Lactobacillus composition and use thereof
The xanthine oxidase activity is significantly inhibited by Lactobacillus compositions (Lactobacillus Grignard, Lactobacillus fermentation and Lactobacillus agile), and the problem of the risk and insufficient effect of hypersensitivity reactions of hyperuricemia treatment drugs in the prior art is solved, thus achieving the goal of achieving It has safe and efficient uric acid reduction and inflammation relief effects.
Patent Information
- Application Number
- PCT/CN2024/101994
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-06-28
- Filing Date
- 2024-06-27
- Publication Date
- 2025-01-02
AI Technical Summary
The existing hyperuricemia treatment drugs have the risk of hypersensitivity reactions, high cardiovascular disease considerations, and high urine pH monitoring requirements. The Lactobacillus strain alone has significantly lower effect in reducing uric acid than existing drugs, and It cannot effectively alleviate the inflammatory reaction caused by high uric acid.
Developed a Lactobacillus composition containing Lactobacillus gasseri BDUP, Lactobacillus fermentum B1B26 and Lactobacillus agilis B13T4, fermenting supernatant by inactivated or uninactivated combination strains The solution, bacterial suspension and cell fragments can significantly inhibit xanthine oxidase activity, reduce uric acid levels and relieve inflammation.
The Lactobacillus composition significantly reduces the uric acid content of high uric acid zebrafish and mice, inhibits the increase in inflammatory factors caused by uricemia, and is significantly better than the effect of the strain alone, providing a safe and efficient treatment plan for reducing uric acid.
Smart Images

Figure CN2024101994_02012025_PF_FP_ABST
Abstract
Description
A Lactobacillus composition and its application Technical Field
[0001] The present invention relates to the field of microorganisms, and in particular to a lactobacillus composition and application thereof in treating hyperuricemia. Background Art
[0002] Hyperuricemia (HUA) refers to the manifestation of abnormally high uric acid levels in the blood. Under normal dietary conditions, excessive uric acid production and / or insufficient excretion in the body will lead to uric acid accumulation. Clinically, when the fasting blood uric acid level on two different days is higher than 420μmol / L for men and higher than 360μmol / L for women, it is called hyperuricemia. Uric acid is the terminal metabolite of human purine compounds, and purine metabolism disorders can easily lead to hyperuricemia. High concentrations of uric acid may cause the deposition of sodium urate crystals in tissues and joints. The deposition of these crystals in the joints can cause gout. If deposited in the kidneys, it can cause uric acid nephropathy. In addition to the three highs (hyperglycemia, hyperlipidemia and hypertension), hyperuricemia is called the fourth high. Hyperuricemia and gout are independent risk factors for chronic kidney disease, cardiovascular and cerebrovascular diseases, and diabetes. At present, the incidence of hyperuricemia is increasing year by year, and the age of onset is also getting younger. There are about 120 million hyperuricemia patients in my country, accounting for about 10% of the total population, and the incidence of gout is as high as 1.1%.
[0003] Controlling blood uric acid levels is fundamental to improving hyperuricemia, gout, and related complications. Uric acid levels are generally controlled through a combination of lifestyle changes and medication. Dietary measures include limiting high-purine and high-fructose foods, strictly controlling the intake of meat, seafood, and animal offal, quitting smoking and alcohol, exercising regularly, and controlling weight. Medications for the treatment of hyperuricemia primarily fall into two categories: drugs that inhibit uric acid production (allopurinol and febuxostat; these inhibit uric acid production by binding to xanthine oxidase and inhibiting its activity) and drugs that promote uric acid excretion (benzbromarone). Although existing drugs can effectively lower uric acid, they still have some risks. For example, allopurinol has a high incidence of hypersensitivity reactions in Asian populations, febuxostat carries risks that require consideration when used in patients with cardiovascular disease, and benzbromarone requires high urine pH monitoring. Therefore, finding safer and more effective uric acid-lowering products is crucial.
[0004] In recent years, researchers have conducted a large number of systematic studies on intestinal microorganisms inhabiting the human gastrointestinal system and found that intestinal flora is closely related to the occurrence and development of hyperuricemia and gout, and the micro-ecosystem in which the intestinal flora resides has been considered a new target for the treatment of hyperuricemia. Among them, Lactobacillus (Lactobacillus) in probiotics has been reported to contain many species that can lower blood uric acid, including Lactobacillus fermentum, Lactobacillus reuteri, etc. Supplementation of probiotics can directly reduce the accumulation of uric acid in the blood. Currently, functional mining of intestinal microbial bacterial libraries is a research hotspot in this field. It can more specifically search for strains with the function of lowering uric acid. Therefore, probiotics have far-reaching significance as the next generation of products (such as food and / or drugs) to improve high uric acid. In addition, it has been reported that a variety of single strains of Lactobacillus have the effect of lowering uric acid, including the Lactobacillus agile B13T4 previously discovered by the inventors (patent publication number CN115109734A), but the uric acid-lowering function of these strains alone is significantly lower than that of existing drugs for treating hyperuricemia, and they cannot significantly alleviate the inflammatory response caused by hyperuricemia.
[0005] Therefore, the development of new strains and probiotic compositions for the preparation of a convenient and efficient drug or functional food for alleviating and treating hyperuricemia / gout has important significance and great market value.
[0006] Summary of the Invention
[0007] The present invention aims to provide a lactobacillus composition having the effect of reducing high uric acid in blood and application thereof.
[0008] According to one aspect of the present invention, the lactobacillus composition comprises Lactobacillus gasseri BDUP, Lactobacillus fermentum B1B26 and Lactobacillus agilis B13T4; the Lactobacillus gasseri BDUP is deposited with CGMCC No. 18357), the Lactobacillus fermentum B1B26 is deposited with CGMCC No. 24785, and the Lactobacillus agilis B13T4 is deposited with CGMCC No. 24786.
[0009] The lactobacillus composition can be one or more of an inactivated or non-inactivated fermentation supernatant, a bacterial suspension, and a cell disruptant supernatant.
[0010] The lactobacillus composition may contain more than 3×10 8 cfu / mL total bacterial count of the Lactobacillus gasseri BDUP, greater than 3×10 8 cfu / mL total bacterial count of the fermented Lactobacillus B1B26 and greater than 3×108 cfu / mL total bacterial count of the Lactobacillus agile B13T4.
[0011] The ratio of the viable counts of the Lactobacillus gasseri BDUP, the Lactobacillus fermentum B1B26 and the Lactobacillus agile B13T4 is 1:1:1.
[0012] According to another aspect of the present invention, the Lactobacillus composition can be used to prepare medicines for lowering blood uric acid.
[0013] According to the third aspect of the present invention, the pharmaceutical composition comprises the Lactobacillus composition.
[0014] Compared with a single strain, the Lactobacillus composition of the present invention significantly inhibits xanthine oxidase activity in vitro, significantly reduces uric acid levels in hyperuricemia zebrafish and hyperuricemia model mice, inhibits the increase in inflammatory factors caused by hyperuricemia in mice, and alleviates hyperuricemia, which is of great development significance. In addition, the Lactobacillus composition can exert an excellent effect in reducing hyperuricemia, enrich the abundance of beneficial bacteria in the intestine, regulate the flora structure, and enhance intestinal stability.
[0015] The Lactobacillus gasseri BDUP described in the present invention was deposited in the General Microorganism Center of the China Culture Collection of Microorganisms on August 2, 2019, with a deposit number of CGMCC No. 18357, and was classified as Lactobacillus gasseri. The fermented Lactobacillus B1B26 was deposited in the General Microorganism Center of the China Culture Collection of Microorganisms on April 27, 2022, with a deposit number of CGMCC No. 24785, and was classified as Lactobacillus fermentum. The agile Lactobacillus B13T4 was deposited in the General Microorganism Center of the China Culture Collection of Microorganisms on April 27, 2022, with a deposit number of CGMCC No. 24786, and was classified as Lactobacillus agilis. The deposit address of the three strains is the Institute of Microbiology, Chinese Academy of Sciences, No. 3, Yard 1, Beichen West Road, Chaoyang District, Beijing. BRIEF DESCRIPTION OF THE DRAWINGS
[0016] The accompanying drawings are used to provide further understanding and description of the present invention and are used to explain the present invention together with the specific embodiments, but not to limit the present invention.
[0017] FIG1 shows the in vitro inhibitory effects of the bacterial culture supernatants of the three lactobacilli species and their combination on xanthine oxidase XOD, with allopurinol as a positive drug, n=8.
[0018] Figure 2 shows the effects of the lactobacilli alone and in combination on uric acid levels in hyperuricemic zebrafish. Allopurinol was used as a positive drug. n = 3. Model group vs. blank (control) group: #, p < 0.05; ##, p < 0.01; ###, p < 0.001. Combination bacteria group vs. single bacteria experimental group and allopurinol group: *, p < 0.05; **, p < 0.01; ***, p < 0.001. Model group vs. single bacteria experimental group: $ , p<0.05; $$ , p<0.01; $$$ , p<0.001.
[0019] Figure 3 shows the effect of the lactobacillus composition of the present invention on xanthine oxidase in the serum of mice with hyperuricemia. Allopurinol was used as a positive drug, n = 8. Model group vs. blank (control) group: #, p < 0.05; ##, p < 0.01; ###, p < 0.001. Combination bacteria group vs. single bacteria experimental group and allopurinol group: *, p < 0.05; **, p < 0.01; ***, p < 0.001. Model group vs. single bacteria experimental group: $ , p<0.05; $$ , p<0.01; $$$ , p<0.001.
[0020] Figure 4 shows the effect of the lactobacillus composition of the present invention on the blood uric acid level of hyperuricemic mice, including IL-1β, IL-6, and TNF-α. Allopurinol was used as a positive drug, n=8. Model group vs blank (control) group: #, p<0.05; ##, p<0.01; ###, p<0.001; combined bacteria group vs single bacteria experimental group and allopurinol group: *, p<0.05; **, p<0.01; ***, p<0.001. Model group vs single bacteria experimental group: $ , p<0.05; $$ , p<0.01; $$$ , p<0.001.
[0021] Figure 5 shows the effect of the lactobacillus composition of the present invention on the levels of inflammatory factors in the blood of hyperuricemia mice, including IL-1β, IL-6, and TNF-α. Allopurinol was used as a positive drug, n=8. Model group vs. blank (control) group: #, p<0.05; ##, p<0.01; ###, p<0.001; combined bacterial group vs. single bacterial experimental group and allopurinol group: *, p<0.05; **, p<0.01; ***, p<0.001. Model group vs. single bacterial experimental group: $ , p<0.05; $$ , p<0.01; $$$ , p<0.001. DETAILED DESCRIPTION
[0022] The present invention first conducted a large number of screenings through in vitro xanthine oxidase (XOD) activity inhibition experiments and discovered a number of intestinal strains that are highly effective in inhibiting XOD activity. Subsequently, various combinations of these strains were tested to find a lactobacillus composition that can significantly inhibit xanthine oxidase activity in vitro, significantly reduce the uric acid content in the hyperuricemia model, and inhibit the increase of inflammatory factors caused by hyperuricemia.
[0023] Example 1 Strain culture and sample preparation
[0024] Lactobacillus gasseri BDUP was derived from stool samples of centenarians in Chengmai, Hainan, China. Prior to collection, the individuals had not taken antibiotics, had no history of probiotics, and had no history of gastrointestinal disease. After isolation and culture, the samples were frozen in a quantitative healthy intestinal bacteria library and were deposited at the General Microbiology Center of the China Culture Collection Administration on August 2, 2019, with the deposit number CGMCC No. 18357.
[0025] Lactobacillus fermentum B1B26 comes from fecal samples of healthy adults in urban Beijing, China. Before collection, the people had not taken antibiotics, had no history of taking probiotics, and had no history of gastrointestinal diseases. After isolation and culture, they were frozen in the quantitative healthy self-owned intestinal bacteria library and were deposited in the General Microbiology Center of the China Culture Collection Administration on April 27, 2022, with the preservation number CGMCC No. 24785.
[0026] Lactobacillus agile B13T4 comes from fecal samples of centenarians in Chengmai, Hainan, China. Before collection, the people had not taken antibiotics, had no history of taking probiotics, and had no history of gastrointestinal diseases. After isolation and culture, they were frozen in the quantitative healthy self-owned intestinal bacteria library. It was deposited in the General Microbiology Center of the China Culture Collection of Microorganisms on April 27, 2022, with the preservation number CGMCC No. 24786.
[0027] During the experiment, the -80°C frozen bacterial liquid of the above strains was spread on an MRS solid plate (10 g of peptone, 10 g of beef extract, 5 g of yeast extract, 2 g of diammonium citrate, 20 g of glucose, 1 mL of Tween 80, 5 g of sodium acetate, 2 g of dipotassium hydrogen phosphate, 0.58 g of magnesium sulfate, 0.25 g of manganese sulfate, 18 g of agar, and 1000 mL of distilled water). After inverted culture at 37°C for 24-48 hours, a single colony was inoculated into liquid MRS medium and cultured at 37°C for 18-24 hours to obtain a first-generation bacterial liquid; 10% of the first-generation bacterial liquid was inoculated into fresh MRS liquid medium and cultured at 37°C for 18-24 hours to obtain a second-generation bacterial liquid; 10% of the second-generation bacterial liquid was inoculated into fresh MRS liquid medium and cultured at 37°C for 18-24 hours to obtain a working bacterial liquid.
[0028] Preparation of strain supernatant: The working bacterial solutions of Lactobacillus gasseri BDUP, Lactobacillus fermentum B1B26, and Lactobacillus agile B13T4 were centrifuged at 13,000 rpm and 4°C for 15 minutes, and the supernatants were collected and filtered through a 0.22 μm filter membrane to obtain the strain fermentation supernatant samples. The supernatants of the respective bacteria were mixed at a ratio of 1:1:1 to obtain the lactobacillus composition sample of the present invention, which can be used for the in vitro enzyme activity assay and zebrafish treatment assay in the following examples.
[0029] Preparation of bacterial suspension: centrifuge the working bacterial suspension of Lactobacillus gasseri BDUP, Lactobacillus fermentum B1B26 and Lactobacillus agile B13T4 at 13000 rpm and 4°C for 15 min, discard the supernatant, collect the precipitate, and resuspend it in physiological saline to obtain a live bacterial suspension with viable cells. After concentration and counting, adjust the bacterial suspension concentration to 1*10 9 CFU / mL, after mixing the bacterial suspensions at a ratio of 1:1:1, the concentration was adjusted to 1*10 9 CFU / mL can be used to obtain the lactobacillus composition sample of the present invention, which can be used for animal experiments in subsequent examples.
[0030] The live bacterial liquid can also be obtained by other methods known in the art, as long as the bacteria can be enriched from the culture liquid, for example, by centrifugation and / or filtration.
[0031] Example 2 In vitro experiment on the effect of strain fermentation supernatant on xanthine oxidase activity
[0032] Xanthine Xan (X8030), xanthine oxidase XOD (X8020), and allopurinol Allopurinol (SA5630) used in the present invention were purchased from Solebao, and the method of use was in accordance with the instructions. The specific method of use is as follows:
[0033] To prepare a 6 mM xanthine solution: Accurately weigh 7.3 mg of xanthine. Add 0.6 ml of 1 mol / L NaOH and 3 ml of deionized water to a beaker. Add the xanthine powder to the beaker and gently shake until the xanthine is completely dissolved and the solution is mixed. Measure the pH of the solution using a pH meter and slowly add 1 mmol / L HCl dropwise to adjust the pH to 7.5-8.5. Pour the adjusted xanthine solution into a clean graduated cylinder and add deionized water to a final volume of 8 ml. Add the solution to the reaction system to a concentration of 0.6 mmol / L before use. Prepare fresh daily.
[0034] Preparation of xanthine oxidase solution: Calculate the original enzyme concentration based on the information on the bottle. Add the working solution to a concentration of approximately 0.074 U / ml. Dilute the original enzyme solution with PBS.
[0035] Preparation of allopurinol solution: Accurately weigh 0.034g of allopurinol, calculated based on the solubility of the reagents, using a minimum volume of 0.5ml of 1M NaOH as solvent, add 6ml of DMSO, and then add PBS to make 25ml of a 10mmol / L stock solution. Adjust the pH to approximately 8.5 and store at 4°C in the dark. When using, dilute to 0.25mmol / L with PBS.
[0036] Xanthine can produce uric acid under the catalysis of xanthine oxidase. The present application added the supernatants of three lactobacilli provided by the present invention to the reaction and observed the effects of each strain in the lactobacilli composition of the present invention on xanthine oxidase, as follows:
[0037] The experimental groups were divided into experimental groups: a lactobacillus group (Lactobacillus gasseri BDUP, Lactobacillus fermentum B1B26, and Lactobacillus agile B13T4) and a blank control group without XOD; an allopurinol-positive group and a blank control group without XOD; and a negative control group (MRS culture medium) and a blank control group without XOD. The experimental procedure was as follows: In a 96-well plate, the following solutions were added to the experimental group and its blank control group, respectively. The order of solution addition was 15 μl of lactobacillus supernatant or MRS culture medium → PBS → 10 μl of xanthine oxidase → 50 μl of xanthine. All blank controls did not add xanthine oxidase, and all groups were supplemented with PBS to a total of 200 μl. After addition, the plates were incubated in a 37°C incubator for 30 minutes. The absorbance at 290 nm was measured using a microplate reader, and this value was used to calculate the inhibitory effect of the three lactobacilli on xanthine oxidase. Three replicate wells were set up for each sample. The results are shown in Figure 1.
[0038] As shown in Figure 1, in three replicate experiments, compared to the blank control, the average inhibition rate of the positive drug allopurinol against xanthine oxidase was 87.65%. The average inhibition rates of Lactobacillus gasseri BDUP, Lactobacillus fermentum B1B26, and Lactobacillus agile B13T4 against xanthine oxidase were 78.7%, 70.96%, and 64.67%, respectively. This indicates that all three strains exhibit excellent xanthine oxidase inhibition. In this example, all three lactobacilli strains demonstrated potential for treating hyperuricemia. The fermentation supernatant of Lactobacillus gasseri BDUP exhibited the highest inhibitory activity against xanthine oxidase, followed by Lactobacillus fermentum, and Lactobacillus agile B13T4 exhibited the weakest xanthine oxidase inhibition. The combined supernatant of the three strains exhibited an inhibition rate of 85.37%. This indicates that a combination of three strains can produce superior xanthine oxidase inhibition compared to individual strains, potentially enabling the development of uric acid-lowering probiotic products.
[0039] Example 3 Effects of Lactobacillus Combination and Individual Strain on Uric Acid Levels in Hyperuricemic Zebrafish
[0040] Wild-type AB zebrafish were cultured in 6-well plates. The experiment included blank, model, positive drug (allopurinol), and sample-treated groups (supernatant of Lactobacillus gasseri BDUP, Lactobacillus fermentum B1B26, and Lactobacillus agile B13T4). Each group was set up in triplicate, with 50 fish per well. A hyperuricemia model was established by treating zebrafish with potassium oxalate (10 mmol / L) and sodium xanthine (0.5 mmol / L) for 24 hours. Five ml of 10% strain supernatant (v / v, diluted in culture water) was added to each well of the sample-treated group, 5 ml of culture water was added to each well of the blank and model groups, and 5 ml of allopurinol solution (100 mg / L) was added to each well of the positive control group. The 6-well plates were placed in a 37°C biochemical incubator for 48 hours. Afterward, the zebrafish were collected into 1.5 ml centrifuge tubes, the liquid was discarded, and 50 μl of 4°C pre-chilled PBS buffer was added to each tube. Then, after ultrasonic disruption, centrifugation was performed at 13,000 rpm and 4°C for 10 min, and the supernatant was collected for the detection of uric acid content in each group.
[0041] Figure 2 shows the effects of the lactobacilli alone and in combination on the uric acid level in hyperuricemia zebrafish. As shown in Figure 2, the average uric acid level in the blank zebrafish group was 19.31 μmol / L, and the uric acid level in the hyperuricemia model zebrafish was as high as 54.26 μmol / L. The uric acid content in the hyperuricemia zebrafish after treatment with the supernatant of Lactobacillus gasseri BDUP, Lactobacillus fermentum B1B26, and Lactobacillus agile B13T4 were 31.36 μmol / L, 32.25 μmol / L, and 34.22 μmol / L, respectively, indicating that the metabolites of these three strains can significantly reduce the uric acid level in the hyperuricemia model animals; after treatment with the combined bacterial group (BDUP+B1B26+B13T4), the uric acid level in the zebrafish dropped to 24.76 μmol / L, which was significantly better than the uric acid-lowering effect of each single strain, and better than the effect of the positive drug allopurinol (27.78 μmol / L). These results indicate that all the strains in this example have excellent efficacy in reducing uric acid, but the combined strain has a better effect and is more valuable for development and utilization.
[0042] Example 4 Effects of Lactobacillus Combination and Individual Strain on Uric Acid Levels in Hyperuricemia Model Mice
[0043] The present application administered the strain to mice to observe the efficacy of the strain and composition of the present invention in reducing blood uric acid. The specific operation is as follows:
[0044] Hyperuricemia mouse model establishment: SPF male Kunming mice, approximately 6 weeks old and weighing 25-30 g, were housed in an animal housing room with a 12-hour day / night lighting cycle, a temperature maintained at approximately 22°C, and a humidity of 50-60%. Water and food were available ad libitum. After one week of adaptive feeding, a hyperuricemia model was established using hypoxanthine combined with potassium oxonate. The animal experiments in this example used 56 5-week-old male Kunming mice weighing 25-30 g. These mice were housed in an animal housing room with a 12-hour day / night lighting cycle, a temperature maintained at approximately 22°C, and a humidity of 50-60%. Water and food were available ad libitum. Mice were randomly divided into 7 groups, with 8 animals in each group, namely normal group, hyperuric acid model group, hyperuric acid + Lactobacillus gasseri BDUP group, hyperuric acid + Lactobacillus fermentum B1B26 group, hyperuric acid + Lactobacillus agile B1B26 group, hyperuric acid + combined bacteria group (BDUP + B1B26 + B13T4) and hyperuric acid + positive drug group (allopurinol). After 7 days of adaptive feeding, modeling and drug administration were carried out. Except for the blank group, the other mice were treated with hypoxanthine and potassium oxonate to establish a hyperuricemia model. Hypoxanthine (250 mg / kg / day) was first gavage at 9 am every day, and potassium oxonate (250 mg / kg / day) was gavage 2 hours later. After 1-2 hours, the bacteria group was gavage with an equal volume of Lactobacillus (1*10 9 CFU / ml), the combined bacterial group was given a mixed bacterial solution of three lactobacilli (1*10 9 CFU / ml), the positive drug allopurinol group was given 40 mg / kg allopurinol solution, and the blank group was given the same volume of normal saline. The modeling lasted for 7 days, the treatment time was 14 days, and the whole cycle was 21 days.
[0045] After the experiment, the mice were anesthetized with chloral hydrate, blood was collected from the orbits, and the supernatant was collected as serum samples after centrifugation at 4°C for measuring xanthine oxidase levels, uric acid UA content, and levels of inflammatory factors IL-1β, IL-6, and TNF-α.
[0046] Figure 3 shows that after modeling, the content of XOD, a key enzyme in purine metabolism, in the blood of mice in the hyperuric acid model group was significantly increased (model group vs. control group, average value 10.23U / L vs. 3.34U / L), indicating that the hyperuric acid mouse model was successfully established. After gavage with the live bacterial suspensions of Lactobacillus gasseri BDUP, Lactobacillus fermentum B1B26 and Lactobacillus agile B13T4 in this application, the activity of XOD in the blood of mice in each treatment group was significantly reduced, reaching 5.24U / L, 5.66U / L and 5.85U / L, respectively; the effect of the combined bacteria (4.55U / L) was significantly better than that of the single strain and the positive drug allopurinol (5.64U / L). The effect of the intervention suggests that due to the reduced XOD activity, uric acid production in mice is inhibited, which can avoid excessive uric acid production. Furthermore, the results of uric acid test on the mice showed (Figure 4): Compared with the blank control group, the UA content in the blood of the mice in the hyperuric acid model group was significantly increased (model group vs control group, average value 299.26 μmol / L vs 119.51 μmol / L). After gavage with the live bacterial suspensions of Lactobacillus gasseri BDUP, Lactobacillus fermentum B1B26 and Lactobacillus agile B13T4 in this application, the uric acid content in the blood was significantly reduced to 215.96 μmol / L, 223.42 μmol / L and 221.05 μmol / L, respectively, showing a significant uric acid-lowering effect; in comparison, the effect of the combined bacteria (183.96 μmol / L) was better than that of the single strain of bacteria and the positive drug allopurinol (224.58 μmol / L).
[0047] In addition, the inflammatory factors in the blood of hyperuricemia mice were detected and found (as shown in Figure 5). The levels of inflammatory factors IL-1β, IL-6, and TNF-α in the blood of hyperuricemia model group mice were significantly higher than those in blank group mice. After gavage with the live bacterial liquid of Lactobacillus gasseri BDUP, Lactobacillus fermentum B1B26, and Lactobacillus agile B13T4 in the present embodiment, the levels of the above inflammatory factors were significantly reduced. The effect of the combined bacteria was better than that of the single strain, indicating that the three strains can alleviate the inflammatory response caused by abnormal uric acid metabolism, and the effect of the combined bacteria is better than that of any single strain. Taken together, compared with the individual strains, the combined bacteria (Lactobacillus gasseri BDUP, Lactobacillus fermentum B1B26, and Lactobacillus agile B13T4) in the present embodiment have excellent ability to reduce uric acid levels in hyperuricemia mice, can effectively alleviate the inflammatory response caused by hyperuricemia, and improve hyperuricemia.
[0048] Based on the above experimental results, it can be determined that the lactobacillus composition provided in this application (Lactobacillus gasseri BDUP, Lactobacillus fermentum B1B26 and Lactobacillus agile B13T4) has excellent efficacy in improving hyperuricemia and has broad application prospects in the preparation of products for lowering hyperuricemia, improving purine metabolism and preventing the occurrence of gout.
Claims
1. A lactobacillus composition having the function of lowering blood uric acid, characterized in that: The lactobacillus composition comprises Lactobacillus gasseri BDUP, Lactobacillus fermentum B1B26 and Lactobacillus agile B13T4; the Lactobacillus gasseri BDUP is deposited with CGMCC No.18357, the Lactobacillus fermentum B1B26 is deposited with CGMCC No.24785, and the Lactobacillus agile B13T4 is deposited with CGMCC No.24786.
2. The lactobacillus composition according to claim 1, characterized in that The lactobacillus composition is one or more of inactivated or non-inactivated fermentation supernatant, bacterial suspension and cell disrupted product supernatant.
3. The lactobacillus composition according to claim 1, characterized in that The lactobacillus composition contains more than 3*10 8 cfu / mL total bacterial count of Lactobacillus gasseri BDUP, greater than 3*10 8 cfu / mL total bacterial count of the fermented lactobacillus B1B26 and greater than 3*10 8 The Lactobacillus agile B13T4 had a total bacterial count of cfu / mL.
4. The lactobacillus composition according to any one of claims 1 to 3, characterized in that The ratio of the live bacterial counts of the Lactobacillus gasseri BDUP, the Lactobacillus fermentum B1B26 and the Lactobacillus agile B13T4 is 1:1:
1.
5. Use of the lactobacillus composition according to claim 1 in the preparation of a medicine for lowering blood uric acid.
Citation Information
Patent Citations
Lactobacillus fermentum capable of reducing blood uric acid
CN110079476A
Lactobacillus gasseri with function of preventing and treating hyperlipidemia, product composition and preparation method and application thereof
CN110628668A
Lactobacillus gasseri and application thereof in relieving and treating hyperuricemia
CN112458027A
Lactobacillus agilis B13T4 with function of relieving hyperuricemia and application of lactobacillus agilis B13T4
CN115109734A
Lactobacillus fermentum A21215 for reducing blood uric acid and application of lactobacillus fermentum A21215
CN116024130A
Cited By
Shea butter fermentation liquor as well as preparation method and application thereof
CN121154476A
A shea butter oil fermentation liquor, a preparation method and application thereof
CN121154476B