Lactobacillus complex for improving insulin resistance and application thereof
By combining Pediococcus lactis NWP-182, Lactobacillus plantarum NWP-242, and Lactobacillus rhamnosus NWP-263, GLP-1 secretion is promoted and hepatocyte insulin sensitivity is improved, solving the problems of insignificant effects of single probiotics and drug side effects, and achieving safe and efficient improvement of insulin resistance.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- LANZHOU UNIV
- Filing Date
- 2026-04-30
- Publication Date
- 2026-06-09
AI Technical Summary
In existing technologies, relying solely on conventional probiotics such as Lactobacillus rhamnosus GG is not effective in improving insulin resistance, and drug treatment has side effects, making it difficult to meet the needs of clinical and functional food fields.
A compound lactobacillus preparation was developed, consisting of Pediococcus lactis NWP-182, Lactobacillus plantarum NWP-242, and Lactobacillus rhamnosus NWP-263, which synergistically improves insulin resistance by promoting GLP-1 secretion and improving hepatocyte insulin sensitivity.
It significantly improves insulin resistance, with better efficacy than single strains used alone, and has high safety, overcoming drug side effects, providing a safe and effective new option for the treatment and prevention of metabolic diseases such as type 2 diabetes.
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Abstract
Description
Technical Field
[0001] This invention relates to the field of microbial application technology, and in particular to a compound lactobacillus for improving insulin resistance and its application. Background Technology
[0002] Insulin resistance is one of the core pathological mechanisms of many metabolic diseases, including type 2 diabetes, obesity, non-alcoholic fatty liver disease, and metabolic syndrome. Improving insulin resistance is crucial for the prevention and treatment of these diseases. However, current treatments for insulin resistance primarily rely on pharmacological interventions, which can have side effects and are not always effective.
[0003] In recent years, the close relationship between gut microbiota and host metabolism has attracted widespread attention, and the use of probiotics to regulate gut microbiota and thereby improve insulin resistance has become a research hotspot. Lactobacillus, as a recognized safe probiotic, has had some strains reported to have the potential to regulate glucose and lipid metabolism and improve insulin sensitivity.
[0004] Currently, commercially available Lactobacillus rhamnosus GG strains ( Lactobacillus rhamnosus Gibberellin (LGG) is one of the most widely researched and applied probiotic strains, exhibiting excellent acid and bile salt tolerance and intestinal colonization capabilities. It demonstrates superior probiotic properties in regulating gut microbiota, enhancing intestinal barrier function, and modulating immunity. However, LGG's role in improving insulin resistance is not prominent. Therefore, relying solely on conventional probiotics like LGG is insufficient to meet the clinical or functional food industry's demand for highly effective improvement of insulin resistance.
[0005] To address the aforementioned shortcomings, developing a compound lactobacillus preparation that can synergistically enhance and target insulin resistance has become a pressing technical problem to be solved in this field. Summary of the Invention
[0006] The purpose of this invention is to provide a compound lactobacillus that improves insulin resistance and its application, so as to overcome the problems of side effects of hypoglycemic drugs and the lack of obvious effects of probiotic strains in the prior art.
[0007] To achieve the above-mentioned objectives, the present invention provides the following technical solution: This invention provides a compound lactobacillus for improving insulin resistance, the compound lactobacillus comprising Pediococcus lactis NWP-182, Lactobacillus plantarum NWP-242 and Lactobacillus rhamnosus NWP-263; Pediococcus acidilactici ( Pediococcus acidilacticiNWP-182, this strain is deposited at Guangdong Provincial Microbial Culture Collection Center, located at 5th Floor, Building 59, No. 100 Xianlie Middle Road, Guangzhou, with a deposit date of January 12, 2026 and accession number of GDMCC No: 67620; Lactobacillus plantarum ( Lactiplantibacillus plantarum NWP-242, this strain is deposited at Guangdong Provincial Microbial Culture Collection Center, located at 5th Floor, Building 59, No. 100 Xianlie Middle Road, Guangzhou, with a deposit date of January 12, 2026 and accession number GDMCC No: 67621; Lactobacillus rhamnosus ( Lacticaseibacillus rhamnosus NWP-263, this strain is deposited at the Guangdong Provincial Microbial Culture Collection Center, located at 5th Floor, Building 59, No. 100 Xianlie Middle Road, Guangzhou, with a deposit date of January 12, 2026 and accession number GDMCC No: 67622.
[0008] Preferably, the mass ratio of *Pediococcus lactis* NWP-182, *Lactobacillus plantarum* NWP-242, and *Lactobacillus rhamnosus* NWP-263 is 1~3:1~3:1~3, and the bacterial content of each is 1×10⁻⁶. 8 ~1×10 10 CFU / g.
[0009] The present invention provides a microbial preparation for improving insulin resistance, wherein the microbial preparation contains a compound of lactobacilli, or a fermentation product containing the compound of lactobacilli.
[0010] Preferably, the fermentation product is prepared by inoculating the compound lactobacillus into MRS medium, collecting the fermentation broth, filtering and sterilizing to obtain the fermentation supernatant.
[0011] Preferably, the culture temperature is 35~37℃ and the time is 24~60h.
[0012] This invention provides the application of the aforementioned compound lactobacillus or the aforementioned microbial preparation in the preparation of a medicament for the treatment or adjunctive treatment of diabetes.
[0013] Preferably, the diabetes is type 2 diabetes.
[0014] This invention provides the application of the aforementioned compound lactobacillus or the aforementioned microbial preparation in the preparation of health foods that help regulate intestinal flora and / or help maintain healthy blood sugar levels.
[0015] This invention provides an application of the aforementioned compound lactobacillus or the aforementioned microbial preparation in the preparation of food.
[0016] Compared with the prior art, the present invention has the following beneficial effects: This invention isolates and screens three lactobacilli strains from yak yogurt that have excellent ability to improve insulin resistance: *Pediococcus lactis* NWP-182, *Lactobacillus plantarum* NWP-242, and *Lactobacillus rhamnosus* NWP-263. These three lactobacilli strains can exhibit clear and significant hypoglycemic and insulin resistance-improving effects at both cellular and animal levels through multiple pathways, including promoting GLP-1 secretion and directly improving hepatocyte insulin sensitivity. Furthermore, the combined application of the three lactobacilli strains is significantly more effective than their individual use.
[0017] The compound lactobacillus described in this invention is naturally sourced, highly safe, and well-tolerated. It overcomes the side effects of traditional drugs and the lack of clear functions of ordinary probiotics. It provides a safe and effective new technology solution for the prevention and / or adjuvant treatment of metabolic diseases such as type 2 diabetes and insulin resistance, and has extremely high social benefits and broad market application prospects. Attached Figure Description
[0018] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the provided drawings without creative effort.
[0019] Figure 1 The results of Gram staining observation of each strain in Example 1 are as follows; Figure 2 The effect of fermentation supernatants of *Pediococcus lactis* NWP-182, *Lactobacillus plantarum* NWP-242, and *Lactobacillus rhamnosus* NWP-263 on the survival rate of HepG2 cells in Example 2. Figure 3 The results of the fermentation supernatant of *Pediococcus lactis* NWP-182, *Lactobacillus plantarum* NWP-242, and *Lactobacillus rhamnosus* NWP-263 in Example 3 promoting the secretion of GLP-1 by NCI-H716 cells; Figure 4 The results of acid resistance tests for *Pediococcus lactis* NWP-182, *Lactobacillus plantarum* NWP-242, and *Lactobacillus rhamnosus* NWP-263 in Example 3 are as follows: Figure 5 The results of bile salt tolerance tests for *Pediococcus lactis* NWP-182, *Lactobacillus plantarum* NWP-242, and *Lactobacillus rhamnosus* NWP-263 in Example 3 are as follows: Figure 6The effects of Pediococcus lactis NWP-182, Lactobacillus plantarum NWP-242, and Lactobacillus rhamnosus NWP-263, used alone and in combination, on glucose tolerance in type 2 diabetic mice in Example 4. Figure 7 The effects of Pediococcus lactis NWP-182, Lactobacillus plantarum NWP-242, and Lactobacillus rhamnosus NWP-263, used alone and in combination, on insulin tolerance in type 2 diabetic mice in Example 4. Figure 8 The effects of Pediococcus lactis NWP-182, Lactobacillus plantarum NWP-242, and Lactobacillus rhamnosus NWP-263, used alone and in combination, on serum GLP-1 secretion levels in type 2 diabetic mice in Example 4.
[0020] Preservation Instructions
[0021] Pediococcus acidilactici ( Pediococcus acidilactici NWP-182, this strain is deposited at the Guangdong Provincial Microbial Culture Collection Center, located at 5th Floor, Building 59, No. 100 Xianlie Middle Road, Guangzhou, with a deposit date of January 12, 2026 and accession number GDMCC No: 67620.
[0022] Lactobacillus plantarum ( Lactiplantibacillus plantarum NWP-242, this strain is deposited at Guangdong Provincial Microbial Culture Collection Center, located at 5th Floor, Building 59, No. 100 Xianlie Middle Road, Guangzhou, with a deposit date of January 12, 2026 and accession number GDMCC No: 67621.
[0023] Lactobacillus rhamnosus ( Lacticaseibacillus rhamnosus NWP-263, this strain is deposited at the Guangdong Provincial Microbial Culture Collection Center, located at 5th Floor, Building 59, No. 100 Xianlie Middle Road, Guangzhou, with a deposit date of January 12, 2026 and accession number GDMCC No: 67622. Detailed Implementation
[0024] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.
[0025] Example 1: Screening and Identification of Strains
[0026] 1. Separation and primary screening
[0027] The inventors isolated multiple strains of lactic acid bacteria from yak yogurt samples. Further in vitro experiments were used to preliminarily screen strains with potential hypoglycemic activity. The screening method is as follows: Preparation of cell-free supernatant (CFS): The activated bacterial strain was inoculated into MRS liquid medium and incubated at 37°C for 24 h to obtain the fermentation broth. The fermentation broth was centrifuged at 4000 r / min for 10 min, and the supernatant was collected. To eliminate the non-specific toxicity of organic acids to cells, the pH of the supernatant was adjusted to 7.3 using 1 mol / L NaOH, and then filtered through a 0.22 μm microporous membrane for sterilization. After aliquoting, the supernatant was stored at -80°C for later use.
[0028] α-Amylase inhibition rate assay: Mix 50 μL of α-amylase solution (120 U / mL) and 50 μL of strain CFS in a 1.5 mL EP tube and incubate at 37 °C for 10 min. Add 100 μL of 2% starch solution, mix well, and incubate at 37 °C for 10 min. Add 400 μL of DNS reagent and incubate at boiling water for 10 min. After cooling, add 900 μL of water and mix well. Add 100 μL to a 96-well plate and measure the absorbance of the sample at 540 nm. PBS-replaced enzyme was used as the sample blank control group (referred to as blank), PBS-replaced strain CFS was used as the positive control group (referred to as control), and PBS-replaced enzyme and strain CFS were used as the blank control group (referred to as blank).
[0029] α-Amylase inhibition rate (%) = [1 - (Sample A - Blank A) / (Control A - Blank A)] × 100.
[0030] α-Glucosidase inhibition rate assay: In a 96-well plate, add 25 μL of 20 mmol / L PNPG solution, 18 μL of strain CFS, and 42 μL of PBS solution (pH=7.0) to each well, and incubate at 37℃ for 10 min. Add 50 μL of α-glucosidase solution (20 U / mL), incubate at 37℃ for 20 min, and terminate the reaction with 100 μL of 0.1 mol / L Na2CO3. Measure the absorbance of the sample at 405 nm using a microplate reader. PBS was used to replace the enzyme as the sample blank (sample blank), PBS was used to replace strain CFS as the positive control (control), and PBS was used to replace both strain CFS and the enzyme as the blank control (blank).
[0031] α-glucosidase inhibition rate (%) = [1 - (A sample - A blank) / (A control - A blank)] × 100.
[0032] Screening results: Three strains with good inhibitory effects on α-amylase and α-glucosidase were screened. The corresponding strain numbers are NWP-182, NWP-242 and NWP-263. The inhibitory effects are shown in Table 1.
[0033] Table 1. Results of α-amylase inhibition rate and α-glucosidase inhibition rate of the strains
[0034] 2. Identification of screening strains
[0035] (1) Morphological observation
[0036] The selected bacterial strains were streaked onto MRS solid plates to form single colonies, and the colony morphology was observed. After staining the bacteria with a Gram staining kit, their morphology was further observed using an optical microscope.
[0037] The results showed that the colonies of strain NWP-182 were milky white, opaque, smooth, round, with regular edges, and a diameter of 0.5 to 1.5 mm; Gram-positive, the cells were spherical, often arranged in pairs or tetrads, and did not produce spores; after growth on the culture medium, they emitted a distinct sour smell. The colonies of strain NWP-242 were milky white, round, opaque, moist, with regular edges, and a diameter of 1 to 2 mm; Gram-positive, the cells were long rods with blunt ends, usually arranged singly or in short chains, and did not produce spores; after growth on the culture medium, they emitted a fresh sour aroma. The colonies of strain NWP-263 were grayish white, round, slightly convex, smooth, and approximately 0.5 to 1 mm in diameter; Gram-positive, the cells were short rods, sometimes slightly curved, usually arranged singly or in chains, and did not produce spores; after growth on the culture medium, they emitted a mild sour smell. The colony morphology observation results of each strain after Gram staining are as follows: Figure 1 As shown.
[0038] (2) Molecular biological identification
[0039] DNA was extracted from each strain, and the bacterial 16S rRNA gene was amplified by PCR using primers 27F and 1492R. The PCR products were purified and then analyzed using NCBI-BLAST. The sequencing results were then compared with the NCBI-BLAST algorithm. The three strains were ultimately identified as *Pediococcus lactis*, *Lactobacillus plantarum*, and *Lactobacillus rhamnosus*, and named *Pediococcus lactis* NWP-182, *Lactobacillus plantarum* NWP-242, and *Lactobacillus rhamnosus* NWP-263, respectively. These strains were then deposited at the Guangdong Provincial Microbial Culture Collection Center.
[0040] Example 2: Preparation and safety evaluation of fermentation products from strains
[0041] 1. Preparation of fermentation products
[0042] *Pediococcus lactis* NWP-182, *Lactobacillus plantarum* NWP-242, and *Lactobacillus rhamnosus* NWP-263 were inoculated into MRS medium (De Man, Rogosa, and Sharpe) and cultured at 36°C for 48 hours. After culture, the fermentation broth was collected by centrifugation at 1000 r / min for 5 min, filtered to remove bacteria, and the fermentation supernatant (CFS) was obtained. CFS is rich in various active metabolites secreted by the strains during growth, which are important material basis for their efficacy.
[0043] 2. Safety evaluation
[0044] The toxicity of CFS to hepatocytes was assessed using a cytotoxicity assay (MTT method).
[0045] Cell seeding and treatment: HepG2 cells in logarithmic growth phase were prepared into a single-cell suspension using RPMI-1640 medium and seeded into 96-well plates at a density of 5000 cells / well. The cells were incubated at 37°C with 5% CO2 until complete cell adhesion (approximately 12 hours). The original medium was discarded, and fresh medium containing 10% CFS was added. To ensure reliable results, three replicates were set up for each concentration. The following control groups were also set up: Control group: medium only, no CFS; Blank group: medium and MTT only, no cells, used to subtract background values. The plates were returned to the incubator and cultured for another 24 hours.
[0046] MTT reaction and detection: After culture, add MTT solution to each well to a final concentration of 0.5 mg / mL and incubate for another 4 hours. Add dimethyl sulfoxide (DMSO) to each well and shake at 800 rpm for 10 minutes to fully dissolve the blue-purple crystals. Measure the absorbance (OD value) of each well at 490 nm using a microplate reader and calculate the cell viability.
[0047] Cell viability (%) = [(As - Ab) / (Ac - Ab)] × 100%, where As: OD value of CFS treatment group, Ac: OD value of control group, and Ab: OD value of blank group.
[0048] Experimental results are as follows Figure 2 As shown, compared with the control group, the cell viability of the three strains treated with CFS did not decrease significantly (P>0.05), and the viability remained above 95%. These results indicate that the three strains and their metabolites screened in this invention have good biosafety and no obvious cytotoxicity, laying the foundation for their development as food or pharmaceutical products.
[0049] Example 3: Functional Study of the Strains
[0050] 1. Promotes the secretion of glucagon-like peptide-1 (GLP-1).
[0051] Fermentation supernatants (CFS) of *Pediococcus lactis* NWP-182, *Lactobacillus plantarum* NWP-242, *Lactobacillus rhamnosus* NWP-263, and commercial *Lactobacillus rhamnosus* LGG (ATCC 53103, Jiangsu Weikang Probiotics) were prepared according to the method in Example 2.
[0052] Human colorectal adenocarcinoma cells NCI-H716 were selected, and the effect of different strains of CFS on the secretion of GLP-1 by NCI-H716 was determined. The assay method was performed according to the instructions of the human glucagon-like peptide-1 (GLP-1) enzyme-linked immunosorbent assay (ELISA) kit.
[0053] The results are as follows Figure 3 As shown, the fermentation supernatant (CFS) of *Pediococcus lactis* NWP-182, *Lactobacillus plantarum* NWP-242, and *Lactobacillus rhamnosus* NWP-263 significantly promoted GLP-1 secretion from NCI-H716 cells. Experimental data showed that compared to the control group (CON, without added strain fermentation supernatant), the GLP-1 secretion levels in the CFS treatment groups of *Pediococcus lactis* NWP-182, *Lactobacillus plantarum* NWP-242, and *Lactobacillus rhamnosus* NWP-263 were increased by 1.9, 2.3, and 1.7 times, respectively (P<0.05 / 0.01); and the effect on promoting GLP-1 secretion was superior to that of commercial *Lactobacillus rhamnosus* LGG.
[0054] GLP-1 is a key incretin for regulating blood sugar. This effect directly proves that the strain of this invention has the potential to improve glucose metabolism by promoting the secretion of endogenous GLP-1, and elucidates one of the mechanisms of its hypoglycemic effect.
[0055] 2. Gastrointestinal tolerance
[0056] The survival rates of *Pediococcus lactis* NWP-182, *Lactobacillus plantarum* NWP-242, and *Lactobacillus rhamnosus* NWP-263 in a simulated gastrointestinal fluid environment were determined.
[0057] (1) Determination of acid resistance
[0058] Simulating the human stomach environment: Adjust the pH of the MRS liquid culture medium to 2.5 using 1 mol / L HCl. Activated bacterial strains (1×10⁻⁶) were then added. 8 Inoculate the bacterial culture (CFU / mL) at a rate of 2% (v / v) into the prepared acidic medium and incubate at 37°C for 3 h. Perform plate counting at 0 h and 3 h. The survival rate is calculated using the following formula:
[0059] Where Nt is the number of viable bacteria (CFU / mL) after 3 h of treatment, and N0 is the initial number of viable bacteria after 0 h.
[0060] (2) Test of bile salt tolerance
[0061] Simulating the human intestinal environment: 0.3% (w / v) porcine bile salts were added to MRS medium. The activated bacterial strain was inoculated at a rate of 2% (v / v) (1×10⁻⁶). 8 The strain was cultured at 37°C for 4 h (CFU / mL) and the survival rate was calculated using the plate count method to assess the strain's tolerance to bile salts.
[0062]
[0063] Where Nt is the number of viable bacteria (CFU / mL) after 4 h of treatment, and N0 is the initial number of viable bacteria at 0 h.
[0064] The results of the acid resistance test are as follows: Figure 4 As shown, the results of the bile salt tolerance test are as follows: Figure 5 As shown, *Pediococcus lactis* NWP-182, *Lactobacillus plantarum* NWP-242, and *Lactobacillus rhamnosus* NWP-263 exhibit good acid and bile salt resistance. This characteristic ensures that they can reach the intestines and colonize as live bacteria after oral administration, which is a prerequisite for them to exert their probiotic effects (such as regulating intestinal flora and interacting with intestinal cells), thus ensuring their feasibility as probiotic products.
[0065] Example 4: Verification of in vivo hypoglycemic effect
[0066] A mouse model of type 2 diabetes mellitus (T2DM) was established using a high-fat diet combined with low-dose streptozotocin (STZ) injections. The specific method was as follows: Forty-two male C57BL / 6 mice were randomly assigned to six standard cages. Cage assignments were rotated every two days, with a seven-day acclimatization period. After the acclimatization period, the mice were randomly divided into seven treatment groups (n=6 per group): NC (normal control group), Model group, MET (positive control metformin group), and four lactic acid bacteria groups (NWP182, NWP242, NWP263 intervention groups and a combined group). Starting from week 5, the Model, MET, and lactic acid bacteria groups received intraperitoneal injections of streptozotocin (STZ, 40 mg / kg / day) dissolved in 0.1 mol / L sodium citrate buffer for five consecutive days. Two days later, a fasting blood glucose level ≥11 mmol / L was considered a successful modeling result.
[0067] After successful modeling, medication was administered: the MET group and the lactic acid bacteria group were administered metformin hydrochloride (Sino-American Shanghai Bristol-Myers Squibb, 200 mg / kg / day) and lactic acid bacteria suspension (5 × 10⁻⁶ mg / kg / day) by gavage, respectively. 9 CFU / bacterium / day, prepared with PBS buffer; the mass ratio of bacteria in the composite group was 1:1:1), and the NC group and the Model group were given an equal volume of physiological saline, and were administered by gavage for a total of 4 weeks.
[0068] During the experiment, the Model group, MET group and lactic acid bacteria group were continuously fed a high-fat diet with a fat content of 60% (Shuyu Biotechnology, SYHF60-1), while the NC group was fed a standard mouse maintenance diet [Keao Xieli (Tianjin) Feed Co., Ltd.] throughout the experiment.
[0069] After the experiment, fasting blood glucose (FBG), glucose tolerance (by oral glucose tolerance test, OGTT), insulin tolerance (by insulin tolerance test, ITT) and serum GLP-1 secretion levels were measured in each group of mice.
[0070] The results are shown in Table 2 and Figures 6-8 As shown, the hypoglycemic effect (FBG, OGTT, ITT) and GLP-1 secretion-promoting effect of the compound group (Mix) were not only significantly better than those of the model group (P<0.01), but also significantly better than any single-strain intervention group (P<0.05), and even exceeded the arithmetic mean of the individual effects of the three, demonstrating a significant synergistic effect among Pediococcus lactis NWP-182, Lactobacillus plantarum NWP-242, and Lactobacillus rhamnosus NWP-263.
[0071] Table 2 Results of fasting blood glucose concentration measurement
[0072] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.
Claims
1. A compound lactobacillus that improves insulin resistance, characterized in that, The compound lactobacillus includes Pediococcus lactis NWP-182, Lactobacillus plantarum NWP-242 and Lactobacillus rhamnosus NWP-263; Pediococcus acidilactici ( Pediococcus acidilactici NWP-182, this strain is deposited at Guangdong Provincial Microbial Culture Collection Center, located at 5th Floor, Building 59, No. 100 Xianlie Middle Road, Guangzhou, with a deposit date of January 12, 2026 and accession number of GDMCC No: 67620; Lactobacillus plantarum ( Lactiplantibacillus plantarum NWP-242, this strain is deposited at Guangdong Provincial Microbial Culture Collection Center, located at 5th Floor, Building 59, No. 100 Xianlie Middle Road, Guangzhou, with a deposit date of January 12, 2026 and accession number GDMCC No: 67621; Lactobacillus rhamnosus ( Lacticaseibacillus rhamnosus NWP-263, this strain is deposited at the Guangdong Provincial Microbial Culture Collection Center, located at 5th Floor, Building 59, No. 100 Xianlie Middle Road, Guangzhou, with a deposit date of January 12, 2026 and accession number GDMCC No: 67622.
2. The compound lactobacillus according to claim 1, characterized in that, The mass ratio of *Pediococcus lactis* NWP-182, *Lactobacillus plantarum* NWP-242, and *Lactobacillus rhamnosus* NWP-263 was 1~3:1~3:1~3, and the bacterial count of each was 1×10⁻⁶. 8 ~1×10 10 CFU / g.
3. A microbial preparation for improving insulin resistance, characterized in that, The microbial preparation contains the compound lactobacillus as described in claim 1 or 2, or a fermentation product containing the compound lactobacillus.
4. The microbial preparation according to claim 3, characterized in that, The method for preparing the fermentation product is as follows: the compound lactobacillus is inoculated into MRS medium for culture, the fermentation broth is collected, and the fermentation supernatant is obtained after filtration and sterilization.
5. The microbial preparation according to claim 4, characterized in that, The culture temperature is 35~37℃ and the time is 24~60h.
6. The use of a compound lactobacillus as described in claim 1 or 2, or a microbial preparation as described in any one of claims 3 to 5, in the preparation of a medicament for the treatment or adjunctive treatment of diabetes.
7. The application according to claim 6, characterized in that, The diabetes mentioned is type 2 diabetes.
8. The use of a compound lactobacillus as described in claim 1 or 2, or a microbial preparation as described in any one of claims 3 to 5, in the preparation of health foods that help regulate intestinal flora and / or help maintain healthy blood sugar levels.
9. The use of a compound lactobacillus as described in claim 1 or 2, or a microbial preparation as described in any one of claims 3 to 5, in the preparation of food.