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

Through the fermentation of strain compositions such as Lactobacillus mucin, liver damage, hyperlipidemia, hyperglycemia and immune disorders caused by postpartum obesity were solved, and the effects of liver function protection, blood lipid and blood sugar regulation, weight loss and immune enhancement were achieved, filling the gap in existing probiotic agents.

CN120591171AActive Publication Date: 2025-09-05AUSNUTRIA DAIRY CHINA
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Patent Information

Application Number
CN202511054688.6
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2025-07-30
Publication Date
2025-09-05
Estimated Expiration
2045-07-30

AI Technical Summary

Technical Problem

The problems caused by liver damage, hyperlipidemia, hyperglycemia, cardiovascular diseases, metabolic disorders and immune disorders caused by postpartum obesity are highly limited and difficult to effectively solve.

Method used

The strain compositions of Lactobacillus fermented mucus grx831, C. rhamnosus 1301, C. plantarum grx16, C. rhamnosus bv-77, Streptococcus thermophilus grx02 and Bifidobacteria animal CP-9 were prepared into a variety of dosage forms through a combination of specific proportions and viable bacteria, combined with prebiotics and physiologically acceptable excipients and carriers, and applied to foods, health products and drugs, affecting metabolism and immunomodulation.

Benefits of technology

Significantly reduces the ALT and AST levels in serum and liver tissues, improves liver function, reduces serum cholesterol and triglycerides, improves high-density lipoprotein levels, reduces fasting blood sugar, loses weight and regulates glycolipid metabolism, enhances immune response, anti-inflammatory and improves immune health, is highly safe and does not easily develop drug resistance.

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Abstract

The invention provides a strain composition for improving metabolic health and immune health and application thereof. The strain composition provided by the invention is high in safety and wide in effect, can fill the vacancy of the existing probiotic agent market, breaks through the limitation of the existing probiotic agent product, and is suitable for industrial production. A new thought can be provided for the fields of protection or auxiliary protection of liver injury, reduction of blood fat or auxiliary reduction of blood fat, reduction of blood sugar or auxiliary reduction of blood sugar, improvement of cardiovascular health, improvement of blood fat metabolism, improvement of liver lipid metabolism, improvement of glycolipid metabolism, weight loss or auxiliary weight loss, treatment or auxiliary treatment of postpartum obesity, anti-inflammation, improvement of immune health, enhancement of immunity and the like.
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Description

Technical Field

[0001] The present invention relates to the field of microbial technology, and in particular to a bacterial strain composition for improving metabolic health and immune health and applications thereof. Background Art

[0002] Postpartum obesity is a condition in which pregnancy causes dysfunction of the hypothalamus, abnormal body fat metabolism, and a sudden increase in body fat, resulting in weight gain and obesity. Medically, this phenomenon is also called "reproductive obesity" or "maternal obesity syndrome" and is a common postpartum pathological reaction. Postpartum obesity not only destroys a woman's physical beauty, but also has many adverse effects on her physical and mental health. It can easily induce emotional problems such as postpartum depression and anxiety, causing a series of physical and psychological distress to women. In addition, it is important to note that studies have shown that the intestinal flora of offspring in early life mainly comes from the mother's intestines and breast milk, and the intestinal flora of obese mothers will be reduced in both quantity and diversity. This change will further affect the colonization process of the offspring's intestinal microorganisms, thereby increasing the risk of metabolic diseases and neurodevelopmental diseases in the offspring.

[0003] In view of the above-mentioned multiple adverse effects of postpartum obesity, research and intervention on this disease have important practical significance and application value. Summary of the Invention

[0004] The invention provides a bacterial strain composition with high safety and wide effects.

[0005] The present invention provides an application of the above-mentioned strain composition in preparing related products for protecting or assisting in protecting liver damage, losing weight 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] The invention provides a strain composition, which comprises a fermentative Lactobacillus muciniphilus grx831 strain with a preservation number of CGMCC No.33875, a rhamnosus Lactobacillus 1301 strain with a preservation number of CGMCC No.8545, a plantarum Lactobacillus grx16 strain with a preservation number of CGMCC No.10921, a rhamnosus Lactobacillus bv-77 strain with a preservation number of CGMCC No.M2014589, a thermophilic Streptococcus grx02 strain with a preservation number of CGMCC No.2525, and a Bifidobacterium animalis CP-9 strain with a preservation number of CGMCC No.M2014588.

[0007] The strain composition as described above, wherein the ratio of the number of viable bacteria of fermentative Lactobacillus mucilaginosus grx831 strain, rhamnosus lactobacillus 1301 strain, plantarum lactobacillus grx16 strain, rhamnosus lactobacillus bv-77 strain, thermophilic Streptococcus grx02 strain and animal Bifidobacterium CP-9 strain is (1-5): (1-5): (1-5): (1-5): (1-5): (1-5).

[0008] The strain composition as described above, wherein the number of viable bacteria of the fermentation Lactobacillus mucilaginosus grx831 strain in the strain composition is ≥1×10 6 CFU / mL, viable count of Lactobacillus rhamnosus 1301 strain ≥1×10 6 CFU / mL, viable count of Lactobacillus plantarum grx16 strain ≥1×10 6 CFU / mL, viable count of Lactobacillus rhamnosus bv-77 strain ≥1×10 6 CFU / mL, viable count of Streptococcus thermophilus grx02 strain ≥1×10 6 CFU / mL, number of viable bacteria of Bifidobacterium animalis CP-9 strain ≥1×10 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, tablets, granules, granules, powders, freeze-dried powders, capsules, pills, aqueous solutions, powders, soft capsules, films, and emulsions.

[0010] The strain composition as described above, wherein the strain composition further comprises prebiotics; the prebiotics comprise at least one of fructooligosaccharides, galacto-oligosaccharides, isomaltooligosaccharides, raffinose, stachyose, inulin, and soybean oligosaccharides.

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

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

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

[0014] The application as described above, wherein the related product includes at least one of food, health products, and medicine.

[0015] The application as described above, wherein the food comprises at least one of a nutritional composition, a nutritional supplement, a dietary supplement, a beverage additive, a snack, and a probiotic powder; and / or,

[0016] The health care product includes at least one of functional beverages, functional granules, functional capsules, and functional powders; and / or,

[0017] The drugs include drugs used for treating or assisting the treatment of at least one of liver damage, treating or assisting the treatment of hyperlipidemia, treating or assisting the treatment of hyperglycemia, treating or assisting the treatment of cardiovascular disease, treating or assisting the treatment of metabolic disorders, treating or assisting the treatment of inflammation, and treating or assisting the treatment of immune disorders.

[0018] The beneficial effects of the present invention are as follows:

[0019] The above-mentioned strain composition is highly safe and has a wide range of effects. It can protect liver damage, alleviate liver damage, and improve liver function; it can lower blood lipids or assist in lowering blood lipids, and at the same time improve the health of blood lipid metabolism and liver lipid metabolism; it can lower blood sugar or assist in lowering blood sugar; it can have the effects of losing weight, reducing weight, and reducing fat, and it also has a special effect of reducing visceral fat; it can effectively regulate sugar and lipid metabolism, and thus can be used to treat or assist in the treatment of postpartum obesity; it can also have anti-inflammatory effects, and by affecting cytokines or signaling pathways, it affects the development and function of immune cells and regulates immune responses, thereby improving immune health and enhancing immunity. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 The serum inflammatory factor IL-6 level of postpartum obese rats in Example 6 of the present invention;

[0021] Figure 2 The serum inflammatory factor IL-27 level of postpartum obese rats in Example 6 of the present invention;

[0022] Figure 3 The level of NF-κB, a inflammatory factor in the serum of postpartum obese rats in Example 6 of the present invention;

[0023] Figure 4The serum inflammatory factor TNF-α level of the postpartum obese rats in Example 6 of the present invention;

[0024] Figure 5 The serum prolactin level of the obese postpartum rats in Example 6 of the present invention;

[0025] Figure 6 This is the serum adiponectin level of postpartum obese rats in Example 6 of the present invention. DETAILED DESCRIPTION

[0026] In order to enable those skilled in the art to better understand the scheme of the present invention, the present invention is further described in detail below. The specific embodiments listed below are only for describing the principles and features of the present invention. The examples are only used to explain 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 of ordinary skill in the art without making creative efforts are within the scope of protection of the present invention.

[0027] In order to improve postpartum obesity, the present invention provides a strain composition after long-term research and a large number of experiments. The strain composition includes Lactobacillus fermentum grx831 strain with a preservation number of CGMCC No. 33875, Lactobacillus rhamnosus 1301 strain with a preservation number of CGMCC No. 8545, Lactobacillus plantarum grx16 strain with a preservation number of CGMCC No. 10921, Lactobacillus rhamnosus bv-77 strain with a preservation number of CGMCC No. M2014589, Streptococcus thermophilus grx02 strain with a preservation number of CGMCC No. 2525 and Bifidobacterium animalis CP-9 strain with a preservation number of CGMCC No. M2014588.

[0028] Specifically, the deposit date of the Lactobacillus fermentum grx831 strain is March 19, 2025, and the depositor is the General Microbiology Center of the China Culture Collection Administration, located at No. 3, Yard 1, Beichen West Road, Chaoyang District, Beijing, China, and the Institute of Microbiology, Chinese Academy of Sciences, with the deposit number CGMCC No. 33875. The deposit date of the Lactobacillus rhamnosus hsryfm 1301 strain is December 6, 2013, and the depositor is the General Microbiology Center of the China Culture Collection Administration, located at No. 3, Yard 1, Beichen West Road, Chaoyang District, Beijing, China, and the Institute of Microbiology, Chinese Academy of Sciences, with the deposit number CGMCC No. 8545. The Lactobacillus plantarum strain grx16 was deposited on August 7, 2015, with the China Center for General Microbiology, China Culture Collection Administration, Institute of Microbiology, Chinese Academy of Sciences, No. 3, Yard 1, Beichen West Road, Chaoyang District, Beijing, China, under the accession number CGMCC No. 10921. The Lactobacillus rhamnosus strain bv-77 was deposited on November 24, 2014, with the China Center for Type Culture Collection, Wuhan University, Luojia Mountain, Wuchang, Hubei Province, China, under the accession number CCTCC No. M2014589. The Streptococcus thermophilus grx02 strain was deposited on May 28, 2008, with the China Center for General Microbiology, China Culture Collection Administration, Institute of Microbiology, Chinese Academy of Sciences, No. 3, Yard 1, Beichen West Road, Chaoyang District, Beijing, China, under the accession number CGMCC No. 2525. The Bifidobacterium animalis CP-9 strain was deposited on November 24, 2014, with the China Center for Type Culture Collection, Wuhan University, Luojia Mountain, Wuchang, Hubei Province, China, under the accession number CCTCC No. M2014588.

[0029] The present invention found that the above bacterial strain composition has the following beneficial effects:

[0030] (1) The bacterial strain 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 elevated levels generally indicate liver cell damage. Therefore, reducing the levels of ALT and AST in serum and liver tissue means that the bacterial strain composition can protect against liver damage, alleviate liver damage, and improve liver function.

[0031] (2) The above-mentioned bacterial strain composition can reduce the levels of serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) in serum and liver tissue, and increase the level of high-density lipoprotein (HDL). 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 in peripheral tissues to the liver for metabolism, thereby reducing the risk of cardiovascular disease. Therefore, reducing the levels of TC, TG and LDL in serum and liver tissue and increasing the level of HDL means that the bacterial strain composition can lower blood lipids or assist in lowering blood lipids, while improving blood lipid metabolism and liver lipid metabolism.

[0032] (3) The above bacterial strain composition can lower fasting blood sugar levels, which means that it can lower blood sugar or assist in lowering blood sugar.

[0033] (4) The above bacterial strain combination can reduce the fallopian tube fat index, mesenteric fat index and perirenal fat index, which means that it can achieve the effects of losing weight, reducing body weight and reducing fat, and has a particular effect of reducing visceral fat.

[0034] (5) The above bacterial composition can increase the levels of adiponectin and prolactin in the serum of postpartum obese subjects. Adiponectin and prolactin play an important role in regulating glucose and lipid metabolism. Increased adiponectin levels can activate adiponectin receptors, which have ceramide hydrolase activity, help to relieve the inhibition of ceramide on the insulin signaling pathway, increase insulin sensitivity, and promote blood sugar reduction. Increased prolactin secretion can activate prolactin receptors, help stimulate the mother and maintain lactation, promote the outflow of nutrients in the mother's body, and reduce blood lipid and liver lipid levels; prolactin also has the biological activity of hormones and cytokines, and can affect the regulation of the immune system. It mainly works by inhibiting the negative selection of autoreactive B lymphocytes. Therefore, increasing the levels of adiponectin and prolactin in the serum of postpartum obese subjects means that the bacterial composition can effectively regulate glucose and lipid metabolism, and thus can be used to treat or assist in the treatment of postpartum obesity.

[0035] (6) The above strain combination can increase the level of interleukin-27 (IL-27) in serum and reduce 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 immunoregulatory function. It can inhibit excessive immune response and maintain immune balance in immune response. The increase in its level helps to enhance the body's immune regulation ability and reduce the damage caused by excessive immunity. IL-6 and TNF-α are both important pro-inflammatory cytokines. Their increased levels are often closely related to the body's chronic inflammatory state, and chronic inflammation is an important driving factor for 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 reducing IL-6, NF-κb, and TNF-α levels means that this strain combination not only has anti-inflammatory effects, but also affects the development and function of immune cells and regulates immune responses by affecting cytokines or signaling pathways, thereby improving immune health and enhancing immunity. In addition, research has shown that the above-mentioned probiotics may affect cytokine expression through the gut-brain axis and the gut-fat axis, thereby improving glucose and lipid metabolism.

[0036] (7) Among the above-mentioned strain compositions, Lactobacillus fermentans grx831, Lactobacillus rhamnosus 1301, Lactobacillus plantarum grx16, Lactobacillus rhamnosus bv-77, Streptococcus thermophilus grx02 and Bifidobacterium animalis CP-9 are all probiotics, which are highly safe and not prone to drug resistance.

[0037] In short, the strain composition provided by the present invention has high safety and wide effects. It can fill the gaps in the existing probiotic market and break through the limitations of existing probiotic products. It can provide new ideas for protecting or assisting in protecting liver damage, lowering blood lipids or assisting in lowering blood lipids, lowering blood sugar or assisting in lowering blood sugar, improving cardiovascular health, improving blood lipid metabolism, improving liver lipid metabolism, improving glucose and lipid metabolism, losing weight or assisting in weight loss, treating or assisting in treating postpartum obesity, anti-inflammation, improving immune health, and enhancing immunity.

[0038] Furthermore, experiments have found that the strain composition provided by the present invention is particularly suitable for solving liver damage, hyperlipidemia, hyperglycemia, cardiovascular disease, metabolic disorders, inflammation or immune disorders caused by postpartum obesity.

[0039] In the strain composition, the ratio of viable cell counts of Lactobacillus mucilaginosus 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). When the viable cell count ratio is within this range, the strain composition is more effective and can further protect against liver damage, lower blood lipids and blood sugar, promote weight loss, fight inflammation, and regulate immune responses.

[0040] In the above strain composition, the number of viable bacteria of the fermentation Lactobacillus mucilaginosus grx831 strain is ≥1×10 6 CFU / mL, viable count of Lactobacillus rhamnosus 1301 strain ≥1×10 6 CFU / mL, viable count of Lactobacillus plantarum grx16 strain ≥1×10 6 CFU / mL, viable count of Lactobacillus rhamnosus bv-77 strain ≥1×10 6 CFU / mL, viable count of Streptococcus thermophilus grx02 strain ≥1×10 6 CFU / mL, number of viable bacteria of Bifidobacterium animalis CP-9 strain ≥1×10 6 CFU / mL; for example, it could be 1×10 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 When the number of viable bacteria is ≥1×10 6 CFU / mL, the strain composition has a better effect and can further protect liver damage, lower blood lipids, lower blood sugar, lose weight, fight inflammation, and regulate immune response.

[0041] In the above technical solution, the dosage form of the strain composition includes at least one of oral liquid, tablets, granules, granules, powders, freeze-dried powders, capsules, pills, aqueous solutions, powders, soft capsules, films, and emulsions.

[0042] The freeze-dried powder can be prepared illustratively by the following method:

[0043] (1) inoculating Lactobacillus mucilaginosus Grx831, Lactobacillus rhamnosus 1301, Lactobacillus plantarum Grx16 or Lactobacillus rhamnosus BV-77 into a bacillus culture medium for culturing, or inoculating Streptococcus thermophilus Grx02 into a cocci culture medium for culturing, or inoculating Bifidobacterium animalis CP-9 into a bifidobacterium culture medium for culturing, to obtain a culture solution;

[0044] (2) Centrifuge the culture medium to obtain bacterial cells;

[0045] (3) Resuspending the cells with a freeze-dried protective agent to obtain a resuspension;

[0046] (4) Lyophilize the resuspension to obtain single-strain lyophilized powder;

[0047] (5) Compound the above-mentioned single-plant freeze-dried powder according to the proportion to obtain the above-mentioned freeze-dried powder.

[0048] Preferably, the formula of the bacillus culture medium includes 38 g / L sucrose, 34 g / L yeast extract powder, 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, 0.1 g / L VB3, and 0.2 g / L cysteine ​​hydrochloride.

[0049] Preferably, the formula of the cocci culture medium includes: 20 g / L lactose, 16.60% enzymatically defatted milk, 18.88 g / L soy 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.

[0050] Preferably, the formula of the bifidobacterium culture medium includes 50 g / L glucose, 32 g / L tryptone peptone, 1.25 g / L MgSO4·7H2O, 1 g / L cysteine, and 1 mL / L Tween 80.

[0051] Preferably, the culture temperature is 36-42°C, and the culture time is 12-24 hours. Exemplarily, the culture temperature can be selected from 36°C, 37°C, 38°C, 39°C, 40°C, 41°C, 42°C, and any value between any two of the above numerical ranges. Exemplarily, the culture time can be selected from 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, 24 hours, and any value between any two of the above numerical ranges.

[0052] Preferably, freeze-drying can be performed by vacuum freezing.

[0053] Preferably, the lyoprotectant may include at least one of sucrose, skim milk, sodium glutamate, inulin, stachyose, mannitol, fructooligosaccharides, xylo-oligosaccharides, galacto-oligosaccharides, and maltodextrin.

[0054] The preparation process of the freeze-dried powder is simple, suitable for industrial large-scale production, and has significant practicality.

[0055] Furthermore, the strain composition also includes prebiotics; the prebiotics include at least one of fructooligosaccharides, galacto-oligosaccharides, isomaltooligosaccharides, raffinose, stachyose, inulin, and soybean oligosaccharides. These prebiotics can work in conjunction with the strain composition, thereby further enhancing the strain composition's efficacy in protecting against liver damage, lowering blood lipids, lowering blood sugar, promoting weight loss, combating inflammation, and regulating immune responses.

[0056] Furthermore, the strain composition also includes physiologically acceptable excipients; the excipients include at least one of excipients, fillers, dispersants, binders, wetting agents, disintegrants, emulsifiers, solubilizers, isotonicity regulators, isotonicity regulators, coating materials, colorants, pH regulators, antioxidants, antibacterial agents, buffers, flavorings, diluents, color and flavor regulators, solvents, metal chelating agents, inert gases, and preservatives.

[0057] Furthermore, the strain composition also includes a physiologically acceptable carrier; the carrier includes at least one of microcapsules, microspheres, nanoparticles, and liposomes.

[0058] Based on the above research, the present invention also provides an application of the above strain composition in the preparation of related products for protecting or assisting in protecting liver damage, lowering blood lipids or assisting in lowering blood lipids, lowering blood sugar or assisting in lowering blood sugar, improving cardiovascular health, improving blood lipid metabolism, improving liver lipid metabolism, improving glucose and lipid metabolism, losing weight or assisting in weight loss, treating or assisting in the treatment of postpartum obesity, anti-inflammation, improving immune health, and enhancing immunity.

[0059] Experiments have shown that the bacterial strain combination can reduce ALT and AST in serum and liver tissue, thereby protecting liver damage, alleviating liver damage, and improving liver function, and can be used to protect or assist in protecting liver damage. The bacterial strain combination can reduce TC, TG, and LDL levels in serum and liver tissue and increase HDL levels, thereby lowering blood lipids or assisting in lowering blood lipids, improving healthy blood lipid metabolism and liver lipid metabolism, and can be used to lower blood lipids or assist in lowering blood lipids, improve cardiovascular health, improve blood lipid metabolism, and improve liver lipid metabolism. The bacterial strain combination can reduce fasting blood sugar levels, thereby lowering blood sugar or assisting in lowering blood sugar, and can be used to lower blood sugar or assist in lowering blood sugar. The bacterial strain combination can reduce the fallopian tube fat index, mesenteric fat index, and perirenal fat index, thereby achieving weight loss, weight loss, and fat reduction effects, and particularly has the effect of reducing visceral fat, and can be used to lose weight or assist in weight loss, and to treat or assist in the treatment of postpartum obesity. The above-mentioned bacterial strain composition can increase the levels of adiponectin and prolactin in the serum of postpartum obese subjects, thereby effectively regulating glucose and lipid metabolism, and can be used to improve glucose and lipid metabolism, treat or assist in the treatment of postpartum obesity. The above-mentioned bacterial strain composition can increase the level of IL-27 in serum and reduce the levels of IL-6, NF-κb, and TNF-α. Therefore, it can not only have anti-inflammatory effects, but also affect the development and function of immune cells and regulate immune responses by affecting cytokines or signaling pathways, thereby improving immune health and enhancing immunity. Moreover, the above-mentioned bacterial strain composition is a probiotic, with high safety and low drug resistance. Therefore, the above-mentioned bacterial strain composition can be used to prepare related products for protecting or assisting in the protection of liver damage, lowering blood lipids or assisting in lowering blood lipids, lowering blood sugar or assisting in lowering blood sugar, improving cardiovascular health, improving blood lipid metabolism, improving liver lipid metabolism, improving glucose and lipid metabolism, losing weight or assisting in weight loss, treating or assisting in the treatment of postpartum obesity, anti-inflammatory, improving immune health, and enhancing immunity.

[0060] It is understood that the above strain composition can also serve as an inhibitor of ALT, AST, TC, TG, LDL, IL-6, NF-κb or TNF-α, and an agonist of HDL, adiponectin, prolactin or IL-27.

[0061] In the above applications, the related products include at least one of food, health products, and medicines.

[0062] Furthermore, the food comprises at least one of a nutritional composition, a nutritional supplement, a dietary supplement, a beverage additive, a snack, and a probiotic powder. It is understood that the strain composition of the present invention can be used in food in the form of a food additive, a dietary supplement, or a nutritional enhancer.

[0063] Furthermore, the health care product includes at least one of functional beverages, functional granules, functional capsules, and functional powders.

[0064] Furthermore, the drugs include drugs for treating or assisting the treatment of at least one of liver damage, treating or assisting the treatment of hyperlipidemia, treating or assisting the treatment of hyperglycemia, treating or assisting the treatment of cardiovascular disease, treating or assisting the treatment of metabolic disorders, treating or assisting the treatment of inflammation, and treating or assisting the treatment of immune disorders.

[0065] When the above-mentioned drugs are actually used, they can be achieved by at least one of intravenous injection, intraperitoneal injection, intramuscular injection, subcutaneous injection, oral administration, sublingual administration, nasal administration, and transdermal administration.

[0066] The technical solutions of this application will be further explained below with reference to specific examples. Experimental methods in the following examples where specific conditions are not specified are generally performed under conventional conditions or as recommended by the manufacturer; all reagents used, unless otherwise specified, are commercially available or publicly available.

[0067] The microbial strain materials involved in the following examples are as follows:

[0068] 1. Limosilactobacillus fermentum grx831 strain:

[0069] The deposit date is March 19, 2025;

[0070] The depository is the General Microbiology Center of China Culture Collection Administration of Microorganisms;

[0071] The address of the depository is Institute of Microbiology, Chinese Academy of Sciences, No. 3, Yard 1, Beichen West Road, Chaoyang District, Beijing, China;

[0072] The deposit number is CGMCC No.33875.

[0073] 2. Lacticaseibacillus rhamnosus hsryfm 1301 strain:

[0074] The deposit date is December 6, 2013;

[0075] The depository is the General Microbiology Center of China Culture Collection Administration of Microorganisms;

[0076] The address of the depository is Institute of Microbiology, Chinese Academy of Sciences, No. 3, Yard 1, Beichen West Road, Chaoyang District, Beijing, China;

[0077] The deposit number is CGMCC No.8545.

[0078] 3. Lactiplantibacillus plantarum grx16 strain:

[0079] The deposit date is August 7, 2015;

[0080] The depository is the General Microbiology Center of China Culture Collection Administration of Microorganisms;

[0081] The address of the depository is Institute of Microbiology, Chinese Academy of Sciences, No. 3, Yard 1, Beichen West Road, Chaoyang District, Beijing, China;

[0082] The deposit number is CGMCC No.10921.

[0083] 4. Lactobacillus rhamnosus bv-77 strain:

[0084] The deposit date is November 24, 2014;

[0085] The preservation unit is China Center for Type Culture Collection;

[0086] The address of the depository is Wuhan University, Luojiashan, Wuchang, Wuhan, Hubei, China;

[0087] The deposit number is CCTCC No.M2014589.

[0088] 5. Streptococcus thermophilus grx02 strain:

[0089] The deposit date is May 28, 2008;

[0090] The depository is the General Microbiology Center of China Culture Collection Administration of Microorganisms;

[0091] The address of the depository is Institute of Microbiology, Chinese Academy of Sciences, No. 3, Yard 1, Beichen West Road, Chaoyang District, Beijing, China;

[0092] The deposit number is CGMCC No.2525.

[0093] 6. Bifidobacterium animalis CP-9 strain

[0094] The deposit date is November 24, 2014;

[0095] The preservation unit is China Center for Type Culture Collection;

[0096] The address of the depository is Wuhan University, Luojiashan, Wuchang, Wuhan, Hubei, China;

[0097] The deposit number is CCTCC No.M2014588.

[0098] Example 1: Construction of animal model

[0099] Lactobacillus fermentum grx831 was cultured and activated in a bacillus culture medium for two generations to obtain an activated bacterial solution. The activated bacterial solution was centrifuged at 4000 × g for 9 min, the supernatant was discarded, and sterile saline was added to the precipitate to wash the cells, and this process was repeated twice. The strain precipitate was suspended in a mixed solution of oligosaccharide prebiotics, and the viable cell count was adjusted to 1.2 × 10 9 CFU / mL, and a bacterial suspension was obtained, which was named bacterial preparation S1.

[0100] Lacticaseibacillus rhamnosus hsryfm 1301, Lactiplantibacillus plantarum grx16, and Lactobacillus rhamnosus bv-77 were cultured and activated in bacillus culture medium for two generations to obtain activated bacterial solutions; Streptococcus thermophilus grx02 was cultured and activated in coccal culture medium for two generations to obtain activated bacterial solutions; and Bifidobacterium animalis CP-9 was cultured and activated in bifidobacterial culture medium for two generations to obtain activated bacterial solutions. The activated bacterial solutions were centrifuged at 4000 × g for 9 min, the supernatant was discarded, and sterile saline was added to the precipitate to wash the cells, and the process was repeated twice. The strain precipitate was suspended in a mixed solution of oligosaccharide prebiotics, and the viable cell count was adjusted to 1.2 × 10 9 CFU / mL to obtain a bacterial suspension; the bacterial suspensions corresponding to the above five strains were mixed to obtain a strain composition, which was named bacterial preparation S2 (i.e., the number of viable bacteria of each of the above five strains in bacterial preparation S2 was 2.4×10 8 CFU / mL, the sum of the viable bacterial counts of the above five strains in bacterial preparation S2 was 1.2×10 9 CFU / mL).

[0101] Lactobacillus fermentum grx831, Lacticaseibacillus rhamnosus hsryfm 1301, Lactiplantibacillus plantarum grx16, and Lactobacillus rhamnosus bv-77 were cultured and activated for two generations in bacillus culture medium to obtain activated bacterial suspensions. Streptococcus thermophilus grx02 was cultured and activated for two generations in coccal culture medium to obtain activated bacterial suspensions. Bifidobacterium animalis CP-9 was cultured and activated for two generations in bifidobacterial culture medium to obtain activated bacterial suspensions. The activated bacterial suspensions were centrifuged at 4000 × g for 9 min, the supernatant was discarded, and sterile saline was added to the precipitate to wash the cells, which was repeated twice. The strain precipitate was suspended in a mixed solution of oligosaccharide prebiotics, and the viable cell count was adjusted to 1.2 × 10 9 CFU / mL to obtain a bacterial suspension; the bacterial suspensions corresponding to the above 6 strains were mixed to obtain a strain composition, which was named bacterial preparation S3 (i.e., the number of viable bacteria of each of the above 6 strains in bacterial preparation S3 was 2×10 8 CFU / mL, the sum of the viable bacterial counts of the above six strains in bacterial preparation S2 was 1.2×10 9 CFU / mL).

[0102] Among them, the formula of Bacillus culture medium includes sucrose 38 g / L, yeast extract powder 34 g / L, K2HPO4 7 g / L, KH2PO47 g / L, MgSO4 0.2 g / L, MnSO4 0.02 g / L, Tween 80 0.1 g / L, glycerol 0.1 g / L, VB3 0.01 g / L, and cysteine ​​hydrochloride 0.2 g / L. The formulation of the cocci culture medium includes 20 g / L lactose, 16.60% enzymatically defatted milk, 18.88 g / L soy 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 bifidobacterium culture medium includes 50 g / L glucose, 32 g / L tryptone, 1.25 g / L MgSO4·7H2O, 1 g / L cysteine, and 1 mL / L Tween 80. The formula of the oligosaccharide prebiotic mixed solution includes 25 g / L of fructooligosaccharide, 106 g / L of galacto-oligosaccharide, 8.5 g / L of raffinose, and 40 g / L of stachyose.

[0103] SPF-grade C57BL / 6J female mice at 6 days postpartum were randomly divided into 5 groups (8 mice in each group), including control group CTL, model group MC, experimental group S1, experimental group S2 and experimental group S3. The control group (CTL) was fed a normal diet, supplemented with feed and water every morning, and each female mouse was gavaged with normal saline every day, at a rate of 100 μL per 10 g 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 gavaged with normal saline every day, at a rate of 100 μL per 10 g body weight, for 5 weeks. The experimental group (S1) was fed a high-fat diet, supplemented with feed and water every morning, and each female mouse was gavaged with bacterial preparation S1 every day, at a rate of 100 μL per 10 g body weight, for 5 weeks. The experimental group (S2) was fed a high-fat diet, supplemented with feed and water every morning, and each female mouse was gavaged with bacterial preparation S2 every day, at a rate of 100 μL per 10 g body weight, for 5 weeks. The experimental group (S3) was fed a high-fat diet, supplemented with feed and water every morning, and each female mouse was gavaged with bacterial preparation S3 every day, at a rate of 100 μL per 10 g body weight, for 5 weeks.

[0104] Example 2: Verification of the effect of the bacterial strain composition on blood lipid metabolism in postpartum obese rats

[0105] The alanine aminotransferase (ALT) detection kit, aspartate aminotransferase (AST) detection kit, total cholesterol (TC) detection kit, triglyceride (TG) detection kit, high-density lipoprotein cholesterol (HDL) detection kit, and low-density lipoprotein cholesterol (LDL) detection kit produced by Ningbo Meikang Biotechnology Co., Ltd. were used according to the instructions of the corresponding kits. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels in the serum of the five groups of female mice were measured using a Hitachi 7020 fully automatic biochemical analyzer. The details can be seen in Table 1 (unit is mmol / L).

[0106] Table 1

[0107]

[0108] The results in Table 1 showed that compared with the control group CTL, the serum TC (40.13%), TG (38.28%) and LDL (95.36%) levels of the model group MC maternal mice were significantly increased, while the serum HDL (35.39%) level was significantly decreased; the data of the experimental group S1 showed that the use of bacterial preparation S1 had no significant effect on the ALT, AST, TC, TG, HDL and LDL in the serum of the maternal mice; the data of the experimental group S2 showed that compared with the model group MC, the use of bacterial preparation S2 significantly reduced the serum TC (22.31%), TG (18.52%) and LDL (30.77%) levels of the maternal mice, and increased the HDL level (33.06%); the data of the experimental group S3 showed that compared with the model group MC, the intervention of bacterial preparation S3 further reduced the serum TC (23.55%), TG (20.99%) and LDL (38.46%) levels, and further increased the HDL level (48.76%). The above results show that bacterial preparation S3 can effectively regulate the blood lipid metabolism of postpartum obese rats.

[0109] 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 demonstrated a significant protective effect against high-fat diet-induced liver injury in postpartum rats by reducing elevated ALT and AST levels. Compared with the model group MC, serum ALT (36.83%) and AST (17.19%) activities in the liver of experimental group S2 were significantly reduced, and serum ALT (49.41%) and AST (20.92%) activities in the liver of experimental group S3 were further reduced. These results demonstrate that bacterial preparations S2 and S3 can exert significant hepatoprotective effects.

[0110] Example 3: Verification of the effect of the bacterial strain composition on liver lipid metabolism in postpartum obese rats

[0111] The alanine aminotransferase (ALT) detection kit, aspartate aminotransferase (AST) detection kit, total cholesterol (TC) detection kit, triglyceride (TG) detection kit, high-density lipoprotein (HDL) cholesterol detection kit, and low-density lipoprotein (LDL) cholesterol detection kit produced by Ningbo Meikang Biotechnology Co., Ltd. were used. Refer to the instructions of the corresponding kits and use a Hitachi 7020 fully automatic biochemical analyzer to detect ALT, AST, TC, TG, HDL, and LDL in the livers of the above five groups of female mice. The specific levels can be seen in Table 2 (unit is mmol / L).

[0112] Table 2

[0113]

[0114] Table 2 shows that compared with the model group MC, the use of bacterial preparation S1 had no significant effect on maternal serum ALT, AST, TC, TG, HDL, and LDL. Data from the experimental group S2 showed that compared with the model group MC, the use of bacterial preparation S2 significantly reduced the levels of TC (23.08%), TG (32.35%), and LDL (10.00%) in the maternal liver, and increased the HDL level (25.00%). Data from the experimental group S3 showed that compared with the model group MC, the use of bacterial preparation S3 further reduced the levels of TC (38.46%), TG (54.41%), and LDL (20.00%) in the liver, and further increased the HDL level (37.50%). These results indicate that bacterial preparation S3 can effectively regulate hepatic lipid metabolism in postpartum obese maternal mice.

[0115] In addition, experimental group S2 was able to reduce the increase of ALT (21.61%) and AST (18.64%), and experimental group S3 was able to further reduce the increase of ALT (30.03%) and AST (24.98%), which had a significant protective effect on liver damage induced by high-fat diet in postpartum rats.

[0116] Example 4: Verification of the effect of the bacterial strain composition on fasting blood glucose in postpartum obese rats

[0117] The fasting blood glucose of the five groups of female mice was measured using a blood glucose meter, as shown in Table 3 (unit: mmol / L).

[0118] Table 3

[0119]

[0120] The results in Table 3 show that fasting blood glucose levels in the model group (MC) were higher than those in the control group (CTL), indicating abnormal glucose metabolism in the model group rats. Data from experimental group S1 showed that compared with the model group (MC), bacterial preparation S1 had no significant effect on fasting blood glucose. Data from experimental group S2 showed that compared with the model group (MC), bacterial preparation S2 reduced fasting blood glucose levels in the rats (5.21%). Data from experimental group S3 showed that compared with the model group (MC), bacterial preparation S3 further reduced fasting blood glucose levels in the rats (7.30%). These results indicate that bacterial preparations S2 and S3 have a protective effect against abnormal glucose metabolism induced by a high-fat diet in postpartum rats.

[0121] Example 5: Verification of the effect of the bacterial strain combination on oviduct fat, mesenteric fat and perirenal fat in postpartum obese rats

[0122] The oviduct, mesenteric, and perirenal fat of the five groups of female mice were collected and rinsed in pre-cooled (4°C) saline to remove blood. The fat tissues were then 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.

[0123] Table 4

[0124]

[0125] Table 4 shows that, compared with the model group MC, bacterial preparation S1 had no significant effect on fallopian tube fat, mesenteric fat, and perirenal fat. Data from the experimental group S2 showed that, compared with the model group MC, 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 the experimental group S3 showed that, compared with the model group MC, 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, thereby reducing fat accumulation.

[0126] Example 6: Verification of the effect of the bacterial strain composition on serum adiponectin, prolactin levels, IL-27, IL-6, NF-kb, and TNF-α in postpartum obese rats

[0127] The serum levels of adiponectin, prolactin, IL-27, IL-6, NF-κb, and TNF-α in the five groups of maternal rats were detected using enzyme-linked immunosorbent assay (ELISA) kits for adiponectin, prolactin, IL-27, IL-6, NF-κb, and TNF-α produced by Shanghai Hualan Chemical Technology Co., Ltd., according to the instructions of the kits. Figure 1 、 Figure 2 、 Figure 3 、 Figure 4 、 Figure 5 and Figure 6 .

[0128] Figure 1 is the serum inflammatory factor IL-6 level in postpartum obese rats, Figure 2 is the serum inflammatory factor IL-27 level in postpartum obese rats, Figure 3 Fasting blood glucose and serum inflammatory factor NF-κB level in postpartum obese rats. Figure 4 is the level of TNF-α, a inflammatory factor in the serum of postpartum obese rats, Figure 5 is the serum prolactin level of postpartum obese rats, Figure 6 is the serum adiponectin level of postpartum obese rats. Figure 1 、 Figure 2 、 Figure 3 、 Figure 4 、 Figure 5 、 Figure 6 As shown in the data, compared with the control group CTL, the serum levels of adiponectin, prolactin and IL-27 of MC in the model group were lower, and the levels of IL-6, NF-kb and TNF-α were higher; compared with the MC in the model group, the experimental group S1 significantly increased the levels of adiponectin (12.06%), prolactin (23.16%) and IL-27 (14.87%), and decreased the levels of IL-6 (18.56%), NF-kb (11.00%) and TNF-α (10.64%); compared with the MC in the model group, the experimental group S2 had no significant effect on the levels of adiponectin, prolactin and IL-27; compared with the MC in the model group, the experimental group S3 further increased the levels of adiponectin (12.12%), prolactin (30.53%) and IL-27 (21.41%), and decreased the levels of IL-6 (21.25%) and TNF-α (11.54%).

[0129] High levels of adiponectin and prolactin in the serum of female mice are consistent with decreased blood lipids and liver fat, lower fasting blood glucose, and reduced visceral fat index. Adiponectin can act on the insulin signaling pathway, improving insulin sensitivity and helping to lower blood glucose. Administration of bacterial preparation S3 increased IL-27 and decreased IL-6, NF-kb, and TNF-α levels. 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 bacterial preparation S3 may affect blood glucose by controlling adiponectin and prolactin levels and may also regulate immune responses by regulating IL-27, IL-6, NF-kb, and TNF-α levels.

[0130] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the above embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements 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 strain composition, characterized in that: The invention includes the fermentative Lactobacillus mucilaginosus grx831 strain with a preservation number of CGMCC No.33875, the rhamnosus Lactobacillus 1301 strain with a preservation number of CGMCC No.8545, the plantarum Lactobacillus grx16 strain with a preservation number of CGMCC No.10921, the rhamnosus Lactobacillus bv-77 strain with a preservation number of CGMCC No.M2014589, the thermophilic Streptococcus grx02 strain with a preservation number of CGMCC No.2525, and the animal Bifidobacterium CP-9 strain with a preservation number of CGMCC No.M2014588.

2. The strain composition according to claim 1, characterized in that The ratio of the number of viable bacteria of the fermentative Lactobacillus mucilaginosus grx831 strain, the rhamnosus Lactobacillus 1301 strain, the plant lactobacillus grx16 strain, the rhamnosus Lactobacillus bv-77 strain, the thermophilic Streptococcus grx02 strain and the animal Bifidobacterium CP-9 strain is (1-5): (1-5): (1-5): (1-5): (1-5): (1-5).

3. The strain composition according to claim 1 or 2, characterized in that In the strain composition, the number of viable bacteria of the fermentation Lactobacillus mucilaginosus grx831 strain is ≥1×10 6 CFU / mL, the viable count of the Lactobacillus rhamnosus 1301 strain ≥1×10 6 CFU / mL, the number of viable bacteria of the Lactobacillus plantarum grx16 strain is ≥1×10 6 CFU / mL, the viable count of the Lactobacillus rhamnosus bv-77 strain ≥1×10 6 CFU / mL, the number of viable bacteria of the thermophilic Streptococcus grx02 strain ≥1×10 6 CFU / mL, the number of viable bacteria of the animal Bifidobacterium CP-9 strain ≥1×10 6 CFU / mL.

4. The strain composition according to claim 1 or 2, characterized in that The dosage form of the strain composition includes at least one of oral liquid, tablets, granules, powders, freeze-dried powders, capsules, pills, aqueous solutions, powders, soft capsules, films, and emulsions.

5. The strain composition according to claim 1 or 2, characterized in that The strain composition further comprises prebiotics; the prebiotics comprise at least one of fructooligosaccharides, galacto-oligosaccharides, isomaltooligosaccharides, raffinose, stachyose, inulin and soybean oligosaccharides.

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

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

8. Use of the strain composition according to any one of claims 1 to 7 in the preparation of products for protecting or assisting in protecting liver damage, lowering blood lipids or assisting in lowering blood lipids, lowering blood sugar or assisting in lowering blood sugar, improving cardiovascular health, improving blood lipid metabolism, improving liver lipid metabolism, improving glucose and lipid metabolism, losing weight or assisting in weight loss, treating or assisting in treating postpartum obesity, anti-inflammatory, improving immune health, and enhancing immunity.

9. The use according to claim 8, characterized in that The related products include at least one of food, health products, and medicines.

10. The use according to claim 9, characterized in that The food comprises at least one of a nutritional composition, a nutritional supplement, a dietary supplement, a beverage additive, a snack, and a probiotic powder; and / or, The health care product includes at least one of functional beverages, functional granules, functional capsules, and functional powders; and / or, The drugs include at least one drug for treating or assisting the treatment of liver damage, treating or assisting the treatment of hyperlipidemia, treating or assisting the treatment of hyperglycemia, treating or assisting the treatment of cardiovascular disease, treating or assisting the treatment of metabolic disorders, treating or assisting the treatment of inflammation, and treating or assisting the treatment of immune disorders.

Citation Information

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