A bacterial agent for alleviating hyperuricemia and its application

Abstract

The present invention relates to a bacterial agent for alleviating hyperuricemia and its application. The bacterial strain in the bacterial agent for alleviating hyperuricemia is Akkermansia muciniphila. Akkermansia muciniphila Akk09 strain and Bifidobacterium animalis subsp. lactis Bifidobacterium animalum subsp. milk The two strains are composed of the BLa80 strain. They complement and enhance each other, synergizing their effects in alleviating hyperuricemia, specifically by lowering blood uric acid levels; inhibiting xanthine oxidase activity; reducing urea nitrogen and creatinine levels; alleviating kidney inflammation and oxidative stress caused by hyperuricemia; and regulating intestinal flora disturbances caused by hyperuricemia.

Description

Technical Field

[0001] The present invention belongs to the technical field of probiotics and relates to a probiotic for alleviating hyperuricemia and an application thereof. Background Art

[0002] Hyperuricemia is a metabolic disease caused by excessively high levels of uric acid in the blood. Hyperuricemia often leads to conditions such as gout and uric acid nephropathy, and is highly susceptible to complications including hypertension, chronic kidney disease, and cardiovascular and cerebrovascular diseases. Current treatments for hyperuricemia primarily rely on dietary interventions and medications. Allopurinol, febuxostat, and benzbromarone are first-line uric acid-lowering medications for patients with hyperuricemia and gout. They are widely used and highly effective, but long-term use of these medications can cause serious side effects and adverse reactions. For example, allopurinol can cause exfoliative dermatitis, febuxostat increases the risk of cardiovascular disease, and benzbromarone can cause severe liver damage, including fulminant hepatitis. Regarding dietary interventions, purines are present in both plant and animal cells, and most foods are made from them. Including purine-rich foods in our daily diet is unavoidable. Therefore, the search for new uric acid-lowering options is urgent.

[0003] Most uric acid in the human body is excreted through the kidneys, while the remaining uric acid is excreted from the intestines or decomposed by intestinal flora. Akkermansia muciniphila is a Gram-negative, strictly anaerobic bacterium that resides in the intestinal mucus layer and is one of the most abundant resident bacteria in the human intestine. However, there are few reports on the use of Akkermansia muciniphila to alleviate hyperuricemia. Therefore, it is of great significance to develop more Akkermansia muciniphila that can alleviate hyperuricemia and further explore its improvement effect on hyperuricemia. Summary of the Invention

[0004] In view of the deficiencies of the prior art, the present invention aims to provide a bacterial agent for alleviating hyperuricemia and its application.

[0005] In order to achieve the purpose of the invention, the present invention adopts the following technical solutions:

[0006] In a first aspect, the present invention provides a bacterial agent for alleviating hyperuricemia, wherein the bacterial agent for alleviating hyperuricemia is composed of Akkermansia muciniphila with a deposit number of CCTCC NO: M 20242401. Akkermansia muciniphila Akk09 strain and Bifidobacterium animalis subsp. lactis with a deposit number of CGMCC No. 22547 Bifidobacterium animalis subsp. lactis BLa80 strain composition.

[0007] The present invention creatively develops a new probiotic compounding method and a new strategy for alleviating hyperuricemia, namely, Akkermansia muciniphila Akkermansia muciniphila Akk09 strain and Bifidobacterium animalis subsp. lactis Bifidobacterium animalis subsp. lactis The BLa80 strain was used in combination, and it was found that the two strains can cooperate with each other, promote each other, and synergize in alleviating hyperuricemia, specifically: (1) reducing blood uric acid levels; (2) inhibiting xanthine oxidase activity; (3) reducing urea nitrogen and creatinine levels; (4) effectively regulating kidney inflammation and oxidative stress caused by hyperuricemia, and significantly improving the levels of inflammatory factors and oxidative stress; (5) effectively regulating intestinal flora disorders caused by hyperuricemia, and significantly improving the structure of intestinal flora.

[0008] When the bacterial dosage is consistent, the combination of Akk09 and BLa80 strains significantly improves the effectiveness of alleviating hyperuricemia compared to interventions using either Akk09 or BLa80 strains alone. Furthermore, both strains are probiotics, making the bacterial agent highly safe and less susceptible to resistance.

[0009] Preferably, the content of live bacteria in the bacterial agent is not less than 1×10 10 CFU / g or 1×10 10 CFU / mL, for example 1×10 10 CFU / g (CFU / mL), 2×10 10 CFU / g (CFU / mL), 5×10 10 CFU / g (CFU / mL), 8×10 10 CFU / g (CFU / mL), 1×10 11 CFU / g (CFU / mL), 5×10 11 CFU / g (CFU / mL), 1×10 12 CFU / g (CFU / mL), 1×10 13 CFU / g (CFU / mL), 1×10 14 CFU / g (CFU / mL), etc. Other specific point values ​​within this numerical range can be selected and will not be detailed here.

[0010] Preferably, the ratio of the number of viable bacteria of the Akk09 strain to the BLa80 strain is 1:10-10:1, for example, 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, etc. Other specific point values ​​within this numerical range can be selected and will not be repeated here.

[0011] Preferably, the dosage form of the bacterial agent includes solution, powder, capsule, tablet or granule.

[0012] The dosage form of the bacterial agent involved in the present invention is not limited, including the most commonly used solutions, powders, or further prepared capsules, tablets or granules.

[0013] Preferably, the bacterial agent for alleviating hyperuricemia further contains a strain protective agent, and the protective agent is selected from any one or a combination of at least two of skim milk, gelatin, dextrin, gum arabic, dextran, sodium alginate, polyvinyl pyrrolidone, sucrose, lactose, trehalose, sorbitol or xylitol.

[0014] Preferably, the bacterial agent for alleviating hyperuricemia further contains a functional auxiliary agent, and the functional auxiliary agent is selected from any one or a combination of at least two of fructooligosaccharides, galacto-oligosaccharides, xylooligosaccharides, isomaltooligosaccharides, soybean oligosaccharides, inulin, versicolor polysaccharide, polydextrose, α-lactalbumin or lactoferrin.

[0015] In the present invention, the bacterial agent inhibits the activity of xanthine oxidase and reduces the level of blood uric acid.

[0016] The bacterial agent improves kidney inflammation, oxidative stress and kidney damage.

[0017] The bacterial agent improves intestinal flora disorder and maintains intestinal microecological balance.

[0018] In a second aspect, the present invention provides use of the bacterial agent according to the first aspect in preparing a product having the efficacy of preventing, improving or treating hyperuricemia.

[0019] Preferably, the product further contains excipients, which are selected from any one or a combination of at least two of fillers, binders, wetting agents, disintegrants, emulsifiers, solubilizers, osmotic pressure regulators, colorants, pH regulators, antioxidants, antibacterial agents or buffers.

[0020] In a third aspect, the present invention provides a bacterial agent for assisting in lowering blood uric acid levels, wherein the bacterial agent for assisting in lowering blood uric acid levels comprises Akkermansia muciniphila with a deposit number of CCTCC NO: M 20242401. Akkermansia muciniphila Akk09 strain and Bifidobacterium animalis subsp. lactis with a deposit number of CGMCC No. 22547 Bifidobacterium animalis subsp. lactis BLa80 strain composition.

[0021] The present invention creatively developed a new strategy to assist in lowering blood uric acid levels, namely, Akkermansia muciniphila Akkermansia muciniphilaAkk09 strain and Bifidobacterium animalis subsp. lactis Bifidobacterium animalis subsp. lactis The combined use of the BLa80 strain and the Akk09 strain demonstrated a synergistic effect in lowering blood uric acid levels. Using the same bacterial dosage, the combination significantly improved the effectiveness of either Akk09 or BLa80 alone in lowering blood uric acid levels.

[0022] Preferably, the content of live bacteria in the bacterial agent is not less than 1×10 10 CFU / g or 1×10 10 CFU / mL, for example 1×10 10 CFU / g (CFU / mL), 2×10 10 CFU / g (CFU / mL), 5×10 10 CFU / g (CFU / mL), 8×10 10 CFU / g (CFU / mL), 1×10 11 CFU / g (CFU / mL), 5×10 11 CFU / g (CFU / mL), 1×10 12 CFU / g (CFU / mL), 1×10 13 CFU / g (CFU / mL), 1×10 14 CFU / g (CFU / mL), etc. Other specific point values ​​within this numerical range can be selected and will not be detailed here.

[0023] Preferably, the ratio of the number of viable bacteria of the Akk09 strain to the BLa80 strain is 1:10-10:1, for example, 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, etc. Other specific point values ​​within this numerical range can be selected and will not be repeated here.

[0024] Compared with the prior art, the present invention has the following beneficial effects:

[0025] The present invention creatively develops a new probiotic compounding method and a new strategy for alleviating hyperuricemia, namely, Akkermansia muciniphila Akkermansia muciniphila Akk09 strain and Bifidobacterium animalis subsp. lactis Bifidobacterium animalis subsp. lactisThe BLa80 strain was used in combination, and it was found that the two strains can cooperate with each other, promote each other, and synergize in the effect of alleviating hyperuricemia, specifically: (1) reducing blood uric acid levels; (2) inhibiting xanthine oxidase activity; (3) reducing urea nitrogen and creatinine levels; (4) effectively regulating kidney inflammation and oxidative stress caused by hyperuricemia, and significantly improving the levels of inflammatory factors and oxidative stress; (5) effectively regulating intestinal flora disorders caused by hyperuricemia, and significantly improving the structure of intestinal flora. When the bacterial dosage is the same, the combination of the two strains significantly improves the effect of alleviating hyperuricemia compared with the intervention of a single Akk09 strain or a single BLa80 strain. At the same time, both strains are probiotics, and the bacterial agent is highly safe and not easy to develop resistance.

[0026] The Akk09 strain involved in the present invention is classified as Akkermansia muciniphila Akk09 Akkermansia muciniphila Akk09, the depository is China Center for Type Culture Collection, the deposit date is October 31, 2024, the deposit number is CCTCC NO: M 20242401, and the address is: Wuhan University, Wuhan, China.

[0027] The BLa80 strain involved in the present invention is classified as Bifidobacterium animalis subsp. lactis Bifidobacterium animalis subsp. lactis The depository is the General Microbiology Center of China Culture Collection Administration, the deposit date is May 17, 2021, the deposit number is CGMCC No. 22547, and the address is: No. 3, Yard 1, Beichen West Road, Chaoyang District, Beijing. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 is the statistical result of weight of mice in each group;

[0029] Figure 2 is the statistical result of blood uric acid level of each group of mice;

[0030] Figure 3 This is a statistical result of xanthine oxidase activity in the liver tissue of mice in each group;

[0031] Figure 4 This is a statistical result graph of xanthine oxidase activity in the serum of mice in each group;

[0032] Figure 5 is the statistical result graph of kidney index of each group of mice;

[0033] Figure 6 This is a statistical graph of the blood creatinine and urea nitrogen content of mice in each group;

[0034] Figure 7 This is a statistical graph of the levels of inflammatory factors (IL-1β, IL-18, TNF-α) in the kidney tissues of mice in each group;

[0035] Figure 8 This is the statistical result of malondialdehyde content in kidney tissue of mice in each group;

[0036] Figure 9 This is the statistical result of the α-diversity index (ACE index) of the intestinal flora of each group of mice;

[0037] Figure 10 This is the statistical result of the α-diversity index (PD_whole_tree index) of the intestinal flora of each group of mice;

[0038] Figure 11 This is the PCoA diagram of the β diversity analysis of the intestinal flora of mice in each group;

[0039] Figure 12 This is the cluster analysis diagram of the β diversity analysis of the intestinal flora of mice in each group;

[0040] Figure 13 This is the result diagram of the changes in the bacterial composition at the phylum level of the intestinal flora of each group of mice;

[0041] Figure 14 This is a graph showing the changes in the composition of the intestinal flora at the genus level in each group of mice. DETAILED DESCRIPTION

[0042] The technical solution of the present invention is further described below by way of specific embodiments. It should be understood by those skilled in the art that the embodiments are merely to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0043] The Akk09 strain involved in the following examples is named Akkermansia muciniphila Akk09 Akkermansia muciniphila Akk09, deposited on October 31, 2024, with the deposit number CCTCC NO: M20242401.

[0044] The BLa80 strain involved in the following examples is named Bifidobacterium animalis subsp. lactis Bifidobacterium animalis subsp. lactis The deposit date is May 17, 2021, and the deposit number is CGMCC No. 22547.

[0045] The mucin involved in the following examples was purchased from Sigma's type II porcine gastric mucin, M2378; brain heart infusion broth (BHI) was purchased from Qingdao Haibo Biotechnology Co., Ltd.; uric acid was purchased from Shanghai MacLean Biochemical Technology Co., Ltd.; a uric acid kit was purchased from Nanjing Jiancheng Bioengineering Institute; BALB / c male mice were purchased from Sibeifu (Beijing) Biotechnology Co., Ltd. and raised in the animal room of Hubei Provincial Center for Disease Control and Prevention. The animal experiment ethics number is: Safety Assessment Center Animal (Fu) No. 202410301. Example 1

[0046] Evaluation of the uric acid-lowering ability of Akk09 strain in vitro:

[0047] (1) Reagent preparation:

[0048] BML medium: BHI + 0.2% mucin + 0.1% cysteine ​​hydrochloride.

[0049] Uric acid solution (5 mmol / L): 0.084 g uric acid in 100 mL distilled water; pH 7.2 ± 0.2; filter through a 0.22 μm filter.

[0050] (2) The Akk09 strain was inoculated into BML medium at a 3% (V / V) inoculum volume and cultured for three generations. 4 mL of the third generation bacterial solution was aspirated into a centrifuge tube and centrifuged at 10,000 rpm for 2 min. The supernatant was removed and the bacteria were retained. The bacteria were washed twice with ddH2O and resuspended in 1 mL of ddH2O. The OD value (600 nm) of the bacterial solution was adjusted to 1.00 ± 0.1 using a UV spectrophotometer. 100 μL of uric acid solution (5 mmol / L) was added to the bacterial solution to a final concentration of 500 μmol / L. The culture was incubated at 37°C for 6 h. After 6 h, the bacterial solution was inactivated and the reaction was terminated by water bathing at 98°C for 10 min. The solution was centrifuged at 10,000 rpm for 2 min. The remaining uric acid content in the supernatant was detected using a uric acid test kit. The uric acid degradation rate was calculated to be 13.61 ± 3.71%. Example 2

[0051] Evaluation of intervention effects on hyperuricemia:

[0052] (1) Experimental animals: 80 healthy male SPF C57BL / 6 mice, 6 weeks old. These mice were housed in a controlled environment with room temperature maintained at 25 ± 2°C, humidity at 50% ± 5%, and a 12-h light / dark cycle. They had ad libitum access to food and water.

[0053] (2) Animal grouping: After one week of adaptive feeding according to the above-mentioned mice, 80 mice were randomly divided into 8 groups (10 mice in each group): blank control group (NC group), model group (MOD group), ADC group (allopurinol group), Akk09 group (denoted as S1 group), BLa80 group (denoted as S2 group), Akk09 + BLa80 group 1 (live bacteria ratio of 10:1, denoted as S3 group), Akk09 + BLa80 group 2 (live bacteria ratio of 1:10, denoted as S4 group), and commercially available composite bacteria group (BNCC341917 + BLa80 group, live bacteria ratio of 10:1, denoted as S5 group).

[0054] (3) Animal modeling and intervention methods:

[0055] Except for the blank control group, all other groups were subjected to hyperuricemia modeling by daily gavage with 0.2 mL of adenine (50 mg / kg) and intraperitoneal injection of 0.2 mL of potassium oxonate solution (250 mg / kg) suspended in 0.5% sodium carboxymethylcellulose solution and adenine suspended in normal saline. Mice in the blank control group were gavaged with the same volume of normal saline and intraperitoneally injected with the same volume of 0.5% sodium carboxymethylcellulose solution.

[0056] After 4 h of adenine and potassium oxonate treatment, the probiotic intervention group was given 0.2 mL of saline-bacterial solution (the bacterial concentration of the bacterial solution or mixed bacterial solution was 1×10 10 CFU / 0.2mL). The ADC group was given 0.2mL of normal saline-allopurinol solution (5mg / kg), while the NC and MOD groups were given an equal volume of normal saline. The intervention was administered once daily for 15 consecutive days.

[0057] (4) Indicator analysis:

[0058] (4.1) Mouse body weight and blood uric acid level:

[0059] After the intervention, the mice in each group were killed and weighed, and blood was collected from the ophthalmic vein to detect serum uric acid levels. The results were as follows: Figure 1 and Figure 2 shown.

[0060] Depend on Figure 1As shown, compared with the NC group, the weight of the MOD group mice was significantly reduced, indicating that the model group mice were in poor health. The intervention of various probiotics alleviated the weight loss observed in the MOD group mice to varying degrees. At the same time, compared with the ADC group, the intervention effect of the Akk09 group was superior, indicating that the Akk09 strain significantly improved the overall health of the mice and the intervention effect was superior to the treatment effect of allopurinol. At the same time, compared with the Akk09 group or the BLa80 group, the intervention effect of the Akk09+BLa80 group was superior, indicating that the Akk09 and BLa80 strains have a synergistic effect in alleviating hyperuricemia.

[0061] Depend on Figure 2 As shown, the blood uric acid levels of mice in the MOD group were significantly higher than those in the NC group, indicating that the hyperuricemia model was successfully established. After probiotic intervention, blood uric acid levels decreased to varying degrees in each group. In the Akk09 group, the levels decreased to levels not significantly different from those in the NC and ADC groups, demonstrating that Akk09 has the ability to lower blood uric acid levels. Furthermore, compared with the Akk09 or BLa80 groups, the blood uric acid levels in the Akk09+BLa80 group were closer to those in the NC group, suggesting that the Akk09 and BLa80 strains have a synergistic effect in alleviating hyperuricemia.

[0062] (4.2) Xanthine oxidase activity in liver and serum:

[0063] Liver tissue and blood were collected from each group of mice, and xanthine oxidase activity in the liver and serum was measured. Xanthine oxidase (XOD) is a key metabolic enzyme in the uric acid production pathway, primarily present in the liver and blood. It catalyzes hypoxanthine into xanthine, and then further into uric acid. Increased XOD activity correlates with increased uric acid production, while decreased XOD activity correlates with decreased uric acid production.

[0064] The results are as follows Figure 3 and Figure 4 As shown in the figure, XOD activity in both the liver and serum of the MOD group was significantly higher than that of the NC group. Allopurinol, a XOD inhibitor, significantly decreased XOD activity in the ADC group compared to the MOD group after treatment with allopurinol. Furthermore, XOD activity decreased to varying degrees in each probiotic group compared to the MOD group. The effects of the Akk09 and ADC groups were similar, indicating that the Akk09 strain can inhibit XOD activity, thereby lowering serum uric acid levels. The Akk09 + BLa80 group showed a greater effect, suggesting that the Akk09 and BLa80 strains synergistically inhibit XOD activity and lower serum uric acid levels.

[0065] (4.3) Evaluation of Renal Impairment:

[0066] Kidney tissue and blood were collected from each group of mice to measure renal index, serum urea nitrogen, and serum creatinine. Urea nitrogen and creatinine are indicators for evaluating kidney function. When blood urea nitrogen and creatinine levels are elevated, it indicates renal insufficiency and may lead to failure, nephritis, acute tubular necrosis, and other diseases. Figure 5 and Figure 6 shown.

[0067] Depend on Figure 5 It can be seen that the renal index of the MOD group and ADC group was significantly higher than that of the NC group, indicating that kidney enlargement and other lesions occurred. The renal index of the Akk09 group and Akk09+BLa80 group was significantly lower, and there was no significant difference between them and the NC group.

[0068] Depend on Figure 6 It can be seen that the creatinine and urea nitrogen levels in the MOD group and ADC group were significantly higher than those in the NC group. The creatinine and urea nitrogen levels in each probiotic group decreased to varying degrees after intervention. Among them, the creatinine and urea nitrogen levels in the Akk09 group were not significantly different from those in the NC group, indicating that Akk09 intervention can improve kidney damage caused by hyperuricemia; among them, the intervention effect of the Akk09+BLa80 group was the best.

[0069] (4.4) Evaluation of renal inflammation and oxidative stress:

[0070] Kidney tissues of mice in each group were collected and the levels of inflammatory factors (IL-1β, IL-18, TNF-α) and oxidative stress (MDA) in the kidney tissues were measured. Figure 7 and Figure 8 shown.

[0071] Depend on Figure 7 Compared with the NC group, the MOD group showed significantly elevated levels of TNF-α, IL-1β, and IL-18 in the kidneys, indicating that hyperuricemia leads to renal inflammation. The probiotic groups showed varying degrees of reduction in TNF-α, IL-1β, and IL-18 levels after intervention, with the Akk09+BLa80 group showing the best effect, followed by the Akk09 group. This result demonstrates that the Akk09 strain can alleviate hyperuricemia-induced renal inflammation, and its effect is further enhanced when combined with BLa80.

[0072] Depend on Figure 8 Compared with the NC group, the MOD group showed significantly elevated levels of malondialdehyde (MDA) in the kidneys, indicating that hyperuricemia leads to oxidative stress in the kidneys. MDA levels decreased to varying degrees after intervention in each probiotic group, with the Akk09+BLa80 group showing the best effect, followed by the Akk09 group. This result demonstrates that the Akk09 strain can alleviate hyperuricemia-induced renal oxidative stress, and its effect is further enhanced when combined with BLa80.

[0073] (4.5) Intestinal flora analysis:

[0074] The cecal tissues of mice in the NC group, MOD group, ADC group, and Akk09 group were collected, and the cecal contents of the mice were subjected to 16S rRNA amplicon sequencing analysis.

[0075] The results of α-diversity analysis are as follows Figure 9 and Figure 10 As shown in Figure 2, there was no significant difference in ACE index between the MOD group and the NC group ( Figure 9 ), but the PD_whole_tree index dropped significantly ( Figure 10 ), indicating that hyperuricemia can lead to a decrease in gut microbial diversity. After Akk09 intervention, the ACE index and PD_whole_tree index significantly increased, indicating that Akk09 can improve the richness and diversity of the gut microbial community.

[0076] The results of β diversity analysis are as follows Figure 11 and Figure 12 As shown in the figure, the MOD group and the NC group are too far apart on the PCA graph, which is significant, indicating that hyperuricemia changes the composition of the intestinal flora ( Figure 11 Through cluster analysis, the intestinal flora composition between the Akk09 group and the NC group was close to that of the NC group ( Figure 12 The combined results of α and β diversity analysis showed that the Akk09 strain could alleviate the damage of hyperuricemia to the intestinal microecology of mice.

[0077] The changes in the mouse intestinal microbial community were analyzed at the phylum and genus levels.

[0078] The gate level results are as follows Figure 13 As shown, compared with the NC group, the MOD group showed a significant decrease in the abundance of Firmicutes and Verrucomicrobia, a significant increase in the abundance of Bacteroidetes, and a significant decrease in the F / B ratio. Firmicutes and Bacteroidetes are the predominant phyla in the intestinal flora. The Firmicutes / Bacteroidetes ratio (F / B) is considered an important indicator of intestinal microbial balance; a decrease in it indicates a disturbance in the intestinal microbiome. After Akk09 intervention, the abundance of Firmicutes, Actinobacteria, and Verrucomicrobia increased significantly, while the abundance of Bacteroidetes decreased significantly.

[0079] Genus level results are as follows Figure 14As shown, the abundance of Lactobacillus, Lactobacillus, and Akkermansia in the MOD group was significantly lower than that in the NC group, while the abundance of Zurichia, UCG-002, and Aerococcus was significantly higher. Akk09 intervention reversed this finding and also significantly increased the abundance of Bifidobacterium and Ducrocea. The abundance of Lactobacillus, Akkermansia, Lactobacillus, and Bifidobacterium was negatively correlated with hyperuricemia; increased abundance of these genera was associated with a decreased risk of hyperuricemia. Furthermore, Zurichia, UCG-002, and Aerococcus were significantly enriched in patients with enteritis and positively correlated with the risk of enteritis. In summary, Akk09 intervention significantly increased the abundance of beneficial bacteria and decreased that of harmful bacteria.

[0080] The applicant declares that the present invention is illustrated by the above-described embodiments, but the present invention is not limited to the above-described embodiments. This does not mean that the present invention must rely on the above-described embodiments in order to be implemented. Those skilled in the art should understand that any improvements to the present invention, equivalent replacements for raw materials in the present invention, additions of auxiliary ingredients, and selection of specific methods, etc., fall within the scope of protection and disclosure of the present invention.

[0081] The preferred embodiments of the present invention are described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the scope of protection of the present invention.

[0082] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any appropriate manner without contradiction. In order to avoid unnecessary repetition, the present invention will not further describe various possible combinations.

Claims

1. A bacterial agent for alleviating hyperuricemia, characterized in that: The bacterial strains in the bacterial agent for alleviating hyperuricemia are composed of Akkermansia muciniphila Akk09 strain with a deposit number of CCTCC NO: M 20242401 and Bifidobacterium animalis subsp. lactis BLa80 strain with a deposit number of CGMCC No. 22547; The ratio of the viable cell count of the Akk09 strain to that of the BLa80 strain is 1:10-10:

1.

2. The bacterial agent for alleviating hyperuricemia according to claim 1, characterized in that The content of live bacteria in the bacterial agent is not less than 1×10 10 CFU / g or 1×10 10 CFU / mL.

3. The bacterial agent for alleviating hyperuricemia according to claim 1, characterized in that The dosage form of the bacterial agent includes solution, powder, capsule, tablet or granule.

4. The bacterial agent for alleviating hyperuricemia according to claim 1, characterized in that The bacterial agent for alleviating hyperuricemia also contains a strain protective agent, which is selected from any one or a combination of at least two of skim milk, gelatin, dextrin, gum arabic, dextran, sodium alginate, polyvinyl pyrrolidone, sucrose, lactose, trehalose, sorbitol or xylitol.

5. The bacterial agent for alleviating hyperuricemia according to claim 1, characterized in that The bacterial agent inhibits xanthine oxidase activity and reduces blood uric acid levels; The bacterial agent improves kidney inflammation, oxidative stress and kidney damage; The bacterial agent improves intestinal flora disorder and maintains intestinal microecological balance.

6. Use of the bacterial agent according to any one of claims 1 to 5 in the preparation of a product having the efficacy of preventing, improving or treating hyperuricemia.

7. A bacterial agent for assisting in lowering blood uric acid levels, characterized in that: The bacterial strains in the bacterial agent for assisting in lowering blood uric acid levels are composed of Akkermansia muciniphila Akk09 strain with a deposit number of CCTCC NO: M 20242401 and Bifidobacterium animalis subsp. lactis BLa80 strain with a deposit number of CGMCC No. 22547; The ratio of the viable cell count of the Akk09 strain to that of the BLa80 strain is 1:10-10:

1.

8. The bacterial agent for assisting in lowering blood uric acid levels according to claim 7, characterized in that: The content of live bacteria in the bacterial agent is not less than 1×10 10 CFU / g or 1×10 10 CFU / mL.

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