Application of Bifidobacterium animalis TY-S01 in the preparation of products that improve lipid metabolism in obese individuals with suboptimal LDL-C levels

Abstract

This invention belongs to the field of probiotic application technology, specifically relating to the application of Bifidobacterium animalis TY-S01 in the preparation of products that improve lipid metabolism in obese individuals with suboptimal LDL-C. This invention applies Bifidobacterium animalis TY-S01 to obese individuals with suboptimal LDL-C, and a randomized, double-blind, placebo-controlled clinical trial has confirmed that daily supplementation with TY-S01 (3 × 10⁻⁶) for 12 consecutive weeks is effective. 10 CFU significantly reduced serum LDL-C levels in subjects (from 4.14±0.88 mmol / L to 3.84±0.89 mmol / L). P < 0.05) and TC levels (decreased from 5.63±1.12 mmol / L to 5.30±1.10 mmol / L, P < 0.05), while significantly reducing weight and BMI.

Description

Technical Field

[0001] This invention belongs to the field of probiotic application technology, specifically involving the application of Bifidobacterium animalis TY-S01 in the preparation of products that improve lipid metabolism in obese individuals with suboptimal LDL-C. Background Technology

[0002] Obesity has become a global public health crisis. In my country, the overweight rate among adults is 34.3%, and the obesity rate is 16.4%, indicating a serious situation regarding overweight and obesity. Obesity is often accompanied by lipid metabolism disorders, among which elevated low-density lipoprotein cholesterol (LDL-C) is a key risk factor for atherosclerotic cardiovascular disease (ASCVD). Studies have shown that obesity-related dyslipidemia features include elevated total cholesterol (TC), triglycerides (TG), and LDL-C, as well as decreased high-density lipoprotein cholesterol (HDL-C). For obese individuals with suboptimal LDL-C (LDL-C > 3.05 mmol / L but not reaching the threshold for pharmacological intervention), there are currently no safe and effective non-pharmacological interventions.

[0003] Probiotics, as a means of regulating the gut microbiota, have shown potential in improving lipid metabolism disorders. Bifidobacterium animalis and its subspecies have attracted considerable attention in lipid-lowering research due to their excellent bile salt hydrolase activity and intestinal colonization characteristics. However, the lipid-lowering effects of different strains vary significantly, and most studies focus on animal models, lacking high-quality human clinical research evidence. Current technologies have not reported effective probiotic intervention strategies for the specific population of obese individuals with suboptimal LDL-C, and there is a lack of specific strains validated through randomized, double-blind, placebo-controlled clinical trials.

[0004] Therefore, developing a safe, effective probiotic formulation suitable for obese individuals with suboptimal LDL-C levels to reduce their LDL-C and TC levels and improve their weight and BMI is of significant clinical and public health importance. Summary of the Invention

[0005] Based on this, the present invention aims to provide a novel application of Bifidobacterium animalis TY-S01, namely its application in the preparation of products for improving lipid metabolism in obese individuals with suboptimal LDL-C levels. This product can significantly reduce LDL-C and TC levels in obese individuals with suboptimal LDL-C levels, while simultaneously improving weight and BMI, and exhibits good safety profile.

[0006] To achieve the above objectives, the present invention can adopt the following technical solutions: This invention provides the application of Bifidobacterium animalis TY-S01 in the preparation of products that improve lipid metabolism in obese individuals with suboptimal LDL-C. The preservation number of Bifidobacterium animalis TY-S01 is CGMCC No. 21255. Obese individuals with suboptimal LDL-C are those who are obese and whose serum LDL-C level is higher than 3.05 mmol / L but has not reached the threshold for drug intervention.

[0007] Preferably, in the above applications, the form of Bifidobacterium animalis TY-S01 is live cells, inactivated cells, fermentation lysate, or freeze-dried bacterial powder.

[0008] Preferably, in the above applications, improving lipid metabolism in obese individuals with suboptimal LDL-C manifests as one or more of the following: a) Lower serum low-density lipoprotein cholesterol (LDL-C) levels; b) Lower serum total cholesterol (TC) levels; c) Reduce weight; d) Reduce body mass index (BMI).

[0009] Preferably, in the above applications, the viable count of Bifidobacterium animalis TY-S01 in the product is 3 × 10⁻⁶ per dose. 10 CFU.

[0010] Preferably, in the above applications, the product is food, health product, or medicine.

[0011] Preferably, in the above applications, the dosage form of the product is selected from solid beverages, capsules, tablets, granules, powders, or sustained-release formulations.

[0012] Preferably, in the above applications, the product also includes food science, health science, or pharmaceutical science acceptable carriers, excipients, or additives.

[0013] The beneficial effects of this invention include: This invention applies Bifidobacterium animalis TY-S01 to obese individuals with suboptimal LDL-C levels. A randomized, double-blind, placebo-controlled clinical trial confirmed that daily supplementation with TY-S01 (3 × 10⁻⁶) for 12 consecutive weeks is effective. 10 CFU significantly reduced serum LDL-C levels in subjects (from 4.14±0.88 mmol / L to 3.84±0.89 mmol / L). P <0.05) and TC levels (decreased from 5.63±1.12 mmol / L to 5.30±1.10 mmol / L, P < 0.05), while significantly reducing weight and BMI. Attached Figure Description

[0014] Figure 1Analysis of LDL-C results in the TY-S01 group and the placebo group before and after intervention; Figure 2 Analysis of TC results in the TY-S01 group and the placebo group before and after intervention. Detailed Implementation

[0015] The embodiments described are provided to better illustrate the present invention, but are not intended to limit the scope of the invention to the embodiments described. Therefore, non-essential improvements and adjustments made to the embodiments by those skilled in the art based on the above description are still within the scope of protection of the present invention.

[0016] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit this disclosure. Singular expressions include plural expressions unless they have a distinct meaning in the context. As used herein, it should be understood that terms such as “comprising,” “having,” “including,” are intended to indicate the presence of features, numbers, operations, components, parts, elements, materials, or combinations thereof. The terminology of the invention is disclosed in the specification and is not intended to exclude the possibility that one or more other features, numbers, operations, components, parts, elements, materials, or combinations thereof may be present or added. As used herein, “ / ” may be interpreted as “and” or “or,” depending on the context.

[0017] This invention provides an application of Bifidobacterium animalis TY-S01 in the preparation of a product to improve lipid metabolism in obese individuals with suboptimal LDL-C. The preservation number of Bifidobacterium animalis TY-S01 is CGMCC No. 21255. Obese individuals with suboptimal LDL-C are those who are obese and whose serum LDL-C level is higher than 3.05 mmol / L but has not reached the threshold for drug intervention.

[0018] It should be noted that *Bifidobacterium animalis* TY-S01 is a screened and identified functional probiotic strain, deposited at the China General Microbiological Culture Collection Center (CGMCC) with accession number CGMCC No. 21255, and possesses specific physiological activity in regulating lipid metabolism. This application precisely targets a specific population that is obese and has abnormal low-density lipoprotein cholesterol (LDL-C). This population exhibits signs of obesity and serum LDL-C levels exceeding the ideal threshold of 3.05 mmol / L, but has not yet met the criteria for clinical drug intervention. Products prepared using this strain can achieve non-invasive and safe lipid metabolism intervention, filling a market gap where suitable conditioning methods are lacking for this population.

[0019] In some specific examples, in the above applications, Bifidobacterium animalis TY-S01 is in the form of live cells, inactivated cells, fermentation lysates, or lyophilized powder.

[0020] It should be noted that Bifidobacterium animalis TY-S01 can be prepared in four forms, namely live cells, inactivated cells, fermentation lysates, or freeze-dried powder, depending on the product processing technology, storage conditions, and applicable scenarios. Among them, live cells can directly colonize the intestine and exert a regulatory effect, while inactivated cells and fermentation lysates can retain active metabolites to exert physiological effects. Freeze-dried powder has strong stability, is easy to store and process into formulations. All four forms can effectively achieve the core function of improving lipid metabolism, thereby enhancing the flexibility and applicability of product development.

[0021] In some specific examples, the above applications demonstrate that improved lipid metabolism in obese individuals with suboptimal LDL-C results in one or more of the following: a) Lower serum low-density lipoprotein cholesterol (LDL-C) levels; b) Lower serum total cholesterol (TC) levels; c) Reduce weight; d) Reduce body mass index (BMI).

[0022] It should be noted that Bifidobacterium animalis TY-S01 achieves multiple lipid metabolism improvement effects through pathways such as regulating the intestinal flora structure, inhibiting cholesterol absorption, and promoting lipid metabolism. It can work alone or in synergy: reducing serum low-density lipoprotein cholesterol to improve core abnormal indicators, reducing serum total cholesterol to comprehensively regulate blood lipid levels, and at the same time helping to reduce weight and body mass index (BMI), thus improving the metabolic abnormality of obese people with suboptimal LDL-C from both blood lipid and body fat dimensions.

[0023] In some specific examples, in the above applications, the viable count of Bifidobacterium animalis TY-S01 in the product was 3 × 10⁻⁶ per dose. 10 CFU.

[0024] It should be noted that each dose is 3×10 10 CFU is the optimal dosage for adding live bacteria. This dosage ensures that the strains can successfully pass through the gastrointestinal digestive environment and colonize the intestines, thus fully exerting their physiological activity in regulating lipid metabolism. Too low a dosage will not achieve the desired conditioning effect, while too high a dosage will increase production costs without providing additional efficacy benefits. This dosage balances efficacy, safety, and economy.

[0025] In some specific examples, the products in the above applications are food, health products, or medicines.

[0026] It should be noted that, based on the safety and functionality of Bifidobacterium animalis TY-S01, it can be developed into three major categories of products: food, health products, and pharmaceuticals. Food focuses on daily dietary supplementation, health products focus on metabolic regulation for specific populations, and pharmaceuticals focus on clinical intervention. These three types of products can cover all scenarios of daily maintenance, health regulation, and clinical support, thus broadening the application scope of the strain.

[0027] In some specific examples, in the above applications, the dosage form of the product is selected from solid beverages, capsules, tablets, granules, powders, or sustained-release formulations.

[0028] It should be noted that the product can be prepared in various dosage forms such as solid beverages, capsules, tablets, granules, powders, and sustained-release formulations to suit the consumption / taken habits of different groups of people. Among them, solid beverages and powders are easy to prepare and drink, capsules, tablets, and granules are easy to carry and consume in measured quantities, and sustained-release formulations can extend the action time of the bacterial strain. Multiple dosage forms can meet different consumption scenarios and usage needs.

[0029] In some specific examples, the products in the above applications also include food science, health science, or pharmaceutical science acceptable carriers, excipients, or additives.

[0030] It should be noted that the addition of food science, health science, or pharmaceutically acceptable carriers, excipients, or additives to the product can improve its formability, stability, palatability, and shelf life. Examples include fillers, flavoring agents, disintegrants, and preservatives. The excipients do not interact with the strain and do not affect the core function of Bifidobacterium animalis TY-S01. At the same time, it complies with the relevant production standards and safety regulations for food, health products, and pharmaceuticals.

[0031] To better understand the present invention, specific examples are provided below to further illustrate the content of the present invention, but the content of the present invention is not limited to the examples below.

[0032] Example 1: Preparation of Bifidobacterium animalis TY-S01 bacterial powder

[0033] (1) Activation of strain: Bifidobacterium animalis TY-S01 (CGMCC No.21255) was inoculated into MRS liquid medium and cultured anaerobically at 37℃ for 24h. The strain was activated by subculturing twice.

[0034] (2) Fermentation culture: The activated strain was inoculated into the fermentation medium (components: glucose 20g / L, peptone 10g / L, beef extract 10g / L, yeast extract 5g / L, sodium acetate 5g / L, diammonium citrate 2g / L, dipotassium hydrogen phosphate 2g / L, magnesium sulfate 0.2g / L, manganese sulfate 0.05g / L and Tween-80 1mL / L, pH 6.5) at 37℃ and anaerobic static culture for 24h.

[0035] (3) Collection of bacterial cells: After fermentation, the bacterial cells were collected by centrifugation (4℃, 6000rpm, 15min) and washed twice with sterile physiological saline.

[0036] (4) Freeze-drying powder preparation: The bacterial cells were mixed with a freeze-drying protectant (10% skim milk powder, 5% trehalose, and 2% glycerol), pre-frozen at -40℃ for 4 hours, and then freeze-dried under vacuum to obtain TY-S01 freeze-dried bacterial powder; the viable bacteria content in the freeze-dried powder was determined to be 1.5 × 10⁻⁶ by plate count method. 11 CFU / g.

[0037] (5) Preparation of finished product: The freeze-dried bacterial powder is mixed with maltodextrin to make a solid beverage in 2g packets, each packet containing 3.0 × 10 TY-S01 live bacteria. 10 CFU.

[0038] Example 2: Clinical trial of Bifidobacterium animalis TY-S01 in obese individuals with suboptimal LDL-C levels.

[0039] In the following trials, the placebo was a maltodextrin solid beverage without TY-S01, which had the same appearance, taste and packaging as the TY-S01 product.

[0040] (1) Research subjects

[0041] Volunteer participants with obesity and suboptimal LDL-C levels are being recruited. Inclusion criteria: 1) Age 18-65 years; 2) BMI ≥ 28 kg / m². 2 ; 3) Low-density lipoprotein cholesterol > 3.05 mmol / L; 4) No use of weight loss drugs or lipid-lowering drugs in the past 3 months; 5) Voluntary participation in this trial and signing of informed consent form.

[0042] Exclusion criteria: Individuals with mental illness, serious diseases of the heart, liver, kidneys, hematopoietic system, immune system, etc.; pregnant or lactating women; those allergic to the test sample; and those who have used probiotics, antibiotics, or other medications within 4 weeks prior to the start of the study.

[0043] (2) Experimental design

[0044] This study employed a randomized, double-blind, placebo-controlled design. A total of 38 eligible participants were recruited and randomly assigned to either the TY-S01 group (n=19) or the placebo group (n=19). All participants underwent a 2-week fasting period (during which they abstained from all probiotic products), followed by a 12-week intervention period. The TY-S01 group received one packet of TY-S01 solid beverage (containing 3×10⁶ live bacteria) dissolved in warm water after lunch or dinner daily. 10 The CFU group received an equal amount of placebo; during the trial, participants were required to maintain their daily diet and exercise habits and were prohibited from consuming other fermented foods and probiotic supplements.

[0045] (3) Observation indicators

[0046] Lipid indicators: Fasting venous blood was collected before intervention (V0) and 12 weeks after intervention (V3) to measure serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels.

[0047] Body composition metrics: Body composition analyzer is used to measure weight, BMI, body fat percentage, muscle mass, and visceral fat area.

[0048] Safety indicators: Observe the general condition of the subjects (mental state, sleep, diet, bowel movements, etc.), and test blood routine and liver and kidney function indicators in V0 and V3 phases.

[0049] (4) Results

[0050] 1) Baseline balance

[0051] As shown in Table 1, before the intervention, there were no significant differences between the TY-S01 group and the placebo group in terms of gender, age, weight, BMI, body fat percentage, TC, TG, LDL-C, and HDL-C. P (>0.05), the two groups are comparable.

[0052] Table 1. Comparison of basic data between the TY-S01 group and the placebo group before intervention.

[0053] 2) Safety evaluation

[0054] As shown in Table 2, no product-related adverse reactions occurred in either group during the trial. Complete blood counts and liver and kidney function indicators (white blood cells, red blood cells, hemoglobin, platelets, serum total protein, human serum albumin, alanine aminotransferase, aspartate aminotransferase, creatinine, urea) were within the normal range before and after intervention, with no significant differences between groups. P >0.05). This indicates that TY-S01 has good safety.

[0055] Table 2. Analysis of blood routine and liver and kidney function results before and after intervention in the TY-S01 group and the placebo group.

[0056]

[0057] 3) Changes in body composition

[0058] As shown in Table 3, the body weight of the TY-S01 group decreased significantly from 80.34±20.95 kg to 79.47±21.08 kg. P <0.05), BMI from 31.26±7.16 kg / m 2It decreased significantly to 30.90±7.14 kg / m³ 2 ( P < 0.05); there were no significant changes in weight and BMI in the placebo group before and after the intervention. The differences in body composition indicators between the two groups did not reach statistical significance. P > 0.05).

[0059] 4) Changes in blood lipid levels

[0060] As shown in Table 3 and Figure 1 and Figure 2 As shown, after 12 weeks of intervention, the LDL-C level in the TY-S01 group significantly decreased from 4.14±0.88 mmol / L to 3.84±0.89 mmol / L. P < 0.05), TC levels decreased significantly from 5.63±1.12 mmol / L to 5.30±1.10 mmol / L ( P < 0.05); No significant changes were observed in LDL-C and TC before and after intervention in the placebo group ( P > 0.05). The differences in any of the blood lipid indicators between the two groups did not reach statistical significance. P > 0.05).

[0061] Table 3. Analysis of body composition and blood lipid levels in the TY-S01 group and placebo group before and after intervention.

[0062] Note: P 1 indicates a significant difference before and after the intervention within the same group; P 2 indicates a significant difference between the TY-S01 group and the placebo group during the same intervention period.

[0063] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention.

Claims

1. Application of Bifidobacterium animalis TY-S01 in the preparation of products to improve lipid metabolism in obese individuals with suboptimal LDL-C. The preservation number of Bifidobacterium animalis TY-S01 is CGMCC No.21255. Obese individuals with suboptimal LDL-C are obese individuals whose serum LDL-C level is higher than 3.05 mmol / L but has not reached the threshold for drug intervention.

2. The application according to claim 1, characterized in that, Bifidobacterium animalis TY-S01 exists in the form of live cells, inactivated cells, fermentation lysates, or freeze-dried powder.

3. The application according to claim 1 or 2, characterized in that, Improving lipid metabolism in obese individuals with suboptimal LDL-C is achieved by one or more of the following: a) Lower serum low-density lipoprotein cholesterol levels; b) Lower serum total cholesterol levels; c) Reduce weight; d) Reduce body mass index.

4. The application according to claim 1 or 2, characterized in that, The viable count of Bifidobacterium animalis TY-S01 in the product is 3 × 10⁻⁶ per dose. 10 CFU.

5. The application according to claim 1 or 2, characterized in that, The product is food, health supplement, or medicine.

6. The application according to claim 5, characterized in that, The dosage form of the product is selected from solid beverages, capsules, tablets, granules, powders, or sustained-release formulations.

7. The application according to claim 6, characterized in that, The products also include carriers, excipients or additives that are acceptable in terms of food science, health science or pharmaceutical science.

Images