoting proliferation of intestinal flora, and a preparation method and application thereof, and relates to the technical field of microorganisms. The probiotic composition comprises the following raw materials: probiotics and prebiotics; the probiotics are a mixture of lactobacillus crispatus, lactobacillus acidophilus and animal bifidobacterium with a mass ratio of (0.1-2):(2-4):(5-7); and the prebiotics are a mixture of xylo-oligosaccharide, oat beta-glucan, arabinoxylan and 2'-fucosyllactose with a mass ratio of (3-5):(1-2):(3-4):(0.1-1). The application significantly promotes proliferation of beneficial flora in the intestines through specific probiotics and specific prebiotics, and interaction between components.

Description

Technical Field

[0001] This invention relates to the field of microbial technology, specifically to a synbiotic composition that can promote the proliferation of intestinal flora, its preparation method, and its application. Background Technology

[0002] The human gut is home to over 1,000 species and approximately 1,014 microorganisms, ten times more than the number of human cells. These microorganisms can attach to the intestinal mucosa to form a barrier against the colonization of pathogens, secrete various enzymes to aid in the digestion and absorption of nutrients such as carbohydrates and proteins, and synthesize many essential vitamins. Furthermore, increasing research indicates a close relationship between gut microbiota and the occurrence and development of obesity, diabetes, and immune disorders. Therefore, the human body is considered a superorganism composed of its own cells and a symbiotic microbial community.

[0003] Based on their biochemical reactions within the host and their effects on the host, gut microbiota can be broadly classified into two categories: beneficial bacteria and harmful bacteria. Harmful bacteria cause various pathogenic effects, including producing toxins that damage the intestinal mucosa, induce infections, lead to tumors, and impair organ function. Beneficial bacteria, in addition to supplying or promoting the absorption of nutrients and facilitating the excretion of harmful substances through their metabolic activities, can also prevent the invasion of pathogenic bacteria through their own metabolism, such as producing large amounts of organic acids and secreting proteins. Under normal circumstances, the gut microbiota, the host, and the external environment establish a dynamic ecological balance, playing a vital role in human health. However, due to factors such as aging, environmental pollution, dietary changes, and antibiotic overuse, the gut microbiota ecosystem is often disrupted, leading to dysbiosis. This disruption of the normal physiological composition results in pathological combinations and clinical symptoms, a condition known as gut microbiota dysbiosis.

[0004] Clinically, patients with gut microbiota dysbiosis often have a reduced number of Bifidobacteria and other gut microbiota that may be reduced or increased. Therefore, increasing the number of probiotics in patients can improve their gut microecological status. Currently, there are two main methods for adjusting gut microbiota: live bacteria supplementation (i.e., probiotic supplementation) and the proliferation of one's own gut microbiota (i.e., prebiotic supplementation). Prebiotics are soluble dietary fibers that can be broken down into short-chain fatty acids by gut microbes, providing energy for intestinal epithelial cells. Probiotics are live microorganisms that colonize the gut and produce substances beneficial to human health.

[0005] Regulating gut microbiota using probiotics or prebiotics is a research hotspot in this field. For example, Chinese patent application CN102138594A discloses a compound sea buckthorn tea preparation with gut microbiota regulation function. This preparation combines oligosaccharides such as fructooligosaccharides and isomaltooligosaccharides with sea buckthorn fruit powder and black tea powder to create a tea beverage used to proliferate beneficial gut bacteria and inhibit harmful gut bacteria. However, relying solely on prebiotics to regulate gut microbiota is time-consuming and the effects are unstable.

[0006] Chinese patent application CN109700033A discloses a probiotic composition for regulating the intestines and preventing constipation, and its preparation method. The composition uses *Lactobacillus plantarum* bacterial powder and *Lactobacillus plantarum* metabolite powder as active ingredients. The *Lactobacillus plantarum* is deposited at the China Center for Type Culture Collection (CCTCCNO: M2018042). The composition also includes a bacterial powder carrier comprising microcrystalline cellulose, pharmaceutical corn starch, inulin, and magnesium stearate. The raw materials of the composition, by mass parts, are: 9-11 parts *Lactobacillus plantarum* bacterial powder, 4-6 parts *Lactobacillus plantarum* metabolite powder, 18-22 parts microcrystalline cellulose, 80-120 parts pharmaceutical corn starch, 8-12 parts inulin, and 8-12 parts magnesium stearate. However, current methods for supplementing probiotics with live bacteria still have many shortcomings, such as colonization capacity, survival rate of live bacteria, and stomach acid, which are problems that need to be solved.

[0007] If specific strains are introduced in the form of synbiotics, these synbiotics, composed of prebiotic-probiotic combinations, allow the prebiotics to be specifically and preferentially fermented by the probiotics. If the synbiotics are formulated to specifically stimulate the growth of accompanying probiotics, the latter will have a greater chance of establishing themselves in the gut. In summary, developing a synbiotic composition consisting of specific probiotics and prebiotics is of great significance. Summary of the Invention

[0008] To address the aforementioned problems, this invention provides a synbiotic composition that promotes the proliferation of intestinal flora, along with its preparation method and application. Through the interaction between specific probiotics and specific prebiotics, the composition significantly promotes the proliferation of beneficial bacteria in the gut.

[0009] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0010] On one hand, the present invention provides a synbiotic composition that can promote the proliferation of intestinal flora, comprising the following raw materials: probiotics and prebiotics; wherein the probiotics are a mixture of Lactobacillus curvaturei, Lactobacillus acidophilus and Bifidobacterium animalis in a mass ratio of (0.1-2):(2-4):(5-7); and the prebiotics are a mixture of xylooligosaccharides, oat β-glucan, arabinoxylan and 2'-fucosylated lactose in a mass ratio of (3-5):(1-2):(3-4):(0.1-1).

[0011] The mass ratio of Lactobacillus curvature, Lactobacillus acidophilus and Bifidobacterium animalis is (0.1-2):(2-4):(5-7).

[0012] Any point value or sub-range value within the range (0.1-2):(2-4):(5-7) is applicable to this invention, including but not limited to 0.1:2:5, 0.1:3:6, 0.1:4:7, 0.1:2:6, 0.1:2:7, 0.1:3:5, 0.1:3:7, 0.1:4:5, 0.1:4:6, 0.5:2:5, 0.5:3:6, 0.5:4:7, 0.5:2: 6, 0.5:2:7, 0.5:3:5, 0.5:3:7, 0.5:4:5, 0.5:4:6, 1:2:5, 1:3:6, 1:4:7, 1:2:6, 1:2:7, 1:3:5, 1:3:7, 1:4:5, 1:4:6, 2:2:5, 2:3:6, 2:4:7, 2:2:6, 2:2:7, 2:3:5, 2:3:7, 2:4:5, 2:4:6.

[0013] Preferably, the mass ratio of the Lactobacillus curvature, Lactobacillus acidophilus, and Bifidobacterium animalis is 1:3:6.

[0014] Preferably, the *Lactobacillus curvatureii* is *Lactobacillus curvatureii* LCR15, with accession number CGMCC No. 6406, and the depository center is the China General Microbiological Culture Collection Center. See Chinese patent application CN103074270A for further information.

[0015] Preferably, the Lactobacillus acidophilus is Lactobacillus acidophilus NCFM, ATCC 700396, and the depository is the American Center for Type Culture Collection. See also Chinese patent application CN114729298A.

[0016] Preferably, the Bifidobacterium animalis is Bifidobacterium animalis CICC 21711, with accession number CICC 21711, and the depository center is the China Industrial Microbial Culture Collection Center. See Chinese patent application CN111004756A for further information.

[0017] Preferably, the viable count of the *Lactobacillus curvatureii* LCR15 is 1 × 10⁻⁶. 6 - 1×10 7 CFU / g.

[0018] Preferably, the viable count of the Lactobacillus acidophilus NCFM is 1 × 10⁻⁶. 9 - 1×10 10 CFU / g.

[0019] Preferably, the viable count of the Bifidobacterium animalis CICC 21711 is 1 × 10⁻⁶. 8 - 1×10 10 CFU / g.

[0020] Preferably, the mass ratio of prebiotics to probiotics is 4-9:1.

[0021] Any point value or sub-range value within the range of 4-9:1 can be applied to this invention, including but not limited to 4:1, 5:1, 6:1, 7:1, 8:1, and 9:1.

[0022] The mass ratio of xylooligosaccharide, oat β-glucan, arabinoxylan and 2'-fucosylated lactose is (3-5):(1-2):(3-4):(0.1-1).

[0023] Any point value or sub-range value within the range of (3-5):(1-2):(3-4):(0.1-1) can be applied to this invention, including but not limited to 3:2:3:0.1, 5:1:4:1, 4:1.5:3.5:1, 3:1:3:0.1, and 5:2:4:1.

[0024] More preferably, the mass ratio of xylooligosaccharide, oat β-glucan, arabinoxylan and 2'-fucosylated lactose is 4:1.5:3.5:1.

[0025] Secondly, the present invention provides a method for preparing the aforementioned synbiotic composition, comprising the following steps: mixing the prebiotic and probiotic.

[0026] Thirdly, the present invention provides the application of the aforementioned synbiotic composition in the preparation of products that promote the proliferation of beneficial intestinal flora.

[0027] Preferably, the product includes a drug.

[0028] Preferably, the dosage form of the drug is selected from pills, capsules, granules, oral liquids, powders, tablets, lozenges, suspensions, syrups, injections, or elixirs.

[0029] Preferably, the drug further includes a pharmaceutically acceptable carrier.

[0030] More preferably, the pharmaceutically acceptable carrier is selected from at least one of buffers, emulsifiers, stabilizers, diluents, binders, preservatives, lubricants, pH adjusters, cryoprotectants, flavoring agents, fillers, or antioxidants.

[0031] Preferably, the buffer is selected from at least one of sodium dihydrogen phosphate, sodium bicarbonate, ammonium bicarbonate, sodium acetate, citrate, histidine, and succinate.

[0032] Preferably, the emulsifier is selected from at least one of magnesium stearate, zinc stearate, calcium stearate, glyceryl stearate, sorbitan isostearate, sorbitan oleate, and polyglycerol-3 polyricinoleate.

[0033] Preferably, the stabilizer is selected from at least one of farnesian gum, agar, alginate, cellulose ether, and carboxymethyl chitosan.

[0034] Preferably, the diluent is selected from at least one of erythritol, mannitol, sorbitol, xylitol, lactose, sucrose, corn starch, potato starch, calcium phosphate, calcium citrate, and crystalline cellulose.

[0035] Preferably, the adhesive is selected from at least one of ethanol, starch paste, pregelatinized starch, dextrin, syrup, hydroxypropyl methylcellulose, methylcellulose, sodium carboxymethylcellulose, ethylcellulose, polyvinyl alcohol, polyethylene glycol, sodium alginate, polyvinylpyrrolidone, gum arabic, gelatin, and alginic acid.

[0036] Preferably, the preservative is selected from at least one of methylparaben, propylparaben, methylparaben, ethylparaben, propylparaben, chlorobutanol, phenoxyethanol, chlorhexidine, benzoic acid, sodium benzoate, chlorocresol, benzalkonium bromide, benzalkonium chloride, and ethylparaben.

[0037] Preferably, the lubricant is selected from at least one of magnesium stearate, zinc stearate, glyceryl monostearate, polyethylene glycol, stearic acid, talc, sodium chloride, sodium oleate, sodium lauryl sulfate, magnesium lauryl sulfate, sodium stearate fumarate, and poloxamer.

[0038] Preferably, the pH adjuster is selected from at least one of citric acid, fumaric acid, succinic acid, tartaric acid, malic acid, and ascorbic acid.

[0039] Preferably, the flavoring agent is selected from at least one of sweet orange flavoring, vanilla flavoring, strawberry flavoring, milk flavoring, banana flavoring, and cherry flavoring.

[0040] Preferably, the filler is selected from at least one of mannitol, xylitol, sorbitol, maltose, microcrystalline cellulose, glucose, lactose, sucrose, dextrin, starch, sodium alginate, and sodium bicarbonate.

[0041] Preferably, the antioxidant may be selected from at least one of L-cysteine ​​hydrochloride, L-cysteine ​​base, 4,4-(2,3-dimethyltetramethylenediamine), tocopherol-rich extracts (natural vitamin E), α-tocopherol (synthetic vitamin E), β-tocopherol, 6-tocopherol, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), propyl gallate, octyl gallate, dodecyl gallate, tert-butylhydroquinone (TBHQ), fumaric acid, malic acid, ascorbic acid (vitamin C), sodium ascorbate, calcium ascorbate, potassium ascorbate, ascorbate palmitate, and ascorbate stearate.

[0042] Compared with the prior art, the present invention has the following beneficial effects:

[0043] 1. This invention utilizes specific probiotics: Lactobacillus curvature LCR15, Lactobacillus acidophilus NCFM, and Bifidobacterium animalis CICC 21711. These three probiotics work together in a specific ratio to not only exhibit strong acid resistance and adhesion, competitively inhibiting the colonization of pathogenic bacteria (such as Escherichia coli and Salmonella), promoting intestinal mucus secretion, and enhancing the physical barrier, but also regulating Th1 / Th2 immune balance, reducing intestinal inflammatory response, efficiently metabolizing oligosaccharides, lowering intestinal pH, and regulating intestinal flora.

[0044] 2. This invention uses a specific combination of prebiotics: xylooligosaccharides, oat β-glucan, arabinoxylan and 2'-fucosylated lactose to form a polysaccharide complex network, which can better provide a more favorable environment for the growth and reproduction of probiotics. The combination of probiotics and prebiotics achieves a synergistic effect of "1+1>2", promoting the proliferation of beneficial bacteria.

[0045] 3. The specific probiotics and prebiotics of this invention achieve a synergistic effect of "strain colonization + nutritional support + barrier repair". Under a specific ratio, it further regulates the intestinal immune homeostasis, provides energy for probiotics, prolongs the survival rate and colonization time of probiotics in the intestine, and enhances the antibacterial and immune regulation capabilities of the organism, so that it can still effectively repair the intestinal barrier even after severe flora imbalance or antibiotic use. Detailed Implementation

[0046] To make the technical means, creative features, achieved objectives, and effects of this invention readily understandable, the invention is further illustrated below with specific embodiments. However, these embodiments are merely preferred embodiments and not all embodiments. Other embodiments obtained by those skilled in the art based on the embodiments described herein without creative effort are all within the scope of protection of this invention. It is worth noting that the raw materials used in this invention are all common commercially available products, and their sources are not specifically limited. The technical and scientific terms used in the embodiments have the meanings commonly understood by those skilled in the art to which this invention pertains.

[0047] Example 1

[0048] A synbiotic composition that promotes the proliferation of intestinal flora comprises the following ingredients: 0.14 parts of Lactobacillus curvature, 0.42 parts of Lactobacillus acidophilus, 0.84 parts of Bifidobacterium animalis, 3.44 parts of xylooligosaccharide, 1.29 parts of oat β-glucan, 3.01 parts of arabinoxylan, and 0.86 parts of 2'-fucosylated lactose. The ingredients are mixed thoroughly to obtain the final product.

[0049] The viable count of the *Lactobacillus curvatureii* LCR15 was 1 × 10⁻⁶. 6 The viable count of the *Lactobacillus acidophilus* NCFM was 1 × 10⁻⁶. 10 The viable count of the animal Bifidobacterium CICC 21711 was 1 × 10⁻⁶. 8 .

[0050] Example 2

[0051] A synbiotic composition that promotes the proliferation of intestinal flora comprises the following ingredients: 0.02 parts of Lactobacillus curvature, 0.88 parts of Lactobacillus acidophilus, 1.1 parts of Bifidobacterium animalis, 2.67 parts of xylooligosaccharide, 1.77 parts of oat β-glucan, 2.67 parts of arabinoxylan, and 0.89 parts of 2'-fucosylated lactose. The ingredients are mixed thoroughly to obtain the final product.

[0052] The viable count of the *Lactobacillus curvatureii* LCR15 was 1 × 10⁻⁶. 7 The viable count of the *Lactobacillus acidophilus* NCFM was 1 × 10⁻⁶. 9 The viable count of the animal Bifidobacterium CICC 21711 was 1 × 10⁻⁶. 10 .

[0053] Example 3

[0054] A synbiotic composition that promotes the proliferation of intestinal flora comprises the following ingredients: 0.18 parts of Lactobacillus curvaturei, 0.18 parts of Lactobacillus acidophilus, 0.64 parts of Bifidobacterium animalis, 4.46 parts of xylooligosaccharide, 0.89 parts of oat β-glucan, 3.56 parts of arabinoxylan, and 0.09 parts of 2'-fucosylated lactose. The ingredients are mixed thoroughly to obtain the final product.

[0055] The viable count of the *Lactobacillus curvatureii* LCR15 was 1 × 10⁻⁶. 6 The viable count of the *Lactobacillus acidophilus* NCFM was 1 × 10⁻⁶. 10 The viable count of the animal Bifidobacterium CICC 21711 was 1 × 10⁻⁶. 8 .

[0056] Comparative Example 1

[0057] A synbiotic composition that promotes the proliferation of intestinal flora, compared with Example 1, only differs in the prebiotic ratio being 1:3:1:2, specifically composed of the following ingredients: 0.14 parts of Lactobacillus curvature, 0.42 parts of Lactobacillus acidophilus, 0.84 parts of Bifidobacterium animalis, 1.23 parts of xylooligosaccharide, 3.69 parts of oat β-glucan, 1.23 parts of arabinoxylan, and 2.45 parts of 2'-fucosylated lactose. The ingredients are mixed evenly to obtain the final product.

[0058] Comparative Example 2

[0059] A synbiotic composition that promotes the proliferation of intestinal flora, compared with Example 1, only differs in the probiotic ratio being 3:1:1, specifically composed of the following ingredients: 0.84 parts of Lactobacillus curvature, 0.28 parts of Lactobacillus acidophilus, 0.28 parts of Bifidobacterium animalis, 3.44 parts of xylooligosaccharide, 1.29 parts of oat β-glucan, 3.01 parts of arabinoxylan, and 0.86 parts of 2'-fucosylated lactose. The ingredients are mixed evenly to obtain the final product.

[0060] Comparative Example 3

[0061] A synbiotic composition that promotes the proliferation of intestinal flora, compared with Example 1, except that Lactobacillus curvature LCR15 is replaced with Lactobacillus reuteri, and the rest is the same as Example 1.

[0062] Comparative Example 4

[0063] A synbiotic composition that promotes the proliferation of intestinal flora, compared with Example 1, except that 2'-fucosylated lactose is replaced with oligomannose, and the rest is the same as Example 1.

[0064] Test Example 1

[0065] The antibacterial effect of synbiotic combination against Escherichia coli and Staphylococcus aureus

[0066] The inhibitory effects of the synbiotic compositions prepared in Examples 1-3 and Comparative Examples 1-4 of this invention on Escherichia coli and Staphylococcus aureus were tested. The specific operation process is as follows:

[0067] (1) Preparation of bacterial culture: Activated Escherichia coli (ATCC25922) and Staphylococcus aureus (ATCC25923) were inoculated into liquid culture medium and cultured at 37°C with shaking until the logarithmic growth phase. The bacterial concentration was adjusted with sterile physiological saline to a final concentration of approximately 1.0 × 10⁻⁶. 6 CFU / mL.

[0068] (2) Spreading the bacterial layer: Take 100 μL of the above Escherichia coli and Staphylococcus aureus bacterial suspensions and drop them onto the surface of a solidified sterile Mueller-Hinton agar plate. Use a sterile spreader to spread the bacterial suspensions evenly over the entire surface of the plate and let it stand at room temperature for 10 minutes to allow the bacterial suspensions to be absorbed by the culture medium.

[0069] (3) Punching and sealing: In a sterile operating table, use a sterilized Oxford cup (6 mm in diameter) to punch a hole vertically on the plate with the bacterial solution spread on it. Carefully remove the small pieces of culture medium from the hole with sterile forceps. Quickly sweep the bottom of the plate over the flame of an alcohol lamp (about 1-2 seconds) to seal it with heat to prevent sample leakage. Be careful to avoid high temperature damage to the surrounding culture medium.

[0070] (4) Adding the sample: Use a pipette to draw 100 μL of the test sample solution and slowly drip it into the round well of the plate to avoid overflow.

[0071] Test samples: The synbiotic compositions prepared in Examples 1-3 and Comparative Examples 1-4 of this invention were respectively prepared with sterile water to form a solution of 100 mg / mL, and then filtered through a 0.22 μm filter membrane for sterilization before use.

[0072] Blank control: Replace the composition solution with an equal volume of sterile water.

[0073] Positive control: 10 μg / mL gentamicin solution was used as a positive control.

[0074] (5) Pre-diffusion and incubation: The plate after sample addition was placed at 4℃ for pre-diffusion for 2 h, and then incubated at 37℃ for 24 h.

[0075] (6) Result measurement: Take out the plate and measure the diameter of the inhibition zone (including the diameter of the hole) with a vernier caliper. Measure each inhibition zone twice using the cross-sectional method and take the average value. Perform three parallel tests on each sample and record the data.

[0076] The formula for calculating the antibacterial rate is:

[0077] Inhibition rate (%) = (diameter of inhibition zone of treated sample - diameter of inhibition zone of blank control) / diameter of inhibition zone of treated sample × 100%.

[0078] The results are shown in Table 1 below:

[0079] Table 1

[0080]

[0081] As shown in Table 1, the synbiotic compositions prepared in Examples 1-3 of this invention have a certain inhibitory effect on Escherichia coli and Staphylococcus aureus, which is close to the effect of the positive control (gentamicin) and significantly higher than that of the comparative groups 1-4.

[0082] Test Example 2

[0083] The probiotic effects of synbiotic combination on Lactobacillus plantarum and Lactobacillus casei

[0084] The probiotic effects of the synbiotic compositions prepared in Examples 1-3 and Comparative Examples 1-4 of this invention on *Lactobacillus plantarum* and *Lactobacillus casei* were tested. The specific operation process is as follows:

[0085] The promoting effect of the composition of the present invention on the proliferation of *Lactobacillus plantarum* and *Lactobacillus casei* was determined using the pour plate method. The specific steps are as follows:

[0086] (1) Preparation of bacterial culture: Lactobacillus plantarum and Lactobacillus casei were inoculated into MRS liquid medium and activated by anaerobic culture at 37℃ for 24 h. The bacterial cells were collected by centrifugation, washed twice with sterile physiological saline, resuspended, and the bacterial concentration was adjusted to approximately 1.0 × 10⁻⁶. 6 CFU / mL.

[0087] (2) Preparation of test samples: Take the synbiotic compositions prepared in Examples 1-3 and Comparative Examples 1-4 of the present invention, add sterile water to prepare a solution of 100 mg / mL, and filter it through a 0.22 μm filter membrane for sterilization before use.

[0088] (3) Casting plate:

[0089] Experimental group: 1 mL of bacterial solution was taken into a sterile petri dish, and 1 mL of the test sample solution was taken into the same petri dish.

[0090] Blank control group: Take 1 mL of bacterial culture into a sterile petri dish, and then take 1 mL of sterile water into the same petri dish.

[0091] Quickly pour approximately 15 mL of melted and cooled MRS agar medium to the above-mentioned petri dish. Immediately and gently rotate the petri dish horizontally to ensure thorough mixing of the medium, bacterial culture, and sample, avoiding the formation of air bubbles or splashing.

[0092] (4) Culture: After the culture medium solidifies, invert the plate and place it in a 37℃ constant temperature incubator for anaerobic culture for 48 h.

[0093] (5) Result counting: Take out the plates and select plates with colony counts between 30 and 300 for counting. Record the colony forming units (CFU) of each plate. Each sample is tested in parallel three times and the average value is taken.

[0094] The formula for calculating the proliferation rate is as follows: Proliferation rate (%) = (Average colony count in the experimental group) The formula is: (mean colony count of blank control group) / (mean colony count of blank control group) × 100%. The results are shown in Table 2.

[0095] Table 2

[0096]

[0097] As shown in Table 2, the synbiotic compositions prepared in Examples 1-3 of this invention have certain probiotic effects on Lactobacillus plantarum and Lactobacillus casei, which are significantly higher than those in Comparative Examples 1-4.

[0098] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, and is not intended to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention do not depart from the essence and scope of the technical solution of the present invention.

Claims

1. A synbiotic composition that promotes the proliferation of intestinal flora, characterized in that, The product comprises the following ingredients: probiotics and prebiotics; the probiotics are a mixture of *Lactobacillus curvaturei*, *Lactobacillus acidophilus*, and *Bifidobacterium animalis* in a mass ratio of (0.1-2):(2-4):(5-7); the prebiotics are a mixture of xylooligosaccharides, oat β-glucan, arabinoxylan, and 2'-fucosylated lactose in a mass ratio of (3-5):(1-2):(3-4):(0.1-1); the *Lactobacillus curvaturei* is *Lactobacillus curvaturei* LCR15, with accession number CGMCC No. 6406; the *Lactobacillus acidophilus* is *Lactobacillus acidophilus* NCFM, with accession number ATCC700396; the *Bifidobacterium animalis* is *Bifidobacterium animalis* CICC 21711, with accession number CICC 21711; and the mass ratio of prebiotics to probiotics is 4-9:

1.

2. The synbiotic composition according to claim 1, characterized in that, The probiotics are a mixture of Lactobacillus curvaturei, Lactobacillus acidophilus, and Bifidobacterium animalis in a mass ratio of 1:3:

6.

3. The synbiotic composition according to claim 2, characterized in that, The viable count of the *Lactobacillus curvatureii* LCR15 was 1 × 10⁻⁶. 6 - 1×10 7 CFU / g; the viable count of the Lactobacillus acidophilus NCFM is 1×10⁻⁶. 9 - 1×10 10 CFU / g; the viable count of the animal Bifidobacterium CICC 21711 was 1×10⁻⁶. 8 - 1×10 10 CFU / g.

4. The synbiotic composition according to claim 1, characterized in that, The prebiotic is a mixture of xylooligosaccharides, oat β-glucan, arabinoxylan and 2'-fucosylated lactose in a mass ratio of 4:1.5:3.5:

1.

5. A method for preparing the synbiotic composition according to any one of claims 1-4, characterized in that, Includes the following steps: Mix the prebiotics and probiotics.

6. The use of the synbiotic composition according to any one of claims 1-4 in the preparation of products that promote the proliferation of Lactobacillus plantarum and Lactobacillus casei.

7. The application according to claim 6, characterized in that, The products include pharmaceuticals.

8. The application according to claim 7, characterized in that, The dosage form of the drug is selected from pills, capsules, granules, oral liquids, powders, tablets, lozenges, suspensions, or injections.

Images