CN116515690A - Lactobacillus plantarum GL-4 and application thereof - Google Patents
Lactobacillus plantarum GL-4 and application thereof Download PDFInfo
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- CN116515690A CN116515690A CN202310433538.0A CN202310433538A CN116515690A CN 116515690 A CN116515690 A CN 116515690A CN 202310433538 A CN202310433538 A CN 202310433538A CN 116515690 A CN116515690 A CN 116515690A
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Abstract
The application discloses lactobacillus plantarum GL-4, wherein the preservation number of lactobacillus plantarum GL-4 is CCTCC M2023303. The invention also provides application of the lactobacillus plantarum GL-4 in reducing blood sugar, reducing blood fat, resisting inflammation, regulating intestinal tracts and the like. The invention also provides a pharmaceutical preparation or composition containing the lactobacillus plantarum GL-4. The composition may be a beverage, dairy product or food. The lactobacillus plantarum GL-4 has the functions of reducing blood sugar, reducing blood fat, resisting inflammation, regulating intestinal tracts and the like, and is superior to lactobacillus plantarum in the prior art.
Description
Technical Field
The application relates to the technical field of food microorganisms, in particular to lactobacillus plantarum GL-4 and application thereof in the aspects of reducing blood sugar, reducing blood fat, resisting inflammation, regulating intestinal tracts and the like.
Background
Lactic acid bacteria are widely found in the intestines of livestock, poultry, many foods, materials and a few clinical samples. Lactic acid bacteria not only can improve the nutritive value of food, improve the flavor of food and improve the preservation property and added value of food, but also have special physiological activity and nutritive function, and are increasingly attracting attention. A large number of researches show that lactic acid bacteria can regulate normal flora of gastrointestinal tract of an organism, maintain microecological balance, improve food digestibility and biological value, reduce serum cholesterol, control endotoxin, inhibit growth and reproduction of putrefying bacteria in the intestinal tract and generation of putrefying products, produce nutrient substances, stimulate tissue development, thereby having effects on nutritional status, physiological functions, cell infection, drug effect, toxic reaction, immune reaction, tumorigenesis, aging process, sudden emergency reaction and the like of the organism. In recent years, with the increasing level of living, the pursuit of people has been shifted from a warm saturated to a healthy diet, and lactic acid bacteria have been known and accepted as a strain which is long in vegetable juice and fermented products, and healthy products fermented with lactic acid bacteria have been known and accepted.
Diabetes is a series of metabolic disorder syndromes of sugar, protein, fat, water, electrolyte and the like caused by islet hypofunction, insulin resistance and the like due to the action of various pathogenic factors such as genetic factors, immune dysfunction, free radical toxins and the like on organisms. The absolute or relative deficiency of insulin causes the rise of blood sugar level, and simultaneously is often accompanied with fat metabolism disorder, and hyperlipidemia occurs. In addition, type 2 diabetes can lead to chronic inflammation, intestinal disorders, and the like. At present, if a patient generates inflammation, various symptomatic medicaments are mostly adopted for treatment, and excessive medicaments usually have a certain degree of side effects on the body.
Therefore, it would be desirable to provide an anti-inflammatory method that improves blood glucose and blood lipid levels in the body.
Disclosure of Invention
The present invention aims to solve at least one of the problems of the prior art, and thus, in a first aspect of the present invention, the present invention provides lactobacillus plantarum GL-4, which is characterized in that the preservation number of lactobacillus plantarum is cctccc M2023303.
By the technical scheme, the lactobacillus plantarum GL-4 is superior to the lactobacillus plantarum in the aspects of reducing blood sugar, controlling blood lipid elevation caused by type II diabetes, inflammatory factor storm, regulating intestinal tracts and the like.
In a second aspect of the invention, the invention provides a pharmaceutical formulation comprising lactobacillus plantarum GL-4 according to the first aspect of the invention.
Preferably, the pharmaceutical formulation comprises lactobacillus plantarum GL-4 according to the first aspect of the invention and metformin.
Through the technical scheme, the lactobacillus plantarum GL-4 and the metformin have a certain synergistic effect in reducing blood sugar, controlling the rise of blood fat, inflammatory factor storm, regulating intestinal tract and the like caused by type II diabetes, and when the lactobacillus plantarum GL-4 is combined with the metformin, the problems of blood fat, inflammation, intestinal tract disorder and the like caused by type II diabetes can be solved without using other medicines, so that side effects can be reduced.
In a third aspect of the invention, the invention provides an application of lactobacillus plantarum GL-4 according to the first aspect of the invention or a pharmaceutical preparation according to the second aspect of the invention in preparing a hypoglycemic drug.
In a fourth aspect of the invention, the invention provides an application of lactobacillus plantarum GL-4 according to the first aspect of the invention or a pharmaceutical preparation according to the second aspect of the invention in preparing a hypolipidemic drug.
In a fifth aspect of the invention, the invention provides the use of lactobacillus plantarum GL-4 according to the first aspect of the invention or the pharmaceutical formulation according to the second aspect of the invention for the preparation of an anti-inflammatory drug.
Preferably, the anti-inflammatory agent is directed against inflammatory factors such as LPS and/or IL6 and/or Insulin.
In a sixth aspect of the invention, the invention provides an application of lactobacillus plantarum GL-4 according to the first aspect of the invention or a pharmaceutical preparation according to the second aspect of the invention in preparing a medicament for regulating intestinal flora.
Preferably, the intestinal flora is Akkermansia flora or Blautia flora.
In a seventh aspect of the invention, the invention provides a composition comprising lactobacillus plantarum GL-4 according to the first aspect of the invention.
Preferably, the composition is a beverage, dairy product or food.
The invention has the beneficial effects that:
1. the invention provides a lactobacillus plantarum GL-4, wherein the lactobacillus plantarum GL-4 has the functions of reducing blood sugar, reducing blood fat, resisting inflammation, regulating intestinal tracts and the like, and is superior to the lactobacillus plantarum in the prior art;
2. the lactobacillus plantarum GL-4 has synergistic effect with metformin in reducing blood sugar, reducing blood lipid, resisting inflammation, regulating intestinal tract and the like, and when the lactobacillus plantarum GL-4 is combined with the metformin, the problems of blood lipid, inflammation, intestinal tract disturbance and the like caused by type II diabetes can be solved without using other medicines.
Drawings
FIG. 1 is a graph showing comparison of blood glucose levels measured for each group of mice after six weeks of intervention in example 3, for 30min, 60min, 90min, and 120min after oral administration of sugar;
FIG. 2 is a graph showing the area under the oral glucose tolerance curve for each group in the oral glucose tolerance test of example 3;
FIG. 3 is a graph showing the distribution of the flora in the intestinal tract of mice;
FIG. 4 is a graph comparing the abundance results of Akkermansia flora for each group of mice;
FIG. 5 is a graph comparing the abundance results of Blautha flora in each group of mice.
Description of the embodiments
The present invention is further described below with reference to specific examples and drawings, but the following examples are only for illustration of the present invention and should not be construed as limiting the scope of the present invention. The following examples are conducted under conventional conditions or conditions recommended by the manufacturer, and the methods used are conventional methods known in the art, and the consumables and reagents used are commercially available unless otherwise specified. Unless otherwise defined, the technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In addition, any method or material similar or equivalent to those described may be used in the present invention.
The invention takes microorganisms in traditional food pickle in China as target flora, adopts MRS lactobacillus culture medium, screens out multifunctional lactobacillus plantarum GL-4, and researches the application of the lactobacillus plantarum GL-4 in regulating blood sugar, blood fat, intestinal flora, organ protection and the like. The invention aims to provide lactobacillus plantarum GL-4, and the other aim of the invention is to provide the application of the lactobacillus plantarum GL-4 in the aspects of reducing blood sugar, reducing blood fat, regulating intestinal flora, protecting viscera and the like.
Example 1 acquisition of Lactobacillus plantarum GL-4
The preparation process of the lactobacillus plantarum (Lactobacillus plantarum) GL-4 provided by the invention comprises the following steps: fresh kimchi is taken as a sample to be diluted with sterile water, the kimchi is diluted in a gradient way and coated on an MRS culture medium for primary screening, typical bacterial colonies are picked up and transferred onto an MRS flat plate for further purification, single bacterial colonies are picked up on the purified flat plate, and sequencing is carried out after PCR amplification. The identified purified lactobacillus plantarum is subjected to glycerol tube preservation for later use. Obtaining the lactobacillus plantarum GL-4.
Extracting the GL-4 genome DNA of the lactobacillus plantarum, carrying out PCR amplification (PCR experiment of 16S rDNA), sequencing, and the sequencing result is shown as SEQ ID NO. 1.
The strain lactobacillus plantarum GL-4 disclosed by the invention has the following preservation information: preservation name: lactobacillus plantarum Lactobacillus plantarum; preservation unit: china center for type culture Collection; preservation address: eight paths of Wuhan city Wuchang district in Hubei province; deposit number: cctccc M2023303; the preservation time is as follows: 2023, 3 and 13.
Examples
Activating Lactobacillus plantarum GL-4, and performing in vitro experiments to verify that the method is mainly carried out from digestive juice tolerance (artificial gastrointestinal juice), alpha-glucosidase inhibitory activity, alpha-amylase inhibitory activity, reducing ability measurement and O 2 The six in vitro indexes of the scavenging capacity measurement and the scavenging rate of the free radical DPPH are verified, and the main indexes are mainly based on the alpha-glucosidase inhibition activity and the alpha-amylase inhibition activity of the strain.
Preparation of the strain: inoculating lactobacillus plantarum GL-4 preserved in glycerol tubes into MRS liquid culture medium, activating, culturing after transferring, centrifuging lactobacillus fermented for 18 hours, discarding supernatant, cleaning thallus with physiological saline, and suspending and mixing with physiological saline.
Animal experiment: STZ+high-fat modeling is carried out by using a C57BL/6j mouse, and the modeling is successful when the fasting blood glucose value is more than 11.1mmol/L. Random grouping intervention was performed on the model-successfully-molded mice.
High-fat feed: 195g/kg casein, 225g/kg dextrin, 89 g/kg sucrose, 33 g/kg soybean oil, 301g/kg lard, 69 g/kg cellulose, 68 g/kg minerals, 14 g/kg vitamins, 3 g/kg L-cysteine, 3 g/kg choline tartrate, 0.067 g/kg TBHQ (available from Nantong Tarufei Co.).
Daily intake of mice, weekly weight changes, and blood glucose changes in mice every two weeks were recorded.
Fecal collection was performed prior to mouse intervention, microbiological diversity analysis 16S, and oral glucose tolerance was determined six weeks after mouse intervention. The mice are sacrificed, whole blood is taken out, organs of the mice are taken out respectively, the kidneys, the livers, the pancreas and the small intestines are fixed by fixing liquid, HE sections are made, and the cecum content of the mice is taken out for microbial diversity analysis. Index determination of mouse serum: triglyceride, total cholesterol, high density cholesterol, low density cholesterol. Inflammatory factors: LPS, IL-6, insulin.
EXAMPLE 3 Regulation of blood sugar by Lactobacillus plantarum GL-4
1. Packet processing method
30C 57BL/6J mice at 5 weeks of age were randomly divided into 6 groups of 5 mice each, and after one week of adaptive growth.
The packet processing is as follows:
modeling of high-fat, low-fat diabetes model mice: the high-fat feed is fed for 5 weeks, 6 weeks, and mice are injected with STZ (streptozotocin) intraperitoneally after 16 hours on an empty stomach, the total dosage is 200mg/kg, the feeding is divided into two times, the interval is 72 hours, and 100mg/kg is injected each time. After 72 hours of the second injection, it was determined whether the blood glucose was greater than 11.1mmol/l for 12 hours on an empty stomach. Blood sugar greater than 11.1mmol/l is successful in molding. The molding result is that all molding is successful. After successful modeling, the high-fat feed is fed to the high-fat diabetes model mice, and the low-fat feed is fed to the low-fat diabetes model mice.
Healthy groups were healthy mice fed with commercial normal feed without intraperitoneal injection of STZ.
Model component group: the method comprises the steps of high-fat +GL-4 intervention group, low-fat +GL-4 intervention group, high-fat +metformin group, low-fat +metformin group, high-fat +metformin +GL-4 group, low-fat +metformin +GL-4 group, high-fat +LGG intervention group, low-fat +LGG intervention group, high-fat +metformin +LGG group, low-fat +metformin +LGG group, high-fat control group and low-fat control group.
The dosage is as follows: metformin 0.2g/kg
The intervention dose of the lactobacillus plantarum GL-4 is as follows: 1010 CFU/only
The intervention mode is as follows: stomach lavage
The high-fat+GL-4 intervention group is to administer Lactobacillus plantarum GL-4 (1010 CFU/mouse) to a model mouse with high-fat diabetes; lactobacillus plantarum GL-4 (1010 CFU/mouse) was administered to low-fat diabetic model mice in the low-fat +GL-4 intervention group; the high fat and metformin group was used for administering metformin (0.2 g/kg) to a model mouse with high fat diabetes; the low-fat and metformin group was used for administering metformin (0.2 g/kg) to low-fat diabetes model mice; the group consisting of high fat, metformin and GL-4 was administered with metformin (0.2 g/kg) and Lactobacillus plantarum GL-4 (1010 CFU/mouse) to a model rat of high fat diabetes; the low-fat and metformin and GL-4 groups were used to administer metformin (0.2 g/kg) and Lactobacillus plantarum GL-4 (1010 CFU/mouse) to low-fat diabetic model mice; the high-fat + LGG intervention group was lactobacillus rhamnosus (LGG) (1010 CFU/min.) administered to a model rat of high-fat diabetes; low-fat + LGG intervention group lactobacillus rhamnosus (LGG) was administered to low-fat diabetes model mice (1010 CFU/min); the group consisting of high fat + metformin + LGG was administered metformin (0.2 g/kg) and lactobacillus rhamnosus (LGG) (1010 CFU/g) to a model rat of high fat diabetes; the low-fat + metformin + LGG group administered metformin (0.2 g/kg) and lactobacillus rhamnosus (LGG) (1010 CFU/min) to low-fat diabetes model mice; the high-fat control group is obtained by administering 10ml/kg of physiological saline to a high-fat diabetes model mouse; the low-fat control group was prepared by administering 10ml/kg of physiological saline to a low-fat diabetes model mouse.
2. Blood glucose monitoring
The tail vein blood sampling is carried out for one week, two weeks, four weeks and six weeks before the intervention respectively to determine the fasting blood glucose value of the mice. The results of fasting blood glucose measurements are shown in table 1. Meanwhile, the oral glucose tolerance of mice was measured six weeks after the intervention, and the blood glucose level was measured for each group of mice at 0min, 15min, 30min, 60min, 90min, 120min after the oral administration of the glucose, and the results are shown in fig. 1. The area under the oral glucose tolerance line in the oral glucose tolerance test is shown in fig. 2.
Experimental procedure for oral glucose tolerance: the glucose usage amount of the glucose tolerance test in mice was 2g per kg body weight (2 g/kg), a glucose solution of an appropriate concentration was prepared according to the test requirements, and a 20% glucose solution was prepared with physiological saline (saline).
1. Preparation of mice: mice were swapped into clean cages for fasting at 5 pm on the day before the experiment for 16 hours to 9 am on the next day. During fasting, mice remained normally drinking water;
2. the glucose tolerance experiment was started the next day, nine am. The body weight of each mouse was weighed.
3. Measurement of fasting basal blood glucose: the mice were removed from the cages, gently placed on top of the iron mesh, the tail ends of the mice were cut off with scissors about 1-2 mm, the tails of the mice were gently squeezed to enrich the blood into one drop, fasting blood glucose was measured with a glucometer, and the measurement value was considered to be a blood glucose value of 0 min. The operation is as gentle as possible, so that the mice are not excessively frightened;
4. after 30min of adaptation, mice were initially prepared for gastric lavage glucose (OGTT).
5. OGTT: the mice were gently grasped and a 1 ml syringe was used to attach a lavage needle to the glucose solution of the mice following standard lavage procedures. The volume of the lavage was determined based on the weight of the mice, and the lavage was 0.01 per g of body weight ml. Starting timing from the moment of finishing the stomach irrigation.
6. Blood glucose values were determined at various time points for each mouse at 0min, 15min,30 min,60 min,90 min,120 min following the procedure of step 3.
Table 1 test group and blank group fasting blood glucose measurement results
| Blood glucose level | Before intervention (mmol/l) | Two weeks of intervention (mmol/l) | Intervention four-week (mmol/l) | Six weeks of intervention (mmol/l) |
| High-fat +GL-4 intervention group | 25.27±8.48 | 24.24±4.97 | 19.97±6.60 | 20.60±7.14 |
| Low-fat +GL-4 intervention group | 24.18±6.62 | 21.58±7.85 | 17.00±5.92 | 18.13±9.56 |
| High fat + metformin intervention group | 25.12±1.66 | 24.80±7.17 | 21.78±4.14 | 22.23±0.90 |
| Low-fat + metformin intervention group | 24.72±3.53 | 21.84±3.07 | 18.50±1.98 | 19.64±1.16 |
| High fat + metformin + GL-4 intervention group | 25.28±3.96 | 20.18±6.24 | 15.98±4.62 | 14.00±2.80 |
| Low-fat + metformin + GL-4 intervention group | 24.61±4.84 | 17.40±3.90 | 11.48±3.23 | 7.18±1.29 |
| High fat + LGG intervention group | 25.22±1.01 | 24.98±5.21 | 22.35±3.21 | 23.15±1.23 |
| Low-fat + LGG intervention group | 24.23±4.23 | 22.31±2.86 | 19.56±3.52 | 21.54±2.56 |
| High fat + metformin + LGG intervention group | 25.34±4.26 | 20.93±5.61 | 17.43±2.35 | 18.91±2.68 |
| Low-fat + metformin + LGG intervention group | 24.46±4.98 | 20.11±4.56 | 16.49±2.88 | 18.57±1.36 |
| High fat control group | 25.25±2.80 | 24.90±5.58 | 24.46±7.48 | 24.99±6.32 |
| Low fat control group | 24.65±6.43 | 22.71±4.02 | 21.08±4.48 | 22.94±4.66 |
| Health group | 7.56±0.47 | 7.59±0.56 | 7.58±0.55 | 7.57±0.61 |
As can be seen from the comparison of the test results in Table 1, the blood glucose level of the mice is reduced, and the combined use of the low-fat metformin and GL-4 intervention group has excellent improvement effect on the blood glucose level of the mice. The blood glucose level was restored to a level of 7.18. In both the high-fat group and the low-fat group, lactobacillus plantarum GL-4 shows the hypoglycemic effect superior to that of the positive drug metformin, the hypoglycemic effect superior to that of the control strain lactobacillus rhamnosus, and notably, the high-fat +GL-4 group, the low-fat +GL-4 group, the high-fat +metformin group, the low-fat +metformin group, the high-fat +LGG group, the low-fat +LGG group, the high-fat +metformin +LGG group, the low-fat +metformin +LGG group, the high-fat control group and the low-fat control group all show the phenomenon that the fasting blood glucose value is increased again after six weeks of intervention, and the inventor surprisingly found that the fasting blood glucose value can be effectively controlled even continuously reduced to a certain level after six weeks of intervention when the metformin is used with GL-4, thereby the metformin is used with GL-4, the synergistic effect on the hypoglycemic effect can be generated at a later stage, the hypoglycemic half-life is prolonged when the combined use alone, and the synergistic effect of lactobacillus plantarum-4 and the strain type 2 diabetes can be remarkably reduced. The results show that the cooperative use of lactobacillus plantarum GL-4 and the metformin strain has a synergistic treatment effect on hyperglycemia of type 2 diabetes, and can obviously reduce fasting blood glucose.
The blood glucose level in the glucose tolerance test is shown in FIG. 1, and the blood glucose level of each group of mice reaches a peak value at the time of gastric lavage for 30 minutes, and shows a better descending trend in the follow-up. From the figure, the high-fat +GL-4 group has better glucose tolerance effect than the positive control high-fat +metformin group. In addition, the high-fat +GL-4 +metformin group has synergistic effect on glucose tolerance between 90min and 120min relative to the high-fat +GL-4 group and the high-fat +metformin group. And the blood glucose level was reduced to 13.13mmol/L at 120 min. The area under the oral glucose tolerance line in the oral glucose tolerance test is shown in FIG. 2, and it is clear from the graph that Lactobacillus plantarum GL-4 has a glucose tolerance effect equivalent to that of the positive drug metformin. According to the minimum area result is that the metformin is matched with GL-4 strain intervention group, the difference among individuals is not obvious, and the GL-4 intervention and the metformin administration have effects on the recovery of the blood glucose level of mice, so that the condition of poor glucose tolerance of the mice is obviously improved.
Example 4 Regulation of blood lipid by Lactobacillus plantarum GL-4
The mice of each group at the end of the test in example 3 (6 weeks of intervention) were collected from the eyeballs and bled, and after standing at 4℃for 8 hours, centrifuged at 3000r/min for 10min, and the supernatant (serum) was collected. Detecting the content of total cholesterol, triglyceride, high density lipoprotein cholesterol and low density lipoprotein cholesterol in serum. The results are shown in Table 2.
TABLE 2 detection of total cholesterol, triglycerides, high Density lipoprotein cholesterol, low Density lipoprotein cholesterol in serum
| Experimental group | TC（mmol/L） | TG（mmol/L） | LDL-C（mmol/L） | HDL-C（mmol/L） |
| High-fat +GL-4 intervention group | 4.40±0.36 | 0.75±0.26 | 7.19±2.04 | 3.11±0.54 |
| Low-fat +GL-4 intervention group | 3.12±1.82 | 0.36±0.02 | 5.76±4.54 | 2.37±0.11 |
| High fat + metformin intervention group | 4.73±1.15 | 0.32±0.05 | 4.22±3.54 | 3.14±0.82 |
| Low-fat + metformin intervention group | 3.04±2.19 | 0.36±0.08 | 3.68±2.75 | 2.46±0.67 |
| High fat + metformin + GL-4 intervention group | 2.52±0.08 | 0.30±0.03 | 3.14±1.01 | 2.37±0.43 |
| Low-fat + metformin + GL-4 intervention group | 2.77±0.34 | 0.35±0.14 | 2.92±1.74 | 1.28±0.18 |
| High fat + LGG intervention group | 4.97±2.36 | 1.21±0.31 | 7.69±2.32 | 3.14±0.26 |
| Low-fat + LGG intervention group | 3.84±2.51 | 0.76±0.18 | 6.23±3.26 | 2.98±0.16 |
| High fat + metformin + LGG intervention group | 3.82±0.87 | 0.32±0.53 | 4.18±2.11 | 3.14±0.28 |
| Low-fat + metformin + LGG group | 3.48±0.96 | 0.36±0.42 | 3.53±2.98 | 2.47±0.16 |
| High fat control group | 6.21±0.19 | 1.93±0.07 | 7.85±1.00 | 3.13±0.15 |
| Low fat control group | 5.94±0.13 | 1.88±0.11 | 6.97±0.86 | 2.97±0.08 |
| Health group | 2.63±0.16 | 0.35±0.21 | 3.08±0.25 | 2.53±0.36 |
The results of blood lipid related factor detection in serum are shown in Table 2. According to the data results, the low-fat +GL-4 intervention group showed the best effect of reducing total cholesterol, and the effect was better than that of the low-fat +metformin group and the low-fat +LGG group. The effect of reducing total cholesterol in the high-fat +GL-4 intervention group is superior to that of the high-fat +metformin group and the high-fat +LGG group. The lactobacillus plantarum GL-4 has good effect of reducing total cholesterol. In addition, the combined use of the metformin and the lactobacillus plantarum GL-4 can obviously reduce the total cholesterol, and the effect of the combined use of the metformin and the LGG is obviously superior. In addition, the lactobacillus plantarum GL-4 has good triglyceride reducing effect, and the triglyceride reducing effect of the lactobacillus plantarum GL-4 is superior to that of LGG. In conclusion, the lactobacillus plantarum GL-4 plays a certain role in regulating the blood lipid metabolism of the mice on the control effect of triglyceride and total cholesterol, and can obviously improve the hyperlipidemia symptoms of the mice.
Comparing the results of the control of the low density lipoprotein cholesterol of each experimental group and the control group, the lactobacillus plantarum GL-4 has the control effect of the low density lipoprotein cholesterol, and the control effect of the GL-4+metformin intervention group on the low density lipoprotein cholesterol is obviously higher than that of the metformin intervention group and the GL-4 intervention group alone. The control effect of the lactobacillus plantarum GL-4 on the low-density lipoprotein cholesterol is superior to that of LGG, and the lactobacillus plantarum GL-4 and the metformin are combined to have a synergistic effect on the control of the low-density lipoprotein cholesterol, especially for a high-fat group. Indicating that the endocrine disturbance caused by diabetes in mice can achieve better effect by using the combination of the metformin and the lactobacillus plantarum GL-4.
In terms of high-density lipoprotein cholesterol control, the comparison of the high-fat groups shows that the single metformin intervention group, the single lactobacillus plantarum GL-4 intervention group and the single LGG intervention group have no obvious effect on the control of the high-density lipoprotein cholesterol, and the metformin+GL-4 group can control the high-density lipoprotein cholesterol to be not higher than 2.6mmol/l, and in the high-fat group, the metformin and the GL-4 group have a synergistic effect in the aspect of high-density lipoprotein cholesterol control. The low-fat group comparison shows that the metformin intervention group alone, the lactobacillus plantarum GL-4 intervention group alone and the LGG intervention group alone have certain effects on the control of high-density lipoprotein cholesterol, and in addition, the metformin and the GL-4 groups have synergistic effects on the control of high-density lipoprotein cholesterol.
Example 5 Regulation of insulin, endotoxin and inflammatory factors by Lactobacillus plantarum GL-4
The mice of each group at the end of the test in example 3 (6 weeks of intervention) were collected from the eyeballs and bled, and after standing at 4℃for 8 hours, centrifuged at 3000r/min for 10min, and the supernatant (serum) was collected. The serum was tested for insulin, endotoxin and interleukin 6 content. The results of the detection of insulin, endotoxin and inflammatory factor in serum are shown in Table 3.
TABLE 3 detection results of insulin, endotoxin and inflammatory factor in serum
| INS(pmol/L) | IL-6(pg/ml) | LPS(ng/ml) | |
| High-fat +GL-4 intervention group | 20.04±8.51 | 142.92±47.34 | 6.68±2.44 |
| Low-fat +GL-4 intervention group | 31.23±12.86 | 72.57±46.55 | 5.62±1.51 |
| High fat + metformin intervention group | 30.18±3.90 | 19.09±10.05 | 5.79±2.02 |
| Low-fat + metformin intervention group | 40.58±5.49 | 23.01±15.53 | 5.61±1.76 |
| High fat + metformin + GL-4 intervention group | 18.06±4.27 | 11.25±10.08 | 4.96±0.10 |
| Low-fat + metformin + GL-4 intervention group | 30.05±8.71 | 11.04±21.04 | 4.44±1.29 |
| High fat + LGG intervention group | 35.29±2.35 | 164.23±53.26 | 6.91±1.94 |
| Low-fat + LGG intervention group | 45.86±3.27 | 92.56±49.23 | 6.13±1.64 |
| High fat + metformin + LGG intervention group | 30.10±2.68 | 18.25±11.23 | 5.12±2.36 |
| Low-fat + metformin + LGG intervention group | 39.60±6.51 | 22.85±14.63 | 5.11±2.53 |
| High fat control group | 63.77±11.12 | 212.88±17.73 | 7.12±0.63 |
| Low fat control group | 59.30±16.34 | 153.26±11.52 | 7.26±0.43 |
| Health group | 33.18±7.65 | 43.55±8.94 | 5.03±0.53 |
Lactobacillus plantarum GL-4, LGG and metformin improve insulin levels in serum to varying degrees, however, only Lactobacillus plantarum GL-4 group and metformin+GL-4 group reduce serum INS levels in mice to levels comparable to and below those in healthy groups. Lactobacillus plantarum GL-4, LGG, metformin improve IL-6 levels in serum to varying degrees. It was demonstrated that Lactobacillus plantarum GL-4 was able to improve INS levels in type 2 diabetic mice and IL-6 levels in type 2 diabetic mice.
Type 2 diabetes causes chronic inflammation in mice, and increases INS, LPS and IL6 levels in serum. By comparison, the LPS level of the lactobacillus plantarum GL-4 group and the LPS content level of mice in the metformin administration group are lower than those of the control group, which shows that GL-4 and metformin play a certain role in relieving the LPS elevation in the serum of the type 2 diabetes mice. LGG also has some relief from elevated LPS levels in mice, however only in combination with lactobacillus plantarum GL-4, metformin, reduced LPS levels to healthy levels and below in type 2 diabetic mice serum.
Example 6 Regulation of the intestinal flora by Lactobacillus plantarum GL-4
1) Effect on Akkermansia in the gut the brains of the groups of mice at the end of the test in example 3 (6 weeks of intervention) were analyzed for diversity of the intestinal flora of mice, the distribution of the intestinal flora of mice was analyzed at the genus level, akkermansia was recognized as a beneficial strain in the gut as shown in fig. 3, the abundance results of Akkermansia flora of the groups of mice were shown in fig. 4, and from the data in fig. 4, in the high-fat group, lactobacillus plantarum GL-4 did not help to increase the abundance of Akkermansia flora, metformin had a slight effect on the increase of Akkermansia flora, however, the inventors unexpectedly found that the combination of lactobacillus plantarum GL-4 and metformin significantly increased the abundance of Akkermansia flora, increasing the abundance of Akkermansia flora of the high-fat group to the healthy group level, and thus, lactobacillus plantarum-4 had an effect on the increase of akmansia abundance of metformin. In the low-fat group, the lactobacillus plantarum GL-4 and the metformin have equivalent effect on improving the abundance of the Akkermansia flora, and both the lactobacillus plantarum GL-4 and the metformin can improve the abundance of the Akkermansia flora to the level of a healthy group, and when the lactobacillus plantarum GL-4 and the metformin are combined, the abundance of the Akkermansia flora can be improved to be significantly higher than the level of the healthy group. Number of Akkermansia and reduction of inflammatory response in vivo to improve intestinal barrier function.
Based on the abundance of the colonies, the high-fat GL-4 intervention group was lower than the low-fat GL-4 intervention group and reached a significant level (p < 0.05), while the low-fat GL-4 and metformin intervention groups were at the same level of Akkermansia flora.
2) Effects on Blauthia in the intestine
Blautha (via Eubacterium mucilaginosa) prevents colonization of pathogens by producing bacteriocins and exhibits anti-inflammatory properties and maintains glucose homeostasis by up-regulating the production of regulatory T cells and SCFAs. The production of butyrate can improve insulin resistance and reduce fat accumulation. The results of the abundance of Blautha flora in each group of mice are shown in FIG. 5, and according to the results in FIG. 5, it is clear that in the high-fat group, metformin has no help to increase the abundance of Blautha flora, lactobacillus plantarum GL-4 has a certain effect on the increase of Blautha flora, however, the inventors have unexpectedly found that the combination of lactobacillus plantarum GL-4 and metformin can increase the abundance of Blautha flora to a significantly higher level than in the healthy group, and thus, it is seen that metformin can promote the increase of Blautha flora by lactobacillus plantarum GL-4, and that the combination of lactobacillus plantarum GL-4 and metformin has a synergistic effect on the increase of Blautha flora. In the low-fat group, the lactobacillus plantarum GL-4 or the metformin is helpful to the improvement of Blautha flora abundance, and the lactobacillus plantarum GL-4 can reach the level equivalent to the improvement effect of the metformin on Blautha flora abundance. According to the analysis of the sequencing result, the intervention of adding lactobacillus plantarum GL-4 under the same intervention condition has a certain promotion effect on the abundance of Blautha flora in the intestinal tract of the mice.
The results show that the lactobacillus plantarum GL-4 increases the quantity of intestinal probiotics, especially Akkermansia bacteria and Blmotia bacteria, adjusts the balance of intestinal microorganisms, improves the barrier function of the intestinal tract, and promotes the body to develop towards the healthy direction.
The foregoing are all preferred embodiments of the present application, and are not intended to limit the scope of the present application in any way, therefore: all equivalent changes in structure, shape and principle of this application should be covered in the protection scope of this application.
Claims (10)
1. The lactobacillus plantarum GL-4 is characterized in that the preservation number of the lactobacillus plantarum GL-4 is CCTCC M2023303.
2. A pharmaceutical formulation comprising lactobacillus plantarum GL-4 as claimed in claim 1.
3. The pharmaceutical formulation of claim 2, further comprising metformin.
4. Use of the lactobacillus plantarum GL-4 of claim 1 or the pharmaceutical formulation of claim 2 for the preparation of a hypoglycemic agent.
5. Use of the lactobacillus plantarum GL-4 of claim 1 or the pharmaceutical formulation of claim 2 for the preparation of a hypolipidemic drug.
6. Use of the lactobacillus plantarum GL-4 of claim 1 or the pharmaceutical formulation of claim 2 for the preparation of an anti-inflammatory drug.
7. The use according to claim 5, characterized in that the anti-inflammatory agent is directed against inflammatory factors LPS and/or IL6 and/or ins.
8. Use of the lactobacillus plantarum GL-4 of claim 1 or the pharmaceutical formulation of claim 2 for the preparation of a medicament for regulating intestinal flora.
9. The use according to claim 7, wherein the intestinal flora is Akkermansia flora or Blautia flora.
10. A composition comprising the lactobacillus plantarum GL-4 of claim 1.
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