Strain composition for improving metabolic health and immune health and uses thereof

Abstract

The application provides a strain composition for improving metabolic health and immune health and application thereof. The strain composition provided by the application has high safety and wide effect, can fill the vacancy in the existing probiotic agent market, break through the limitation of the existing probiotic agent product, and can provide a new idea for protecting or assisting in protecting liver damage, reducing blood lipids or assisting in reducing blood lipids, reducing blood sugar or assisting in reducing blood sugar, improving cardiovascular health, improving blood lipid metabolism, improving liver lipid metabolism, improving sugar and lipid metabolism, reducing weight or assisting in reducing weight, treating or assisting in treating postpartum obesity, resisting inflammation, improving immune health, enhancing immunity and the like.

Description

Technical Field

[0001] This invention relates to the field of microbial technology, and more particularly to a bacterial strain composition that improves metabolic and immune health and its application. Background Technology

[0002] Postpartum obesity is a condition caused by hypothalamic dysfunction due to pregnancy, resulting in abnormal fat metabolism and a sudden increase in body fat, leading to weight gain and obesity. Medically, this phenomenon is also known as "reproductive obesity" or "maternal obesity syndrome," a common postpartum pathological response. Postpartum obesity not only affects a woman's physical appearance but also has many adverse effects on her physical and mental health, easily inducing postpartum depression, anxiety, and other emotional problems, causing a series of physiological and psychological distresses. Furthermore, it is important to note that research shows that the gut microbiota of offspring in early life mainly originates from the mother's gut and breast milk. Obese mothers often experience a decrease in both the quantity and diversity of their gut microbiota. This change further affects the colonization process of offspring's gut microbiota, thereby increasing the risk of metabolic and neurodevelopmental diseases in their offspring.

[0003] Given the various adverse effects of postpartum obesity, research and intervention for this condition have significant practical implications and application value. Summary of the Invention

[0004] This invention provides a bacterial strain composition that is highly safe and has a wide range of applications.

[0005] This invention provides the application of the above-mentioned bacterial composition in the preparation of related products for protecting or assisting in the protection of liver damage, weight loss or assisting in weight loss, lowering blood lipids or assisting in lowering blood lipids, lowering blood sugar or assisting in lowering blood sugar, improving metabolic health, improving immune health, enhancing immunity, or anti-inflammation.

[0006] This invention provides a bacterial strain composition comprising: *Lactobacillus fermentum* strain grx831 (CGMCC No. 33875), *Lactobacillus rhamnosus* strain 1301 (CGMCC No. 8545), *Lactobacillus plantarum* strain grx16 (CGMCC No. 10921), *Lactobacillus rhamnosus* strain bv-77 (CCTCC No. M2014589), *Streptococcus thermophilus* strain grx02 (CGMCC No. 2525), and *Bifidobacterium animalis* strain CP-9 (CCTCC No. M2014588).

[0007] The strain composition described above, wherein the viable count ratio of Lactobacillus fermentum grx831 strain, Lactobacillus rhamnosus 1301 strain, Lactobacillus plantarum grx16 strain, Lactobacillus rhamnosus bv-77 strain, Streptococcus thermophilus grx02 strain and Bifidobacterium animalis CP-9 strain is (1-5): (1-5): (1-5): (1-5): (1-5): (1-5): (1-5).

[0008] The strain composition described above, wherein the viable count of *Lactobacillus fermentum* strain grx831 in the strain composition is ≥1×10⁻⁶. 6 CFU / mL, viable count of Lactobacillus rhamnosus strain 1301 ≥ 1×10⁻⁶ 6 CFU / mL, viable count of Lactobacillus plantarum strain grx16 ≥1×10 6 CFU / mL, viable count of Lactobacillus rhamnosus bv-77 strain ≥1×10⁻⁶ 6 CFU / mL, viable count of Streptococcus thermophilus strain grx02 ≥1×10 6 CFU / mL, viable count of Bifidobacterium animalis CP-9 strain ≥1×10⁻⁶ 6 CFU / mL.

[0009] The strain composition as described above, wherein the dosage form of the strain composition includes at least one of oral liquid, tablet, granule, powder, lyophilized powder, capsule, pill, aqueous solution, powder, soft capsule, film, and emulsion.

[0010] The strain composition as described above further includes prebiotics; the prebiotics include at least one of fructooligosaccharides, galactooligosaccharides, isomaltooligosaccharides, raffinose, stachyose, inulin, and soybean oligosaccharides.

[0011] The strain composition as described above further includes physiologically acceptable excipients; the excipients include at least one of the following: excipients, fillers, dispersants, binders, wetting agents, disintegrants, emulsifiers, solubilizers, isotonic regulators, isotonic regulators, coating materials, colorants, pH adjusters, antioxidants, antibacterial agents, buffers, flavoring agents, diluents, color and flavor modifiers, solvents, metal complexing agents, inert gases, and preservatives.

[0012] The strain composition as described above further includes a physiologically acceptable carrier; the carrier includes at least one of microcapsules, microspheres, nanoparticles, and liposomes.

[0013] The present invention also provides the application of the above-mentioned bacterial composition in the preparation of related products for protecting or assisting in the protection of liver damage, lowering or assisting in the lowering of blood lipids, lowering or assisting in the lowering of blood sugar, improving cardiovascular health, improving blood lipid metabolism, improving liver lipid metabolism, improving glucose and lipid metabolism, weight loss or assisting in weight loss, treating or assisting in the treatment of postpartum obesity, anti-inflammatory, improving immune health, and enhancing immunity.

[0014] The applications described above include at least one of health supplements and pharmaceuticals.

[0015] As described above, the health supplement includes at least one of functional beverages, functional powders, functional capsules, and functional powders; and / or,

[0016] The drugs include those used to treat or assist in the treatment of at least one of the following: liver injury, hyperlipidemia, hyperglycemia, cardiovascular disease, metabolic disorders, inflammation, and immune disorders.

[0017] The beneficial effects of this invention are as follows:

[0018] The above-mentioned bacterial strain composition has high safety and a wide range of effects. It can protect against liver damage, alleviate liver damage, and improve liver function; it can lower blood lipids or assist in lowering blood lipids, while improving blood lipid metabolism and liver lipid metabolism; it can lower blood sugar or assist in lowering blood sugar; it can achieve weight loss, fat reduction, and visceral fat reduction effects; it can effectively regulate glucose and lipid metabolism, thus it can be used to treat or assist in the treatment of postpartum obesity; it can also have anti-inflammatory effects, and by influencing cytokines or signaling pathways, it can affect the development and function of immune cells and regulate immune responses, thereby improving immune health and enhancing immunity. Attached Figure Description

[0019] Figure 1 The serum inflammatory factor IL-6 level in postpartum obese female mice in Example 6 of this invention;

[0020] Figure 2 The serum inflammatory factor IL-27 level in postpartum obese female mice in Example 6 of this invention;

[0021] Figure 3 The serum inflammatory factor NF-κB level in postpartum obese female mice in Example 6 of this invention;

[0022] Figure 4 The serum inflammatory factor TNF-α level in postpartum obese female mice in Example 6 of this invention;

[0023] Figure 5 The serum prolactin level in postpartum obese female mice in Example 6 of this invention;

[0024] Figure 6 The serum adiponectin level of postpartum obese female mice in Example 6 of this invention. Detailed Implementation

[0025] To enable those skilled in the art to better understand the present invention, the present invention will be further described in detail below. The specific embodiments listed below are merely descriptions of the principles and features of the present invention, and the examples are only for explaining the present invention and are not intended to limit the scope of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0026] To address postpartum obesity, this invention, after long-term research and extensive experimentation, provides a bacterial strain composition comprising: *Lactobacillus fermentum* strain grx831 (CGMCC No. 33875), *Lactobacillus rhamnosus* strain 1301 (CGMCC No. 8545), *Lactobacillus plantarum* strain grx16 (CGMCC No. 10921), *Lactobacillus rhamnosus* strain bv-77 (CCTCC No. M2014589), *Streptococcus thermophilus* strain grx02 (CGMCC No. 2525), and *Bifidobacterium animalis* strain CP-9 (CCTCC No. M2014588).

[0027] Specifically, the deposit date of *Limosilactobacillus fermentum* strain grx831 is March 19, 2025, at the China General Microbiological Culture Collection Center (CGMCC), located at No. 3, Courtyard 1, Beichen West Road, Chaoyang District, Beijing, China, Institute of Microbiology, Chinese Academy of Sciences, with accession number CGMCC No. 33875. The deposit date of *Lacticaseibacillus rhamnosus hsryfm* strain 1301 is December 6, 2013, at the same institution, the China General Microbiological Culture Collection Center (CGMCC), located at No. 3, Courtyard 1, Beichen West Road, Chaoyang District, Beijing, China, Institute of Microbiology, Chinese Academy of Sciences, with accession number CGMCC No. 8545. The deposit date of *Lactiplantibacillus plantarum* strain grx16 is August 7, 2015, at the China General Microbiological Culture Collection Center (CGMCC), located at No. 3, Courtyard 1, Beichen West Road, Chaoyang District, Beijing, China (Institute of Microbiology, Chinese Academy of Sciences), with accession number CGMCC No. 10921. The deposit date of *Lactobacillus rhamnosus* strain bv-77 is November 24, 2014, at the China Center for Type Culture Collection (CCTCC), located at Wuhan University, Luojia Mountain, Wuchang District, Wuhan, Hubei Province, China, with accession number CCTCC No. M2014589. The deposit date of *Streptococcus thermophilus* strain grx02 is May 28, 2008, at the China General Microbiological Culture Collection Center (CGMCC), located at No. 3, Courtyard 1, Beichen West Road, Chaoyang District, Beijing, China (Institute of Microbiology, Chinese Academy of Sciences), with accession number CGMCC No. 2525. The deposit date of *Bifidobacterium animalis* strain CP-9 is November 24, 2014, at the China Center for Type Culture Collection (CCTCC), located at Wuhan University, Luojia Mountain, Wuchang District, Wuhan, Hubei Province, China, with accession number CCTCC No. M2014588.

[0028] The present invention has found that the above-mentioned bacterial composition has the following beneficial effects:

[0029] (1) The above-mentioned bacterial composition can reduce the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and liver tissue. ALT and AST are important indicators of liver function, and their elevated levels usually indicate hepatocyte damage. Therefore, reducing the levels of ALT and AST in serum and liver tissue means that the bacterial composition can protect against liver damage, alleviate liver damage, and improve liver function.

[0030] (2) The above-mentioned bacterial composition can reduce serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels in serum and liver tissue, and increase high-density lipoprotein (HDL) levels. Abnormal levels of TC, TG, LDL, and HDL are manifestations of abnormal lipid metabolism in the body. Among them, elevated TC, TG, and LDL are important risk factors for cardiovascular diseases such as atherosclerosis and coronary heart disease. HDL has the function of reverse cholesterol transport, which can transport excess cholesterol from peripheral tissues to the liver for metabolism, thereby reducing the risk of cardiovascular disease. Therefore, reducing TC, TG, and LDL levels in serum and liver tissue and increasing HDL levels means that the bacterial composition can lower blood lipids or assist in lowering blood lipids, while improving blood lipid metabolism health and liver lipid metabolism health.

[0031] (3) The above-mentioned bacterial composition can reduce fasting blood glucose levels, which means that it can lower blood glucose or assist in lowering blood glucose.

[0032] (4) The above-mentioned bacterial composition can reduce the fallopian tube fat index, mesenteric fat index and perirenal fat index, which means that it can achieve the effects of weight loss, fat reduction and fat reduction, and also has the effect of visceral fat reduction.

[0033] (5) The above-mentioned bacterial composition can increase the serum levels of adiponectin and prolactin in postpartum obese individuals. Adiponectin and prolactin play important roles in the regulation of glucose and lipid metabolism. Increased adiponectin levels can activate adiponectin receptors, which have ceramide hydrolase activity, helping to relieve the inhibition of insulin signaling pathways by ceramides, increasing insulin sensitivity, and promoting blood glucose reduction. Increased prolactin secretion can activate prolactin receptors, helping to stimulate the mother and maintain lactation, promoting the outflow of nutrients from the mother's body, and reducing blood lipid and liver lipid levels; prolactin also has the biological activity functions of hormones and cytokines, and can affect the regulation of the immune system, mainly by inhibiting the negative selection of self-reactive B lymphocytes. Therefore, increasing the serum levels of adiponectin and prolactin in postpartum obese individuals means that the bacterial composition can effectively regulate glucose and lipid metabolism, and thus can be used for the treatment or adjunctive treatment of postpartum obesity.

[0034] (6) The above-mentioned bacterial strain composition can increase the serum level of interleukin-27 (IL-27) and decrease the levels of interleukin-6 (IL-6), nuclear factor kappa-B (NF-κB), and tumor necrosis factor-α (TNF-α). IL-27 is a cytokine with immunomodulatory function. It can play a role in inhibiting excessive immune response and maintaining immune balance in the immune response. Its increased level helps to enhance the body's immune regulation capacity and reduce damage caused by excessive immunity. IL-6 and TNF-α are important pro-inflammatory cytokines. Their elevated levels are often closely related to the body's chronic inflammatory state. Chronic inflammation is an important driving factor in the occurrence and development of many diseases (such as metabolic syndrome, cardiovascular disease, etc.). NF-κB, as a key transcription factor, plays a core role in the regulation of inflammatory response. Its enhanced activity will promote the expression of various pro-inflammatory factors and aggravate the inflammatory response. Therefore, increasing serum IL-27 levels and decreasing IL-6, NF-κB, and TNF-α levels indicates that this bacterial composition not only has anti-inflammatory effects but also influences the development and function of immune cells and regulates immune responses by affecting cytokines or signaling pathways, thereby improving immune health and enhancing immunity. Furthermore, studies have shown that these probiotics may improve glucose and lipid metabolism by influencing cytokine expression through the gut-brain axis and gut-fat axis.

[0035] (7) Among the above strains, Lactobacillus fermentum grx831 strain, Lactobacillus rhamnosus 1301 strain, Lactobacillus plantarum grx16 strain, Lactobacillus rhamnosus bv-77 strain, Streptococcus thermophilus grx02 strain and Bifidobacterium animalis CP-9 strain are all probiotics, which have high safety and are not prone to developing drug resistance.

[0036] In summary, the bacterial strain composition provided by this invention has high safety and wide range of effects, which can fill the gap in the existing probiotic agent market, break through the limitations of existing probiotic agent products, and provide new ideas for protecting or assisting in the protection of liver damage, lowering or assisting in the lowering of blood lipids, lowering or assisting in the lowering of blood sugar, improving cardiovascular health, improving blood lipid metabolism, improving liver lipid metabolism, improving glucose and lipid metabolism, weight loss or assisting in weight loss, treating or assisting in the treatment of postpartum obesity, anti-inflammation, improving immune health, and enhancing immunity.

[0037] Furthermore, experiments have shown that the bacterial composition provided by this invention is particularly suitable for addressing liver damage, hyperlipidemia, hyperglycemia, cardiovascular disease, metabolic disorders, inflammation, or immune disorders caused by postpartum obesity.

[0038] In the above-mentioned bacterial composition, the viable count ratio of *Lactobacillus fermentum* grx831, *Lactobacillus rhamnosus* 1301, *Lactobacillus plantarum* grx16, *Lactobacillus rhamnosus* bv-77, *Streptococcus thermophilus* grx02, and *Bifidobacterium animalis* CP-9 is (1-5):(1-5):(1-5):(1-5):(1-5):(1-5). When the viable count ratio is within the above range, the bacterial composition is more effective and can further protect against liver damage, lower blood lipids, lower blood sugar, promote weight loss, reduce inflammation, and regulate immune response.

[0039] In the above-mentioned bacterial composition, the viable count of *Lactobacillus fermentum* strain grx831 is ≥1×10⁻⁶. 6 CFU / mL, viable count of Lactobacillus rhamnosus strain 1301 ≥ 1×10⁻⁶ 6 CFU / mL, viable count of Lactobacillus plantarum strain grx16 ≥1×10 6 CFU / mL, viable count of Lactobacillus rhamnosus bv-77 strain ≥1×10⁻⁶ 6 CFU / mL, viable count of Streptococcus thermophilus strain grx02 ≥1×10 6 CFU / mL, viable count of Bifidobacterium animalis CP-9 strain ≥1×10⁻⁶ 6 CFU / mL; for example, it could be 1×10⁻⁶. 6 CFU / mL, 5×10 6 CFU / mL, 1×10 7CFU / mL, 5×10 7 CFU / mL, 1×10 8 CFU / mL, 5×10 8 CFU / mL, 1×10 9 CFU / mL, 5×10 9 CFU / mL, 1×10 10 CFU / mL, 5×10 10 etc. When the number of live bacteria is ≥1×10 6 At a concentration of CFU / mL, the combination of this strain is more effective, and can further protect against liver damage, lower blood lipids, lower blood sugar, promote weight loss, reduce inflammation, and regulate immune response.

[0040] In the above technical solutions, the dosage form of the bacterial composition includes at least one of oral liquid, tablet, granule, powder, lyophilized powder, capsule, pill, aqueous solution, powder, soft capsule, film, and emulsion.

[0041] The lyophilized powder can be prepared by, for example, the following method:

[0042] (1) Inoculate Lactobacillus fermentum grx831 strain, Lactobacillus rhamnosus 1301 strain, Lactobacillus plantarum grx16 strain or Lactobacillus rhamnosus bv-77 strain into a culture medium for culture, or inoculate Streptococcus thermophilus grx02 strain into a culture medium for culture, or inoculate Bifidobacterium animalis CP-9 strain into a Bifidobacterium culture medium for culture, to obtain a culture solution;

[0043] (2) Centrifuge the culture medium to obtain bacterial cells;

[0044] (3) Resuspend the bacterial cells in a lyophilization protectant to obtain a resuspension;

[0045] (4) Freeze-dry the suspension to obtain freeze-dried powder of a single plant;

[0046] (5) The above-mentioned single-plant freeze-dried powder is compounded according to the proportion to obtain the above-mentioned freeze-dried powder.

[0047] Preferably, the culture medium for Bacillus includes 38 g / L sucrose, 34 g / L yeast extract, 7 g / L K2HPO4, 7 g / L KH2PO4, 0.2 g / L MgSO4, 0.02 g / L MnSO4, 0.1 g / L Tween 80, 0.1 g / L glycerol, 0.01 g / L VB3, and 0.2 g / L cysteine ​​hydrochloride.

[0048] Preferably, the formulation of the coccal culture medium includes: 20 g / L lactose, 16.60% enzymatically defatted milk, 18.88 g / L soybean oligopeptides, 1.69 g / L whey protein powder, 10 mM histidine, 10 mM isoleucine, 5 mM tyrosine, 1 mM cysteine, 1 mM glutamic acid, 2 mg / L niacin, 0.5 g / L ascorbic acid, 40 mg / L magnesium chloride, 2 mg / L calcium pantothenate, 4 mg / L thiamine hydrochloride, and 0.4 g / L calcium chloride.

[0049] Preferably, the formulation of the Bifidobacterium culture medium includes 50 g / L glucose, 32 g / L casein peptone, 1.25 g / L MgSO4·7H2O, 1 g / L cysteine, and 1 mL / L Tween 80.

[0050] Preferably, the culture temperature is 36-42℃, and the culture time is 12-24 h. Exemplarily, the culture temperature can be selected from 36℃, 37℃, 38℃, 39℃, 40℃, 41℃, 42℃, and any value between any two of the above ranges. Exemplarily, the culture time can be selected from 12 h, 13 h, 14 h, 15 h, 16 h, 17 h, 18 h, 19 h, 20 h, 21 h, 22 h, 23 h, 24 h, and any value between any two of the above ranges.

[0051] Preferably, freeze drying can be performed using a vacuum freezing method.

[0052] Preferably, the freeze-drying protectant may include at least one of sucrose, skim milk, monosodium glutamate, inulin, stachyose, mannitol, fructooligosaccharides, xylooligosaccharides, galactooligosaccharides, and maltodextrin.

[0053] The above-mentioned freeze-dried powder has a simple preparation process, is suitable for large-scale industrial production, and has significant practical value.

[0054] Furthermore, the bacterial strain composition also includes prebiotics; the prebiotics include at least one of fructooligosaccharides, galactooligosaccharides, isomaltooligosaccharides, raffinose, stachyose, inulin, and soybean oligosaccharides. These prebiotics can work synergistically with the bacterial strain composition to further enhance its efficacy in protecting against liver damage, lowering blood lipids, lowering blood sugar, weight loss, anti-inflammation, and regulating immune responses.

[0055] Furthermore, the strain composition also includes physiologically acceptable excipients; the excipients include at least one of the following: excipients, fillers, dispersants, binders, wetting agents, disintegrants, emulsifiers, solubilizers, solvents, isotonic regulators, isotonic regulators, coating materials, colorants, pH adjusters, antioxidants, antibacterial agents, buffers, flavoring agents, diluents, color and flavor modifiers, solvents, metal complexing agents, inert gases, and preservatives.

[0056] Furthermore, the strain composition also includes a physiologically acceptable carrier; the carrier includes at least one of microcapsules, microspheres, nanoparticles, and liposomes.

[0057] Based on the above research, the present invention also provides the application of the above-mentioned strain composition in the preparation of related products for protecting or assisting in the protection of liver damage, lowering or assisting in the lowering of blood lipids, lowering or assisting in the lowering of blood sugar, improving cardiovascular health, improving blood lipid metabolism, improving liver lipid metabolism, improving glucose and lipid metabolism, weight loss or assisting in weight loss, treating or assisting in the treatment of postpartum obesity, anti-inflammatory, improving immune health, and enhancing immunity.

[0058] Experiments have shown that the above-mentioned bacterial strain composition can reduce ALT and AST levels in serum and liver tissue, thus protecting against liver damage, alleviating liver damage, and improving liver function. It can be used for protective or adjunctive protection against liver damage. The above-mentioned bacterial strain composition can reduce TC, TG, and LDL levels in serum and liver tissue while increasing HDL levels, thus lowering or adjunctively lowering blood lipids, improving lipid metabolism and liver lipid metabolism. It can be used for lowering or adjunctively lowering blood lipids, improving cardiovascular health, and improving lipid metabolism and liver lipid metabolism. The above-mentioned bacterial strain composition can lower fasting blood glucose levels, thus lowering or adjunctively lowering blood sugar. It can be used for lowering or adjunctively lowering blood sugar. The above-mentioned bacterial strain composition can reduce fallopian tube fat index, mesenteric fat index, and perirenal fat index, thus achieving weight loss, fat reduction, and visceral fat reduction effects. It also has a particular effect on visceral fat reduction and can be used for weight loss or adjunctive weight loss, and for the treatment or adjunctive treatment of postpartum obesity. The above-mentioned bacterial strain composition can increase the serum levels of adiponectin and prolactin in postpartum obese individuals, thus effectively regulating glucose and lipid metabolism, and can be used to improve glucose and lipid metabolism and treat or assist in the treatment of postpartum obesity. The above-mentioned bacterial strain composition can increase serum IL-27 levels and decrease IL-6, NF-κB, and TNF-α levels, thus not only exerting anti-inflammatory effects, but also influencing the development and function of immune cells and regulating immune responses by affecting cytokines or signaling pathways, thereby improving immune health and enhancing immunity. Furthermore, the above-mentioned bacterial strain composition consists of probiotics, which have high safety and are unlikely to induce drug resistance. Therefore, the above-mentioned bacterial strain composition can be applied to the preparation of products for protecting or assisting in the protection of liver damage, lowering or assisting in lowering blood lipids, lowering or assisting in lowering blood sugar, improving cardiovascular health, improving lipid metabolism, improving hepatic lipid metabolism, improving glucose and lipid metabolism, weight loss or assisting in weight loss, treating or assisting in the treatment of postpartum obesity, anti-inflammation, improving immune health, and enhancing immunity.

[0059] It is understood that the above-mentioned bacterial compositions can also act as inhibitors of ALT, AST, TC, TG, LDL, IL-6, NF-κb or TNF-α, and agonists of HDL, adiponectin, prolactin or IL-27.

[0060] In the above applications, the relevant products include at least one of health supplements and medicines.

[0061] Furthermore, health products include at least one of functional beverages, functional powders, functional capsules, and functional powders.

[0062] Furthermore, the medicine includes medicines used to treat or assist in the treatment of at least one of the following: liver injury, hyperlipidemia, hyperglycemia, cardiovascular disease, metabolic disorders, inflammation, and immune disorders.

[0063] In actual use, the above-mentioned drugs can be administered via at least one of the following methods: intravenous injection, intraperitoneal injection, intramuscular injection, subcutaneous injection, oral administration, sublingual administration, nasal administration, and transdermal administration.

[0064] The technical solution of this application will be further explained below with reference to specific embodiments. Experimental methods in the following embodiments that do not specify specific conditions are generally performed under conventional conditions or as recommended by the manufacturer; reagents used, unless otherwise specified, are commercially available or obtained through public channels.

[0065] The microbial strains involved in the following examples are as follows:

[0066] 1. *Limosilactobacillus fermentum* strain grx831:

[0067] The deposit date is March 19, 2025;

[0068] The depository is the China General Microbiological Culture Collection Center, China Committee on the Preservation and Management of Microbial Culture Collections;

[0069] The address of the depositary institution is No. 3, Courtyard 1, Beichen West Road, Chaoyang District, Beijing, China; Institute of Microbiology, Chinese Academy of Sciences

[0070] The accession number is CGMCC No. 33875.

[0071] 2. Lactobacillus rhamnosus hsryfm 1301 strain:

[0072] The date of deposit is December 6, 2013;

[0073] The depository is the China General Microbiological Culture Collection Center, China Committee on the Preservation and Management of Microbial Culture Collections;

[0074] The address of the depositary institution is No. 3, Courtyard 1, Beichen West Road, Chaoyang District, Beijing, China; Institute of Microbiology, Chinese Academy of Sciences

[0075] The accession number is CGMCC No. 8545.

[0076] 3. Lactiplantibacillus plantarum grx16 strain:

[0077] The date of deposit is August 7, 2015;

[0078] The depository is the China General Microbiological Culture Collection Center, China Committee on the Preservation and Management of Microbial Culture Collections;

[0079] The address of the depositary institution is No. 3, Courtyard 1, Beichen West Road, Chaoyang District, Beijing, China; Institute of Microbiology, Chinese Academy of Sciences

[0080] The accession number is CGMCC No.10921.

[0081] 4. Lactobacillus rhamnosus bv-77 strain:

[0082] The date of deposit is November 24, 2014;

[0083] The depositary institution is the China Center for Type Culture Collection;

[0084] The address of the depositary is Wuhan University, Luojia Mountain, Wuchang District, Wuhan City, Hubei Province, China.

[0085] The accession number is CCTCC No.M2014589.

[0086] 5. Streptococcus thermophilus strain grx02:

[0087] The date of deposit is May 28, 2008;

[0088] The depository is the China General Microbiological Culture Collection Center, China Committee on the Preservation and Management of Microbial Culture Collections;

[0089] The address of the depositary institution is No. 3, Courtyard 1, Beichen West Road, Chaoyang District, Beijing, China; Institute of Microbiology, Chinese Academy of Sciences

[0090] The accession number is CGMCC No. 2525.

[0091] 6. Bifidobacterium animalis CP-9 strain

[0092] The date of deposit is November 24, 2014;

[0093] The depositary institution is the China Center for Type Culture Collection;

[0094] The address of the depositary is Wuhan University, Luojia Mountain, Wuchang District, Wuhan City, Hubei Province, China.

[0095] The accession number is CCTCC No.M2014588.

[0096] Example 1: Constructing an animal model

[0097] The *Limosilactobacillus fermentum* grx831 strain was cultured in a bacterial culture medium and activated for two generations to obtain an activated bacterial suspension. The activated bacterial suspension was centrifuged at 4000 × g for 9 min, the supernatant was discarded, and sterile physiological saline was added to the precipitate to wash the bacterial cells. This process was repeated twice. The bacterial suspension was then resuspended in an oligosaccharide-prebiotic mixture, and the viable count was adjusted to 1.2 × 10⁻⁶ cells / day. 9 The bacterial suspension was obtained at CFU / mL and named bacterial preparation S1.

[0098] Lactaseibacillus rhamnosus hsryfm 1301, Lactiplantibacillus plantarum grx16, and Lactaseibacillus rhamnosus bv-77 were cultured in aerobic culture medium for two generations to obtain activated bacterial solutions. Streptococcus thermophilus grx02 was cultured in aerobic culture medium for two generations to obtain activated bacterial solutions. Bifidobacterium animalis CP-9 was cultured in aerobic culture medium for two generations to obtain activated bacterial solutions. All activated bacterial solutions were centrifuged at 4000 × g for 9 min, the supernatant was discarded, and sterile physiological saline was added to the precipitate to wash the bacterial cells, repeating this process twice. The bacterial precipitate was then resuspended in an oligosaccharide-prebiotic mixture, and the viable count was adjusted to 1.2 × 10⁻⁶. 9 CFU / mL was used to obtain bacterial suspensions; the bacterial suspensions corresponding to the above 5 strains were mixed to obtain a bacterial composition, named bacterial preparation S2 (i.e., the viable count of each of the above 5 strains in bacterial preparation S2 is 2.4 × 10⁻⁶). 8 CFU / mL, the sum of the viable counts of the above 5 strains in bacterial preparation S2 was 1.2 × 10⁻⁶. 9 (CFU / mL).

[0099] *Limosilactobacillus fermentum* grx831, *Lactaseibacillus rhamnosus* hsryfm 1301, *Lactiplantibacillus plantarum* grx16, and *Lactobacillus rhamnosus* bv-77 were cultured in aerobic culture medium for two generations to obtain activated bacterial solutions. *Streptococcus thermophilus* grx02 was cultured in aerobic culture medium for two generations to obtain activated bacterial solutions. *Bifidobacterium animalis* CP-9 was cultured in aerobic culture medium for two generations to obtain activated bacterial solutions. All activated bacterial solutions were centrifuged at 4000 × g for 9 min, the supernatant was discarded, and sterile physiological saline was added to the precipitate to wash the bacterial cells, repeating this process twice. The bacterial precipitate was then resuspended in an oligosaccharide-prebiotic mixture, and the viable count was adjusted to 1.2 × 10⁻⁶. 9 CFU / mL was used to obtain bacterial suspensions; the bacterial suspensions corresponding to the above 6 strains were mixed to obtain a bacterial composition, named bacterial preparation S3 (i.e., the viable count of each of the above 6 strains in bacterial preparation S3 is 2×10⁶). 8 CFU / mL, the sum of the viable counts of the above 6 strains in bacterial preparation S2 was 1.2 × 10⁻⁶. 9 (CFU / mL).

[0100] The culture medium for Bacillus includes 38 g / L sucrose, 34 g / L yeast extract, 7 g / L K2HPO4, 7 g / L KH2PO4, 0.2 g / L MgSO4, 0.02 g / L MnSO4, 0.1 g / L Tween 80, 0.1 g / L glycerol, 0.01 g / L VB3, and 0.2 g / L cysteine ​​hydrochloride. The formulation of the cocci culture medium includes 20 g / L lactose, 16.60% enzymatically defatted milk, 18.88 g / L soybean oligopeptides, 1.69 g / L whey protein powder, 10 mM histidine, 10 mM isoleucine, 5 mM tyrosine, 1 mM cysteine, 1 mM glutamic acid, 2 mg / L niacin, 0.5 g / L ascorbic acid, 40 mg / L magnesium chloride, 2 mg / L calcium pantothenate, 4 mg / L thiamine hydrochloride, and 0.4 g / L calcium chloride. The formulation of the bifidobacteria culture medium includes 50 g / L glucose, 32 g / L casein peptone, 1.25 g / L MgSO4·7H2O, 1 g / L cysteine, and 1 mL / L Tween 80. The formulation of the oligosaccharide prebiotic mixed solution includes 25 g / L of fructooligosaccharide, 106 g / L of galactooligosaccharide, 8.5 g / L of raffinose, and 40 g / L of stachyose.

[0101] Six days after giving birth, SPF-grade C57BL / 6J female mice were randomly divided into 5 groups (n=8 per group), including the control group CTL, the model group MC, the experimental group S1, the experimental group S2, and the experimental group S3. In this study, the control group (CTL) was fed a regular diet, supplemented with feed and water every morning, and each female mouse was given saline solution by gavage daily at a rate of 100 μL per 10 g of body weight for 5 weeks. The model group (MC) was fed a high-fat diet, supplemented with feed and water every morning, and each female mouse was given saline solution by gavage daily at a rate of 100 μL per 10 g of body weight for 5 weeks. The experimental groups (S1, S2, and S3) were fed a high-fat diet, supplemented with feed and water every morning, and each female mouse was given probiotic preparation S1 by gavage daily at a rate of 100 μL per 10 g of body weight for 5 weeks.

[0102] Example 2: Validation of the effect of the bacterial strain composition on lipid metabolism in postpartum obese female rats

[0103] The alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL) levels in the serum of the above five groups of female mice were detected using a Hitachi 7020 fully automated biochemical analyzer, following the instructions of the respective kits. The results are shown in Table 1 (unit: mmol / L).

[0104] Table 1

[0105]

[0106] Table 1 shows that, compared with the control group CTL, the serum levels of TC (40.13%), TG (38.28%), and LDL (95.36%) in the model group MC mother mice were significantly increased, while the serum HDL (35.39%) level was significantly decreased. Data from experimental group S1 showed that the use of bacterial preparation S1 had no significant effect on serum ALT, AST, TC, TG, HDL, and LDL in mother mice. Data from experimental group S2 showed that, compared with the model group MC, the use of bacterial preparation S2 significantly reduced serum TC (22.31%), TG (18.52%), and LDL (30.77%) levels in mother mice and increased HDL levels (33.06%). Data from experimental group S3 showed that, compared with the model group MC, the intervention of bacterial preparation S3 further reduced serum TC (23.55%), TG (20.99%), and LDL (38.46%) levels and further increased HDL levels (48.76%). The above results indicate that the bacterial preparation S3 can effectively regulate lipid metabolism in postpartum obese female mice.

[0107] When the liver is damaged, ALT and AST are released from damaged hepatocytes into the serum, causing elevated serum ALT and AST levels. Experimental groups S2 and S3 significantly protected against liver injury induced by a high-fat diet in postpartum female rats by reducing the elevation of ALT and AST. Compared with the model group MC, the serum ALT (36.83%) and AST (17.19%) activities in the liver of experimental group S2 were significantly reduced, while those in experimental group S3 were further reduced (49.41%) and (20.92%). These results indicate that the bacterial preparations S2 and S3 can exert significant hepatoprotective effects.

[0108] Example 3: Validation of the effect of the bacterial strain composition on liver lipid metabolism in postpartum obese female rats

[0109] Using the alanine aminotransferase (ALT) assay kit, aspartate aminotransferase (AST) assay kit, total cholesterol (TC) assay kit, triglyceride (TG) assay kit, high-density lipoprotein cholesterol (HDL) assay kit, and low-density lipoprotein cholesterol (LDL) assay kit produced by Ningbo Meikang Biotechnology Co., Ltd., and referring to the instructions of the respective kits, ALT, AST, TC, TG, HDL, and LDL in the livers of the above five groups of female mice were detected using a Hitachi 7020 fully automated biochemical analyzer. The results are shown in Table 2 (unit: mmol / L).

[0110] Table 2

[0111]

[0112] Table 2 shows that, compared with the model group MC, the use of bacterial preparation S1 had no significant effect on serum ALT, AST, TC, TG, HDL, and LDL in maternal mice. Data from experimental group S2 showed that, compared with the model group MC, the use of bacterial preparation S2 significantly reduced TC (23.08%), TG (32.35%), and LDL (10.00%) levels in the liver of maternal mice, and increased HDL levels (25.00%). Data from experimental group S3 showed that, compared with the model group MC, the use of bacterial preparation S3 further reduced TC (38.46%), TG (54.41%), and LDL (20.00%) levels in the liver, and further increased HDL levels (37.50%). These results indicate that bacterial preparation S3 can effectively regulate hepatic lipid metabolism in postpartum obese maternal mice.

[0113] In addition, experimental group S2 reduced the increase of ALT (21.61%) and AST (18.64%), and experimental group S3 further reduced the increase of ALT (30.03%) and AST (24.98%), showing a significant protective effect against liver damage induced by a high-fat diet in postpartum female rats.

[0114] Example 4: Validation of the effect of the bacterial strain composition on fasting blood glucose in postpartum obese female rats

[0115] Fasting blood glucose levels in the five groups of female mice were measured using a blood glucose meter. The results are shown in Table 3 (unit: mmol / L).

[0116] Table 3

[0117]

[0118] Table 3 shows that the fasting blood glucose level of the model group (MC) was higher than that of the control group (CTL), indicating abnormal glucose metabolism in the model group mothers. Data from experimental group S1 showed that, compared with the model group (MC), the use of probiotic preparation S1 had no significant effect on fasting blood glucose. Data from experimental group S2 showed that, compared with the model group (MC), the use of probiotic preparation S2 reduced fasting blood glucose in mothers by 5.21%. Data from experimental group S3 showed that, compared with the model group (MC), the use of probiotic preparation S3 further reduced fasting blood glucose in mothers by 7.30%. These results indicate that probiotic preparations S2 and S3 have a protective effect against glucose metabolism abnormalities induced by a high-fat diet in postpartum mothers.

[0119] Example 5: Validation of the effects of the bacterial strain composition on oviductal fat, mesenteric fat, and perirenal fat in postpartum obese female rats.

[0120] The oviducts, mesentery, and perirenal fat of the above 5 groups of female mice were rinsed in pre-cooled (4℃) physiological saline to remove blood, wiped dry with filter paper, weighed and recorded; the corresponding adipose tissue weight was divided by the body weight to obtain the adipose tissue fat index, as shown in Table 4.

[0121] Table 4

[0122]

[0123] Table 4 shows that, compared with the model group MC, the use of bacterial preparation S1 had no significant effect on fallopian tube fat, mesenteric fat, and perirenal fat. Data from experimental group S2 showed that, compared with the model group MC, the use of bacterial preparation S2 significantly reduced the fallopian tube fat index (20.90%), mesenteric fat index (16.15%), and perirenal fat index (17.04%). Data from experimental group S3 showed that, compared with the model group MC, the use of bacterial preparation S3 further reduced the fallopian tube fat index (33.05%), mesenteric fat index (52.08%), and perirenal fat index (55.56%). These results indicate that bacterial preparations S2 and S3 can effectively reduce the mesenteric fat index, perirenal fat index, and fallopian tube fat index, thus reducing fat accumulation.

[0124] Example 6: Validation of the effects of the bacterial strain composition on serum adiponectin, prolactin, IL-27, IL-6, NF-κB, and TNF-α levels in postpartum obese female rats.

[0125] Using an enzyme-linked immunosorbent assay (ELISA) kit for adiponectin, prolactin, IL-27, IL-6, NF-κB, and TNF-α produced by Shanghai Hualan Chemical Technology Co., Ltd., and following the kit's instructions, the serum levels of adiponectin, prolactin, IL-27, IL-6, NF-κB, and TNF-α in the above five groups of maternal mice were measured. (See details at [link to kit]). Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 and Figure 6 .

[0126] Figure 1 Serum IL-6 levels in postpartum obese female mice. Figure 2 The serum inflammatory factor IL-27 level in postpartum obese female mice. Figure 3 The fasting blood glucose level and serum inflammatory factor NF-κB level in postpartum obese female mice. Figure 4 The serum inflammatory factor TNF-α level in postpartum obese female mice. Figure 5 Serum prolactin levels in postpartum obese female mice. Figure 6 Serum adiponectin levels in postpartum obese female mice. Figure 1 , Figure 2 , Figure 3 , Figure 4 , Figure 5 , Figure 6 As shown, compared with the control group CTL, the model group MC had lower serum adiponectin, prolactin, and IL-27 levels, and higher levels of IL-6, NF-κB, and TNF-α. Compared with the model group MC, the experimental group S1 significantly increased adiponectin (12.06%), prolactin (23.16%), and IL-27 (14.87%) levels, and decreased IL-6 (18.56%), NF-κB (11.00%), and TNF-α (10.64%) levels. Compared with the model group MC, the experimental group S2 had no significant effect on adiponectin, prolactin, and IL-27 levels. Compared with the model group MC, the experimental group S3 further increased adiponectin (12.12%), prolactin (30.53%), and IL-27 (21.41%) levels, and decreased IL-6 (21.25%) and TNF-α (11.54%) levels.

[0127] The high levels of adiponectin and prolactin in the serum of female mice were consistent with their decreased blood lipids and liver lipids, decreased fasting blood glucose, and decreased visceral fat index. Adiponectin can act on the insulin signaling pathway, improving insulin sensitivity and helping to lower blood glucose. After administration of the bacterial preparation S3, IL-27 levels increased, while IL-6, NF-κB, and TNF-α levels decreased. The expression and signaling pathways of these factors affect the development and function of immune cells and the regulation of immune responses. These results suggest that the bacterial preparation S3 may affect blood glucose by controlling adiponectin and prolactin levels, and may also regulate immune responses by modulating IL-27, IL-6, NF-κB, and TNF-α levels.

[0128] 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 them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A bacterial strain composition, characterized in that, This includes the following strains: Limosilactobacillus fermentum grx831 (CGMCC No. 33875), Lacticaseibacillus rhamnosus hsryfm 1301 (CGMCC No. 8545), Lactiplantibacillus plantarum grx16 (CGMCC No. 10921), Lactiplantibacillus rhamnosus bv-77 (CCTCC No. M2014589), Streptococcus thermophilus grx02 (CGMCC No. 2525), and Bifidobacterium animalis CP-9 (CCTCC No. M2014588).

2. The bacterial composition according to claim 1, characterized in that, The viable count ratio of the Lactobacillus fermentum grx831 strain, the Lactobacillus rhamnosus 1301 strain, the Lactobacillus plantarum grx16 strain, the Lactobacillus rhamnosus bv-77 strain, the Streptococcus thermophilus grx02 strain, and the Bifidobacterium animalis CP-9 strain is (1-5):(1-5):(1-5):(1-5):(1-5):(1-5):(1-5).

3. The bacterial composition according to claim 1 or 2, characterized in that, In the strain composition, the viable count of the *Lactobacillus fermentans* grx831 strain is ≥1×10⁻⁶. 6 CFU / mL, viable count of the *Lactobacillus rhamnosus* strain 1301 ≥ 1 × 10⁻⁶ 6 CFU / mL, viable count of the *Lactobacillus plantarum* grx16 strain ≥ 1 × 10⁻⁶ 6 CFU / mL, viable count of the *Lactobacillus rhamnosus* bv-77 strain ≥ 1 × 10⁻⁶ 6 CFU / mL, viable count of the *Streptococcus thermophilus* strain grx02 ≥ 1 × 10⁻⁶ 6 CFU / mL, viable count of the *Bifidobacterium animalis* CP-9 strain ≥ 1 × 10⁻⁶ 6 CFU / mL.

4. The bacterial composition according to claim 1 or 2, characterized in that, The dosage form of the strain composition includes at least one of the following: oral liquid, tablet, granule, powder, lyophilized powder, capsule, pill, aqueous solution, film, and emulsion.

5. The bacterial composition according to claim 1 or 2, characterized in that, The bacterial composition further includes prebiotics; the prebiotics include at least one of fructooligosaccharides, galactooligosaccharides, isomaltooligosaccharides, raffinose, stachyose, inulin, and soybean oligosaccharides.

6. The bacterial composition according to claim 1 or 2, characterized in that, The strain composition further includes physiologically acceptable excipients; the excipients include at least one of the following: fillers, dispersants, binders, wetting agents, disintegrants, emulsifiers, solubilizers, solvents, isotonic regulators, coating materials, pH adjusters, antioxidants, antibacterial agents, buffers, diluents, color and flavor regulators, solvents, metal complexing agents, inert gases, and preservatives.

7. The bacterial composition according to claim 1 or 2, characterized in that, The strain composition also includes a physiologically acceptable carrier; the carrier includes at least one of microcapsules, microspheres, nanoparticles, and liposomes.

8. The use of a bacterial composition according to any one of claims 1-7 in the preparation of health products for assisting in lowering blood lipids, assisting in lowering blood sugar, and weight loss.

9. The use of a bacterial composition according to any one of claims 1-7 in the preparation of a medicament for lowering or assisting in lowering blood lipids, lowering or assisting in lowering blood sugar, losing weight or assisting in losing weight, or treating or assisting in the treatment of postpartum obesity.

10. The application according to claim 8, characterized in that, The health products include at least one of functional beverages, functional powders, functional capsules, and functional powders.

11. The application according to claim 9, characterized in that, The drugs include those used to treat or assist in the treatment of at least one of hyperlipidemia and hyperglycemia.

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