Application of mouse combined lactobacillus

Abstract

The invention relates to application of mouse combined lactobacillus. According to the application disclosed by the invention, the lactobacillus murins DSM 28683 can be applied to the preparation of a product for treating type 2 diabetes mellitus or a product for reducing body fat. A T2D mouse is subjected to intragastric administration by using the Ligilbacillus murins DSM 28683, and it is found that the Ligilbacillus murins DSM 28683 can significantly improve metabolism of the T2D mouse, effectively improve insulin sensitivity of the T2D mouse, reduce body weight and improve fatty liver, and has a good application prospect in treatment of type 2 diabetes mellitus.

Description

Technical Field

[0001] The invention relates to the technical field of microorganisms, in particular to an application of mouse-associated lactobacillus. Background Art

[0002] The probiotic Ligilactobacillus murins is a lactic acid bacterium belonging to the phylum Lactobacillaceae, which is mainly found in the digestive tract of humans and animals. They play an important role in maintaining intestinal health and have a variety of potential health benefits. Lactic acid bacteria have some very important functions such as: (1) Improving intestinal microecological balance: Lactic acid bacteria can inhibit the growth of harmful bacteria and help maintain the balance of microorganisms in the intestine, thereby promoting digestive health. (2) Enhancing immune function: Studies have shown that lactic acid bacteria may enhance the body's resistance to disease by promoting the function of the immune system. (3) Biosynthesis: These probiotics are able to produce beneficial metabolites, such as lactic acid, which has a positive effect on the acid-base balance of the intestinal environment. (4) Relieve intestinal symptoms: Lactic acid bacteria are believed to be able to relieve intestinal-related symptoms such as diarrhea and irritable bowel syndrome. (5) Improve nutrient absorption: By improving the digestion and absorption of food, lactic acid bacteria help the body absorb nutrients more efficiently. At present, the application of lactic acid bacteria is mainly used in the following aspects: Food industry: Lactic acid bacteria are often used in the production of fermented foods, such as yogurt, cheese and other fermented dairy products, to increase the nutritional value and health function of food. Dietary supplements: Lactobacillus is added as an active ingredient in many health supplements and probiotic products to improve intestinal health and overall health. Clinical applications: In some cases, lactobacillus may be used to assist in the treatment of certain digestive system diseases and immune system-related diseases. Animal feed: In the livestock industry, lactobacillus can be used as a feed additive to promote animal health and improve growth efficiency.

[0003] Type 2 diabetes mellitus (T2DM) is a chronic disease that affects the global population. Its treatment goals are mainly to control blood sugar levels, prevent complications, and improve the quality of life of patients. At present, the treatment status of type 2 diabetes includes the following aspects: (1) Lifestyle intervention: diet management, exercise and weight management. (2) Drug treatment: oral hypoglycemic drugs, such as sulfonamides, and when oral drugs are ineffective, insulin treatment can be used. (3) Monitoring and follow-up: blood sugar testing and complication screening. Although the current treatment methods have achieved some success, there are still the following shortcomings: (1) Insufficient individualized treatment: The disease progression and response to drugs vary from patient to patient, and the treatment plan is often not personalized, resulting in unsatisfactory efficacy. (2) Drug side effects: Many hypoglycemic drugs may cause side effects, such as weight gain and hypoglycemia, making it difficult for patients to adhere to treatment. (3) Lack of psychological support: Diabetic patients often face psychological and emotional problems, such as anxiety and depression, but there are few related psychological support and intervention measures. (4) Insufficient education and publicity: Many patients lack sufficient knowledge of diabetes and self-management ability, which affects the treatment effect. (5) Economic burden: Some new drugs and treatments are expensive and difficult for patients with limited financial resources to afford. Overall, the treatment of type 2 diabetes is improving, but further improvements are needed in personalized treatment, drug side effect management, and patient psychological care.

[0004] Fatty liver is a disease caused by various reasons, such as genetic susceptibility, environmental factors and metabolic stress, with the basic pathological feature of fatty liver in liver cells. It can be divided into alcoholic fatty liver disease, non-alcoholic fatty liver disease and special types of fatty liver, among which non-alcoholic fatty liver disease is the most common.

[0005] Research on the use of probiotics to treat type 2 diabetes and fatty liver is still ongoing. Although there are some positive results, there are also some shortcomings and limitations: (1) Inconsistent research results: At present, the research results on the effects of probiotics on patients with type 2 diabetes and fatty liver are not unified. Some studies show that probiotics can improve blood sugar control, but some studies have not found significant effects. (2) Lack of standardization: There is a lack of unified standards for the type, dosage and duration of use of probiotics, which makes it difficult to compare different studies and affects the reproducibility of results. (3) Individual differences: Different individuals may have large differences in their responses to probiotics. Some people may not see obvious effects from probiotic supplementation or may even experience discomfort. (4) Potential side effects: Although probiotics are generally considered safe, in some cases, such as people with impaired immune systems, side effects such as infection may occur. In addition, large intake of certain probiotics may cause problems such as indigestion. (5) Failure to replace drug treatment: Probiotics cannot replace traditional diabetes treatments such as diet control, exercise and drug treatment. Reliance on probiotics may cause patients to ignore other effective treatments. (6) Long-term effects are still unclear: Data on the safety and effectiveness of long-term use of probiotics is still insufficient, and more long-term studies are necessary to evaluate its potential risks and benefits. (7) Cost issues: Some probiotic products are expensive, and long-term use may bring financial burdens to some patients with limited financial conditions.

[0006] In summary, although probiotics may have some potential in the management of type 2 diabetes and fatty liver, caution is needed when using them. Summary of the invention

[0007] Therefore, the technical problem to be solved by the present invention is to overcome the problem in the prior art of lacking a probiotic that is effective in treating type 2 diabetes and fatty liver.

[0008] To solve the above technical problems, the present invention provides an application of Lactobacillus murins. The probiotics of the present invention select Lactobacillus murins (Ligilactobacillus murins DSM 28683), and by gavage of Lactobacillus murins DSM 28683 to T2D mice, it is found that the probiotics can significantly improve the metabolism of T2D mice, effectively improve the insulin sensitivity of T2D mice, reduce body weight, and improve fatty liver, and has good application prospects in the treatment of type 2 diabetes and fatty liver.

[0009] The first object of the present invention is to provide an application of Ligilactobacillus murins in preparing a product for treating type 2 diabetes.

[0010] Furthermore, the product for treating type 2 diabetes is achieved by improving insulin sensitivity.

[0011] The second object of the present invention is to provide a use of Ligilactobacillus murins in preparing a product for treating fatty liver.

[0012] Furthermore, the product for treating fatty liver is achieved by reducing body fat.

[0013] Furthermore, the Lactobacillus murins is Ligilactobacillus murins DSM 28683.

[0014] Furthermore, the application is to prepare the Ligilactobacillus murins DSM 28683 into a medicine containing the Ligilactobacillus murins DSM 28683.

[0015] Furthermore, the medicine is an oral preparation.

[0016] Furthermore, the application is a bacterial agent containing the Lactobacillus murins DSM28683.

[0017] Furthermore, the viable count of the Lactobacillus murins DSM 28683 in the bacterial agent is not less than 1×10 8 CFU / g.

[0018] Furthermore, the bacterial agent is in solid or liquid state.

[0019] Beneficial effects of the present invention:

[0020] The present invention effectively solves the problems in traditional treatment methods for type 2 diabetes and fatty liver, such as the inability of patients to adhere to long-term dietary control and the adverse reactions of drugs to the patient's gastrointestinal tract. In addition, traditional treatment methods are usually accompanied by a large loss of muscle mass in patients and cannot improve the fatty liver phenomenon of patients. Oral administration of the probiotic Ligilactobacillus murins DSM 28683 significantly increased the metabolic rate of T2D mice, improved insulin sensitivity, and effectively curbed weight loss and muscle mass loss, and achieved the effect of weight loss and improvement of fatty liver. The application of this technology will greatly improve the blood sugar control and overall health of patients. At the same time, it has a low risk of hypoglycemia, and has broad application prospects and industry leadership. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In order to make the content of the present invention more clearly understood, the present invention is further described in detail below according to specific embodiments of the present invention in conjunction with the accompanying drawings, wherein

[0022] Figure 1 is a flow chart of intragastric administration of the probiotic Ligilactobacillus murins DSM 28683 of the present invention to T2D mice;

[0023] Figure 2 This is a comparison of the differences in body shape and weight between T2D mice in the Saline group and the Ligi group;

[0024] Figure 3 The body composition of different groups of T2D mice was analyzed and measured using a body fat analyzer;

[0025] Figure 4 It is a measure of insulin sensitivity;

[0026] Figure 5 This is a comparison of liver morphology and weight of T2D mice gavaged with Ligi and normal saline. DETAILED DESCRIPTION

[0027] The present invention is further described below in conjunction with the accompanying drawings and specific embodiments so that those skilled in the art can better understand the present invention and implement it, but the embodiments are not intended to limit the present invention.

[0028] Example 1: Feeding of T2D mice

[0029] Leptin receptor knockout T2D mice purchased from Cytox were housed in the Animal Husbandry Center of China Agricultural University (Suzhou) with free access to acidified water and standard rodent chow (irradiated and autoclaved). All animal care and experimental use were performed in accordance with protocols approved by the Animal Care and Use Committee of Civil Aviation University of China. Animals were housed on a 12-h light / dark cycle with free supply of food and water, and the temperature (22 ± 2 °C) and humidity (40%-60%) were kept constant. This animal study was conducted in accordance with the ARRIVE guidelines.

[0030] Example 2: Cultivation of Ligilactobacillus murins

[0031] Ligilactobacillus murins DSM 28683 was cultured under laboratory conditions. The specific culture method was as follows: Ligilactobacillus murins DSM 28683 bacteria were cultured on brain heart infusion broth (BHI) plates supplemented with mucin and placed in anaerobic culture bags (bio-72771, China Biopharmaceutical Co., Ltd.) with carbon dioxide generation bags (bio-72870, China Biopharmaceutical Co., Ltd.) and oxygen sensors (bio-56236, China Biopharmaceutical Co., Ltd.). After 3 days of culture, bacterial colonies were scraped and washed with sterile saline, and finally resuspended in sterile saline at a concentration of OD 600 = 1 and stored at -80°C until use.

[0032] Example 3: Ligilactobacillus murins DSM 28683 can reduce body weight in T2D mice

[0033] The mouse combined lactobacillus murins DSM 28683 obtained in Example 2 was gavaged into T2D mice every other day through a curved stainless steel feeding needle (12G, 55 mm). The T2D mouse group gavaged with saline was called the Saline group, and the T2D mouse group gavaged with Ligilactobacillus murins DSM 28683 bacteria was called the Ligi group. After two months of gavage, it was found that the body shape and weight of the two groups of mice were significantly different, as shown in Figure 2. Figure 2 As shown, T2D mice gavaged with Ligilactobacillus murins DSM 28683 had a significant decrease in body weight. The LF50 body composition analyzer was used to measure body fat and lean body mass in the control group and T2D mice gavaged with Ligilactobacillus murins DSM 28683 bacteria. The specific operation steps are as follows: T2D mice are placed in a specially sized transparent plastic stand without sedation or anesthesia. The stand is then inserted into the tubular space on the side of the small nuclear magnetic resonance LF50 system. In order to ensure the accuracy of the scanning results, the mice are forced to not move in the stand. Each scan takes about 80 seconds. The scanning results are statistically analyzed as shown below. Figure 3 As shown, the body weight and adipose tissue weight of T2D mice gavaged with Ligilactobacillus murins DSM 28683 were significantly reduced, but the difference in lean body weight was not significant. At the same time, it was found that the tissue weight of iWAT and eWAT in adipose tissue was significantly reduced.

[0034] Example 4: Ligilactobacillus murins DSM 28683 can improve insulin sensitivity and fatty liver in T2D mice

[0035] In the ITT test, T2D mice were fasted for 6 hours and then intravenously injected with 10 μL / g body weight of insulin (4 μg / mL). Blood glucose concentration in tail vein blood was measured by a blood glucose meter (Accu-Chek Active; Roche, Switzerland) at 0, 30, 60, 90 and 120 minutes after injection. Mice were randomly housed in single cages throughout the entire process of each experiment. The results of the ITT experiment are shown in Figure 2. Figure 4 As shown in the results, the insulin sensitivity of T2D mice gavaged with Ligilactobacillus murins DSM 28683 was significantly higher than that of T2D mice gavaged with normal saline. And when the mice were dissected, it was found that the fatty liver phenomenon of T2D mice was significantly improved after gavage with Ligi, and the liver weight was significantly lower than that of the control group ( Figure 5 ).

[0036] Obviously, the above embodiments are merely examples for clear explanation and are not intended to limit the implementation methods. For those skilled in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation methods here. The obvious changes or modifications derived from these are still within the protection scope of the invention.

Claims

1. Application of Lactobacillus murins in the preparation of products for treating type 2 diabetes.

2. The use according to claim 1, characterized in that: The product for treating type 2 diabetes is achieved by improving insulin sensitivity.

3. Application of Ligilactobacillus murins in the preparation of products for treating fatty liver.

4. The use according to claim 1, characterized in that: The product for treating fatty liver is achieved by reducing body fat.

5. The use according to any one of claims 1 to 4, characterized in that: The mouse lactobacillus is Ligilactobacillus murins DSM 28683.

6. The use according to claim 5, characterized in that: The application is to prepare the Ligilactobacillus murins DSM 28683 into a medicine containing the Ligilactobacillus murins DSM 28683.

7. The use according to claim 6, characterized in that: The medicine is an oral preparation.

8. The use according to claim 5, characterized in that: The application is a bacterial agent containing the Ligilactobacillus murins DSM 28683.

9. The use according to claim 8, characterized in that: The viable count of the Lactobacillus murins DSM 28683 in the bacterial agent is not less than 1×10 8 CFU / g.

10. The use according to claim 9, characterized in that: The bacterial agent is in solid or liquid state.

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