Lactic acid bacteria composition and compound lactic acid bacteria probiotic agent for adjuvant treatment of diabetes and application of lactic acid bacteria composition and compound lactic acid bacteria probiotic agent

By using the compound probiotic agent in the lactic acid bacteria composition, the gastrointestinal function is improved and the blood sugar and blood lipid levels are adjusted, which solves the problems of side effects and insignificant blood sugar lowering effect of existing diabetes treatment methods, and provides a safe and efficient auxiliary Treatment options.

CN119331778APending Publication Date: 2025-01-21BIOGROWING CO LTD
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Patent Information

Application Number
CN202411776505.7
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-12-04
Publication Date
2025-01-21

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Abstract

The invention provides a lactic acid bacteria composition for adjuvant treatment of diabetes, a compound lactic acid bacteria probiotic agent and application, and belongs to the technical field of functional microorganisms. The lactic acid bacteria composition provided by the invention is obtained by compounding eight specific lactic acid bacteria strains, has the effects of reducing blood sugar, blood fat and insulin level for people with high blood sugar and diabetics, and also has the effect of regulating gastrointestinal tract disorder. Therefore, the compound lactic acid bacteria probiotic agent prepared on the basis of the lactic acid bacteria composition has a good blood sugar control effect on people with high blood sugar and patients with type II diabetes mellitus. Meanwhile, the compound lactic acid bacteria probiotic agent has no side effect, and the purpose of safe prevention and treatment can be achieved.
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Description

Technical Field

[0001] The present invention belongs to the technical field of functional microorganisms, and in particular relates to a lactic acid bacteria composition and a composite lactic acid bacteria probiotic agent for assisting the treatment of diabetes and applications thereof. Background Art

[0002] The number of patients with diabetes has increased significantly in the past two decades. It is known as a "rich disease" and seriously threatens people's health. Among them, type 2 diabetes (T2D) is a common type of diabetes. It is usually a type of sugar metabolism disease caused by the combined effects of environmental and genetic factors. The main characteristics are insufficient insulin secretion and insulin resistance. The current clinical treatment for type 2 diabetes is mainly based on diet control and drug therapy, which can control the patient's blood sugar level and reduce the risk of complications. However, metformin, a commonly used and better hypoglycemic drug for type 2 diabetes, can improve insulin resistance and reduce weight. But metformin also has certain side effects. The most common one is gastrointestinal reactions. Patients will experience symptoms such as nausea, abdominal pain, loss of appetite, and poor appetite. In addition, patients may also experience liver damage and changes in kidney function. Some patients will experience diarrhea and constipation symptoms, which may even make the gastrointestinal function of patients with type 2 diabetes worse, and it is often difficult to obtain satisfactory treatment effects. Some other commonly used hypoglycemic drugs (such as sodium-glucose co-transporter 2 inhibitors, i.e. SGLT2 inhibitors) excrete sugar from urine, and the blood sugar lowering effect is often not obvious. At the same time, the side effects of the gliflozin series are urinary and reproductive system infections. It may also cause some irritation to the liver, or have a certain impact on kidney metabolism, causing physical discomfort.

[0003] Clinically, more and more studies have found that the occurrence and progression of type 2 diabetes are closely related to gastrointestinal dysfunction. Therefore, improving the flora in the body and regulating gastrointestinal function have become a possible means of conditioning and assisting the treatment of diabetes. Pendulum Therapeutics has launched the first probiotic special medical food, which helps improve blood sugar and glycosylated hemoglobin levels by promoting the richness of intestinal flora. There are currently no similar alternative products in China. Summary of the invention

[0004] In view of this, the purpose of the present invention is to provide a lactic acid bacteria composition for auxiliary treatment of people with high blood sugar or diabetes, which can reduce blood sugar, blood lipids and insulin levels without toxic side effects, and also has the function of regulating gastrointestinal dysfunction.

[0005] The invention provides a lactic acid bacteria composition, comprising Lactobacillus plantarum strain Lp-G18, Bifidobacterium animalis subsp. lactis strain BL-G101, Lactobacillus casei strain LC-G11, Lactobacillus acidophilus strain LA-G80, Lactobacillus johnsonii strain LJ-G55, Lactobacillus reuteri strain LR-G100, Bifidobacterium longum subsp. lactis strain BL-G101, and Lactobacillus acidophilus strain LA-G80. subsp. longum strain BL-G301 and Bifidobacterium bifidum strain BB-G90;

[0006] The deposit number of the Lactobacillus plantarum strain Lp-G18 is CCTCC NO: M 2013690;

[0007] The deposit number of the Bifidobacterium animalis subsp. lactis strain BL-G101 is CCTCC NO: M2013336;

[0008] The deposit number of the Lactobacillus casei strain LC-G11 is CCTCC NO: M 2013196;

[0009] The deposit number of the Lactobacillus acidophilus strain LA-G80 is CCTCC NO: M 2013337;

[0010] The deposit number of the Lactobacillus johnsonii strain LJ-G55 is CCTCC NO: M 2017116;

[0011] The deposit number of the Lactobacillus reuteri strain LR-G100 is CCTCC NO: M 2013692;

[0012] The deposit number of the Bifidobacterium longum subspecies longum strain BL-G301 is CCTCC NO: M2013689;

[0013] The deposit number of the Bifidobacterium bifidum strain BB-G90 is CCTCC NO: M 2013194.

[0014] Preferably, the ratio of the number of viable bacteria of the plant lactobacillus strain Lp-G18, the animal bifidobacterium lactis subspecies BL-G101, the Lactobacillus casei strain LC-G11, the Lactobacillus acidophilus strain LA-G80, the Lactobacillus johnsonii strain LJ-G55, the Lactobacillus reuteri strain LR-G100, the Bifidobacterium longum subspecies longum strain BL-G301 and the Bifidobacterium bifidum strain BB-G90 is (12-24): (10-15): (6-10): (4-8): (1-4): (1-4): (0.5-2.0): (0.5-2.0).

[0015] The present invention provides a composite lactic acid bacteria probiotic agent, which comprises the following components in percentage by mass, based on the mass of the probiotic agent being 100%: 33% to 57% of bacterial powder of the lactic acid bacteria composition, 20% to 30% of a filler, 15% to 25% of oligosaccharides, 0% to 20% of L-arabinose and the remainder of a cooling agent.

[0016] Preferably, the composition comprises the following components in percentage by mass: 33% to 50% of the lactic acid bacteria composition, 20% to 30% of a filler, 20% to 25% of oligosaccharides, 0 to 18% of L-arabinose and the remainder of a cooling agent.

[0017] Preferably, the filler comprises resistant dextrin;

[0018] The cooling agent includes xylitol.

[0019] Preferably, the oligosaccharide comprises at least one of the following components: isomaltooligosaccharide, fructooligosaccharide, inulin and xylo-oligosaccharide;

[0020] When the compound lactic acid bacteria probiotics comprises isomaltooligosaccharide, the mass percentage of the isomaltooligosaccharide in the compound lactic acid bacteria probiotics is 10% to 12.5%;

[0021] When the compound lactic acid bacteria probiotics comprises oligofructose, the mass percentage of the oligofructose in the compound lactic acid bacteria probiotics is 4.5% to 5.625%;

[0022] When the composite lactic acid bacteria probiotics comprises inulin, the mass percentage of the inulin in the composite lactic acid bacteria probiotics is 3% to 3.75%;

[0023] When the compound lactic acid bacteria probiotics comprises xylooligosaccharides, the mass percentage of the xylooligosaccharides in the compound lactic acid bacteria probiotics is 2.5% to 3.12%.

[0024] Preferably, the live bacteria concentration of the lactic acid bacteria composition is not less than 10 billion CFU / g.

[0025] The present invention provides the use of the lactic acid bacteria composition or the composite lactic acid bacteria probiotic in preparing a product for reducing blood sugar, blood pressure and insulin level.

[0026] The present invention provides the use of the lactic acid bacteria composition or the composite lactic acid bacteria probiotic in combination with an SGLT2 inhibitor in the preparation of a product for reducing blood sugar, blood pressure and insulin levels.

[0027] Preferably, the population whose blood sugar, blood pressure and insulin levels are to be lowered includes people with high blood sugar or patients with type 2 diabetes.

[0028] The invention provides a lactic acid bacteria composition, comprising Lactobacillus plantarum strain Lp-G18, Bifidobacterium animalis subspecies lactis strain BL-G101, Lactobacillus casei strain LC-G11, Lactobacillus acidophilus strain LA-G80, Lactobacillus johnsonii strain LJ-G55, Lactobacillus reuteri strain LR-G100, Bifidobacterium longum subspecies longum strain BL-G301 and Bifidobacterium bifidum strain BB-G90, with a live cell count ratio of (10-30):(8-16):(5-12):(3-9):(1-5):(1-5):(0.5-2.5):(0.5-2.5). The invention uses 8 kinds of intestinal probiotic strains to compound, and animal Bifidobacterium lactis subspecies BL-G101, Bifidobacterium longum subspecies BL-G301, Bifidobacterium bifidum BB-G90 and Lactobacillus acidophilus strain LA-G80 all have the functions of promoting vitamin synthesis, regulating fat metabolism and polysaccharide metabolism, reducing fat deposition, avoiding insulin resistance, and reducing blood sugar increase; at the same time, Lactobacillus acidophilus strain LA-G80, Lactobacillus plantarum strain Lp-G18 and Lactobacillus casei strain LC-G11 have the functions of fermenting and producing multiple active ingredients. The lactobacillus composition provided by the present invention has a synergistic effect, through extracellular protease, peptidase, bacterial component, angiotensin I converting enzyme (ACE), gamma-aminobutyric acid, (GABA), etc. that may be produced during the fermentation process, including the bacterial body itself, which may promote the body's absorption of some minerals that can regulate blood pressure (dietary potassium, magnesium, dietary calcium, etc. have a hypotensive effect); the generated bacteriocin, anti-inflammatory factors, etc. are beneficial to the repair of inflammation in the body. The increase of the flora in the body reduces endotoxins, makes the intestinal permeability reasonable, reduces the entry of inflammatory factors and toxic and harmful factors into the body, and ultimately leads to the reduction and repair of damage to pancreatic β (beta) cells, thereby effectively reducing insulin and blood sugar concentrations, leading to a healthy development. At the same time, the lactic acid bacteria composition has good safety and has no obvious side effects on the liver, kidneys, etc.

[0029] The present invention also provides a composite lactic acid bacteria probiotic agent, which, based on 100% probiotic agent, comprises the following components in percentage by mass: 33% to 57% of bacterial powder of the lactic acid bacteria composition, 20% to 30% of filler, 15% to 25% of oligosaccharide, 0 to 20% of L-arabinose and the remainder of cooling agent. The present invention has been verified by animal levels and clinical patients, and the probiotic agent has a good effect of lowering blood sugar in people with high blood sugar or patients with type 2 diabetes, and can also reduce blood lipid content and insulin levels, while improving the intestinal function of the test population and increasing albumin levels. At the same time, the probiotic agent also has the problem of improving gastrointestinal dysfunction, and can assist in the treatment of symptoms such as constipation and chronic diarrhea. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 To regulate the overall results of changes in blood sugar levels before and after diagnosis and treatment;

[0031] Figure 2 To adjust the overall results of blood pressure level changes before and after diagnosis and treatment;

[0032] Figure 3 It is the overall result of the changes of alanine aminotransferase and aspartate aminotransferase levels before and after conditioning diagnosis and treatment;

[0033] Figure 4 The overall results of changes in hemoglobin and blood urea nitrogen levels before and after conditioning diagnosis and treatment;

[0034] Figure 5 To adjust the overall results of the changes in creatinine and insulin levels before and after diagnosis and treatment;

[0035] Figure 6 This is the change result of blood sugar level before and after conditioning treatment in Group A;

[0036] Figure 7 This is the change result of blood pressure level before and after conditioning and treatment of Group A;

[0037] Figure 8 This is the change result of alanine aminotransferase and aspartate aminotransferase levels before and after conditioning and treatment in group A;

[0038] Fig. 9 This is the change result of hemoglobin and blood urea nitrogen level before and after conditioning treatment in group A;

[0039] Fig.10 This is the change result of creatinine and insulin level before and after conditioning and treatment in group A;

[0040] Fig.11 This is the change result of blood sugar level before and after conditioning and treatment of group B;

[0041] Fig.12 This is the change result of blood pressure level before and after conditioning and treatment of group B;

[0042] Fig.13 This is the change result of alanine aminotransferase and aspartate aminotransferase levels before and after conditioning and treatment of group B;

[0043] Fig.14 This is the change result of hemoglobin and blood urea nitrogen level before and after conditioning treatment in group B;

[0044] Fig.15 These are the changes in creatinine and insulin levels in Group B before and after conditioning and treatment.

[0045] Biomaterial Deposit Information

[0046] Lactobacillus plantarum strain Lp-G18, deposited in China Center for Type Culture Collection (abbreviated as CCTCC), Wuhan University, Wuhan, China, on December 23, 2013, with a deposit number of CCTCC NO: M 2013690;

[0047] Bifidobacterium animalis subsp. lactis strain BL-G101 was deposited in China Center for Type Culture Collection (abbreviated as CCTCC), located at Wuhan University, Wuhan, China, on July 16, 2013, with a deposit number of CCTCC NO: M 2013336;

[0048] Lactobacillus casei strain LC-G11 was deposited in China Center for Type Culture Collection (abbreviated as CCTCC), located at Wuhan University, Wuhan, China, on May 9, 2013, with a deposit number of CCTCC NO: M 2013196;

[0049] Lactobacillus acidophilus strain LA-G80 was deposited in China Center for Type Culture Collection (abbreviated as CCTCC), located at Wuhan University, Wuhan, China, on July 16, 2013, with a deposit number of CCTCC NO: M 2013337

[0050] Lactobacillus johnsonii strain LJ-G55 was deposited in China Center for Type Culture Collection (abbreviated as CCTCC), located at Wuhan University, Wuhan, China, on March 15, 2017, with a deposit number of CCTCC NO: M 2017116

[0051] Lactobacillus reuteri strain LR-G100 was deposited in China Center for Type Culture Collection (abbreviated as CCTCC), located at Wuhan University, Wuhan, China, on December 23, 2013, with a deposit number of CCTCC NO: M 2013692

[0052] Bifidobacterium longum subsp. longum strain BL-G301 was deposited in China Center for Type Culture Collection (abbreviated as CCTCC), located at Wuhan University, Wuhan, China, on December 23, 2013, with a deposit number of CCTCC NO: M 2013689

[0053] The Bifidobacterium bifidum strain BB-G90 was deposited in China Center for Type Culture Collection (abbreviated as CCTCC), located at Wuhan University, Wuhan, China. The deposit date was May 9, 2013, and the deposit number was CCTCC NO: M 2013194. DETAILED DESCRIPTION

[0054] The invention provides a lactic acid bacteria composition, comprising a plant lactobacillus strain Lp-G18, a bifidobacterium animalis subsp. lactis strain BL-G101, a lactobacillus casei strain LC-G11, a lactobacillus acidophilus strain LA-G80, a lactobacillus johnsonii strain LJ-G55, a lactobacillus reuteri strain LR-G100, a bifidobacterium longum subsp. longum strain BL-G301 and a bifidobacterium bifidum strain BB-G90, wherein the viable cell count ratio is (10-30): (8-16): (5-12): (3-9): (1-5): (1-5): (0.5-2.5): (0.5-2.5); the plant lactobacillus strain Lp-G18 has a preservation number of CCTCC NO: M 2013690; the animal bifidobacterium subsp. lactis strain BL-G101 has a preservation number of CCTCC NO: M 2013336; the preservation number of the Lactobacillus casei strain LC-G11 is CCTCC NO: M 2013196; the preservation number of the Lactobacillus acidophilus strain LA-G80 is CCTCC NO: M2013337; the preservation number of the Lactobacillus johnsonii strain LJ-G55 is CCTCC NO: M 2017116; the preservation number of the Lactobacillus reuteri strain LR-G100 is CCTCC NO: M 2013692; the preservation number of the Bifidobacterium longum subsp. longum strain BL-G301 is CCTCC NO: M 2013689; the preservation number of the Bifidobacterium bifidum strain BB-G90 is CCTCC NO: M2013194.

[0055] In the present invention, the viable cell count ratio of Lactobacillus plantarum strain Lp-G18, Bifidobacterium animalis subspecies lactis strain BL-G101, Lactobacillus casei strain LC-G11, Lactobacillus acidophilus strain LA-G80, Lactobacillus johnsonii strain LJ-G55, Lactobacillus reuteri strain LR-G100, Bifidobacterium longum subspecies longum strain BL-G301 and Bifidobacterium bifidum strain BB-G90 is preferably (12 to 15). 24): (10~15): (6~10): (4~8): (1~4): (1~4): (0.5~2.0): (0.5~2.0), can be (15~20): (11~13): (7~9): (5~6): (2~3): (2~3): (1~1.5): (1~1.5), can also be: 18:12:8:5:2:2:1.5:1.5.

[0056] In the present invention, animal bifidobacterium lactis subspecies strain BL-G101 is a kind of bifidobacterium, belonging to probiotics. It can inhibit the putrefactive bacteria in the human intestinal tract, enhance the intestinal barrier function, and relieve chronic inflammation. And it can also participate in the work of synthesizing vitamins in the intestinal tract, which is very important for the significance of human health. Secondly, animal bifidobacterium lactis subspecies strain BL-G101 can also promote food absorption and degradation, and has the effect of preventing osteochondrosis and iron deficiency anemia. Once again, animal bifidobacterium lactis subspecies strain BL-G101 can also improve human immunity and have anti-tumor effect. In addition, animal bifidobacterium lactis subspecies strain BL-G101 can promote the decomposition and utilization of lactose by the human body and increase the absorption effect. As is well known, animal bifidobacterium lactis subspecies strain BL-G101 can synthesize multiple vitamins in the human intestinal tract, such as substances such as vitamin B1, vitamin B2, vitamin B6, niacin, pantothenic acid, folic acid, vitamin B12, vitamin K and biotin. The intake of animal Bifidobacterium lactis subsp. lactis, itself and the vitamins it produces, may act on the gene loci that regulate the signaling pathway of IGF-1. IGF-1 has metabolic activities similar to insulin, such as promoting anabolism and lowering blood sugar; this allows the intake of Bifidobacterium lactis to upregulate the level of carbohydrate metabolism. Similarly, after ingestion, lipid metabolism increases by upregulating fatty acid β-oxidation. Therefore, animal Bifidobacterium lactis subsp. lactis strain BL-G101 can regulate energy metabolism in a positive way, increase energy expenditure and avoid fat deposition. Insulin resistance can lead to weight gain. The intake of animal Bifidobacterium lactis subsp. lactis strain BL-G101 and itself and the vitamins it produces can reduce insulin resistance, regulate insulin sensitivity and avoid fat deposition. Obesity can lead to increased blood sugar and then diabetes. Therefore, reducing fat deposition is conducive to reducing the occurrence of obesity, thereby reducing increased blood sugar.

[0057] The long subspecies of Bifidobacterium longum BL-G301 is a kind of Bifidobacterium and belongs to probiotics. It can regulate the composition of intestinal microorganisms and promote overall intestinal health. It can also promote digestive health. It can significantly reduce the level of C-reactive protein (CRP), an inflammatory factor in the human body; superoxide dismutase (SOD) significantly increases; and the total antioxidant capacity (TAC) of body cells significantly increases. Long subspecies of Bifidobacterium longum BL-G301 has a strong ability to generate B2 and B6. Vitamin B2 is a vitamin that helps fat burn into heat energy. When diabetic patients cannot fully burn and metabolize sugars, they must burn fat, so they also need a large amount of vitamin B2 supplementation. Vitamin B6 can be synthesized in the intestines, but it is not easy to remain in the human body and must be taken every day. After the long subspecies of Bifidobacterium longum BL-G301 is colonized in the human intestine, it can continuously produce vitamin B6. Vitamin B6 participates in fat and sugar metabolism. Vitamin B6 can prevent the production of substances that hinder insulin, so that insulin can fully function, and it is even more indispensable. Bifidobacterium longum subsp. longum strain BL-G301 can increase the production of butyrate, thereby reducing the concentrations of p-CS and IS. At the same time, butyrate can promote postprandial insulin secretion and lower blood sugar levels.

[0058] The Bifidobacterium bifidum strain BB-G90 is a kind of Bifidobacterium, which is a kind of beneficial bacteria in the intestine. The Bifidobacterium bifidum strain BB-G90 can usually relieve constipation. It can improve intestinal flora imbalance, help improve the phenomenon of gastrointestinal flora disorder, and maintain the balance of intestinal flora. The Bifidobacterium bifidum strain BB-G90 has certain effects on acute and chronic gastroenteritis, gastrointestinal dysfunction, indigestion, constipation and diarrhea caused by long-term use of antibiotics. It enhances immunity, promotes digestion, has auxiliary protection function for gastric mucosa, and assists in lowering blood lipids. At the same time, the Bifidobacterium bifidum strain BB-G90 has a strong ability to produce B1. Vitamin B1 is an indispensable substance for converting sugar in the body into heat energy. Diabetic patients have poor sugar metabolism and high blood sugar, and need more vitamin B1 and all other vitamins.

[0059] The Lactobacillus acidophilus strain LA-G80 can use food nutrients to increase ornithine, serotonin, 4-aminobutyric acid, citrulline, etc. Among them, ornithine can increase the hormone level in the body, which is beneficial to maintaining the normal physiological functions of various tissues and organs of the body. At the same time, it can also promote the body's metabolism and play a certain anti-aging role. It will also participate in the body's metabolism, improve the body's immune function, and prevent diseases. Citrulline can help regulate blood sugar concentration, which is especially important for diabetic patients. It is beneficial to balance normal blood sugar levels. Through the action of serotonin, it can affect eating behavior and satiety, thereby preventing excessive energy intake and fat deposition. γ-aminobutyric acid is an active amino acid that plays an important role in the energy metabolism process of the human brain. It has multiple physiological functions such as activating glucose metabolism in the brain, promoting acetylcholine synthesis, reducing blood ammonia toxins, anticonvulsant, lowering blood pressure, improving brain function, mental stability, and promoting growth hormone secretion.

[0060] The plant lactobacillus strain Lp-G18 is a kind of lactobacillus and belongs to probiotics. It can significantly reduce the level of serum inflammatory cytokine TNF-α and significantly increase the level of serum anti-inflammatory cytokine IL-10. At the same time, the plant lactobacillus strain Lp-G18 can use food nutrients to increase the content of pantothenic acid, riboflavin and kynurenine. Among them, pantothenic acid participates in the metabolic process of sugar, fat and protein, is an important component of the immune system, can promote the proliferation and differentiation of immune cells, and improve the body's immunity. Riboflavin mainly has the effect of promoting cell regeneration in the body. Appropriate supplementation of riboflavin is beneficial to the health of diabetics; kynurenine participates in metabolism and is beneficial to tissue repair.

[0061] The Lactobacillus casei strain LC-G11 is a kind of lactobacillus, and can utilize food nutrients to enhance ornithine, citrulline, etc. Ornithine can improve the hormone level in the body, is conducive to maintaining the normal physiological functions of various tissues and organs of the body, and can also promote the body's metabolism, and can play a certain anti-aging effect. It will also participate in the body's metabolism, can improve the body's immune function, and prevent diseases. Citrulline can help regulate blood sugar concentration, which is particularly important for diabetic patients, and it is conducive to balancing normal blood sugar levels.

[0062] The Lactobacillus reuteri strain LR-G100 is a kind of bacteria that normally exists in the body, which can inhibit the growth and reproduction of harmful bacteria in the intestinal tract, thereby preventing intestinal infection. There are a large number of Lactobacillus reuteri in the human small intestine, which helps to improve the distribution of intestinal flora, enhance immune response, improve immunity, and reduce intestinal inflammation. The adhesion of Lactobacillus reuteri strain LR-G100 is very good. It can prevent Helicobacter pylori from colonizing on the human intestinal mucosa and inhibit Helicobacter pylori infection. Lactobacillus reuteri strain LR-G100 has both antibacterial effect and does not inhibit the beneficial bacteria in the gastrointestinal tract. Lactobacillus reuteri strain LR-G100 can synthesize and secrete reuterin, which is a non-protein broad-spectrum antibacterial substance that can effectively inhibit the growth of harmful bacteria and is harmless to humans and animals. In addition, Lactobacillus reuteri strain LR-G100 also contains a specific ingredient that can effectively inhibit harmful oral bacteria, reduce the risk of disease entering the body through the mouth, reduce the chance of pathogens entering the body, reduce the chance of intestinal infection and intestinal abnormalities, thereby reducing the chance of harmful factors entering the body, and reducing the chance of pancreatic β cell damage, allowing insulin to be secreted normally and function.

[0063] The Lactobacillus johnsonii strain LJ-G55 is a kind of lactobacillus, belongs to probiotics, can be colonized in the intestine, has the function of inhibiting the growth of Candida albicans, inhibiting the formation of Candida albicans biofilm and reducing harmful bacteria in the body. The supplementation of Lactobacillus johnsonii strain LJ-G55 can stabilize the structure of intestinal flora, maintain the intestinal ecological status of more good bacteria and less bad bacteria, and then stimulate the mucosa to strengthen the immune system. Healthy gastrointestinal tract, adjust flora, and promote nutrient absorption. Prevent and treat acute diarrhea, flatulence, and dry bowel syndrome. Promote the discharge of intestinal toxins and delay aging. Lactobacillus johnsonii strain LJ-G55 is also widely present in anti-allergic probiotics. Lactobacillus johnsonii strain LJ-G55 can improve intestinal metabolic rate, increase intestinal peristalsis, shorten the reabsorption time of food in the intestine, and promote the timely discharge of excess nutrients. Lactobacillus johnsonii strain LJ-G55 can also block fat and cholesterol absorption, increase fat cell burning metabolism, and produce serotonin, help control weight, improve easy fat physique, etc., thus preventing obesity from causing blood sugar to rise. Some lactic acid bacteria can inhibit the growth of harmful bacteria and further promote the growth of other beneficial bacteria, such as promoting the growth of Lactobacillus acidophilus, and then producing citrulline, which can help regulate blood sugar concentration, and produce serotonin to increase satiety, thereby preventing excessive energy intake and fat deposition. Further prevent obesity from causing blood sugar to rise. In general, on the one hand, the increase of probiotic flora in the body reduces endotoxins, makes intestinal permeability reasonable, reduces inflammatory factors and toxic and harmful factors from entering the body, and ultimately leads to the reduction and repair of pancreatic β cell damage, thereby effectively reducing insulin and blood sugar concentrations, and developing in a healthy direction. On the other hand, probiotics ferment lactose into lactic acid, which has a good promoting effect on the absorption of calcium, iron, zinc, chromium, selenium, etc. At the same time, the process of probiotic growth and reproduction can produce short-chain fatty acids in the body, improving the metabolic absorption of metal ions such as calcium, iron, zinc, chromium, etc. The amino acids produced by beneficial bacteria can also form coordination bond compounds with zinc, chromium, calcium, etc. to promote absorption. As an important blood sugar regulator, chromium can control blood sugar and treat diabetes. Zinc is also a supplement that people with high blood sugar and diabetes need to take in time. Because vitamin B6 participates in fat and sugar metabolism, it can prevent the production of substances that hinder insulin and enable insulin to fully function. When taking a large amount of vitamin B6, it is necessary to increase zinc intake so that vitamin B6 can better participate in sugar metabolism and enable insulin to fully function.

[0064] In one embodiment of the present invention, different plant lactobacillus strains and lactobacillus acidophilus strains of fermented products of different kinds and contents are carried out, screening out for hypoglycemic, hypolipidemic, adjuvant treatment of diabetes strains, while the present invention is compounded with different plant lactobacillus strains and lactobacillus acidophilus strains and other 6 kinds of strains, 6 kinds of different lactobacillus compositions are obtained, animal experiments show that plant lactobacillus strains Lp-G18 and lactobacillus acidophilus strains LA-G80 are compounded with other 6 kinds of strains in terms of hypoglycemic and have more advantages. This shows that in the lactobacillus composition provided by the present invention, 8 kinds of strains have a synergistic effect in terms of hypoglycemic.

[0065] In the present invention, the preparation method of the lactic acid bacteria composition preferably includes the following steps: inoculating activated Lactobacillus plantarum strain Lp-G18, Bifidobacterium animalis subsp. lactis strain BL-G101, Lactobacillus casei strain LC-G11, Lactobacillus acidophilus strain LA-G80, Lactobacillus johnsonii strain LJ-G55, Lactobacillus reuteri strain LR-G100, Bifidobacterium longum subsp. longum strain BL-G301 and Bifidobacterium bifidum strain BB-G90 into sterilized culture medium for expansion culture, collecting various bacterial bodies from the culture solution, mixing various bacterial bodies according to the ratio of live bacterial count, and obtaining a lactic acid bacteria composition. The culture medium for expanding the culture of the plant lactobacillus strain Lp-G18 preferably includes, by mass percentage, 5% to 6% glucose, 1% to 1.2% peptone, 0.8% beef extract powder, 1.2% to 1.5% yeast extract, 0.5% anhydrous sodium acetate, 0.1% Tween-80, 0.025% magnesium sulfate heptahydrate, 0.005% manganese sulfate monohydrate, 0.2% diammonium hydrogen citrate, 0.2% dipotassium hydrogen phosphate, and the remainder is water. The culture medium for expanding the culture of the animal Bifidobacterium lactis subspecies BL-G101 preferably includes, by mass percentage, 3% to 3.5% glucose, 0.8% to 1% peptone, 1.5% to 2% yeast powder, 0.5% anhydrous sodium acetate, 0.1% Tween-80, 0.025% magnesium sulfate heptahydrate, 0.005% manganese sulfate monohydrate, 0.2% diammonium hydrogen citrate, 0.2% dipotassium hydrogen phosphate, 0.05% L-cysteine ​​hydrochloride, and the rest is water. The culture medium for expanding the culture of the Lactobacillus casei strain LC-G11 preferably comprises, by mass percentage, 4-5% glucose, 0.8% beef extract powder, 0.8-1% peptone, 0.8-1% yeast extract, 0.5% anhydrous sodium acetate, 0.1% Tween-80, 0.025% magnesium sulfate heptahydrate, 0.005% manganese sulfate monohydrate, 0.1% diammonium hydrogen citrate, 0.2% dipotassium hydrogen phosphate, and the remainder is water. The culture medium for expanding the culture of the Lactobacillus acidophilus strain LA-G80 preferably includes the following mass percentages: 3% to 4% glucose, 0.8% to 1% beef extract powder, 0.8% to 1% peptone, 0.8% to 1.2% yeast extract, 0.5% anhydrous sodium acetate, 0.1% Tween-80, 0.025% magnesium sulfate heptahydrate, 0.005% manganese sulfate monohydrate, 0.2% diammonium hydrogen citrate, 0.2% dipotassium hydrogen phosphate, 0.05% L-cysteine ​​hydrochloride, 0.4% to 0.5% calcium carbonate, and the rest is water.The culture medium for expanding the culture of the Lactobacillus johnsonii strain LJ-G55 preferably includes, by mass percentage, 2.5% to 3% glucose, 0.5% to 0.8% beef extract powder, 0.5% to 0.8% soy peptone, 0.4% to 0.5% peptone, 0.6% to 0.8% yeast extract, 0.5% anhydrous sodium acetate, 0.1% Tween-80, 0.025% magnesium sulfate heptahydrate, 0.005% manganese sulfate monohydrate, 0.2% diammonium hydrogen citrate, 0.2% dipotassium hydrogen phosphate, and the rest is water. The culture medium for expanding the culture of the Lactobacillus reuteri strain LR-G100 preferably includes, by mass percentage, 3% to 3.5% glucose, 0.8% to 1% beef extract powder, 0.8% to 1% soy peptone, 0.8% to 1% peptone, 1.8% to 2% yeast extract, 0.6% anhydrous sodium acetate, 0.1% Tween-80, 0.05% magnesium sulfate heptahydrate, 0.0075% manganese sulfate monohydrate, 0.15% diammonium hydrogen citrate, 0.3% dipotassium hydrogen phosphate, 0.05% L-cysteine ​​hydrochloride, and the rest is water. The culture medium for expanding the culture of the Bifidobacterium longum subspecies longum strain BL-G301 preferably includes the following components in percentage by mass: 1.5% to 2% lactose, 0.5% galacto-oligosaccharide, 0.8% to 1% beef extract powder, 0.8% to 1% peptone, 0.8% to 1% yeast extract, 0.5% anhydrous sodium acetate, 0.1% Tween-80, 0.06% magnesium sulfate heptahydrate, 0.02% manganese sulfate monohydrate, 0.2% diammonium hydrogen citrate, 0.2% dipotassium hydrogen phosphate, 0.1% L-cysteine ​​hydrochloride, 0.1% calcium chloride, and the rest is water. The culture medium for the expansion culture of the Bifidobacterium bifidum strain BB-G90 preferably includes the following components in percentage by mass: lactose 2% to 2.5%, beef extract powder 0.8% to 1%, peptone 0.8% to 1%, soy peptone 0.15% to 0.2%, yeast extract 0.8% to 1%, anhydrous sodium acetate 0.5%, Tween-80 0.1%, magnesium sulfate heptahydrate 0.06%, manganese sulfate monohydrate 0.02%, diammonium hydrogen citrate 0.2%, dipotassium hydrogen phosphate 0.2%, L-cysteine ​​hydrochloride 0.1%, calcium chloride 0.1%, and the rest is water. The temperature of the expansion culture is preferably 36 to 39° C., and can be 37 to 38° C. The time of the expansion culture is preferably 8 to 20 hours, and can be 10 to 14 hours.

[0066] The present invention provides a composite lactic acid bacteria probiotic agent, which comprises the following components in percentage by mass based on 100% of the probiotic agent: 33% to 57% of bacterial powder of the lactic acid bacteria composition, 20% to 30% of a filler, 15% to 25% of oligosaccharides, 0% to 20% of L-arabinose and the remainder of a cooling agent.

[0067] In the present invention, the composite lactic acid bacteria probiotic preferably includes the following components in percentage by weight: 33% to 50% of the bacterial powder of the lactic acid bacteria composition, 20% to 30% of the filler, 20% to 25% of the oligosaccharide, 0 to 18% of L-arabinose and the remainder of the cooling agent. It may be 33% to 42% of the bacterial powder of the lactic acid bacteria composition, 22% to 30% of the filler, 23% to 25% of the oligosaccharide, 2% to 15% of the L-arabinose and the remainder of the cooling agent; it may be 33% of the bacterial powder of the lactic acid bacteria composition, 30% of the resistant dextrin, 25% of the oligosaccharide and 12% of the cooling agent; or it may be 33% of the bacterial powder of the lactic acid bacteria composition, 25% of the resistant dextrin, 23% of the oligosaccharide, 7% of the L-arabinose and 12% of the cooling agent. The live bacteria concentration of the lactic acid bacteria composition is preferably not less than 10 billion CFU / g (or not less than 10 billion CFU / ml), and can be 11 billion CFU / g, 12 billion CFU / g, 13 billion CFU / g, 14 billion CFU / g, 15 billion CFU / g, 16 billion CFU / g, 17 billion CFU / g, 18 billion CFU / g, 20 billion CFU / g, 22 billion CFU / g, 24 billion CFU / g and 25 billion CFU / g. The filler preferably includes resistant dextrin; the filler does not play a pharmacological role, and mainly improves material performance, solubilizes, increases weight, and reduces material costs. The oligosaccharide preferably includes at least one of the following components: oligomaltolsaccharides, oligofructose, inulin and oligoxylose. The polymerization degree of the oligomaltolsaccharide is preferably 2 to 8, which can be 3, 4, 5, 6 and 7. The polymerization degree of the oligofructose is preferably 2 to 7, and may be 3, 4, 5, or 6. The polymerization degree of the oligoxylose is preferably 2 to 12, and may be 3, 4, 5, 6, 7, 8, 9, 10, and 11. The isomaltooligosaccharide, the fructooligosaccharide, and the oligoxylose are further preferably powders with a content of more than 90%. When the composite lactic acid bacteria probiotic includes isomaltooligosaccharide, the mass percentage of the isomaltooligosaccharide in the composite lactic acid bacteria probiotic is preferably 10% to 12.5%; it may be 11%. When the composite lactic acid bacteria probiotic includes fructooligosaccharide, the mass percentage of the fructooligosaccharide in the composite lactic acid bacteria probiotic is preferably 4.5% to 5.625%; it may be 5.2%. When the composite lactic acid bacteria probiotic includes inulin, the mass percentage of the inulin in the composite lactic acid bacteria probiotic is preferably 3% to 3.75%, and may be 3.5%. When the composite lactic acid bacteria probiotics include oligoxylose, the mass percentage of the oligoxylose in the composite lactic acid bacteria probiotics is preferably 2.5% to 3.12%, and can be 2.8%. The oligosaccharides are used as nutritional components of probiotics, and at the same time do not increase the stimulation of high-sugar foods to the human body. The cooling agent preferably includes xylitol. The function of the cooling agent is to improve the taste. The function of the L-arabinose is to reduce the increase in blood sugar after a meal.

[0068] In the present invention, the form of the compound lactic acid bacteria probiotic preferably includes at least one of the following: powder, granule, capsule and oral liquid. When the compound lactic acid bacteria probiotic is in the form of solid, the specification of the compound lactic acid bacteria probiotic is preferably 2-5g / bag, which can be 3-4g / bag. When the compound lactic acid bacteria probiotic is in the form of liquid, the specification of the compound lactic acid bacteria probiotic is preferably 2-5mL / bottle, which can be 3-4mL / bottle. The method of taking the compound lactic acid bacteria probiotic is to take it directly orally or brew it. The daily dosage does not exceed 71 packs or 71 bottles. The compound lactic acid bacteria probiotic is not suitable for infants and young children. The age of the infant is 0 to 3 years old.

[0069] In the present invention, the preparation method of the composite lactic acid bacteria probiotic agent preferably comprises the following steps:

[0070] The seed liquid of each strain is inoculated into a sterilized expansion culture medium for expansion culture and fermentation, the bacterial bodies are collected, the bacterial bodies are mixed with nutrients, and low-temperature freeze-dried to obtain a composite lactic acid bacteria probiotic agent.

[0071] In the present invention, the number of live bacteria of the bacterial powder after low-temperature freeze drying is measured, and the mixture is mixed according to the ratio and packaged. The specification of each package of composite lactic acid bacteria probiotics is preferably 3-5g during packaging, and the specific addition amount of each strain is plant bacillus LP-G1812-18 billion / package, Bifidobacterium lactis BL-G10110-12 billion / package, Lactobacillus casei LC-G150-6 billion / package, Lactobacillus acidophilus LA-G8020-2500 million / package, Lactobacillus johnsonii LJ-G5515-200 million / package, Lactobacillus reuteri LR-G10015-200 million / package, Bifidobacterium bifidum BB-G9010-1500 million / package, Bifidobacterium longum subspecies longum BL-G301100 million / package). The mass fraction of the nutrients is preferably 12.5% ​​of oligomaltolsaccharide, 5.625% of oligofructose, 3.75% of inulin, 3.125% of oligoxylose, and 12% of xylitol. They are mixed evenly and set aside. Resistant dextrin is weighed so that the mass ratio of the entire material reaches 100%. The above preparation process is preferably carried out under the following purified environment: the air purification standard is not lower than Class D, and the temperature is between 15 and 24°C and the humidity is between 15 and 35%.

[0072] The present invention provides the use of the lactic acid bacteria composition or the composite lactic acid bacteria probiotic in the preparation of a product for at least one of lowering blood sugar, lowering blood pressure and lowering insulin levels.

[0073] The present invention provides the use of the lactic acid bacteria composition or the composite lactic acid bacteria probiotic in combination with an SGLT2 inhibitor in the preparation of a product for at least one of lowering blood sugar, lowering blood pressure and lowering insulin levels.

[0074] In the present invention, the disease population preferably includes people with high blood sugar or type II diabetes. People with high blood sugar refer to people whose fasting blood sugar level is 6.2-8.2 mmol / L. The product preferably includes at least one of the following: medicine, food, food additives and health products.

[0075] In the present invention, the lactic acid bacteria composition or the composite lactic acid bacteria probiotic agent helps to better control blood sugar and blood lipid levels in the treatment of patients with type 2 diabetes, and can also improve the intestinal function of patients, reduce the systolic blood pressure of patients in a healthy direction, and reduce the function of serum insulin in a healthy direction. Moreover, the lactic acid bacteria composition or the composite lactic acid bacteria probiotic agent improves the symptoms of intestinal dysfunction such as constipation and chronic diarrhea in patients, and there are statistically significant differences compared with the levels before treatment. The results of liver and kidney test indicators show that the lactic acid bacteria composition or the composite lactic acid bacteria probiotic agent has good safety for the liver and kidneys (such as reducing the activity of alanine aminotransferase), and will not produce adverse consequences such as nephrotoxicity and liver damage.

[0076] The lactic acid bacteria composition for assisting the treatment of diabetes and its probiotic agent and application provided by the present invention are described in detail below in conjunction with the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0077] Example 1

[0078] Screening test of different Lactobacillus plantarum strains

[0079] 1. Source of Lactobacillus plantarum strains

[0080] The source of Lactobacillus plantarum strain LP-1 was traditional kimchi;

[0081] The source of Lactobacillus plantarum strain Lp-G18 is naturally fermented yogurt in Yili area of ​​Xinjiang Uygur Autonomous Region, and its preservation number is CCTCC NO: M 2013690.

[0082] The source of Lactobacillus plantarum strain ZJUFT17 was sourdough, provided by Zhejiang University, and the deposit number was CCTCC NO:M2017342.

[0083] 2. Fermentation culture

[0084] Different activated Lactobacillus plantarum strains were inoculated into the same sterilized food medium, and the fermentation broth was collected after fermentation at 37±1°C for 12 hours. Some components in the fermentation broth were detected by mass spectrometry, and the results are shown in Table 1.

[0085] Table 1 Detection results of fermentation products of different Lactobacillus plantarum strains

[0086]

[0087] From the results in Table 1, it can be seen that different strains of the same genus produce different substances and the amount of substances when fermenting the same material. The main focus is on substances that are helpful or indirectly helpful in lowering blood sugar. From Table 1, phenylalanine, citrulline, pantothenic acid, vitamin B6, riboflavin, etc. have obvious direct help and effects on diabetes, while uridine, xanthosine, kynurenine, tyrosine, etc. have more indirect effects. After comprehensive evaluation, it is believed that Lactobacillus plantarum strain LP-G18 is a strain that has an advantage in helping blood sugar.

[0088] Example 2

[0089] Screening test of different Lactobacillus acidophilus strains

[0090] 1. Sources of different Lactobacillus acidophilus strains

[0091] The source of Lactobacillus acidophilus strain LA1 was intestinal excreta of healthy adults in Shanghai;

[0092] The source of Lactobacillus acidophilus strain LA2 was intestinal excreta of healthy adults in Jiangsu;

[0093] The source of Lactobacillus acidophilus strain LA-G80 is the excrement of healthy elderly people in Bama area of ​​Guangxi Zhuang Autonomous Region, and the preservation number is CCTCC NO: M 2013690.

[0094] 2. Fermentation culture

[0095] Different activated Lactobacillus acidophilus strains were inoculated into the sterilized culture medium at an inoculum rate of 2%, and fermented at 36-38° C. for 24 hours, and the fermentation broth was collected. The metabolites in the fermentation broth were detected by mass spectrometry, and the results are shown in Table 2.

[0096] Table 2 Detection results of fermentation products of different Lactobacillus acidophilus strains

[0097]

[0098] As can be seen from Table 2, different strains of Lactobacillus acidophilus of the same genus produce different metabolites and their contents when fermenting the same material. The main focus is on substances that are helpful or indirectly helpful in lowering blood sugar. From Table 2, phenylalanine, citrulline, pantothenic acid, vitamin B6, 3-aminopropionic acid, etc. have obvious direct help and effects on diabetes, while serotonin, lactic acid, glycylglutamine, ornithine, 4-aminobutyric acid, formyltyrosine, etc. have more indirect effects. After comprehensive evaluation, it is believed that Lactobacillus acidophilus strain LA-G80 is a strain that is relatively advantageous in helping blood sugar.

[0099] Example 3

[0100] A preparation method of composite lactic acid bacteria probiotics

[0101] 1. The composition of the probiotics is as follows: the mass percentage of the lactic acid bacteria composition is 33%, the resistant dextrin is 30%, the oligosaccharide is 25% and the xylitol is 12%. The specification of each package of probiotics is 3g.

[0102] The lactic acid bacteria composition includes the following specific strains: Lactobacillus plantarum LP-G18, Bifidobacterium lactis BL-G101, Lactobacillus casei LC-G11, Lactobacillus acidophilus LA-G80, Lactobacillus johnsonii LJ-G55, Lactobacillus reuteri LR-G100, Bifidobacterium bifidum BB-G90 and Bifidobacterium longum subspecies longum BL-G301, and the ratio of the number of live bacteria is 18:12:8:5:2:2:1.5:1.5. The number of live bacteria of the Lactobacillus plantarum LP-G18 in each package of probiotics is 18 billion CFU.

[0103] The 25% oligosaccharide includes the following components in mass fractions: 12.5% ​​isomaltooligosaccharide, 5.625% fructooligosaccharide, 3.75% inulin and 3.125% xylo-oligosaccharide.

[0104] 2. Preparation method

[0105] The activated seed liquid of each strain is inoculated into a sterilized culture medium for expansion culture, and the obtained culture liquid is centrifuged to collect the bacterial cells to obtain the bacterial cells of each strain. The bacterial cells of each strain are mixed with resistant dextrin, oligosaccharide and xylitol, and freeze-dried to obtain a probiotic agent.

[0106] Comparative Example 1

[0107] A preparation method of composite lactic acid bacteria probiotic agent 1

[0108] 1. The composition of the probiotic is as follows: the mass percentage of the lactic acid bacteria composition is 33%, the resistant dextrin is 30%, the oligosaccharide is 25% and the xylitol is 12%.

[0109] The lactic acid bacteria composition includes the following strains: Lactobacillus plantarum ZJUFT17, Bifidobacterium lactis BL-G101, Lactobacillus casei LC-G11, Lactobacillus acidophilus LA1, Lactobacillus johnsonii LJ-G55, Lactobacillus reuteri LR-G100, Bifidobacterium bifidum BB-G90, Bifidobacterium longum subspecies longum BL-G301, and the ratio of live bacteria count is 18:12:8:5:2:2:1.5:1.5. The live bacteria count of Lactobacillus plantarum ZJUFT17 in each package of probiotics is 18 billion CFU. The specification of each package of probiotics is 3g.

[0110] 25% oligosaccharides include the following components in mass fractions: 12.5% ​​isomaltooligosaccharide, 5.625% fructooligosaccharide, 3.75% inulin and 3.125% xylo-oligosaccharide.

[0111] 2. Preparation method The probiotic agent 1 was prepared according to the method of Example 3.

[0112] Comparative Example 2

[0113] A preparation method of composite lactic acid bacteria probiotic agent 2

[0114] 1. The composition of the probiotics is as follows: the mass percentage of the lactic acid bacteria composition is 33%, the resistant dextrin is 30%, the oligosaccharide is 25% and the xylitol is 12%. The specification of each package of the probiotics is 3g.

[0115] The lactic acid bacteria composition includes the following strains: Lactobacillus plantarum 1, Bifidobacterium lactis BL-G101, Lactobacillus casei LC-G11, Lactobacillus acidophilus LA1, Lactobacillus johnsonii LJ-G55, Lactobacillus reuteri LR-G100, Bifidobacterium bifidum BB-G90, Bifidobacterium longum subspecies longum BL-G301, and the ratio of live bacteria count is 18:12:8:5:2:2:1.5:1.5. The live bacteria count of Lactobacillus plantarum 1 in each package of probiotics is 18 billion CFU.

[0116] 25% oligosaccharides include the following mass fractions: 12.5% ​​isomaltooligosaccharide, 5.625% fructooligosaccharide, 3.75% inulin and 3.125% xylo-oligosaccharide.

[0117] 2. Preparation method Probiotic 2 was prepared according to the method of Example 3.

[0118] Comparative Example 3

[0119] A preparation method of composite lactic acid bacteria probiotic agent 3

[0120] 1. The composition of the probiotic is as follows: the mass percentage of the lactic acid bacteria composition is 33%, the resistant dextrin is 30%, the oligosaccharide is 25% and the xylitol is 12%.

[0121] The lactic acid bacteria composition includes the following strains: Lactobacillus plantarum 1, Bifidobacterium lactis BL-G101, Lactobacillus casei LC-G11, Lactobacillus acidophilus LA-G80, Lactobacillus johnsonii LJ-G55, Lactobacillus reuteri LR-G100, Bifidobacterium bifidum BB-G90 and Bifidobacterium longum subspecies longum BL-G301, and the ratio of live bacteria count is 18:12:8:5:2:2:1.5:1.5. The live bacteria count of Lactobacillus plantarum 1 in each package of probiotics is 18 billion CFU. The specification of each package of probiotics is 3g.

[0122] 25% oligosaccharides include the following components in mass fractions: 12.5% ​​isomaltooligosaccharide, 5.625% fructooligosaccharide, 3.75% inulin, and 3.125% xylo-oligosaccharide.

[0123] 2. Preparation method Probiotic 3 was prepared according to the method of Example 3.

[0124] Comparative Example 4

[0125] A preparation method of composite lactic acid bacteria probiotic agent 4

[0126] 1. The composition of the probiotics is as follows: the mass percentage of the lactic acid bacteria composition is 33%, the resistant dextrin is 30%, the oligosaccharide is 25% and the xylitol is 12%. The specification of each package of the probiotics is 3g.

[0127] The lactic acid bacteria composition comprises the following strains: plant bacillus LP-G18, Bifidobacterium lactis BL-G101, Lactobacillus casei LC-G11, Lactobacillus acidophilus LA1, Lactobacillus johnsonii LJ-G55, Lactobacillus reuteri LR-G100, Bifidobacterium bifidum BB-G90, Bifidobacterium longum subspecies longum BL-G301, and the ratio of live bacteria count is 18:12:8:5:2:2:1.5:1.5. The live bacteria count of the plant bacillus LP-G18 in each package of probiotics is 18 billion CFU.

[0128] 25% oligosaccharides include the following components in mass fractions: 12.5% ​​isomaltooligosaccharide, 5.625% fructooligosaccharide, 3.75% inulin and 3.125% xylo-oligosaccharide.

[0129] 2. Preparation method Probiotic agent 4 was prepared according to the method of Example 3.

[0130] Comparative Example 5

[0131] A preparation method of composite lactic acid bacteria probiotic agent 5

[0132] 1. The composition of the probiotics is as follows: the mass percentage of the lactic acid bacteria composition is 33%, the resistant dextrin is 30%, the oligosaccharide is 25% and the xylitol is 12%. The specification of each package of the probiotics is 3g.

[0133] The lactic acid bacteria composition comprises the following strains: plant bacillus LP-G18, Bifidobacterium lactis BL-G101, Lactobacillus casei LC-G11, Lactobacillus acidophilus LA-G80, Lactobacillus johnsonii LJ-G55, Lactobacillus reuteri LR-G100, Bifidobacterium bifidum BB-G90, Bifidobacterium breve, and the ratio of live bacteria count is 18:12:8:5:2:2:1.5:1.5. The live bacteria count of plant bacillus LP-G18 in each package of probiotics is 18 billion CFU.

[0134] The oligosaccharide 25% includes the following components in mass fractions: 12.5% ​​of isomaltooligosaccharide, 5.625% of fructooligosaccharide, 3.75% of inulin and 3.125% of xylo-oligosaccharide.

[0135] 2. Preparation method Probiotic agent 5 was prepared according to the method of Example 3.

[0136] Example 4

[0137] Rat animal experiment

[0138] 100 healthy rats (male) weighing 180-200g were selected, raised for 1 week, fasted for 24h, and injected with 1% alloxan 0.45mL / 100g through the tail vein. After 72h of modeling, fasted for 4-5 hours, and blood was collected from the orbital venous plexus to measure blood sugar. Rats with blood sugar levels below 160mg / dl and above 400mg / dl after modeling were eliminated, and the remaining rats were successfully modeled as diabetic animal models.

[0139] A model control group (4 rats with blood sugar levels between 160-240 mg / dl, 240-320 mg / dl, and 320-400 mg / dl) and 4 regimen groups (4 rats with blood sugar levels between 160-240 mg / dl, 240-320 mg / dl, and 320-400 mg / dl) were randomly selected. The regimen groups were given different test samples (the number of viable bacteria in the formulas of different regimen groups was kept equivalent). The model control group was given the solvent once a day for 15 consecutive days, and blood was taken 1 hour after the last dose to measure the blood sugar content. The absolute average of the blood sugar reduction of each group of animals (i.e., the average of the difference in blood sugar before and after the experiment) was compared.

[0140] Table 3 Blood sugar reduction before and after administration of different probiotics

[0141] Control group Comparative Example 1 Comparative Example 2 Comparative Example 3 Example 3 Comparative Example 4 Comparative Example 5 160–240 mg / dL -23.2 15.4 16.8 17.2 18.7 17.0 16.9 240–320 mg / dL -25.8 14.6 15.1 16.5 17.4 16.4 15.0 320–400 mg / dL -32.3 13.1 14.4 15.3 17.1 15.6 14.2

[0142] From the experimental data of rats in Table 3, the probiotics prepared in Example 3 are the most effective formula, so this combination is considered to be used in the subsequent human experimental formula.

[0143] From the above animal experimental data, in addition to the traditional belief that the existing mechanism of action may include the following pathways: (1) Probiotics can form a biological immune barrier with the intestinal mucosa, maintain the balance of intestinal flora, and thus improve glucose metabolism. (2) Probiotics can reduce insulin resistance and repair oxidative damage to pancreatic B cells, thereby regulating blood sugar. (3) Probiotics attach to the intestinal mucosa through adhesive substances on the surface of the intestinal mucosa, forming a biological protective barrier, releasing related immune factors, thereby enhancing the body's immune function and improving blood sugar. (4) Probiotics may reduce oxidative stress by reducing chronic and low-grade inflammation. Relieve the production of inflammation, so that the function of pancreatic B cells tends to be normal (5) Probiotics can increase autonomic nervous activity, regulate the activity of enzymes related to glucose and lipid metabolism, and alleviate blood sugar changes. (6) Probiotics can produce substances such as bacteriocins to protect pancreatic islet cells, promote pancreatic islet function, and inhibit a-glucosidase, playing an important role in regulating blood sugar. (7) The peptides produced during the proliferation of probiotics can inhibit the activity of postsynaptic neurons through the brain-gut axis and improve glucose metabolism. Another possible mechanism is that probiotics can break down related foods and produce corresponding substances such as citrulline, phenylalanine, pantothenic acid, vitamin B6, riboflavin, niacin, etc. These substances have a beneficial health effect in helping to regulate blood sugar concentration, participating in sugar metabolism, facilitating sugar metabolism, reducing related complications, and preventing metabolic disorders that affect the body's biological oxidation process.

[0144] At the same time, it can be found that the effects of combinations of different strains are not the same. In the existing animal experiments of the above-mentioned groups of formulas, the probiotic prepared by the lactic acid bacteria composition of Example 3 is the most effective formula.

[0145] Example 5

[0146] Clinical application trial of compound lactic acid bacteria probiotics

[0147] A total of 32 patients with mild hyperglycemia (fasting blood glucose 6.2-8.2 mmol / L) and type 2 diabetes collected from 6 hospitals in Jiangsu Province from August 2021 to October 2022 were selected and divided into study group A and study group B (the number of people in each group is the same and the number of men and women is also equal). Group A was treated with simple diet control (reducing the intake of sugar and high-glycemic index foods) + probiotics (composite lactic acid bacteria probiotics prepared in Example 3, twice a day, one bag each after meals in the morning and evening) for 8 weeks, and group B was treated with oral SGLT2 inhibitor drugs (drugs are taken as prescribed by the doctor) For people whose blood sugar is still high for more than three months (fasting blood sugar is above 6.5mmol / L), a composite lactic acid bacteria probiotic product (composite lactic acid bacteria probiotic agent prepared in Example 3, twice a day, one bag each after meals in the morning and evening) was used for auxiliary treatment for 8 weeks, and the changes in blood sugar level (conventional glucose oxidase method), transaminase level (measured by conventional biochemical method for alanine aminotransferase, conventional absorption method for aspartate aminotransferase enzyme activity), glycosylated hemoglobin (conventional ion exchange high pressure liquid chromatography) and gastrointestinal function indexes before and after treatment in the two groups were analyzed and compared. The results are shown in Tables 4 and 5.

[0148] Table 4 FPG, 2hFPG, HbAlc levels in the two groups of patients

[0149]

[0150] Table 5 Improvement results of gastrointestinal dysfunction in patients before and after treatment

[0151]

[0152]

[0153] The results in Table 4 show that there were significant differences in FPG, 2hFPG and HbAlc levels between the two groups of patients before treatment (P>0.05), and the blood glucose level in Group A was slightly elevated. After 8 weeks of treatment with the compound lactic acid bacteria probiotic product, the FPG, 2hFPG and HbAlc levels of the two groups of patients decreased to varying degrees, and there were significant differences in FPG, 2hFPG and HbAlc levels compared with the levels before treatment (P<0.05). At the same time, there was no significant difference in the levels between the two groups after treatment (P>0.05).

[0154] The results in Table 4 and Table 5 show that there were statistically significant differences in glycated hemoglobin (HbA1c) and gastrointestinal function levels between the two groups of patients before and after treatment (P<0.05). After 8 weeks of treatment with the compound lactic acid bacteria probiotic product TM, the symptoms of intestinal dysfunction such as constipation and chronic diarrhea in the two groups of patients were significantly improved, and there was a statistically significant difference compared with the levels before treatment (P<0.05). Correspondingly, the systolic blood pressure of the patients, the activity of aspartate aminotransferase in the blood, and serum insulin also further decreased in a healthy direction.

[0155] Conclusion: Compound lactobacillus probiotic products can help better control blood sugar and blood lipid levels in the adjuvant treatment of patients with type 2 diabetes. At the same time, they can also improve the intestinal function of patients, control glycosylated hemoglobin (HbA1c), and help patients improve their nutritional scores and maintain good immune function. Comparison of gastrointestinal function improvement between the two groups before and after treatment. There was no statistically significant difference in the levels of gastrointestinal dysfunction such as constipation and chronic diarrhea between the two groups before treatment; after 8 weeks of adjuvant treatment with probiotics, the symptoms of intestinal dysfunction such as constipation and chronic diarrhea in the two groups were improved, and there was a statistically significant difference compared with the levels before treatment.

[0156] 2. Patients in Group A and Group B filled out questionnaires before and after treatment, which included the patient's name, age, gender, known history of high blood sugar, time of consultation, medication status, etc. 18 parameters including blood pressure (systolic and diastolic), blood sugar (before breakfast, after breakfast, before lunch, after lunch, before dinner, after dinner, before bedtime), glycosylated hemoglobin, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine, insulin, etc. were tested and recorded, and the data changes before and after conditioning. At the same time, the physical sensations and bowel movements of the patients before and after the process were consulted and counted. See the results. Figure 1 to Figure 15 .

[0157] Results Analysis

[0158] From the overall situation, the blood sugar levels before breakfast, after breakfast, and before lunch in group A and group B decreased significantly. Blood sugar levels after dinner and before bedtime also decreased, but blood sugar levels before dinner also increased. Among them, the changes in blood sugar and alanine aminotransferase before lunch were the most obvious, and statistics showed that they reached more than 20%. Systolic and diastolic blood pressure decreased overall. Systolic and diastolic blood pressure decreased from an average of 131.8 mmHg and 80.5 mmHg before conditioning and treatment to 125 mmHg and 76 mmHg after conditioning and treatment, respectively. For patients with type 2 diabetes who are usually suspected of high insulin levels, the average is more than 7%. Glycated hemoglobin has changed significantly and is on a downward trend, specifically from a high 7.69% to 6.90%, indicating that blood sugar control is ideal and tends to be normal 4% to 6%. Alanine aminotransferase and aspartate aminotransferase are on a downward trend; usually, alanine aminotransferase is the most sensitive indicator of liver damage. The downward trend of alanine aminotransferase indicates good liver function. Aspartate aminotransferase is on a downward trend. Aspartate aminotransferase is mainly distributed in the myocardium, followed by the liver, skeletal muscle and kidneys. It is often used as an auxiliary examination for myocardial infarction and myocarditis in clinical practice. The normal value of aspartate aminotransferase is 0-40U / L. When aspartate aminotransferase is significantly elevated, it reflects liver damage, indicating that the liver damage is more serious. At the same time, the AST / ALT value has increased (from the original 0.842 to 0.924, which is still less than the normal value of 1 (the increase is less than 9%, which is not significant). The creatinine value has changed significantly and is on a downward trend. The specific normal value of blood creatinine is in the range of 30-110μmol / L. The creatinine value is a classic indicator of renal function. The appropriate decline in the data indicates that the decline in renal function has been alleviated. It can even be predicted that the patient has no tendency to uremia. That is, it is generally beneficial to kidney health. The normal value of BUN is 3.2-7.1mmol / L, and the statistical average data shows that there is no significant change before and after use.

[0159] The statistical analysis of Group A data is as follows:

[0160] 1. Blood sugar levels before breakfast, after breakfast, before lunch, after lunch, before dinner, and before bedtime also decreased. The changes in the morning were obvious, and the blood sugar levels before meals tended to be stable.

[0161] 2. The changes in alanine aminotransferase and aspartate aminotransferase were the most obvious, and statistics showed that they reached more than 20%.

[0162] 3. Systolic and diastolic blood pressures decreased overall, from 134 / 82.1 mmHg to 125 / 75.5 mmHg, which was quite obvious.

[0163] 4. The high insulin level of the patients with type 2 diabetes mellitus (II) was improved. The average decrease was about 15%. The decrease rate was not as fast as that of group B.

[0164] 5. Glycated hemoglobin has changed significantly, showing a downward trend, from a high 7.775% to 6.706%, indicating that blood sugar control is ideal and tends to the normal 4% to 6%.

[0165] 6. Alanine aminotransferase and aspartate aminotransferase showed a downward trend; among them, alanine aminotransferase is the most sensitive indicator of liver damage. The data show that liver function is good or recovering. At the same time, it was found that the AST / ALT value increased (from the original 0.877 to 0.951, which is still less than the normal value of 1 (the increase is less than 9%, not significant).

[0166] 7. The creatinine value has changed significantly. It is on a downward trend. The normal value of blood creatinine is 30-110 μmol / L. The creatinine value is a classic indicator of renal function. The appropriate decrease in the data at least indicates that the decline in renal function has been alleviated. It can even predict that the patient has no tendency to uremia. In general, it is beneficial to kidney health.

[0167] 8. The normal value of BUN is 3.2-7.1mmol / L. The statistical average data is 4.94mmol / L before use and 5.24mmol / L after use, with no significant change. At the same time, after use, it is closer to the median of the normal value. This indicates that there is no organic renal damage. However, attention should be paid to prevent continuous increase. Simple increase in blood urea nitrogen may be caused by food.

[0168] The data of group B were statistically analyzed as follows:

[0169] 1. When probiotics are used in combination with hypoglycemic drugs that promote the excretion of glucose from the body through urine, blood sugar levels before breakfast, after breakfast, before lunch, and before bedtime also decrease.

[0170] 2. The systolic blood pressure decreased slightly, and the overall change in diastolic blood pressure was not obvious.

[0171] 3. Blood sugar rose after lunch and before dinner. This is different from the effect of simply using probiotics on people with mildly high blood sugar. Perhaps it is because the effect is not obvious enough for diabetic patients (those with severely high blood sugar).

[0172] 4. For the high insulin level of people with type 2 diabetes (Ⅱ), there is a significant improvement. The normal value of fasting insulin is 4.03-23.46pmol / mL (or 5-20mU / L). The average decrease is more than 22%. It may be that the use of probiotics and drugs together has an additive effect. However, after 8 weeks, the values ​​are still generally high and slightly high. The original values ​​may be high. But according to its trend, there will be a chance to exceed it.

[0173] 5. Glycated hemoglobin has a downward trend (7.53-7.28), but it is not as obvious as the effect of simply using probiotics on people with mildly high blood sugar.

[0174] 6. Alanine aminotransferase is on a downward trend, and alanine aminotransferase is the most sensitive indicator of liver damage. The data shows that liver function is good or recovering. But at the same time, aspartate aminotransferase is on an upward trend; the AST / ALT value has increased (from the original 0.748 to 0.87, which is still less than the normal value of 1. At the same time, the ratio has increased rapidly (more than 15%), which is more significant. It may be caused by the side effects of medication (such as metformin may cause changes in liver and kidney function).

[0175] 7. The creatinine value has changed significantly. It is on an upward trend. The normal value of blood creatinine is 30-110umol / L. The creatinine value is a classic indicator of renal function. The increase in the data indicates a decrease in renal function. It may be caused by drugs. For example, metformin drugs may cause liver and kidney damage.

[0176] 8. The normal value of BUN is 3.2-7.1mmol / L. The average data is 5.1mmol / L before use and 5.16mmol / L after use, with no significant change. Although the increase in data may mean renal damage, it is closer to the median of normal value after use. It means there is no organic renal damage. But attention should be paid to prevent continuous increase. Simple increase in blood urea nitrogen may be caused by drugs, food, etc. Combined with the increase in creatinine value, more attention should be paid to prevent renal function decline and renal failure.

[0177] Comparing the results of Group A and Group B, we can see that:

[0178] 1) For those with slightly elevated blood sugar levels and a tendency to develop diabetes (Group A), the participants' systolic and diastolic blood pressures decreased overall, moving toward healthier data. However, the participants in Group B did not experience the same significant effect.

[0179] 2) For those with slightly elevated blood sugar levels and a tendency to develop diabetes (Group A), the blood sugar levels of the participants before dinner decreased. However, the blood sugar levels of the participants in Group B increased before dinner. The blood sugar levels of Group A also decreased after dinner. However, the blood sugar levels of Group B remained basically the same.

[0180] 3) The average insulin level of group B decreased by more than 8%. However, the value was still higher than that of group A. The average insulin level of group A decreased by about 7%.

[0181] 4) Glycated hemoglobin showed a downward trend in both groups A and B. However, the decrease in blood sugar in group B was not as significant as that in group A, which only used probiotics for people with mildly high blood sugar.

[0182] 5) After conditioning and treatment, the blood sugar levels before breakfast, after breakfast, before lunch, and before bedtime of Group A and Group B also decreased.

[0183] 6) After conditioning and treatment, the alanine aminotransferase of group A and group B showed a downward trend, while the aspartate aminotransferase of group A showed a downward trend and that of group B showed an upward trend. This may be due to the influence of the medication used by group B.

[0184] 7) After treatment, the creatinine values ​​of group A and group B changed significantly. They showed a downward trend. Creatinine value is a classic indicator of renal function. The appropriate decrease in the data indicates that the decline in renal function has been alleviated. It can even be predicted that the patient has no tendency to uremia.

[0185] 8) The normal value of BUN is 3.2-7.1mmol / L. The statistical average data is 4.94mmol / L before use and 5.24mmol / L after use. There is no significant change between them, but after using them together, they are closer to the median of the normal value. This shows that there is no organic renal damage, and even renal function has been effectively improved.

[0186] in conclusion

[0187] 1. Compound lactobacillus probiotics help to slightly increase blood sugar levels. The systolic and diastolic blood pressure of those who are prone to diabetes (Group A) have generally decreased, tending to a healthier level. Oral hypoglycemic drugs (SGLT2 inhibitors) that promote glucose excretion through urine have less impact on blood pressure in those whose blood sugar remains high for more than three months.

[0188] 2. The compound lactobacillus probiotics helped to reduce the blood sugar levels before breakfast, after breakfast, before lunch, and before bedtime. It was effective for those with slightly elevated blood sugar levels and a tendency to develop diabetes (Group A). ​​It also helped to reduce their blood sugar levels after dinner.

[0189] 3. Compound lactic acid bacteria probiotics can help reduce the insulin level of relevant personnel, with an overall average reduction of more than 7%.

[0190] 4. The compound lactic acid bacteria probiotics helped the relevant personnel to have a downward trend in glycosylated hemoglobin (HbA1c). And for those with slightly elevated blood sugar levels and a tendency to develop diabetes (Group A), the effect was obvious. It was about 14%. For Group B, it was about 3%. The difference between the two was obvious, and both indicators were better than a certain foreign brand product.

[0191] 5. Compound lactobacillus probiotics can help the relevant personnel to have a significant downward trend in alanine aminotransferase (ALT). For those with mildly elevated blood sugar levels and those who are prone to diabetes, aspartate aminotransferase (AST) also has a significant downward trend (statistics show a decrease of about 29% and 23% respectively). For those who take oral hypoglycemic drugs (SGLT2 inhibitors) that promote glucose excretion through urine, and whose blood sugar is still high for more than three months, alanine aminotransferase also shows a downward trend when used with SGLT2 inhibitors. (A decrease of about 6%) Aspartate aminotransferase has an upward trend. (An increase of about 9%) This may be related to the effects of the use of drugs. Long-term use may cause the ratio of aspartate aminotransferase (AST) / alanine aminotransferase (ALT) to exceed 1. Usually in medicine and clinical practice, when aspartate aminotransferase is significantly elevated, reflecting liver damage, it indicates that the liver damage is more serious. If the degree of elevation of AST is greater than that of ALT, the ratio of AST to ALT will be greater than 1, indicating extensive substantial liver damage and a poor prognosis. Experimental application cases are obviously not included in this list.

[0192] 6. The compound lactic acid bacteria probiotics help the relevant personnel to have a significant change in creatinine (Cr) value after conditioning and treatment, showing a downward trend. The value of blood urea nitrogen (BUN) has increased and is closer to the median of normal values ​​after use. This shows that there is no organic renal damage. Even renal function has been effectively improved.

[0193] Summarize:

[0194] 1) Compound lactobacillus probiotic products. They help people control their blood sugar. Specifically, blood sugar before breakfast, after breakfast, before lunch, and before bedtime also decrease. They are effective for people with slightly high blood sugar levels and help reduce blood sugar after dinner.

[0195] 2) Compound lactic acid bacteria probiotic products. They help lower the insulin level of relevant personnel. The overall average decrease is more than 14%.

[0196] 3) Compound lactobacillus probiotic products. They help reduce the glycosylated hemoglobin (HbA1c) of the relevant personnel. And they are more effective for those with slightly elevated blood sugar levels and a tendency to develop diabetes (Group A).

[0197] 4) Compound lactic acid bacteria probiotic products. It helps the relevant personnel to have a downward trend in alanine aminotransferase (ALT). For those with slightly elevated blood sugar levels and a tendency to develop diabetes, aspartate aminotransferase (AST) also has a significant downward trend. However, there is no significant alanine aminotransferase (ALT) (statistics of this experiment show a decrease of about 29% and 23% respectively). For those who take oral hypoglycemic drugs (SGLT2 inhibitors) that promote glucose excretion through urine, and whose blood sugar is still high for more than three months, when used with SGLT2 inhibitors, alanine aminotransferase also shows a downward trend, but aspartate aminotransferase (AST) increases. It is estimated that it is the influence of drug side effects.

[0198] 5) Compound lactic acid bacteria probiotic products. It helps relevant personnel to have a downward trend in creatinine (Cr) value after conditioning and treatment. The value of blood urea nitrogen (BUN) increases and approaches the median of normal value after use.

[0199] 6) Compound lactic acid bacteria probiotic products. They can help people with mildly high blood sugar levels lower their blood pressure and move it toward a healthier level.

[0200] In summary, the above-mentioned compound lactic acid bacteria probiotics are helpful for the relevant personnel to control blood sugar (especially fasting and in the morning), and glycosylated hemoglobin (HbA1c) has a downward trend. Combined with the changes in blood sugar parameters, it is preliminarily determined that insulin is declining in a healthy manner. In addition to the effects of lowering blood sugar, it also assists in lowering blood pressure, protects the kidneys, is beneficial to the health of kidney function, reduces the burden on the liver and protects the liver function. Especially for those with slightly elevated blood sugar levels and a tendency to develop diabetes. At the same time, there is some improvement in gastric and intestinal dysfunction. Therefore, the above-mentioned compound lactic acid bacteria probiotic products are good products for conditioning, intervention and auxiliary treatment (Ⅱ) of type 2 diabetes. It has market promotion value.

[0201] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A lactic acid bacteria composition, characterized in that Including the live bacteria count ratio of (10-30): (8-16): (5-12): (3-9): (1-5): (1-5): (0.5-2.5): (0.5-2.5) Lactobacillus plantarum strain Lp-G18, Bifidobacterium animalissubsp.lactis strain BL-G101, Lactobacillus casei strain LC-G11, Lactobacillus acidophilus strain LA-G80, Lactobacillus johnsonii strain LJ-G55, Lactobacillus reuteri strain LR-G100, Bifidobacterium longum subsp. longum strain BL-G301 and Bifidobacterium bifidum strain BB-G90; The deposit number of the Lactobacillus plantarum strain Lp-G18 is CCTCC NO: M 2013690; The deposit number of the Bifidobacterium animalis subsp. lactis strain BL-G101 is CCTCC NO: M2013336; The deposit number of the Lactobacillus casei strain LC-G11 is CCTCC NO: M 2013196; The deposit number of the Lactobacillus acidophilus strain LA-G80 is CCTCC NO: M 2013337; The deposit number of the Lactobacillus johnsonii strain LJ-G55 is CCTCC NO: M 2017116; The deposit number of the Lactobacillus reuteri strain LR-G100 is CCTCC NO: M 2013692; The deposit number of the Bifidobacterium longum subspecies longum strain BL-G301 is CCTCC NO: M2013689; The deposit number of the Bifidobacterium bifidum strain BB-G90 is CCTCC NO: M 2013194.

2. The lactic acid bacteria composition according to claim 1, characterized in that The ratio of the number of live bacteria among the plant lactobacillus strain Lp-G18, the animal bifidobacterium lactis subspecies strain BL-G101, the lactobacillus casei strain LC-G11, the lactobacillus acidophilus strain LA-G80, the lactobacillus johnsonii strain LJ-G55, the lactobacillus reuteri strain LR-G100, the bifidobacterium longum subspecies longum strain BL-G301 and the bifidobacterium bifidum strain BB-G90 is (12-24): (10-15): (6-10): (4-8): (1-4): (1-4): (0.5-2.0): (0.5-2.0).

3. A composite lactic acid bacteria probiotic agent, characterized in that: Taking the mass of the probiotic as 100%, the following components are included in the mass percentage: The lactic acid bacteria composition according to claim 1 or 2 comprises 33% to 57% bacterial powder, 20% to 30% filler, 15% to 25% oligosaccharide, 0 to 20% L-arabinose and the remainder a cooling agent.

4. The composite lactic acid bacteria probiotic according to claim 3, characterized in that: Includes the following components in percentage by mass: The lactic acid bacteria composition comprises 33% to 50% of bacterial powder, 20% to 30% of a filler, 20% to 25% of oligosaccharides, 0% to 18% of L-arabinose and the remainder of a cooling agent.

5. The composite lactic acid bacteria probiotic according to claim 3 or 4, characterized in that: The filler includes resistant dextrin; The cooling agent includes xylitol.

6. The composite lactic acid bacteria probiotic according to claim 3 or 4, characterized in that: The oligosaccharide comprises at least one of the following components: isomaltooligosaccharide, fructooligosaccharide, inulin and xylo-oligosaccharide; When the compound lactic acid bacteria probiotics comprises isomaltooligosaccharide, the mass percentage of the isomaltooligosaccharide in the compound lactic acid bacteria probiotics is 10% to 12.5%; When the compound lactic acid bacteria probiotics comprises oligofructose, the mass percentage of the oligofructose in the compound lactic acid bacteria probiotics is 4.5% to 5.625%; When the composite lactic acid bacteria probiotics comprises inulin, the mass percentage of the inulin in the composite lactic acid bacteria probiotics is 3% to 3.75%; When the compound lactic acid bacteria probiotics comprises xylooligosaccharides, the mass percentage of the xylooligosaccharides in the compound lactic acid bacteria probiotics is 2.5% to 3.12%.

7. The composite lactic acid bacteria probiotic according to claim 3 or 4, characterized in that: The live bacteria concentration of the lactic acid bacteria composition is not less than 10 billion CFU / g.

8. Use of the lactic acid bacteria composition according to claim 1 or 2 or the composite lactic acid bacteria probiotic according to any one of claims 3 to 7 in the preparation of a product for reducing blood sugar, blood pressure and insulin levels.

9. Use of the lactic acid bacteria composition according to claim 1 or 2 or the composite lactic acid bacteria probiotic according to any one of claims 3 to 7 in combination with an SGLT2 inhibitor in the preparation of a product for lowering blood sugar, blood pressure and insulin levels.

10. The use according to claim 8 or 9, characterized in that: The population whose blood sugar, blood pressure and insulin levels are to be lowered includes people with high blood sugar or patients with type 2 diabetes.

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