Space bacteria bacillus subtilis CEGF-TKJ-005 and hypolipidemic preparation

Abstract

The present application relates to a kind of space bacteria Bacillus subtilis CEGF-TKJ-005 and hypolipidemic preparation, the space bacteria Bacillus subtilis CEGF-TKJ-005 is by the Bacillus subtilis subsp.subtilis CEGF012 strain with preservation number CCTCC NO:M20241702 is obtained by space mutagenesis, its classification designation is Bacillus subtilis CEGF-TKJ-005, preservation number is CCTCC NO:M2025502, and preservation date is March 17, 2025.The fermentation mixture obtained by using the space bacteria Bacillus subtilis CEGF-TKJ-005 to Cistanche is fermented with obvious hypolipidemic effect, can be used for preparing hypolipidemic preparation, can be used for preventing the cardiovascular disease caused by hyperlipidemia.

Description

Technical Field

[0001] This invention relates to the technical field of microbial preservation, and more specifically to a space bacterium, Bacillus subtilis CEGF-TKJ-005, and a lipid-lowering preparation. Background Technology

[0002] Dyslipidemia poses a wide and profound threat to health, primarily affecting the cardiovascular and metabolic systems and multiple organs, and is closely related to various diseases. For example, dyslipidemia is a significant risk factor for cardiovascular and cerebrovascular diseases, with a close correlation between the two. In China, approximately 3.5 million people die from cardiovascular and cerebrovascular diseases each year, with over 50% of these deaths related to dyslipidemia. Dyslipidemia is mainly characterized by elevated total cholesterol (T-CHO), triglycerides (TG), or low-density lipoprotein cholesterol (LDL-C), and decreased high-density lipoprotein cholesterol (HDL-C). Elevated triglyceride levels may affect blood viscosity, slowing blood flow and increasing the risk of thrombosis. Furthermore, dyslipidemia often promotes obesity and insulin resistance, increasing the risk of diabetes, fatty liver, and hyperuricemia. Therefore, early intervention for dyslipidemia is beneficial in reducing the risk of cardiovascular and cerebrovascular events and metabolic complications.

[0003] Current methods for lowering blood lipids include lifestyle interventions and drug therapy, with drug therapy including statins, fibrates, or niacin. Statins, such as simvastatin tablets, are mainly for high LDL-C, while fibrates or niacin are mainly for hypertriglyceridemia. However, lipid-lowering drugs have certain side effects, including abnormal liver function, muscle pain, gastrointestinal reactions, abnormal blood sugar, and allergic reactions. For example, statins may cause muscle toxicity, abnormal liver function, headache, gastrointestinal discomfort (nausea, diarrhea), and allergic reactions (rash), and long-term use may increase the risk of diabetes. Fibrates may cause liver dysfunction such as elevated transaminases, muscle toxicity, and may worsen proteinuria in patients with renal insufficiency, as well as gastrointestinal adverse reactions such as bloating, abdominal pain, and diarrhea. Niacin may increase insulin resistance, and high doses can lead to hepatitis. Therefore, researching a formulation with fewer side effects that can effectively lower blood lipids, especially one suitable for different types of dyslipidemia, would help reduce the risk of cardiovascular and cerebrovascular diseases. Summary of the Invention

[0004] To address the aforementioned deficiencies or improvement needs of existing technologies, this invention provides a space-bred bacterium, Bacillus subtilis CEGF-TKJ-005, and a lipid-lowering preparation. The purpose is to discover that a new strain, Bacillus subtilis subsp. subtilis CEGF012 (accession number CCTCC NO:M20241702), was obtained through space mutagenesis and named Bacillus subtilis CEGF-TKJ-005. The fermentation mixture obtained by fermenting Cistanche deserticola using this space-bred bacterium exhibits significant lipid-lowering effects and can be used to prepare lipid-lowering preparations, thereby solving the technical problems of limited application and certain side effects of existing lipid-lowering drugs.

[0005] To achieve the above objectives, according to one aspect of the present invention, a space-bred bacterium, Bacillus subtilisCEGF-TKJ-005, is provided. This bacterium is obtained by space mutagenesis of the Bacillus subtilis subsp. subtilis CEGF012 strain with accession number CCTCC NO:M 20241702. It is classified as Bacillus subtilisCEGF-TKJ-005, with accession number CCTCC NO:M2025502 and accession date of March 17, 2025.

[0006] According to another aspect of the present invention, a combined microbial agent is also provided, comprising the space bacterium Bacillus subtilis CEGF-TKJ-005 as described in the present invention.

[0007] According to another aspect of the present invention, the application of space bacterium Bacillus subtilis CEGF-TKJ-005 in the preparation of lipid-lowering preparations is also provided.

[0008] Preferably, in the application, the space bacterium Bacillus subtilis CEGF-TKJ-005 is used to carry out solid-state fermentation of Cistanche deserticola, and the fermentation mixture obtained after maturation is used to prepare a lipid-lowering preparation.

[0009] Preferably, in the application, the fermentation mixture comprises Bacillus subtilis CEGF-TKJ-005 cells and the product of fermentation and decomposition of Cistanche deserticola.

[0010] According to another aspect of the present invention, a lipid-lowering preparation is also provided, comprising the Bacillus subtilis CEGF-TKJ-005 bacterial cells as described in the present invention and the product of fermentation and decomposition of Cistanche deserticola, wherein the fermentation of Cistanche deserticola is carried out by solid-state fermentation with Bacillus subtilis CEGF-TKJ-005.

[0011] Preferably, the formulation is used to lower triglycerides, total cholesterol, and / or low-density lipoprotein cholesterol.

[0012] Preferably, the preparation comprises Bacillus subtilis CEGF-TKJ-005 cells and the product of solid-state fermentation of Cistanche deserticola for 24 hours, and is used to lower triglycerides at a dosage of 32 mg / kg or more per day.

[0013] Preferably, the preparation comprises Bacillus subtilis CEGF-TKJ-005 cells and the product of solid-state fermentation of Cistanche deserticola for 24 hours, and is used to lower total cholesterol at a dosage of 113 mg / kg or more per day.

[0014] Preferably, the preparation comprises Bacillus subtilis CEGF-TKJ-005 cells and the product of solid-state fermentation of Cistanche deserticola for 24 hours, and is used to lower low-density lipoprotein cholesterol at a dosage of 64 mg / kg or more per day.

[0015] Overall, the above-described technical solutions conceived by this invention can achieve the following beneficial effects compared with the prior art.

[0016] The space-malignant bacterium Bacillus subtilis CEGF-TKJ-005 provided in this invention is obtained by space mutagenesis of strain Bacillus subtilis subsp. subtilis CEGF012 with accession number CCTCC NO:M20241702. It has been deposited at the China Center for Type Culture Collection (Wuhan University Collection Center) with accession number CCTCC NO:M 2025502, classified as Bacillus subtilis CEGF-TKJ-005, and deposited on March 17, 2025. When used to ferment Cistanche deserticola, the fermentation mixture obtained by fermenting Cistanche deserticola with the space-mutated space-malignant bacterium Bacillus subtilis CEGF-TKJ-005 showed a significant lipid-lowering effect compared to commercially available standard strains. It can be used to prepare lipid-lowering preparations applicable to different types of dyslipidemia. Attached Figure Description

[0017] Figure 1 The effect of Bacillus subtilis CEGF-TKJ-005 fermentation product on serum lipid levels. Detailed Implementation

[0018] To further illustrate the technical means and effects of the present invention in achieving its intended purpose, the following detailed description of the specific implementation methods, structures, features, and effects of the present invention, in conjunction with the accompanying drawings and preferred embodiments, is provided below.

[0019] This invention obtains space-bred Bacillus subtilis by space mutagenesis from a Bacillus subtilis strain screened from the Populus euphratica forest in the Taklamakan Desert of Xinjiang. The space-bred Bacillus subtilis was then deposited at the China Center for Type Culture Collection (CCCCC) at No. 299 Bayi Road, Wuchang District, Wuhan City, Hubei Province (Wuhan University Collection Center). The space-bred Bacillus subtilis is classified as Bacillus subtilis CEGF-TKJ-005, with accession number CCTCC NO:M2025502 and deposit date of March 17, 2025.

[0020] Furthermore, we studied its efficacy through animal experiments. The results showed that the fermented mixture of Cistanche deserticola obtained by fermenting Cistanche deserticola with the space bacterium Bacillus subtilis CEGF-TKJ-005 had a significant effect on lowering triglycerides, total cholesterol, and low-density lipoprotein cholesterol. It can be applied to different types of dyslipidemia and can be used to prepare lipid-lowering preparations.

[0021] Based on this, the present invention provides a space bacterium, Bacillus subtilis CEGF-TKJ-005, which was obtained by space mutagenesis of Bacillus subtilis subsp. subtilis CEGF012 strain with accession number CCTCC NO:M 20241702. Its classification name is Bacillus subtilis CEGF-TKJ-005, accession number is CCTCC NO:M2025502, and accession date is March 17, 2025.

[0022] In addition, the present invention also provides a combined bacterial agent, which includes the space bacterium Bacillus subtilis CEGF-TKJ-005 as described in the present invention.

[0023] In addition, the present invention also provides the application of the space bacterium Bacillus subtilis CEGF-TKJ-005 as described in the present invention in the preparation of lipid-lowering preparations.

[0024] In some embodiments of the application described herein, the space-bred bacterium Bacillus subtilis CEGF-TKJ-005 is used to perform solid-state fermentation of Cistanche deserticola, and the fermentation mixture obtained after maturation is used to prepare a lipid-lowering preparation. The fermentation mixture comprises Bacillus subtilis CEGF-TKJ-005 cells and the products from the fermentation and decomposition of Cistanche deserticola.

[0025] In some embodiments, the fermentation mixture is prepared by solid-state fermentation for 24 hours and maturation for 20 hours.

[0026] According to another aspect of the present invention, a lipid-lowering preparation is also provided, comprising the Bacillus subtilis CEGF-TKJ-005 bacterial cells as described in the present invention and the product of fermentation and decomposition of Cistanche deserticola, wherein the fermentation of Cistanche deserticola is carried out by solid-state fermentation with Bacillus subtilis CEGF-TKJ-005.

[0027] The formulations described in this invention are used to lower triglycerides, total cholesterol, and / or low-density lipoprotein cholesterol. In some embodiments, the formulations comprise Bacillus subtilis CEGF-TKJ-005 cells and the product of solid-state fermentation of Cistanche deserticola for 24 hours, used to lower triglycerides at a dosage of 32 mg / kg or more per day; to lower total cholesterol at a dosage of 113 mg / kg or more per day; and to lower low-density lipoprotein cholesterol at a dosage of 64 mg / kg or more per day.

[0028] Cistanche deserticola is

[0029] The fermentation mixture obtained by fermenting Cistanche deserticola with Bacillus subtilis CEGF-TKJ-005 bacteria as described in this invention has high safety and few side effects.

[0030] The following are examples.

[0031] Example 1: Space-induced mutagenesis of Bacillus subtilis

[0032] Bacillus subtilis (strain CCTCC NO: M20241702, Bacillus subtilis subsp. subtilis CEGF012), screened from poplar forests in the Taklamakan Desert of Xinjiang, was obtained by space mutagenesis after being returned to Earth via a spacecraft. The space-bred Bacillus subtilis (space breeding number: CEGF-TKJ-005) was then isolated and purified and deposited at the China Center for Type Culture Collection (Wuhan University Collection Center), No. 299 Bayi Road, Wuchang District, Wuhan City, Hubei Province, with accession number CCTCC NO: M 2025502, classified and named Bacillus subtilis CEGF-TKJ-005, and the deposit date is March 17, 2025.

[0033] Example 2: Fermentation of Cistanche deserticola using space-bred Bacillus subtilis CEGF-TKJ-005

[0034] Solid-state fermentation of Cistanche deserticola was carried out using Bacillus subtilis CEGF-TKJ-005 with accession number CCTCC NO:M 2025502. Cistanche deserticola was used as the main raw material, and the mixture was prepared by mixing Cistanche deserticola with a nitrogen source (chickpea) at a mass ratio of 50–83:17–50. After sterilization, the mixture was inoculated with the space-bred Bacillus subtilis CEGF-TKJ-005 with accession number CCTCC NO:M 2025502. Solid-state fermentation was carried out at a suitable temperature for 24–36 hours. After maturation, the product was freeze-dried and pulverized into powder to obtain the fermented product of space-bred Bacillus subtilis CEGF-TKJ-005.

[0035] The fermented product of the space bacterium Bacillus subtilis CEGF-TKJ-005 is a fermented mixture of Cistanche deserticola, which includes the Bacillus subtilis CEGF-TKJ-005 cells and the products of fermentation and decomposition of Cistanche deserticola.

[0036] Example 3: The fermentation product of space bacterium Bacillus subtilis CEGF-TKJ-005 has a lipid-lowering effect.

[0037] Total cholesterol (T-CHO, abbreviated TC) refers to the sum of cholesterol contained in all lipoproteins in the blood, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and very low-density lipoprotein cholesterol (VLDL-C). The measurement of total cholesterol is one of the important indicators in blood lipid tests, often used to assess the risk of cardiovascular disease. Low-density lipoprotein cholesterol (LDL-C) is a complex formed by the binding of low-density lipoprotein and cholesterol, and is known as "bad cholesterol." Elevated levels of LDL-C have many adverse effects on human health, such as increasing the risk of cardiovascular and cerebrovascular diseases and dyslipidemia. Hyperlipidemia is a common metabolic disease, and its diagnostic criteria are: fasting serum total cholesterol (TC) ≥ 5.2 mmol / L, triglycerides (TG) ≥ 1.7 mmol / L, or low-density lipoprotein cholesterol (LDL-C) ≥ 4.14 mmol / L. Hypercholesterolemia is defined as a fasting serum total cholesterol (TC) level exceeding 5.2 mmol / L, hypertriglyceridemia is defined as a triglyceride (TG) level ≥1.7 mmol / L, and mixed hyperlipidemia is defined as both being elevated.

[0038] To investigate the efficacy of the fermentation product of the space bacterium Bacillus subtilis CEGF-TKJ-005, its effect on serum lipid levels was studied using a hyperlipidemic animal model. The specific experimental details are as follows:

[0039] (1) Experimental materials: 8-week-old APOE (- / -) male mice, SPF grade, single mouse weight 18-22g, D12108C high-fat diet (containing 1.25% cholesterol), normal diet (cholesterol-free);

[0040] Space bacterium Bacillus subtilis CEGF-TKJ-005 fermentation product: Following the method in Example 2, the inoculum amount was 6%, solid fermentation was carried out for 24 hours, maturation was carried out for 20 hours, and after freeze drying, it was pulverized into powder to obtain the space bacterium Bacillus subtilis CEGF-TKJ-005 fermentation mixture.

[0041] The Bacillus subtilis standard strain fermentation product was obtained by fermenting Cistanche deserticola with commercially available Bacillus subtilis standard strain according to the same ratio and fermentation process to obtain a fermentation mixture.

[0042] (2) Experimental Grouping

[0043] All mice underwent a one-week acclimatization diet and were housed separately in a pathogen-free environment with a 12-hour light and 12-hour dark cycle daily. The indoor humidity was maintained at 50%-60%, and the indoor temperature at 20-24°C. Free access to water and food was provided. After one week of acclimatization, the mice were randomly assigned to groups of 6 mice each, as follows:

[0044] Group 1 was the healthy control group: fed with normal feed for 10 weeks;

[0045] Group 2 was the model group: a hyperlipidemia model was established by feeding the patients a high-fat diet for 10 weeks;

[0046] Group 3 was the low-dose drug group: fed with high-fat feed + 0.4g / kg / time of space bacteria Bacillus subtilis CEGF-TKJ-005 fermentation product;

[0047] Group 4 was the medium-dose drug group: fed with high-fat feed + 0.8g / kg / time of space bacteria Bacillus subtilis CEGF-TKJ-005 fermentation product;

[0048] Group 5 was the high-dose drug group: fed with high-fat feed + 1.4g / kg / sub-times of Bacillus subtilis CEGF-TKJ-005 fermentation product;

[0049] Group 6 was the positive control group: fed a high-fat diet plus simvastatin tablets 2mg / kg / time;

[0050] Group 7 was the drug control group 1: fed with high-fat diet + Bacillus subtilis bacterial solution 100μL / animal / time;

[0051] Group 8 was the drug control group 2: fed with high-fat feed + unfermented Cistanche deserticola 1g / kg / time;

[0052] Group 9 was the drug control group 3: Bacillus subtilis standard strain fermentation product 1.4g / kg / time;

[0053] After acclimatization, mice in group 1 were fed a normal diet for 10 weeks with normal access to water. Mice in other groups were fasted for one night after acclimatization and then fed a high-fat diet. Group 2 was fed a high-fat diet for 10 weeks to establish a hyperlipidemia animal model. The remaining groups were fed a high-fat diet for 4 weeks and then given equal amounts of high-fat diet and corresponding drugs once a day for 6 weeks with normal access to water.

[0054] (3) Indicator detection:

[0055] ① Weigh yourself

[0056] All mice were weighed once a week, and their weight changes were recorded. The weight changes of mice in each group are shown in Table 1.

[0057] Table 1 Comparison of body weight levels in experimental mice ( n = 6, unit g)

[0058]

[0059] Note: Compared with the healthy control group (Group 1), "a" in the table means "P < 0.05" and "b" means "P < 0.01"; compared with the model group (Group 2), "c" in the table means "P < 0.05" and "d" means "P < 0.01".

[0060] As shown in Table 1, there was no significant difference in the initial weight of mice in each group (P>0.05). After 5 weeks of feeding, compared with the healthy control group, the mice in each group fed with high-fat diet had a faster rate of weight gain.

[0061] After 5 weeks of feeding, compared with the model group, the body weight of mice in groups 3, 4 and 5 treated with Bacillus subtilis CEGF-TKJ-005 fermentation was significantly reduced (P<0.05).

[0062] After 10 weeks of feeding, compared with the model group, the body weight of mice in intervention group 3, which was given Bacillus subtilis CEGF-TKJ-005 fermentation product, was significantly reduced (P < 0.05), while the body weight of mice in intervention groups 4 and 5 was significantly reduced (P < 0.01). This indicates that administration of Bacillus subtilis CEGF-TKJ-005 fermentation product can effectively improve the weight gain induced by a high-fat diet in mice.

[0063] ② Four blood lipid tests

[0064] Ten weeks into the experiment, all mice were fasted for 12 hours prior to the experiment. Blood was collected from the eyeballs, allowed to stand at room temperature for 30 minutes, and then centrifuged at 4°C and 3500 rpm for 10 minutes to obtain serum. Reagent kits produced by Nanjing Jiancheng Bioengineering Institute were used for detection. Specifically, the triglyceride test kit (A110-1-1) was used for TG detection, the total cholesterol test kit (A111-1-1) was used for T-CHO detection, the low-density lipoprotein cholesterol test kit (A113-1-1) was used for LDL-C detection, and the high-density lipoprotein cholesterol test kit (A112-1-1) was used for HDL-C detection. Fasting serum triglyceride (TG), total cholesterol (T-CHO), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were measured according to the kit instructions. The results of the four fasting serum lipid tests for each group of mice are shown below. Figure 1 As shown in the figure, "***" means "P < 0.001", "**" means "P < 0.01", and "*" means "P < 0.05".

[0065] The core evaluation indicators for animal models of hyperlipidemia are the serum levels of total cholesterol (T-CHO), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Changes in these indicators can reflect whether the model has been successfully established. For example, in mouse models induced by a high-fat diet, a significant increase in serum TC, TG, or LDL-C levels indicates that the hyperlipidemia model has been successfully established.

[0066] Depend on Figure 1 The results showed that, compared with the healthy control group, the model group mice had significantly higher levels of triglycerides (TG), cholesterol (T-CHO), and low-density lipoprotein cholesterol (LDL-C), indicating that the hyperlipidemia model was successfully established in this study. Compared with the model group mice, intervention with Bacillus subtilis CEGF-TKJ-005 fermentation product significantly reduced blood lipid levels in a dose-dependent manner.

[0067] Compared to the model group, administration of Bacillus subtilis CEGF-TKJ-005 fermentation product at doses of 0.4 g / kg or higher significantly reduced serum triglyceride levels. Specifically, group 3 (administered 0.4 g / kg of Bacillus subtilis CEGF-TKJ-005 fermentation product) showed a similar reduction effect to group 6 (administered with the positive control drug simvastatin tablets), group 4 (administered 0.8 g / kg of Bacillus subtilis CEGF-TKJ-005 fermentation product) showed a slightly better reduction effect than group 6, and group 5 (administered 1.4 g / kg of Bacillus subtilis CEGF-TKJ-005 fermentation product) showed a significantly better reduction effect than group 6. Furthermore, compared to group 9, which contains commercially available standard strain fermentation product, the fermentation product obtained using Bacillus subtilis CEGF-TKJ-005 fermentation product at the same dose significantly further reduced serum triglyceride levels.

[0068] Compared to the model group, administration of Bacillus subtilis CEGF-TKJ-005 fermentation product at doses of 1.4 g / kg or higher significantly reduced serum total cholesterol levels. Among them, group 5 (administered with 1.4 g / kg of Bacillus subtilis CEGF-TKJ-005 fermentation product) showed a better reduction effect than group 6 (administered with positive control drug). Administration of the same dose of standard strain fermentation product had almost no effect on serum total cholesterol levels. Administration of Bacillus subtilis CEGF-TKJ-005 bacterial solution or Cistanche deserticola alone did not show a reduction effect on serum total cholesterol levels.

[0069] Compared to the model group, administration of Bacillus subtilis CEGF-TKJ-005 fermentation product at doses of 0.8 g / kg or higher significantly reduced serum low-density lipoprotein cholesterol (LDL-C) levels. Group 4 (administered with 0.8 g / kg of Bacillus subtilis CEGF-TKJ-005 fermentation product) showed a similar reduction effect to the positive control group 6, while Group 5 (administered with 1.4 g / kg of Bacillus subtilis CEGF-TKJ-005 fermentation product) showed a better reduction effect than the positive control group 6. Administration of the same dose of standard strain fermentation product, or administration of only Bacillus subtilis CEGF-TKJ-005 bacterial solution or Cistanche deserticola, did not show a reduction effect on serum LDL-C levels.

[0070] Compared to the model group, serum high-density lipoprotein cholesterol increased after each drug intervention, with group 5 (treated with 1.4 g / kg of Bacillus subtilis CEGF-TKJ-005 fermentation product) showing better results than other groups.

[0071] In summary, the fermented product obtained by fermenting Cistanche deserticola using the space-bred Bacillus subtilis CEGF-TKJ-005 has the effect of lowering triglycerides, total cholesterol, and low-density lipoprotein cholesterol, and can be used to prepare lipid-lowering preparations. Simultaneously, it can also increase the level of high-density lipoprotein cholesterol (HDL-C), which is considered "good cholesterol" and can reduce cholesterol deposition on blood vessel walls. Increased HDL-C levels help reduce the risk of cardiovascular diseases such as atherosclerosis.

[0072] Based on the "Equivalent Dose Conversion Between Animals and Between Animals and Humans in Pharmacological Experiments" published by Huang Jihan et al., according to the dose conversion table from animal a to animal b for standard-weight animals (the values ​​in the table are conversion coefficients Rab), the Rab value for mouse row a and adult column b is 0.081. Therefore, the adult dose can be converted by multiplying the mouse dose by 0.081. For lowering triglycerides, a dosage of 32 mg / kg or more per day can be used; for lowering total cholesterol, a dosage of 113 mg / kg or more per day can be used; and for lowering LDL cholesterol, a dosage of 64 mg / kg or more per day can be used. Because the fermented mixture obtained by fermenting Cistanche deserticola using the space bacterium Bacillus subtilis CEGF-TKJ-005 has high safety and can be used long-term, it has fewer side effects than existing lipid-lowering drugs and is applicable to different types of dyslipidemia.

[0073] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A space bacterium, Bacillus subtilis CEGF-TKJ-005, characterized in that, The strain Bacillus subtilis subsp. subtilis CEGF012 with accession number CCTCCNO:M 20241702 was obtained through space mutagenesis. It was classified as Bacillus subtilis CEGF-TKJ-005 with accession number CCTCC NO:M 2025502 and accession date of March 17, 2025.

2. A combined microbial agent, characterized in that, Includes the space bacterium Bacillus subtilis CEGF-TKJ-005 as described in claim 1.

3. Application of Bacillus subtilis CEGF-TKJ-005, a space bacterium, in the preparation of lipid-lowering agents.

4. The application as described in claim 3, characterized in that, The space bacterium Bacillus subtilis CEGF-TKJ-005 was used to carry out solid-state fermentation of Cistanche deserticola. The fermentation mixture obtained after maturation was used to prepare lipid-lowering preparations.

5. The application as described in claim 4, characterized in that, The fermentation mixture includes Bacillus subtilis CEGF-TKJ-005 cells and the products of fermentation and decomposition of Cistanche deserticola.

6. A lipid-lowering preparation, characterized in that, It includes the Bacillus subtilis CEGF-TKJ-005 bacterial cells as described in claim 1 and the products after fermentation and decomposition of Cistanche deserticola, wherein the fermentation of Cistanche deserticola is carried out by solid-state fermentation with Bacillus subtilis CEGF-TKJ-005.

7. The formulation according to claim 6, characterized in that, The formulation is used to lower triglycerides, total cholesterol, and / or low-density lipoprotein cholesterol.

8. The formulation as described in claim 7, characterized in that, The preparation comprises Bacillus subtilis CEGF-TKJ-005 cells and the product of solid-state fermentation of Cistanche deserticola for 24 hours, and is used to lower triglycerides. The dosage is above 32 mg / kg per day.

9. The formulation as described in claim 7, characterized in that, The preparation comprises Bacillus subtilis CEGF-TKJ-005 cells and the product of solid-state fermentation of Cistanche deserticola for 24 hours, and is used to lower total cholesterol. The dosage is above 113 mg / kg per day.

10. The formulation of claim 7, characterized in that, The preparation comprises Bacillus subtilis CEGF-TKJ-005 cells and the product of solid-state fermentation of Cistanche deserticola for 24 hours, and is used to lower low-density lipoprotein cholesterol. The dosage is above 64 mg / kg per day.

Images