Probiotic compound capable of reducing uric acid and application of probiotic compound

Abstract

The invention relates to a probiotic compound capable of reducing uric acid and application of the probiotic compound. The probiotic compound comprises lactobacillus reuteri FPH2951 and bifidobacterium breve FPHC4024. Wherein the lactobacillus reuteri FPH2951 is classified and named as lactobacillus reuteri, and the preservation number of the lactobacillus reuteri FPH2951 is GDMCC NO.62946; the bifidobacterium breve FPHC4024 is classified and named as bifidobacterium breve, and the preservation number of the bifidobacterium breve FPHC4024 is GDMCC NO.62945. The invention further discloses a preparation method of the bifidobacterium breve FPHC4024. According to the probiotic compound, through the synergistic effect of the lactobacillus reuteri FPH2951 and the bifidobacterium breve FPHC4024, the levels of uric acid (UA), creatinine (Cr) and urea nitrogen (BUN) in serum can be remarkably reduced, the excretion amount of the creatinine (Cr) and the urea nitrogen (BUN) in urine is increased, and the probiotic compound has a wide application prospect.

Description

Technical Field

[0001] The invention belongs to the technical field of health food and biomedicine, and specifically relates to a uric acid-lowering probiotic complex and an application thereof. Background Art

[0002] Hyperuricemia (HUA) is an idiopathic inflammatory disease characterized by long-term purine metabolism disorders and a continuous increase in blood uric acid (UA) concentration. In recent years, with the continuous improvement of people's living standards and changes in dietary structure, especially the increasing intake of high-purine foods such as seafood, meat and beer, the incidence of HUA has increased year by year, and it is showing a trend of younger people. Although HUA is not a fatal disease, when uric acid exceeds the saturation concentration, it may cause UA crystal deposition, thereby causing aseptic inflammatory reactions in local tissues of the human body, increasing the burden of high complications, and then causing tissue damage such as gout, atherosclerosis, type 2 diabetes, vascular damage, and chronic kidney disease. It will eventually develop into gout. In addition, hyperuricemia is also related to a variety of high-incidence metabolic diseases, such as diabetes, hypertension, dyslipidemia and other metabolic diseases, becoming the fourth "high" after "hypertension, hyperglycemia, and hyperlipidemia".

[0003] Existing HUA treatments include drug therapy and non-drug therapy, but both have adverse reactions. Among them, the drugs used in clinical practice are mainly uricosuric drugs, drugs that inhibit uric acid production, and alkaline drugs, which relieve the symptoms of hyperuricemia by increasing uric acid excretion, inhibiting uric acid production, or alkalizing urine. However, the above drugs all have problems such as low tolerance, excessive drug dependence, and many complications and side effects. In terms of dietary control, since most foods contain purines due to animal and plant cells, it is extremely difficult to relieve hyperuricemia simply by limiting purine intake, and the restriction of purine acid intake can easily cause nutritional imbalance. Based on the defects and shortcomings of existing treatment methods, there is an urgent need to seek an effective, stable, safe, and convenient HUA treatment strategy.

[0004] As a normal flora in the human intestine, lactic acid bacteria can regulate the metabolic processes of human blood lipids, blood sugar, etc. Lactic acid bacteria are increasingly valued in the clinical treatment and prevention of metabolic intestinal diseases due to their non-toxic, harmless and no side effects, and have shown broad clinical application prospects and market potential in effectively regulating gastrointestinal metabolic functions. For example, in the Chinese authorized invention patent CN118222464B, a plant lactobacillus and its application in uric acid-lowering products are disclosed. The strain can effectively inhibit the increase of serum uric acid, blood urea nitrogen and serum creatinine levels, reduce the occurrence of hyperuricemia; maintain normal serum lipid levels; improve oxidative stress damage; inhibit the secretion of inflammatory cytokines, promote the expression of anti-inflammatory factors, and have a protective effect on the liver and colon; regulate and improve intestinal flora imbalance. Provide technical support for the preparation of uric acid-lowering functional foods, probiotic preparations, fermented products and drugs. For another example, China's authorized invention patent CN118147019B discloses fermented mucus Lactobacillus GS31 and its application in lowering uric acid. The fermented mucus Lactobacillus can significantly lower uric acid levels, promote the excretion of excess uric acid in the body, and reduce the production of uric acid in the body, further alleviating damage to kidney function, and reducing inflammatory factors in the body. It has a certain improvement and preventive effect on hyperuricemia and related diseases caused by hyperuricemia.

[0005] The applicant's previously authorized invention patent CN116970530B discloses a Bifidobacterium breve FPHC4024 and its application for preventing and treating diarrhea in children, belonging to the field of probiotic technology. The Bifidobacterium breve FPHC4024 is classified and named Bifidobacterium breve, with a deposit number of GDMCC NO.62945 and a deposit date of November 3, 2022. The depository is the Guangdong Provincial Microbial Culture Collection Center, address: 5th Floor, Building 59, No. 100, Xianlie Middle Road, Guangzhou, Institute of Microbiology, Guangdong Academy of Sciences, Postal Code: 510070. The invention provides a Bifidobacterium breve FPHC4024 that can cause the absorption of excess water in the colon, and has a good effect on preventing, alleviating and treating diarrhea in children, with the advantages of good efficacy, quick effect, safety, no side effects, and short treatment cycle. However, the invention patent does not disclose that it can reduce uric acid.

[0006] The applicant's prior invention patent application CN117018043A discloses a probiotic strain and its application, a composition for preventing and treating diarrhea in children, which belongs to the field of probiotic technology. The probiotic strain is Lactobacillus reuteri FPH2951, classified and named Lactobacillus reuteri, with a deposit number of GDMCC NO.62946, a deposit date of November 3, 2022, and a depository unit of Guangdong Provincial Microbiological Culture Collection Center, address: 5th Floor, Building 59, No. 100, Xianlie Middle Road, Guangzhou, Institute of Microbiology, Guangdong Academy of Sciences, Postal Code: 510070. The inventive probiotic can play a good role in preventing, alleviating and treating diarrhea in children, and has the advantages of good efficacy, quick effect, short treatment cycle, etc., and has broad application prospects. However, the invention patent does not disclose that it can reduce uric acid.

[0007] To this end, the inventors of the present application conducted further research and found that the above-mentioned strains can reduce uric acid, thereby completing the present invention. Summary of the invention

[0008] In order to solve the defects of the prior art, the present invention proposes a uric acid-lowering probiotic complex and its application. Specifically, in order to achieve the purpose of the present invention, the present invention intends to adopt the following technical solutions:

[0009] One aspect of the present invention relates to a uric acid-lowering probiotic complex, characterized in that the probiotic complex comprises Lactobacillus reuteri FPH2951 and Bifidobacterium breve FPHC4024; wherein Lactobacillus reuteri FPH2951 is classified and named as Lactobacillus reuteri, and its preservation number is GDMCC NO.62946; Bifidobacterium breve FPHC4024 is classified and named as Bifidobacterium breve, and its preservation number is GDMCC NO.62945.

[0010] In a preferred embodiment of the present invention, the uric acid-lowering probiotic complex further comprises prebiotics.

[0011] In a preferred embodiment of the present invention, the ratio of the number of Lactobacillus reuteri FPH2951 to that of Bifidobacterium breve FPHC4024 is 1-2:1-2; preferably 1-1.25:1-1.25.

[0012] Another aspect of the present invention relates to the use of the above-mentioned uric acid-lowering probiotic complex in the preparation of common food and / or special functional food and / or health food and / or cosmetics and / or medical devices and / or disinfectants and / or medicines for lowering uric acid.

[0013] Preferably, the common food, special functional food, health food, medicine, cosmetic, medical device, disinfectant has at least one of the following effects: reducing the uric acid level of hyperuricemia mice, specifically reducing the levels of uric acid (UA), creatinine (Cr) and urea nitrogen (BUN) in serum, and increasing the excretion of creatinine (Cr) and urea nitrogen (BUN) in urine.

[0014] In a preferred embodiment of the present invention, the common food and / or special functional food and / or health food is a fermented food, and the fermented food contains active Lactobacillus reuteri FPH2951 and active Bifidobacterium breve FPHC4024.

[0015] Beneficial Effects

[0016] The probiotic complex of the present invention can significantly reduce the levels of uric acid (UA), creatinine (Cr) and urea nitrogen (BUN) in serum and increase the excretion of creatinine (Cr) and urea nitrogen (BUN) in urine through the synergistic effect of Lactobacillus reuteri FPH2951 and Bifidobacterium breve FPHC4024, and has broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 : Microscope photo of Lactobacillus reuteri FPH2951.

[0018] Figure 2 : Microscope photo of Bifidobacterium breve FPHC4024. DETAILED DESCRIPTION

[0019] In order to further understand the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below in combination with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0020] Unless otherwise specified, the reagents involved in the embodiments of the present invention are all commercially available products and can be purchased through commercial channels.

[0021] Example 1

[0022] Cultivated probiotics:

[0023] Lactobacillus reuteri FPH2951 is a Gram-positive rod-shaped bacterium that does not produce spores. After anaerobic culture at 36°C for 2 days on an MRS (lactic acid bacteria culture medium shown in Table 1), the colonies are milky white, round, convex, with smooth surfaces and neat edges. The microscopic photos are as follows Figure 1 shown.

[0024] Table 1: Culture medium for Lactobacillus reuteri FPH2951

[0025]

[0026]

[0027] Bifidobacterium breve FPHC4024 is a Gram-positive rod-shaped bacterium that does not produce spores. After anaerobic culture at 37°C for 2 days on an MRS (lactic acid bacteria culture medium shown in Table 2), the colonies are milky white, round, convex, with smooth surfaces and neat edges. The microscopic photos are as follows Figure 2 shown.

[0028] Table 2: Culture medium for Bifidobacterium breve FPHC4024

[0029]

[0030]

[0031] Experimental methods:

[0032] 70 SPF Balb / c mice, male, with a body weight of 18-20g, were raised at a temperature of 20-25°C, a relative humidity of (50±5)%, and a light intensity of 12h / 12h. They were randomly divided into 7 groups, 10 mice in each group, and set as a normal group (i.e., blank control group), a model group, a positive control group, a control experimental group (single strain), and an experimental group (i.e., a mixed strain group). ① Blank control group: fed with normal feed, and the solvent was gavaged alone; ② Model group: given potassium oxonate (250 mg / kg, the solvent was 5% CMC-Na aqueous solution); ③ Positive control group: given potassium oxonate (250 mg / kg, the solvent was 5% CMC-Na aqueous solution) + allopurinol (5 mg / kg); ④ Control experimental group 1 (i.e., Bifidobacterium breve FPHC4024 group): given potassium oxonate (250 mg / kg, the solvent was 5% CMC-Na aqueous solution) + Bifidobacterium breve FPHC4024 group (1.8×10 10 CFU / kg); ⑤ Control experimental group 2 (i.e., Lactobacillus reuteri FPH2951 group): potassium oxonate (250 mg / kg, the solvent was 5% CMC-Na aqueous solution) + Lactobacillus reuteri FPH2951 group (1.8×10 10 CFU / kg); ⑥ Experimental group 1 (i.e., mixed strain group): potassium oxonate (250 mg / kg, the solvent was 5% CMC-Na aqueous solution) + Lactobacillus reuteri FPH2951 (1.0×10 10 CFU / kg)+ Bifidobacterium breve FPHC4024 group (0.8×1010 CFU / kg); ⑦ Experimental group 2 (i.e., mixed strain group): potassium oxonate (250 mg / kg, solvent was 5% CMC-Na aqueous solution) + Lactobacillus reuteri FPH2951 (0.8×10 10 CFU / kg)+ Bifidobacterium breve FPHC4024 group (1.0×10 10 CFU / kg)

[0033] Except for the blank control group, the other groups were gavaged at the above doses, and the blank group was given an equal volume of solvent (i.e., 5% CMC-Na aqueous solution by mass concentration). For all groups, the gavage volume was 0.3 mL / 100 g, once a day, and fed continuously for 14 days. After 14 days of fasting for 12 hours, blood was collected from the eyeballs, and centrifuged at 3000 r / min for 20 minutes to separate the serum; urine was collected in mouse cages for 24 hours, and the levels of uric acid (UA), creatinine (Cr) in serum and urine and urea nitrogen (BUN) in serum were determined using commercially available kits (the uric acid (UA) detection kit, urea nitrogen (BUN) detection kit and creatinine (CRE) detection kit were all purchased from Solarbio).

[0034] Table 3: Effects of each experimental group on UA, Cr and BUN in hyperuricemia mice (n=10)

[0035]

[0036] As shown in Table 1, the levels of UA, BUN and Cr in the serum of each group were compared. After oral administration of potassium oxonate, the UA level of the mice in the model group was significantly higher than that in the normal group (P<0.05), indicating that the hyperuricemia mouse model was successfully established.

[0037] After 14 days of treatment with the mixed strain, the serum uric acid levels of the mixed strain experimental groups 1 and 2 were significantly reduced (P<0.05) compared with the model group and the control experimental groups 1 and 2. The serum creatinine and urea nitrogen levels of the mixed strain experimental groups 1 and 2 were significantly reduced (P<0.05) compared with the model group and the control experimental groups 1 and 2. The changes in urea nitrogen and creatinine indicate that the mixed strain has a strong protective effect on the kidneys through the synergistic effect of the strains, and the creatinine level excreted in the urine is close to that of the normal group.

[0038] The above describes the preferred embodiments of the present invention, but it is not intended to limit the present invention. Those skilled in the art may make improvements and changes to the embodiments disclosed herein without departing from the scope and spirit of the present invention.

Claims

1. A uric acid-lowering probiotic complex, characterized in that: The probiotic complex comprises Lactobacillus reuteri FPH2951 and Bifidobacterium breve FPHC4024; wherein, Lactobacillus reuteri FPH2951 is classified and named as Lactobacillus reuteri, and its preservation number is GDMCC NO.62946; Bifidobacterium breve FPHC4024 is classified and named as Bifidobacterium breve, and its preservation number is GDMCC NO.62945. 2 . The probiotic complex according to claim 1 , further comprising prebiotics. 3 . The probiotic complex according to claim 1 , wherein the ratio of the number of Lactobacillus reuteri FPH2951 to that of Bifidobacterium breve FPHC4024 is 1-2:1-2. 4 . The probiotic complex according to claim 1 , wherein the ratio of the number of Lactobacillus reuteri FPH2951 to that of Bifidobacterium breve FPHC4024 is 1-1.25:1-1.

25.

5. Use of the uric acid-lowering probiotic complex according to any one of claims 1 to 4 in the preparation of common food and / or special functional food and / or health food and / or cosmetics and / or medical devices and / or disinfectants and / or medicines for lowering uric acid.

6. The use according to claim 5, wherein the ordinary food, special functional food, health food, medicine, cosmetics, medical device, and disinfectant have at least one of the following effects: reducing the uric acid level of hyperuricemia mice, specifically reducing the levels of uric acid (UA), creatinine (Cr) and urea nitrogen (BUN) in serum, and increasing the excretion of creatinine (Cr) and urea nitrogen (BUN) in urine.

7. The use according to claim 5, wherein the common food and / or special functional food and / or health food is a fermented food, and the fermented food contains active Lactobacillus reuteri FPH2951 and active Bifidobacterium breve FPHC4024.

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