Application of selenium-enriched lactobacillus rhamnosus microbial agent in preparation of medicine for improving ulcerative colitis

Abstract

The invention discloses application of a selenium-enriched lactobacillus rhamnosus microbial agent in preparation of a medicine for improving ulcerative colitis, and particularly relates to the technical field of biology. Selenium-enriched lactobacillus rhamnosus is prepared through a selenium-enriched fermentation process, nano-selenium can be converted into organic selenium suitable for being absorbed by organisms, oxidation resistance can be achieved in intestinal tracts, DSS-induced ulcerative colitis can be remarkably relieved, disease activity indexes and body weight changes can be reduced, the intestinal barrier function can be protected, accordingly, ulcerative colitis can be relieved, and the selenium-enriched lactobacillus rhamnosus has wide application prospects.

Description

Technical Field

[0001] The invention relates to the field of biotechnology, and in particular to application of a selenium-enriched Lactobacillus rhamnosus agent in preparing a medicine for improving ulcerative colitis. Background Art

[0002] Ulcerative colitis (UC) is a chronic inflammatory bowel disease that mainly affects the colon and rectum, causing persistent inflammation and ulcer formation of the conjunctival mucosa. Patients often experience symptoms such as abdominal pain, diarrhea, bloody stools, and weight loss. Severe cases may be complicated by intestinal perforation, massive bleeding, and other symptoms. UC is a difficult-to-cure recurrent disease that usually alternates between remission and active phases. Long-term inflammatory states carry the risk of developing colorectal cancer, which seriously affects the patient's quality of life. In recent years, the global incidence of UC has continued to rise, bringing great economic and medical burdens. However, the specific cause of UC is not clear, and may be related to factors such as genetic factors, environmental stress, immune system abnormalities, and intestinal flora disorders.

[0003] Currently, the treatment of UC is mainly based on drug therapy, with the goal of controlling inflammation, relieving symptoms and preventing complications. Commonly used drugs include aminosalicylic acids, corticosteroids, immunosuppressants and biological agents, but these drugs usually have strong side effects, low patient compliance, and easy drug resistance. Therefore, although there are many treatment methods, in order to meet the efficacy and safety issues, it is still necessary to develop safer and more efficient treatment strategies.

[0004] UC patients often have intestinal flora imbalance, which is manifested by changes in flora composition, reduced diversity, a decrease in beneficial bacteria and an increase in pathogenic bacteria, which can lead to increased inflammation, damaged mucosal barriers and aggravated symptoms. With the change of public perceptions, more patients hope to alleviate UC through non-drug approaches such as dietary supplements or functional foods. Therefore, the treatment strategy of restoring the balance of intestinal flora through probiotics such as lactic acid bacteria and bifidobacteria has been increasingly recognized. Lactobacillus rhamnosus is a common probiotic that is widely present in the human intestine and certain fermented foods. It has the ability to regulate intestinal flora, enhance intestinal barrier function, and regulate immune and inflammatory signaling pathways. Therefore, it is widely used in food, medicine and health products, and is expected to be developed as a drug or carrier for the treatment of IBD.

[0005] Enteritis can cause intestinal inflammation and oxidative stress. The antioxidant and anti-inflammatory effects of selenium make it a potential treatment for enteritis. Selenium can be a component of glutathione peroxidase, scavenging free radicals and exerting antioxidant capacity; selenium can reduce the release of pro-inflammatory cytokines by inhibiting inflammatory pathways such as NF-κB; selenium can also improve the body's immunity and inhibit excessive immune responses by regulating the function of immune cells. Therefore, selenium is used in combination with conventional drugs (such as 5-aminosalicylic acid and corticosteroids) to improve efficacy. However, dietary selenium supplements are mainly in inorganic form and are difficult to be absorbed by the body.

[0006] Currently, there is a lack of a selenium-enriched Lactobacillus rhamnosus agent for use in the preparation of drugs for improving ulcerative colitis. Summary of the invention

[0007] In order to solve the problems of the prior art, the purpose of the present invention is to provide a use of a selenium-enriched Lactobacillus rhamnosus agent in the preparation of a drug for improving ulcerative colitis.

[0008] In order to achieve the above object, the present invention adopts the following technical solution:

[0009] In a first aspect, the present application provides a use of a selenium-enriched Lactobacillus rhamnosus agent in the preparation of a drug for improving ulcerative colitis.

[0010] In a second aspect, the present application provides a probiotic preparation for improving the intestinal environment for preventing and / or treating ulcerative colitis.

[0011] In a third aspect, the present application provides a use of a selenium-enriched Lactobacillus rhamnosus agent in the preparation of a drug for preventing and / or treating ulcerative colitis in combination with conventional immunosuppressants, small molecule drugs, traditional Chinese medicines, and biological preparations.

[0012] The first aspect of the present application provides a use of a selenium-enriched Lactobacillus rhamnosus agent in the preparation of a drug for preventing and / or treating ulcerative colitis, wherein the selenium-enriched Lactobacillus rhamnosus agent is prepared by fermenting Lactobacillus rhamnosus with selenium, and the selenium content is 5-100 μg / g. The therapeutic effect of selenium-enriched Lactobacillus rhamnosus on enteritis is significantly better than that of a non-treatment group.

[0013] After the Lactobacillus rhamnosus was revived in the solid culture medium, a single colony was picked to 200 mL of liquid culture medium and activated at 40°C for 24 hours. The activated Lactobacillus rhamnosus seed solution was inoculated into 1 L of culture medium at a concentration of 1:50, and a sterilized and filtered nano-selenium solution was added to a final concentration of 2-20 mg / L. The culture was statically cultured at 40°C for 24 hours, and the fermented bacteria were collected by centrifugation at 8000g for 10 minutes. The colitis was DSS-induced ulcerative colitis.

[0014] Furthermore, the selenium-enriched Lactobacillus rhamnosus agent includes a combination of one or more of a fermentation culture of Lactobacillus rhamnosus, a fermentation supernatant, a fermentation liquid precipitate, an ultrasonic lysis supernatant, an ultrasonic lysis precipitate or a freeze-dried powder.

[0015] Furthermore, the fermentation medium of selenium-enriched Lactobacillus rhamnosus contains the following components: vitamin C, 4 g / L; NaCl, 2.4 g / L; Na2HPO4, 5.8 g / L; KH2PO4, 0.528571 g / L; glucose, 5 g / L; yeast extract, 3 g / L; beef extract, 1.7 g / L; soy peptone, 2 g / L; beef peptone, 20 g / L; nano-selenium solution, 2-20 mg / L.

[0016] The second aspect of the present application provides a probiotic preparation for improving the intestinal environment for preventing and / or treating ulcerative colitis, wherein the probiotic preparation comprises the selenium-enriched Lactobacillus rhamnosus agent according to claim 1.

[0017] Furthermore, the content of selenium-enriched Lactobacillus rhamnosus is not less than 1×10 8 CFU / g.

[0018] Furthermore, the probiotic preparation includes any one of freeze-dried powder, tablets, capsules or granules.

[0019] The third aspect of the present application provides a use of a selenium-enriched Lactobacillus rhamnosus agent in the preparation of a drug for preventing and / or treating ulcerative colitis in combination with conventional immunosuppressants, small molecule drugs, traditional Chinese medicines, and biological preparations.

[0020] Beneficial effects: The present invention combines nano-selenium with Lactobacillus rhamnosus and uses Lactobacillus rhamnosus as a biological carrier for delivering selenoproteins, which has many advantages such as higher selenoprotein delivery efficiency, unchanged probiotic intestinal colonization ability, low treatment cost, convenient administration, good anti-enteritis effect, etc. The therapeutic effect of selenium-enriched Lactobacillus rhamnosus on enteritis is significantly better than that of the non-treatment group.

[0021] Compared with the prior art, the present invention has the following advantages: (1) The present invention uses probiotics as a biological carrier of selenium, and through selenium-enriched fermentation technology, inorganic selenium is converted into an organic selenium form that is easily absorbed by the body. Compared with other selenium sources, it not only improves the conversion efficiency and delivery efficiency of selenium, but also has the advantages of simple preparation method of probiotics and is suitable for industrial production. Lactobacillus rhamnosus, as a biological carrier of selenium, increases the targeting efficiency and bioavailability of selenium, while the antioxidant capacity of selenoprotein enhances the barrier function of the intestine, reduces oxidative damage, improves the colonization efficiency and biological activity of probiotics, and jointly exerts the ability to inhibit intestinal inflammation.

[0022] (2) The selenium-enriched Lactobacillus rhamnosus of the present invention has the characteristics that probiotics can be administered orally, and also has the characteristics of being used in the preparation of drugs for preventing and / or treating ulcerative colitis in combination with conventional immunosuppressants, small molecule drugs, traditional Chinese medicines, and biological preparations.

[0023] (3) The selenium-enriched Lactobacillus rhamnosus of the present invention is characterized in that in a mouse acute colitis model, compared with non-treated mice, it can significantly inhibit intestinal inflammatory lesions and protect intestinal barrier function; after treatment with selenium-enriched Lactobacillus rhamnosus, the weight of mice changes stably, and the colon length and disease activity index are close to those of healthy mice.

[0024] (4) The selenium-enriched rhamnosus Lactobacillus of the present invention has a surprising and significant effect: its therapeutic effect on inflammatory bowel disease is superior to that of Bifidobacterium longum expressing endostatin in multiple prognostic evaluation parameters (the efficacy of this strain has been peer-reviewed and published in international journals, Frontiers in Microbiology, 2022, 13: 927277.), and there is no obvious inflammatory area inside the intestine, and the stool has a high degree of formation.

[0025] (5) The selenium-enriched fermentation process adopted by the present invention can not only utilize the probiotic Lactobacillus rhamnosus as a carrier of selenium to convert it into an organic form that is easily absorbed by the body and improve bioavailability, but also cooperate with the anti-inflammatory effect of the probiotics themselves to enhance the intestinal barrier function, relieve the symptoms of ulcerative colitis, and reduce adverse reactions. It is expected to be developed as a safe and effective probiotic treatment strategy for the prevention or treatment of inflammatory bowel disease. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] In order to more clearly illustrate the technical solutions in the test examples of the present application, the drawings required for use in the test examples or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some test examples of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0027] Description of Abbreviations

[0028] 1: healthy control group; 2: DSS non-treatment group; 3: Bifidobacterium longum expressing endostatin; 4: Selenium-enriched Lactobacillus rhamnosus.

[0029] Figure 1 This is a flow chart of an experiment on treating acute colitis induced by DSS using the strain of the present invention;

[0030] Figure 2 The effect of the strain of the present invention on the body weight of mice with acute colitis model induced by DSS;

[0031] Figure 3 The effect of the strain of the present invention on the disease activity index of DSS-induced acute colitis model mice;

[0032] FIG4 shows the effect of the strain of the present invention on the colon length of mice with acute colitis model induced by DSS;

[0033] Figure 4A Representative images of the colon of mice with acute colitis model after treatment with the strain of the present invention.

[0034] Figure 4B The colon length statistics of mice with acute colitis model after treatment with the strain of the present invention. DETAILED DESCRIPTION

[0035] The present invention is described in detail below in conjunction with the accompanying drawings and specific embodiments. The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention. The experimental methods in the following examples of the present invention that do not specify specific conditions are usually carried out under conventional conditions or under conditions recommended by the manufacturer. The various commonly used chemical reagents used in the examples are all commercially available products.

[0036] Unless otherwise defined, all technical and scientific terms used in the present invention have the same meaning as those commonly understood by those skilled in the art of the present invention. The terms used in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention.

[0037] The terms "including" and "having" and any variations thereof of the present invention are intended to cover non-exclusive inclusions. For example, a process, method, device, product or equipment comprising a series of steps is not limited to the listed steps or modules, but may optionally include steps not listed, or may optionally include other steps inherent to these processes, methods, products or equipment.

[0038] In the present invention, the term "multiple" refers to two or more than two. "And / or" describes the association relationship of associated objects, indicating that three relationships may exist. For example, A and / or B can represent the following three situations: A exists alone, A and B exist at the same time, and B exists alone. The character " / " generally indicates that the associated objects are in an "or" relationship.

[0039] The first aspect of the embodiment of the present application provides an application of a selenium-enriched Lactobacillus rhamnosus agent in the preparation of a drug for improving ulcerative colitis. An application of a selenium-enriched Lactobacillus rhamnosus agent in the preparation of a drug for preventing and / or treating ulcerative colitis, wherein the selenium-enriched Lactobacillus rhamnosus agent is prepared by fermenting Lactobacillus rhamnosus with selenium, and the selenium content is 5-100 μg / g. The therapeutic effect of selenium-enriched Lactobacillus rhamnosus on enteritis is significantly better than that of the non-treatment group.

[0040] After the Lactobacillus rhamnosus was revived in the solid culture medium, a single colony was picked to 200 mL of liquid culture medium and activated at 40°C for 24 hours. The activated Lactobacillus rhamnosus seed solution was inoculated into 1 L of culture medium at a concentration of 1:50, and a sterilized and filtered nano-selenium solution was added to a final concentration of 2-20 mg / L. The culture was statically cultured at 40°C for 24 hours, and the fermented bacteria were collected by centrifugation at 8000g for 10 minutes. The colitis was DSS-induced ulcerative colitis.

[0041] In some embodiments, the selenium-enriched Lactobacillus rhamnosus agent includes a combination of one or more of a fermentation culture, a fermentation supernatant, a fermentation broth precipitate, an ultrasonic lysis supernatant, an ultrasonic lysis precipitate, or a lyophilized powder of Lactobacillus rhamnosus.

[0042] In some embodiments, the fermentation medium of selenium-enriched Lactobacillus rhamnosus comprises the following components: vitamin C, 4 g / L; NaCl, 2.4 g / L; Na2HPO4, 5.8 g / L; KH2PO4, 0.528571 g / L; glucose, 5 g / L; yeast extract, 3 g / L; beef extract, 1.7 g / L; soy peptone, 2 g / L; beef peptone, 20 g / L; nano-selenium solution, 2-20 mg / L.

[0043] A second aspect of the embodiments of the present application provides a probiotic preparation for improving the intestinal environment for preventing and / or treating ulcerative colitis, wherein the probiotic preparation comprises the selenium-enriched Lactobacillus rhamnosus agent according to claim 1.

[0044] In some embodiments, the content of selenium-enriched Lactobacillus rhamnosus is not less than 1×10 8 CFU / g.

[0045] In some embodiments, the probiotic preparation comprises any one of a lyophilized powder, a tablet, a capsule or a granule.

[0046] The third aspect of the embodiments of the present application provides a use of a selenium-enriched Lactobacillus rhamnosus agent in the preparation of a drug for preventing and / or treating ulcerative colitis in combination with conventional immunosuppressants, small molecule drugs, traditional Chinese medicines, and biological preparations.

[0047] Example 1

[0048] The invention discloses an application of a selenium-enriched Lactobacillus rhamnosus bacterial agent in the preparation of a drug for preventing and / or treating ulcerative colitis, wherein the selenium-enriched Lactobacillus rhamnosus bacterial agent is prepared by fermenting Lactobacillus rhamnosus with selenium, and the selenium content is 5-100 μg / g. The treatment effect of the selenium-enriched Lactobacillus rhamnosus on enteritis is significantly better than that of a non-treatment group.

[0049] After the Lactobacillus rhamnosus was revived in the solid culture medium, a single colony was picked to 200 mL of liquid culture medium and activated at 40°C for 24 hours. The activated Lactobacillus rhamnosus seed solution was inoculated into 1 L of culture medium at a concentration of 1:50, and a sterilized and filtered nano-selenium solution was added to a final concentration of 2-20 mg / L. The culture was statically cultured at 40°C for 24 hours, and the fermented bacteria were collected by centrifugation at 8000g for 10 minutes. The colitis was DSS-induced ulcerative colitis.

[0050] The selenium-enriched Lactobacillus rhamnosus agent comprises a combination of one or more of the fermentation culture, fermentation supernatant, fermentation broth precipitate, ultrasonic lysis supernatant, ultrasonic lysis precipitate or freeze-dried powder of Lactobacillus rhamnosus.

[0051] The fermentation medium of selenium-enriched Lactobacillus rhamnosus contains the following components: vitamin C, 4g / L; NaCl, 2.4g / L; Na2HPO4, 5.8g / L; KH2PO4, 0.528571g / L; glucose, 5g / L; yeast extract, 3g / L; beef extract powder, 1.7g / L; soy peptone, 2g / L; beef peptone, 20g / L; nano-selenium solution, 2-20mg / L.

[0052] Selenium-enriched Lactobacillus rhamnosus preparation method of the present invention

[0053] (1) Prepare 3 L of Lactobacillus rhamnosus culture medium, adjust the pH to 7.4 with NaOH, and load into a 5 L fermentation tank. The culture medium contains the following components:

[0054]

[0055] (2) Sterilize at 121°C for 20 minutes and cool to room temperature;

[0056] (3) inoculating 1 mL of thawed Lactobacillus rhamnosus seed solution into 200 mL of culture medium and performing activation culture at 40° C. for 24 hours;

[0057] (4) The activated Lactobacillus rhamnosus seed solution is transferred to 1L culture medium at an inoculum volume of 3%, and a nano-selenium solution filtered through a 0.22 μm filter membrane is added to a final concentration of 2-20 mg / L (the preparation method refers to the patents applied for: a method for preparing a nano-selenium solution, application number: 2024110944130; a selenium-enriched Lactobacillus rhamnosus agent and its preparation method, application number: 2024112008120). Static culture is carried out at 40°C for 24 hours; the Lactobacillus rhamnosus of the present invention comes from the China Industrial Microbiological Culture Collection Management Center, and the strain number is: CICC 6137.

[0058] (5) Centrifuge at 8000 g for 10 min at 4°C to collect the fermented bacteria and obtain a selenium-enriched Lactobacillus rhamnosus agent.

[0059] Example 2

[0060] The difference between Example 2 and Example 1 is that the selenium-enriched Lactobacillus rhamnosus bacterial agent is a fermentation culture of Lactobacillus rhamnosus.

[0061] Example 3

[0062] The difference between Example 3 and Example 1 is that the selenium-enriched Lactobacillus rhamnosus bacterial agent is a combination of three of the fermentation culture, fermentation supernatant and fermentation liquid precipitate of Lactobacillus rhamnosus.

[0063] Example 4

[0064] The difference between Example 4 and Example 1 is that the selenium-enriched Lactobacillus rhamnosus agent is a combination of three of the following: ultrasonic lysis supernatant, ultrasonic lysis precipitate and freeze-dried powder.

[0065] Example 5

[0066] The difference between Example 5 and Example 1 is that the selenium-enriched Lactobacillus rhamnosus bacterial agent is a fermentation broth precipitate.

[0067] Example 6

[0068] The present invention provides a probiotic preparation for improving the intestinal environment for preventing and / or treating ulcerative colitis, wherein the probiotic preparation comprises a selenium-enriched Lactobacillus rhamnosus bacterial agent. The content of selenium-enriched Lactobacillus rhamnosus is not less than 1×10 8 CFU / g. Probiotic preparations are freeze-dried powders.

[0069] Example 7

[0070] The difference between Example 7 and Example 6 is that the probiotic preparation is a tablet.

[0071] Example 8

[0072] The difference between Example 8 and Example 6 is that the probiotic preparation is a capsule.

[0073] Example 9

[0074] The difference between Example 9 and Example 6 is that the probiotic preparation is a granule.

[0075] Example 10

[0076] The invention discloses an application of a selenium-enriched Lactobacillus rhamnosus bacterial agent in the preparation of a drug for preventing and / or treating ulcerative colitis in combination with conventional immunosuppressants, small molecule drugs, traditional Chinese medicines and biological preparations.

[0077] Test Example 1

[0078] The detection methods involved in the following embodiments are as follows:

[0079] Disease Activity Index (DAI) detection method:

[0080] The disease activity index is scored by three aspects: weight loss, stool shape and blood in the stool (the specific scoring criteria are shown in Table 1). During the mouse modeling and treatment period, the mouse weight, stool shape and blood in the stool were observed and recorded every day, and scored according to Table 1, DAI = (weight loss score + stool shape score + blood in the stool degree score) / 3. Weight loss is divided into 5 levels: 0%, 1-5%, 6-10%, 11-15%, >15%; stool shape is divided into 5 levels: normal, soft, loose, unshaped, and loose stools; blood in the stool is divided into 4 levels: normal, a small amount of blood, a large amount of blood, and blood in the stool visible to the naked eye. The disease activity index scoring criteria are shown in Table 1:

[0081] Table 1

[0082] Fraction Weight loss Stool shape Blood in stool 0 0％ normal normal 1 1-5％ Softer 2 6-10％ Loose Small amount of blood 3 11-15％ No shape Large amounts of blood 4 ＞15％ Loose stools Naked bloody stool

[0083] Test Example 2

[0084] Effect of selenium-enriched Lactobacillus rhamnosus on the symptoms of DSS-induced acute colitis in mice

[0085] The selenium-enriched Lactobacillus rhamnosus in the present invention is obtained by fermenting Lactobacillus rhamnosus and its derivatives or genetically modified strains through selenium enrichment, and its colonization ability remains unchanged. The following only takes Lactobacillus rhamnosus as an example.

[0086] Experimental grouping: 20 SPF-grade 6-8-week-old (19±1g) female C57BL / 6 mice were purchased from Changzhou Cavens Experimental Animal Co., Ltd. They were kept in an environment with an ambient temperature of 25±2℃ and a humidity of 50±5%, with 12h of light and dark alternation every day, free access to sterilized water, and adaptive feeding for 7 days. They were randomly divided into 3 groups, 6 mice in each group (3 healthy control groups); the 3 groups were 1: healthy control group; 2: DSS non-treatment group; 3: Bifidobacterium longum expressing endostatin (positive control group, a strain that has been shown to have significant enteritis treatment effects in previous studies in this laboratory, expressing recombinant human endostatin protein through plasmid pBV222 plasmid; Frontiers in Microbiology, 2022, 13: 927277.); 4: Selenium-enriched Lactobacillus rhamnosus.

[0087] 3% DSS solution: 9 g of dextran sulfate sodium (DSS) was dissolved in 300 mL of sterile water to prepare a DSS solution with a concentration of 3% (w / v).

[0088] Treatment plan: During the modeling period, the healthy control group (group 1) freely drank sterilized water, and the non-treatment group and treatment group (groups 2-4) freely drank 3% DSS solution; the healthy control group and non-treatment group (groups 1 and 2) were gavaged with 200 μL of sterile PBS buffer every day, and the treatment group (groups 3 and 4) was gavaged with 200 μL of bacterial solution (Bifidobacterium longum expressing endostatin or selenium-enriched Lactobacillus rhamnosus resuspended in sterile PBS buffer, 1.5×10 10 CFU / kg; the mice in each group were weighed daily, and the disease activity index (DAI, Table 1) of each group of mice was observed and recorded. The treatment lasted for 8 days ( Figure 1 After the experiment, the mice were anesthetized and killed, and the entire colon (from the end of the cecum to the anus) was removed and placed in pre-cooled PBS on ice. The length of the colon was then measured and representative images were taken.

[0089] During the modeling period, the weight of mice in the healthy control group was stable and did not decrease significantly. The weight of mice in the DSS non-treatment group began to decrease rapidly on the 5th day, and by the end of the experiment, the average weight loss was 11.2% ( Figure 2 ). In contrast, the body weight of mice treated with endostatin-expressing Bifidobacterium longum (4 groups) and selenium-enriched Lactobacillus rhamnosus (4 groups) was relatively stable. At the end of the experiment, the average body weight decreased by 6.6% and 6.0%, respectively, which was significantly better than that of the non-treated group, showing a good health status.

[0090] During the modeling period, along with weight loss, the mice in the DSS non-treatment group showed symptoms such as reduced stool formation and blood in the stool after the 5th day. At the end of the treatment, the average DAI of the DSS non-treatment group mice increased to 2.9, indicating that DSS induced severe ulcerative colitis. The stool formation and blood in the stool of the group treated with endostatin-expressing Bifidobacterium longum were not serious, and the enteritis progressed slowly. At the end of the treatment, the average DAI dropped to 1.6. The treatment effect of selenium-enriched Lactobacillus rhamnosus was the best. At the end of the treatment, the average DAI was 1.2, which was 58.5% less than that of the non-treatment group mice, showing a good enteritis inhibition effect ( Figure 3 ).

[0091] At the end of the experiment, the colon length of each group of mice was counted. The average colon length of the healthy control group of mice was 6.4 cm, and the feces in the intestine were highly formed. The colon of the mice in the DSS non-treatment group was significantly shortened, with an average length of 5.0 cm, which was 21.8% shorter than that of normal mice. The intestine was pink, no formed feces were seen, and the degree of ulcerative enteritis was severe. The colon atrophy of Bifidobacterium longum expressing endostatin was alleviated, and the average length recovered to 5.6 cm. Treatment with selenium-enriched Lactobacillus rhamnosus significantly alleviated the atrophy of the colon length, and the average length recovered to 5.6 cm. There was no obvious inflammatory area in the intestine, and the feces were highly formed ( Figure 4A , 4B).

[0092] The above results show that selenium-enriched Lactobacillus rhamnosus has a good alleviating effect on DSS-induced ulcerative colitis in mice, and can relieve intestinal atrophy and bloody stool symptoms caused by enteritis. Its therapeutic effect is better than that of Bifidobacterium longum expressing endostatin in multiple treatment prognosis evaluation parameters (the efficacy of this strain has been peer-reviewed and published in international journals, Frontiers in Microbiology, 2022, 13: 927277.), indicating that the selenium-enriched Lactobacillus rhamnosus of the present invention is expected to be developed as a drug for the treatment of enteritis, or as a carrier for other anti-enteritis drugs, or in combination with other probiotics.

[0093] The above shows and describes the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited by the above test examples, and the above test examples and descriptions are only for explaining the principles of the present invention. Without departing from the spirit and scope of the present invention, the present invention may have various changes and improvements, and the scope of protection of the present invention is defined by the attached claims, description and their equivalents.

Claims

1. An application of a selenium-enriched Lactobacillus rhamnosus agent in the preparation of a drug for improving ulcerative colitis, characterized in that: The selenium-enriched Lactobacillus rhamnosus agent is prepared by fermenting Lactobacillus rhamnosus through selenium enrichment, and the selenium content is 5-100 μg / g.

2. The application according to claim 1, characterized in that: The selenium-enriched Lactobacillus rhamnosus agent comprises a combination of one or more of a fermentation culture of Lactobacillus rhamnosus, a fermentation supernatant, a fermentation liquid precipitate, an ultrasonic lysis supernatant, an ultrasonic lysis precipitate or a freeze-dried powder.

3. The application according to claim 1, characterized in that: The fermentation medium of the selenium-enriched Lactobacillus rhamnosus contains the following components: vitamin C, 4 g / L; NaCl, 2.4 g / L; Na2HPO4, 5.8 g / L; KH2PO4, 0.528571 g / L; glucose, 5 g / L; yeast extract, 3 g / L; beef extract powder, 1.7 g / L; soy peptone, 2 g / L; beef peptone, 20 g / L; and nano-selenium solution, 2-20 mg / L.

4. A probiotic preparation for improving the intestinal environment for preventing and / or treating ulcerative colitis, characterized in that: The probiotic preparation comprises the selenium-enriched Lactobacillus rhamnosus agent according to claim 1.

5. The probiotic preparation according to claim 4, characterized in that: The content of selenium-enriched Lactobacillus rhamnosus is not less than 1×10 8 CFU / g.

6. The probiotic preparation according to claim 4, characterized in that: The probiotic preparation includes any one of freeze-dried powder, tablets, capsules or granules.

7. Use of the selenium-enriched Lactobacillus rhamnosus agent according to any one of claims 1 to 6 in the preparation of a drug for preventing and / or treating ulcerative colitis in combination with conventional immunosuppressants, small molecule drugs, traditional Chinese medicines, and biological preparations.

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