Use of lactobacillus gasseri TF08-1 in prevention and treatment of helicobacter pylori infection

Abstract

Disclosed is a use of Lactobacillus gasseri TF08-1 in the prevention and treatment of Helicobacter pylori infection. The strain has the beneficial effect of inhibiting the proliferation of Helicobacter pylori and urease activity in vitro; in animal experiments, probiotics (live bacteria preparations) and postbiotics (inactivated bacteria preparations) thereof were able to effectively prevent and treat Helicobacter pylori infection, inhibit the proliferation of Helicobacter pylori in the body, and improve gastric mucosal damage and systemic inflammatory response caused by Helicobacter pylori infection.

Description

Application of Lactobacillus gasseri TF08-1 in preventing and treating Helicobacter pylori infection Technical Field

[0001] The present invention relates to the technical field of microorganisms, and in particular to application of Lactobacillus gasseri in preventing and treating Helicobacter pylori infection. Background Art

[0002] Helicobacter pylori (Hp) is a Gram-negative, microaerophilic bacillus with a spiral, S-shaped, or seagull-shaped structure. It was first discovered and isolated by scientists Warren and Marshall in 1983 from gastric tissue of patients with chronic gastritis. Hp can survive in highly acidic environments and often colonizes the gastric mucosa. It is associated with the development of chronic gastritis, gastrointestinal ulcers, gastric cancer, and gastric mucosa-associated lymphoma. Gastric cancer is the second-leading cause of cancer mortality worldwide, and Hp-induced gastritis is the single most potent cause of gastric cancer. Consequently, Hp was designated a Group 1 biological carcinogen by the World Health Organization in 2022. Hp infection presents no obvious symptoms in the early stages. Some may experience acute gastritis symptoms, including upper abdominal pain, bloating, belching, nausea and vomiting, and loss of appetite. However, nearly all patients develop varying degrees of chronic active gastritis. Once infected, Hp is extremely difficult to resolve on its own, and infected individuals suffer lifelong consequences. The transmission routes of Hp include oral-oral and fecal-oral transmission, and group infections often occur. Studies have shown that the infection rate of Helicobacter pylori in my country is as high as 56%. Due to its unclear symptoms, it is often ignored by patients and not eradicated and treated in time.

[0003] The diagnosis of Helicobacter pylori mainly includes urea breath test (UBT), fecal Helicobacter pylori antigen test (HpSA), Helicobacter pylori serological antibody test and histological examination. Timely examination and eradication treatment are important intervention measures to avoid the development of the disease.

[0004] Currently, there are reports of lactobacilli being used to treat Helicobacter pylori. Patent US6596530B1 discloses that Lactobacillus gasseri OLL2716 can grow in low pH conditions and achieve a 90.5% inhibition rate after 48 hours of co-culture with H. pylori. However, current Lactobacillus gasseri has insufficient antibacterial activity, and there is a lack of a method to prevent H. pylori infection. Furthermore, live bacteria are difficult to store and transport, making it difficult to expand their application.

[0005] Summary of the Invention

[0006] The technical problem to be solved by the present invention is that the existing Lactobacillus gasseri has insufficient antibacterial ability and lacks a method for preventing Helicobacter pylori infection.

[0007] In a first aspect of the present invention, an active probiotic product is provided, which comprises a bacterial solution or powder of Lactobacillus gasseri; wherein the Lactobacillus gasseri is Lactobacillus gasseri TF08-1, which has a deposit number of GDMCC60092; when the bacterial solution is used, the content of the Lactobacillus gasseri is at least 1.0×10 8 CFU / mL; when in the form of bacterial powder, the content of Lactobacillus gasseri is at least 1.0×10 9 CFU / g.

[0008] In the present invention, when the active probiotic product is a bacterial liquid, the content of Lactobacillus gasseri is at least 1.0×10 8 CFU / mL means 1.0×10 8 CFU / mL, 2.0×10 8 CFU / mL, 3.0×10 8 CFU / mL, 4.0×10 8 CFU / mL, 5.0×10 8 CFU / mL, 6.0×10 8 CFU / mL, 7.0×10 8 CFU / mL, 8.0×10 8 CFU / mL, 9.0×10 8 CFU / mL, 1.0×10 9 CFU / mL, 2.0×10 9 CFU / mL, 5.0×10 9 CFU / mL, 1.0×10 10 CFU / mL, 2.0×10 10 CFU / mL, 5.0×10 10 CFU / mL, 1.0×10 11 CFU / mL is equivalent to 1.0×10 8 The appropriate concentration can be determined by measuring CFU / mL.

[0009] In the present invention, when the active probiotic product is a bacterial liquid, the content of Lactobacillus gasseri can be 1.0×10 8 -1.0×10 11 CFU / mL, for example 1.0×10 8 -1.0×10 9 CFU / mL, 1.0×10 9 -1.0×10 10 CFU / mL, 1.0×10 10 -1.0×10 11 CFU / mL; 5.0×10 8 -5.0×10 9CFU / mL, 5.0×10 9 -5.0×10 10 CFU / mL, 5.0×10 10 -1.0×10 11 CFU / mL, etc.

[0010] In the present invention, when the active probiotic product is bacterial powder, the content of Lactobacillus gasseri is at least 1.0×10 9 CFU / g means that it can be 1.0×10 9 CFU / g, 2.0×10 9 CFU / g, 3.0×10 9 CFU / g, 4.0×10 9 CFU / g, 5.0×10 9 CFU / g, 6.0×10 9 CFU / g, 7.0×10 9 CFU / g, 9.0×10 9 CFU / g, 10.0×10 9 CFU / g, 1.0×10 10 CFU / g, 2.0×10 10 CFU / g, 5.0×10 10 CFU / g, 1.0×10 11 CFU / g, 2.0×10 11 CFU / g, 5.0×10 11 CFU / g, 1.0×10 12 CFU / g is based on 1.0×10 9 The appropriate concentration can be determined by measuring CFU / g.

[0011] In the present invention, when the active probiotic product is bacterial powder, the content of Lactobacillus gasseri can be 1.0×10 9 -1.0×10 12 CFU / g, for example 1.0×10 9 -1.0×10 10 CFU / g, 1.0×10 10 -1.0×10 11 CFU / g, 1.0×10 11 -1.0×10 12 CFU / g; 5.0×10 9 -5.0×10 10 CFU / g, 5.0×10 10 -5.0×10 11 CFU / g, 5.0×10 11 -1.0×10 12CFU / g, etc.

[0012] In a second aspect of the present invention, a postbiotic product is provided, which is prepared by inactivating the active probiotic product described in the first aspect.

[0013] In some embodiments, the postbiotic product is prepared by inactivating the active probiotic product of the first aspect by heating at 63-65° C. for 30 minutes.

[0014] In a third aspect, the present invention provides a Lactobacillus gasseri, the active probiotic product described in the first aspect, or the postbiotic product described in the second aspect, for use in the preparation of a product for preventing and / or treating diseases caused by Helicobacter pylori infection; wherein the Lactobacillus gasseri is Lactobacillus gasseri TF08-1, and its deposit number is GDMCC60092.

[0015] In some embodiments, the disease caused by Helicobacter pylori infection is a gastrointestinal disease or an inflammatory response.

[0016] In some embodiments, the gastrointestinal disease or inflammatory response is systemic inflammatory response syndrome, gastritis, gastric tissue damage or gastric mucosal atrophy; the gastritis is, for example, acute gastritis or chronic gastritis.

[0017] In a fourth aspect, the present invention provides a Lactobacillus gasseri, the active probiotic product described in the first aspect, or the postbiotic product described in the second aspect, which is used to regulate the levels of serum anti-inflammatory factors and / or serum pro-inflammatory factors; wherein the Lactobacillus gasseri is Lactobacillus gasseri TF08-1, and its deposit number is GDMCC60092.

[0018] In some embodiments, the serum anti-inflammatory factor is IL-10; the serum pro-inflammatory factor is TNF-α, IL-1β or IL-6.

[0019] In a fifth aspect, the present invention provides a Lactobacillus gasseri, the active probiotic product according to the first aspect, or the postbiotic product according to the second aspect, for inhibiting urease activity; wherein the Lactobacillus gasseri is Lactobacillus gasseri TF08-1, and its deposit number is GDMCC60092.

[0020] In some embodiments, the urease is urease produced by Helicobacter pylori.

[0021] In a sixth aspect, the present invention provides a method for inhibiting the activity of Helicobacter pylori or urease, the method comprising adding Lactobacillus gasseri, the active probiotic preparation described in the first aspect, or the postbiotic preparation described in the second aspect to Helicobacter pylori or a sample containing Helicobacter pylori and / or urease; wherein the Lactobacillus gasseri is Lactobacillus gasseri TF08-1, and its preservation number is GDMCC60092.

[0022] In some embodiments, the urease is urease produced by Helicobacter pylori.

[0023] In some embodiments, the methods are for non-diagnostic and / or non-therapeutic purposes.

[0024] In the seventh aspect of the present invention, a method for treating a disease caused by Helicobacter pylori infection is provided, the method comprising administering Lactobacillus gasseri, the active probiotic preparation described in the first aspect, or the postbiotic preparation described in the second aspect to a subject in need; wherein the Lactobacillus gasseri is Lactobacillus gasseri TF08-1, and its deposit number is GDMCC60092.

[0025] In some embodiments, the disease caused by Helicobacter pylori infection is a gastrointestinal disease or an inflammatory response.

[0026] In some specific embodiments, the gastrointestinal disease or inflammatory response is systemic inflammatory response syndrome, gastritis, gastric tissue damage or gastric mucosal atrophy; the gastritis is, for example, acute gastritis or chronic gastritis.

[0027] In an eighth aspect, the present invention provides a method for regulating the levels of serum anti-inflammatory factors and / or serum pro-inflammatory factors, the method comprising administering Lactobacillus gasseri, the active probiotic preparation described in the first aspect, or the postbiotic preparation described in the second aspect to a subject or sample in need; wherein the Lactobacillus gasseri is Lactobacillus gasseri TF08-1, and its deposit number is GDMCC60092.

[0028] In some embodiments, the serum anti-inflammatory factor is IL-10; the serum pro-inflammatory factor is TNF-α, IL-1β or IL-6.

[0029] In some embodiments, the method is an in vitro regulation method.

[0030] Compared with the prior art, the present invention has the following beneficial effects:

[0031] The use of active Lactobacillus gasseri TF08-1 products or postbiotic products can effectively inhibit Helicobacter pylori and inhibit the activity of urease; the use of postbiotics can effectively solve transportation and storage problems, making the application scenarios more extensive; finally, active Lactobacillus gasseri products or postbiotic products can be used to prevent Helicobacter pylori infection and achieve the effect of nourishing and protecting the stomach. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] FIG1 shows the gastric infection and damage conditions of mice in each group in the prevention experiment of Example 4 of the present application.

[0033] FIG2 shows the serum cytokine levels of mice in each group in the prevention experiment of Example 4 of the present application.

[0034] FIG3 shows the gastric infection and damage conditions of mice in each group in the treatment experiment of Example 5 of the present application.

[0035] FIG4 shows the serum cytokine levels of mice in each group in the treatment experiment of Example 5 of the present application. DETAILED DESCRIPTION

[0036] Helicobacter pylori is a spiral-shaped bacterium that colonizes the stomach. The bacterium produces urease, which raises the stomach's pH and protects it from gastric acid. The bacterium can penetrate the mucosa and settle on epithelial cells. This infection activates the body's immune system, but the immune response is insufficient to effectively eliminate the infection. Instead, the enhanced immune response can lead to a range of chronic inflammatory conditions and diseases, such as gastritis or gastric ulcers.

[0037] Inflammatory responses within the intestinal mucosa lead to a loss of epithelial integrity and increased permeability. Disruption of the epithelial barrier allows immune cells to access luminal materials, leading to immune system activation and inflammation and the production of inflammatory cytokines, such as chemokines, tumor necrosis factor (TNF), and interferon (IFN). IFN and TNF disrupt tight junctions, while TNF may induce epithelial cell apoptosis. The associated increased permeability of the epithelial barrier further exacerbates the inflammatory process and initiates a viscous cycle. When this process becomes chronic, it may progress to inflammatory bowel disease.

[0038] Tumor necrosis factor-α (TNF-α) can inhibit the replication of various influenza viruses and possesses a potent antiviral effect. TNF-α primarily regulates immune cell function. As an endogenous pyrogen, it can induce fever, apoptosis, sepsis (by inducing the production of IL-1 and IL-6), cachexia, inflammation, and inhibit tumorigenesis and viral replication.

[0039] The active Lactobacillus gasseri TF08-1 preparation or postbiotic preparation of the present invention can be used to protect against Helicobacter pylori infection. Therefore, if taken before infection, the active Lactobacillus gasseri TF08-1 preparation or postbiotic preparation of the present invention effectively protects against Helicobacter pylori infection, thereby providing a preventative effect by making Helicobacter pylori infection more difficult and, even if infected, easier to cure. Therefore, the active Lactobacillus gasseri TF08-1 preparation or postbiotic preparation of the present invention is also preferably taken daily.

[0040] The administration time of the active Lactobacillus gasseri TF08-1 preparation or the postbiotic preparation of the present invention is not particularly limited and can be before or after Helicobacter pylori infection.

[0041] Those skilled in the art can, according to actual production needs, combine conventional technical means or basic common sense of pharmaceutical production processes (for example, "Encyclopedia of Preparation Technology", "Pharmaceutical Preparation Technology", etc.) to make conventional selection or adjustment of pharmaceutical excipients, and then prepare Helicobacter pylori strain TF08-1 with a preservation number of GDMCC60092 into products with different dosage forms, different storage conditions, and different shelf lives. This is possible and easy to do without technical obstacles for those skilled in the art.

[0042] The present invention is further illustrated by way of examples below, but the present invention is not limited to the scope of the examples. Experimental methods in the following examples where specific conditions are not specified were performed according to conventional methods and conditions, or selected according to the product specifications.

[0043] The main experimental consumables involved in the following examples are as follows:

[0044] MRS broth medium: 10.0 g of peptone, 10.0 g of beef extract, 5.0 g of yeast powder, 20.0 g of glucose, 5.0 g of sodium acetate, 2.0 g of diammonium hydrogen citrate, 1.0 mL of Tween-80, 2.0 g of dipotassium hydrogen phosphate, 0.2 g of magnesium sulfate heptahydrate, 0.05 g of manganese sulfate heptahydrate, and 1000 mL of distilled water. After mixing the above components, adjust the pH to 6.2-6.4, and sterilize in an autoclave at 121°C for 15 min.

[0045] MRS agar medium: Based on the formula of MRS broth medium, add 20g / L agar, adjust the pH to 6.2-6.4, and place it in a high pressure sterilizer at 121℃ for 15 minutes.

[0046] GSSA-Hp selective Columbia blood plate: 12.0 g of tryptic peptone, 5.0 g of animal tissue protein digest, 3.0 g of yeast extract, 3.0 g of beef extract, 1.0 g of corn starch, 5.0 g of sodium chloride, 15 g of agar, 0.5 mg of polymyxin B, 2 mg of nalidixic acid, 2.5 mg of amphotericin, 200 mg of bacitracin, 6 mg of vancomycin, and 1000 mL of distilled water. After mixing the above components, adjust the pH to 7.2-7.4, place in an autoclave and sterilize at 121°C for 15 min. After cooling to 50°C, add 70 mL of sterile defibrinated sheep blood.

[0047] Urea-phenol red solution: Dissolve 10 g of urea and 0.006 g of phenol red, mix well, adjust the pH of the solution to 6.5, and make up to 50 mL. The concentrations of urea and phenol red are 20% and 0.012%, respectively.

[0048] The Helicobacter pylori strain used in the experiment was H. pylori ATCC 43504 from the American Type Culture Collection (ATCC). Elisa assay kits for TNF-α, IL-1β, IL-6, and IL-10 were purchased from Nanjing Jiancheng Biotechnology Co., Ltd., and a bacterial genomic DNA extraction kit (DP302) was purchased from Tiangen Biotechnology (Beijing). All other experimental materials and equipment were common microbiology laboratory consumables and equipment.

[0049] Example 1 Preparation of Lactobacillus gasseri TF08-1 probiotic and postbiotic products

[0050] A glycerol cryopreserved tube of Lactobacillus gasseri TF08-1 was quickly thawed in a 37°C water bath. The tube was streaked onto MRS agar using a sterile inoculating needle and incubated anaerobically at 37°C for 48 hours. A single colony was selected and inoculated into MRS broth. The culture was incubated anaerobically at 37°C for 18 hours to activate the culture. The culture was then inoculated into sterilized MRS broth at a 1% (v / v) inoculum and incubated anaerobically at 37°C for 24 hours to obtain a TF08-1 fermentation broth. The fermentation broth was then subjected to conventional treatments such as spray drying (or freeze drying) to produce a TF08-1 probiotic (live bacteria product) with a cell concentration of 1.0×10 9 CFU / g or 1.0×10 9 CFU / mL; The TF08-1 probiotics (live bacteria products) were inactivated by heating at 63-65°C for 30 min to obtain TF08-1 postbiotics (inactivated bacteria products), the cell concentration of which was 1.0×10 9 Cell / g or 1.0×10 9 Cell / mL.

[0051] Example 2 Helicobacter pylori antibacterial ability of Lactobacillus gasseri TF08-1

[0052] This example aims to determine the antibacterial ability of Lactobacillus gasseri TF08-1 against Helicobacter pylori: After activation, Lactobacillus gasseri TF08-1 was centrifuged at 10,000 rpm for 10 minutes to remove the bacteria, and then filtered through a 0.22 μm aqueous filter to obtain the TF08-1 cell-free fermentation supernatant (CFS) as the test sample. The antibacterial ability of CFS against Helicobacter pylori was determined using a microplate antibacterial assay: Helicobacter pylori ATCC43504 was inoculated on GSSA-Hp selective Columbia blood agar plates and revived for 3 to 4 days. After the culture was completed, the bacteria were scraped and the bacterial concentration was adjusted to 5.0×10 7Take 50 μL of H. pylori suspension after adjusting the bacterial concentration and place it in a 96-well plate with 150 μL of sample. Mix well and culture at 37°C for 18 h before measuring OD 600 nm value, the results are recorded as the experimental group data, blank MRS liquid culture medium is used as the control group instead of the sample for the test, and the results are recorded as the control group data. The above experiment was repeated 3 times, and the results are expressed as mean ± standard deviation. The Helicobacter pylori inhibition rate was calculated according to the following formula:

[0053] Helicobacter pylori inhibition rate (%) = [(OD control group - OD experimental group) / OD control group] × 100

[0054] The experimental results showed that after culture, the control group grew well, while the growth of the experimental group co-cultured with the cell-free supernatant of Lactobacillus gasseri TF08-1 was inhibited. Its Helicobacter pylori inhibition rate was 92.44±3.51%, showing extremely strong Helicobacter pylori inhibition properties, which suggests that Lactobacillus gasseri TF08-1 has the probiotic potential to inhibit the growth and reproduction of Helicobacter pylori.

[0055] Example 3 Urease inhibition test of Lactobacillus gasseri TF08-1

[0056] Urease is one of the important physiological functional enzymes of Helicobacter pylori. It can hydrolyze urea in gastric juice into carbon dioxide and ammonia, thereby neutralizing gastric acid and protecting the growth and survival of Helicobacter pylori. Therefore, inhibiting urease is a key target for effectively inhibiting Helicobacter pylori. According to the method of Example 2, the Lactobacillus gasseri TF08-1 test sample was prepared, and its urease inhibition ability against Helicobacter pylori was determined using the microplate method: 40 μL of Helicobacter pylori suspension after adjusting the bacterial concentration was taken, and placed in a 96-well plate with 10 μL of the test sample, and co-cultured in a microaerobic environment for 48 hours. After the cultivation was completed, 150 μL of urea-phenol red solution was added, and the absorbance was measured at a wavelength of 550 nm after shaking. The results were recorded as the test group data. At the same time, a control test was carried out using a blank MRS liquid culture medium instead of the sample, and the data were recorded as the control group data. The above experiment was repeated 3 times, and the results were expressed as the mean ± standard deviation. The urease activity inhibition rate was calculated according to the following formula:

[0057] Urease activity inhibition rate (%) = [(OD control group - OD test group) / OD control group] × 100

[0058] The experimental results showed that after culture, the control group did not show any urease activity inhibition, while the urease activity inhibition rate of the cell-free supernatant of Lactobacillus gasseri TF08-1 was 80.66±4.55%. The above results show that Lactobacillus gasseri TF08-1 can effectively inhibit the urease activity of Helicobacter pylori, prevent it from neutralizing gastric acid, and has the probiotic potential to reduce the reproduction and infection of Helicobacter pylori in the stomach.

[0059] Example 4 Verification of the efficacy of Lactobacillus gasseri TF08-1 in preventing Helicobacter pylori infection

[0060] A total of 56 6-week-old SPF-grade C57BL / 6 male mice were purchased from Zhuhai Baishitong Biotechnology Co., Ltd. for animal experiments on the prevention of Helicobacter pylori infection with Lactobacillus gasseri TF08-1 probiotics and postbiotics. The mice were divided into 4 groups. The experimental groups and intervention methods are shown in Table 1:

[0061] Table 1 Groups and interventions in prevention trials

[0062] During the above-mentioned grouping and intervention process, the infection dose of Helicobacter pylori liquid was 100 million CFU / day / mouse, and the mice were gavaged every other day for a total of 5 times to infect with Helicobacter pylori. After the experiment, the mice were dissected, and the serum TNF-α, IL-1β, IL-6, and IL-10 levels were determined using the corresponding ELISA detection kits. The Hp load in the stomach was counted using GSSA-Hp selective Columbia blood agar plates. At the same time, HE staining was used to perform histopathological analysis of the gastric tissue. The pathological sections were scored according to the severity of five indicators, including Hp number, activity, chronic inflammatory response, atrophy, and intestinal metaplasia area (normal: 0 points, mild: 1 point, moderate: 2 points, severe: 3 points).

[0063] The experimental results are shown in Figures 1 and 2. In the figures, "*" indicates that there is a difference between the intervention group and the model control group (p < 0.05), "**" indicates that there is a significant difference between the intervention group and the model control group (p < 0.01), and "***" indicates that there is an extremely significant difference between the intervention group and the model control group (p < 0.001). The experimental results show that compared with the normal control group, the model control group had H. pylori infection in the stomach, with a significantly increased load, a significantly increased level of pro-inflammatory factors such as serum TNF-α, IL-1β, and IL-6, and a significantly decreased level of the anti-inflammatory factor IL-10. The gastric tissue pathology analysis score of the model group was 7.17 ± 1.17. The above data show that: without any intervention protection, Helicobacter pylori can colonize and survive in the stomach, destroy gastric mucosal tissue, and cause a systemic inflammatory response. Before Helicobacter pylori infection, Lactobacillus gasseri TF08-1 probiotics and postbiotics were used. After Helicobacter pylori infection, the number of Hp in the stomach showed a very significant decrease compared with the model control group without any preventive measures (p < 0.01). Among them, the Hp load in the stomach decreased by 94.33% and 84.22% after preventive gavage of Lactobacillus gasseri TF08-1 probiotics and postbiotics, respectively (see Figure 1A for details), and the pathological score decreased to 4.17 ± 1.60 and 4.83 ± 1.17, with a decrease rate of 41.85% and 32.56%, respectively. This shows that Gastric tissue damage caused by Helicobacter pylori infection was significantly alleviated (see Figures 1B and 1C for details). In addition, the levels of pro-inflammatory factors such as serum TNF-α, IL-1β, and IL-6 decreased to varying degrees (see Figures 2A, B, and C for details), and the level of serum anti-inflammatory factor IL-10 increased significantly (see Figure 2D for details). The above results indicate that the pre-use of Lactobacillus gasseri TF08-1 probiotics and their postbiotics before Helicobacter pylori infection can significantly reduce the Hp load in gastric tissue after infection, improve gastric tissue damage caused by Helicobacter pylori infection, and improve the systemic inflammatory response caused by the infection.

[0064] Example 5 Verification of the efficacy of Lactobacillus gasseri TF08-1 in treating Helicobacter pylori infection

[0065] A total of 40 6-week-old SPF-grade C57BL / 6 male mice were purchased from Zhuhai Baishitong Biotechnology Co., Ltd. The Lactobacillus gasseri TF08-1 probiotic and postbiotic treatment of Helicobacter pylori infection were divided into 5 groups. The experimental groups and intervention methods are shown in Table 2:

[0066] Table 2 Treatment trial groups and intervention methods

[0067] During the above-mentioned grouping and intervention process, the Hp-infected mouse model was established by first gavage with an antibiotic mixed solution (containing 10 mg / mL ampicillin, 2 mg / mL gentamicin, and 10 mg / mL azithromycin) for 3 consecutive days to eliminate the gastric flora, followed by gavage with Hp bacterial solution at a dose of 100 million / day / mouse, every other day, for a total of 5 times to establish a Helicobacter pylori infection model and verify the model; antibiotic triple therapy included omeprazole 0.12 mg / mL, amoxicillin 6 mg / mL, and clarithromycin 3 mg / mL, twice daily, 0.5 mL each time. After the experiment, experimental indicators such as cytokines, gastric Hp load counts, and gastric tissue sections were measured, and the detection method was the same as in Example 4.

[0068] The experimental results are shown in Figures 3 and 4. The "*" marked in the chart indicates that there is a difference between the intervention group and the model control group (p < 0.05), the "**" marked indicates that there is a significant difference between the intervention group and the model control group (p < 0.01), and the "***" marked indicates that there is an extremely significant difference between the intervention group and the model control group (p < 0.001). Compared with the normal control group, after modeling, the mice showed increased gastric Hp load, gastric tissue damage, increased levels of pro-inflammatory factors such as serum TNF-α, IL-1β, and IL-6, and decreased levels of anti-inflammatory factors IL-10. The above results indicate that Helicobacter pylori successfully survived and colonized in the stomach of mice, and the gastric tissue was also damaged to a certain extent, causing a systemic inflammatory response, indicating that the Helicobacter pylori infection mouse model was successfully established. After 28 days of intervention with Lactobacillus gasseri TF08-1 probiotics and postbiotics, the Hp load in the stomach of infected mice decreased to varying degrees. After probiotic intervention, the Hp load decreased by 99.18% (p<0.001), and after postbiotic intervention, the Hp load decreased by 99.28% (p<0.001) (see Figure 3A for details), both showing extremely strong Helicobacter pylori inhibition ability. Compared with the model control group, after intervention with Lactobacillus gasseri TF08-1 probiotics and postbiotics, the gastric tissue pathology scores of infected mice were significantly reduced from 8.67±1.63 to 4.5±0.55 (p<0.01) and 5.0±1.79 (p<0.01), respectively (see Figures 3B and C for details). In addition, serum TNF-α, IL-1β, IL-6 and other pro-inflammatory factors decreased to varying degrees (see Figures 4A, B, and C for details), and the serum anti-inflammatory factor IL-10 level increased significantly (see Figure 4D for details). The effect of Lactobacillus gasseri TF08-1 probiotics and postbiotics was superior to conventional triple antibiotic therapy. The above results show that after infection with Helicobacter pylori, the use of Lactobacillus gasseri TF08-1 probiotics and their postbiotics can significantly reduce the post-infection Hp load, improve gastric tissue damage, and improve the systemic inflammatory response caused by the infection, and have excellent efficacy in treating Helicobacter pylori infection.

[0069] Although the above describes specific embodiments of the present invention, it should be understood by those skilled in the art that these are merely illustrative and that various changes or modifications may be made to these embodiments without departing from the principles and essence of the present invention. Therefore, the scope of protection of the present invention is defined by the appended claims.

Claims

1. An active probiotic product, characterized in that: The invention comprises a bacterial solution or powder of Lactobacillus gasseri; wherein the Lactobacillus gasseri is Lactobacillus gasseri TF08-1, and its deposit number is GDMCC60092; when the bacterial solution is used, the content of the Lactobacillus gasseri is at least 1.0×10 8 CFU / mL; when in bacterial powder, the content of Lactobacillus gasseri is at least 1.0×10 9 CFU / g.

2. A postbiotic product, characterized in that: The active probiotic preparation is prepared by inactivating the active probiotic preparation as claimed in claim 1; preferably, the active probiotic preparation is inactivated by heating at 63-65° C. for 30 minutes.

3. Use of Lactobacillus gasseri, the active probiotic product according to claim 1 or the postbiotic product according to claim 2 in the preparation of a medicine or health product for preventing and / or treating diseases caused by Helicobacter pylori infection; wherein the Lactobacillus gasseri is Lactobacillus gasseri TF08-1, and its deposit number is GDMCC60092.

4. The use according to claim 3, characterized in that: The disease caused by Helicobacter pylori infection is a gastrointestinal disease or an inflammatory reaction.

5. The use according to claim 4, characterized in that: The gastrointestinal disease or inflammatory response is systemic inflammatory response syndrome, gastritis, gastric tissue damage or gastric mucosal atrophy; the gastritis is, for example, acute gastritis or chronic gastritis.

6. Use of Lactobacillus gasseri, the active probiotic product according to claim 1 or the postbiotic product according to claim 2 in the preparation of a medicament for regulating the levels of serum anti-inflammatory factors and / or serum pro-inflammatory factors; wherein the Lactobacillus gasseri is Lactobacillus gasseri TF08-1, and its deposit number is GDMCC60092.

7. The use according to claim 6, characterized in that: The serum anti-inflammatory factor is IL-10; the serum pro-inflammatory factor is TNF-α, IL-1β or IL-6.

8. Use of Lactobacillus gasseri, the active probiotic product according to claim 1 or the postbiotic product according to claim 2 in inhibiting urease activity; wherein the Lactobacillus gasseri is Lactobacillus gasseri TF08-1, and its deposit number is GDMCC60092; preferably, the urease is the urease produced by Helicobacter pylori.

9. A method for inhibiting Helicobacter pylori or urease activity, characterized in that: The method comprises adding Lactobacillus gasseri, the active probiotic preparation according to claim 1 or the postbiotic preparation according to claim 2 to Helicobacter pylori or a sample containing Helicobacter pylori and / or urease; wherein the Lactobacillus gasseri is Lactobacillus gasseri TF08-1, and its deposit number is GDMCC60092; preferably, the urease is urease produced by Helicobacter pylori.

10. The method according to claim 9, characterized in that The method is for non-diagnostic and / or non-therapeutic purposes.

11. A method for treating a disease caused by Helicobacter pylori infection, characterized in that: The method comprises administering Lactobacillus gasseri, the active probiotic preparation according to claim 1 or the postbiotic preparation according to claim 2 to a subject in need thereof; wherein the Lactobacillus gasseri is Lactobacillus gasseri TF08-1, and its deposit number is GDMCC60092.

12. The method according to claim 11, characterized in that The disease caused by Helicobacter pylori infection is a gastrointestinal disease or an inflammatory reaction.

13. The method according to claim 12, characterized in that The gastrointestinal disease or inflammatory response is systemic inflammatory response syndrome, gastritis, gastric tissue damage or gastric mucosal atrophy; the gastritis is, for example, acute gastritis or chronic gastritis.

14. A method for regulating the level of serum anti-inflammatory factors and / or serum pro-inflammatory factors, characterized in that: The method comprises administering Lactobacillus gasseri, the active probiotic preparation according to claim 1 or the postbiotic preparation according to claim 2 to a subject or sample in need thereof; wherein the Lactobacillus gasseri is Lactobacillus gasseri TF08-1, and its deposit number is GDMCC60092.

15. The method according to claim 14, characterized in that The serum anti-inflammatory factor is IL-10; the serum pro-inflammatory factor is TNF-α, IL-1β or IL-6; preferably, the method is an in vitro regulation method.

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