Application of lactobacillus helveticus HH-LPH17 in preparation of medicine for assisting in relieving inflammatory bowel disease

Abstract

The invention relates to application of lactobacillus helveticus HH-LPH17 in preparation of medicine for assisting in relieving inflammatory bowel diseases and relates to the technical field of probiotic compositions.The probiotic composition for treating the inflammatory bowel diseases comprises, by weight, 10 parts to 80 parts of lactobacillus johnsonii LBJ 456, 10 parts to 60 parts of lactobacillus helveticus HH-LPH17, 10 parts to 60 parts of lactobacillus acidophilus HH-LA26 and 10 parts to 60 parts of bifidobacterium longum HH-BL18. The composition comprises the following components in parts by weight: 10-60 parts of bifidobacterium bifidum HH-BB27 and 10-60 parts of bifidobacterium longum subspecies infantis HH-BI27. According to the probiotic composition for treating the inflammatory bowel disease, probiotic strains with specific effects are screened out, the combination proportion of the probiotic strains is optimized, the probiotic composition for treating the inflammatory bowel disease is prepared, and a novel safe and effective adjuvant therapy method is provided for treatment of the inflammatory bowel disease.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of probiotic composition, and particularly relates to application of lactobacillus helveticus HH-LPH17 in preparation of a medicine for assisting in relieving inflammatory bowel disease. BACKGROUND

[0002] Inflammatory Bowel Disease (IBD) is a spectrum of diseases characterized by chronic and recurrent inflammation of the digestive tract, and Crohn's Disease (CD) and Ulcerative Colitis (UC) are the most representative types. Due to the extremely complex pathogenesis of IBD, involving genetic susceptibility, environmental factor interaction, immune regulation dysfunction, and intestinal microecological disorder, and other multi-dimensional factors interweaving and jointly driving, there is currently a lack of effective means to completely cure the disease in clinical practice, and treatment mainly focuses on relieving symptoms, controlling inflammation, maintaining remission, and improving the quality of life of patients, but existing treatment drugs and methods often have limited efficacy, many adverse reactions, and high recurrence rates.

[0003] In recent years, intestinal microecological imbalance as a key pathogenic link in the pathogenesis of IBD has gradually become a research hotspot in this field. Under physiological conditions, intestinal microbial communities construct a precise and complex microecological network through dynamic balance between bacterial populations, which can maintain the integrity of the intestinal barrier function and immune homeostasis. However, when the intestinal flora structure is pathologically changed, i.e., ecological imbalance occurs, a series of characteristic changes that are not conducive to intestinal health will follow. For example, opportunistic pathogens may proliferate excessively, disrupting the original balance of the flora, and these bacteria that are not pathogenic under normal circumstances may cause intestinal inflammation after abnormal proliferation; at the same time, the metabolic product spectrum also appears abnormal, and these abnormal metabolic products may further interfere with the normal physiological function of the intestine, forming a vicious cycle and aggravating intestinal inflammation.

[0004] Based on the important role of intestinal microecological imbalance in the pathogenesis of IBD, treating IBD by regulating intestinal microecology has become a potential treatment strategy. Probiotics, as beneficial microorganisms that can regulate intestinal microecological balance, have a significant effect on improving intestinal barrier function, regulating immune response, and inhibiting the growth of harmful bacteria. Therefore, developing a probiotic composition that can effectively regulate intestinal microecology and improve the intestinal symptoms of IBD patients has important clinical significance and application value. SUMMARY

[0005] To solve the above problems, the present application provides application of lactobacillus helveticus HH-LPH17 in preparation of a medicine for assisting in relieving inflammatory bowel disease.

[0006] In a first aspect, the present application provides a probiotic composition for treating inflammatory bowel disease, comprising the following components in parts by weight:

[0007] Lactobacillus johnsonii LBJ 456 10-80 parts, Lactobacillus helveticus HH-LPH17 10-60 parts, Lactobacillus acidophilus HH-LA26 10-60 parts, Bifidobacterium longum HH-BL18 10-60 parts, Bifidobacterium bifidum HH-BB27 10-60 parts, Bifidobacterium longum subsp. infantis HH-BI27 10-60 parts.

[0008] Further, Lactobacillus johnsonii LBJ 456 35 parts, Lactobacillus helveticus HH-LPH17 25 parts, Lactobacillus acidophilus HH-LA26 10 parts, Bifidobacterium longum HH-BL18 10 parts, Bifidobacterium bifidum HH-BB27 10 parts, Bifidobacterium longum subsp. infantis HH-BI27 10 parts.

[0009] In a second aspect, based on the same inventive concept, the present application provides use of the probiotic composition for treating inflammatory bowel disease according to any one of the first aspect in the preparation of a product for treating inflammatory bowel disease.

[0010] The above technical solution provided by the embodiments of the present application has at least the following advantages compared with the prior art:

[0011] The embodiments of the present application provide use of Lactobacillus helveticus HH-LPH17 in the preparation of a drug for assisting in relieving inflammatory bowel disease, and the present application screens probiotic strains with specific efficacy and optimizes the combination ratio thereof, so as to prepare a probiotic composition for treating inflammatory bowel disease, and provides a new safe and effective adjuvant therapy method for the treatment of inflammatory bowel disease. DETAILED DESCRIPTION

[0012] So that the objects, technical solutions and advantages of the embodiments of the present application are more apparent, the technical solutions in the embodiments of the present application will be described clearly and completely below. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments of the present application. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative work fall within the scope of protection of the present application.

[0013] Unless otherwise specifically indicated, all the various raw materials, reagents, instruments and equipment and the like used in the present application can be purchased from the market or can be prepared by the existing method.

[0014] The application will be further described in conjunction with specific examples. It should be understood that these examples are only used to illustrate the application and not used to limit the scope of the application. The experimental methods in the following examples are not specified, and the methods are generally determined according to the national standards. If there is no corresponding national standard, the methods are determined according to the general international standards, conventional conditions, or the conditions recommended by the manufacturers.

[0015] The main strain information involved in the application is as follows:

[0016] The specific preservation information of Lactobacillus johnsonii LBJ 456 is as follows: preserved in China Center for Type Culture Collection on December 5, 2019, the preservation address is No. 299, Bayi Road, Wuchang District, Wuhan City, Hubei Province, and the preservation number is CCTCC NO: M 20191013.

[0017] The specific preservation information of Lactobacillus helveticus HH-LPH17 is as follows: preserved in China Center for Type Culture Collection on June 15, 2021, the preservation address is No. 299, Bayi Road, Wuchang District, Wuhan City, Hubei Province, and the preservation number is CCTCC NO: M 2021725.

[0018] The specific preservation information of Lactobacillus acidophilus HH-LA26 is as follows: preserved in China Center for Type Culture Collection on March 24, 2022, the preservation address is No. 299, Bayi Road, Wuchang District, Wuhan City, Hubei Province, and the preservation number is CCTCC NO: M 2022305.

[0019] The specific preservation information of Bifidobacterium longum HH-BL18 is as follows: preserved in China Center for Type Culture Collection on March 24, 2022, the preservation address is No. 299, Bayi Road, Wuchang District, Wuhan City, Hubei Province, and the preservation number is CCTCC NO: M 2022306.

[0020] The specific preservation information of Bifidobacterium longum subsp. infantis HH-BI27 is as follows: preserved in China Center for Type Culture Collection on July 5, 2023, the preservation address is No. 299, Bayi Road, Wuchang District, Wuhan City, Hubei Province, and the preservation number is CCTCC NO: M 20231197.

[0021] The specific preservation information of Bifidobacterium bifidum HH-BB27 is: preserved in China Center for Type Culture Collection on July 5, 2023, the preservation address is No. 299, Bajiyi Road, Wuchang District, Wuhan City, Hubei Province, China, and the preservation number is CCTCC NO: M 20231198.

[0022] Example 1

[0023] The example provides a probiotic composition for treating inflammatory bowel disease, the probiotic composition for treating inflammatory bowel disease includes the following components in parts by weight:

[0024] Lactobacillus johnsonii LBJ 456 35 parts, Lactobacillus helveticus HH-LPH17 25 parts, Lactobacillus acidophilus HH-LA26 10 parts, Bifidobacterium longum HH-BL18 10 parts, Bifidobacterium bifidum HH-BB27 10 parts, Bifidobacterium longum subsp. infantis HH-BI27 10 parts.

[0025] The preparation method of the probiotic composition for treating inflammatory bowel disease includes: mixing each probiotic to form a composite bacteria powder.

[0026] Example 2

[0027] The example provides a probiotic composition for treating inflammatory bowel disease, the probiotic composition for treating inflammatory bowel disease includes the following components in parts by weight:

[0028] Lactobacillus johnsonii LBJ 456 10 parts, Lactobacillus helveticus HH-LPH17 10 parts, Lactobacillus acidophilus HH-LA26 10 parts, Bifidobacterium longum HH-BL18 10 parts, Bifidobacterium bifidum HH-BB27 10 parts, Bifidobacterium longum subsp. infantis HH-BI27 10 parts.

[0029] The preparation method of the probiotic composition for treating inflammatory bowel disease includes: mixing each probiotic to form a composite bacteria powder.

[0030] Example 3

[0031] The example provides a probiotic composition for treating inflammatory bowel disease, the probiotic composition for treating inflammatory bowel disease includes the following components in parts by weight:

[0032] Lactobacillus johnsonii LBJ 456 80 parts, Lactobacillus helveticus HH-LPH17 60 parts, Lactobacillus acidophilus HH-LA26 60 parts, Bifidobacterium longum HH-BL18 60 parts, Bifidobacterium bifidum HH-BB27 60 parts, Bifidobacterium longum subsp. infantis HH-BI27 60 parts.

[0033] The method for preparing the probiotic composition for treating inflammatory bowel disease comprises mixing each probiotic to form a composite bacteria powder.

[0034] Test Example

[0035] This example aims to investigate the therapeutic effect of the probiotic composition for treating inflammatory bowel disease obtained in Example 1 above on inflammatory bowel disease.

[0036] Test method: C57BL / 6L mice were used, and the test was divided into 4 groups, namely the control group, the model group, the probiotic group (including the composite bacteria powder group, the single bacteria group), and the drug group (the specific drug is 5-aminosalicylic acid). The control group and the model group were given 0.2 mL of normal saline by gavage every day, the probiotic group and the drug group were given 0.2 mL (concentration of 100 mg / kg) of corresponding experimental materials by gavage, and the probiotic + drug group was given 0.1 mL (concentration of 100 mg / kg) of probiotic and drug by gavage. Except for the control group which drank sterile water, the other groups were free to drink 2.3% DSS solution for 7 days, and then changed to 0.8% DSS solution until the 21st day. After the end of the test, the mice were anesthetized and executed by cervical dislocation, and the corresponding samples were collected for detection. After weighing the intestinal segments, they were cut into small pieces on ice, and pre-cooled PBS was added at a weight to volume ratio of 1:9 into a homogenization tube. The colon tissue homogenate was prepared by a biological sample grinder, centrifuged at 3000 rpm for 15 min, and the supernatant was detected by ELISA for IL-1β, TNF-α, IFN-γ, IL-4, IL-6, IL-10 and IL-17A content in colon tissue, and the operation process was strictly according to the corresponding ELISA kit instruction. The content of myeloperoxidase (MPO) and glutathione peroxidase (GSH-PX) in colon tissue was detected by ELISA, and the operation process was strictly according to the corresponding ELISA kit instruction; the test results are shown in Tables 1, 2 and 3.

[0037] Table 1

[0038]

[0039]

[0040] Table 2

[0041]

[0042] Table 3

[0043]

[0044] From table 1, it can be concluded that the expression amount of each inflammatory factor in the intestine can be significantly changed after probiotic treatment, compared with the control group, the IL-1beta, TNF-alpha, IFN-gamma, IL-6, IL-17A, IL-10 of the model group are significantly increased, and the IL-4 is obviously decreased. After probiotic treatment, each factor is close to the normal control group level, and the difference is significant compared with the model group.

[0045] From table 2, it can be concluded that, similar to the results of intestinal related inflammatory factors, each factor in the serum of mice is obviously changed after probiotic treatment, each factor has not restored to the normal control group level, but all are restored to the normal level, and the difference is significant compared with the model group, and the serum immunoglobulin content is up-regulated.

[0046] From table 3, it can be concluded that, after probiotic treatment, the content of myeloperoxidase (MPO) and glutathione peroxidase (GSH-PX) in the colon tissue is better than that of the control group.

[0047] Various embodiments of the present application can exist in a range of forms; it should be understood that the description in a range form is merely for the convenience and brevity, and should not be understood as a rigid limitation on the scope of the present application; therefore, it should be considered that the described range has disclosed all possible sub-ranges and single values in the range. For example, it should be considered that the range description from 1 to 6 has disclosed sub-ranges, such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., and single numbers in the described range, such as 1, 2, 3, 4, 5 and 6, regardless of the range. In addition, whenever a numerical range is indicated in this text, it means that any cited number (fraction or integer) in the indicated range is included.

[0048] The above description is only a specific embodiment of the present application, enabling those skilled in the art to understand or implement the present application. Various modifications of these embodiments will be apparent to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present application. Therefore, the present application will not be limited to these embodiments shown herein, but will conform to the widest scope consistent with the principles and novel features applied herein.

Claims

1. A probiotic composition for treating inflammatory bowel disease, characterized in that: The probiotic composition for treating inflammatory bowel disease comprises the following components in parts by weight: 10-80 parts of Lactobacillus johnsonii LBJ 456, 10-60 parts of Lactobacillus helveticus HH-LPH17, 10-60 parts of Lactobacillus acidophilus HH-LA26, 10-60 parts of Bifidobacterium longum HH-BL18, 10-60 parts of Bifidobacterium bifidum HH-BB27, and 10-60 parts of Bifidobacterium longum subsp. infantis HH-BI27.

2. The probiotic composition for treating inflammatory bowel disease according to claim 1, characterized in that 35 parts of Lactobacillus johnsonii LBJ 456, 25 parts of Lactobacillus helveticus HH-LPH17, 10 parts of Lactobacillus acidophilus HH-LA26, 10 parts of Bifidobacterium longum HH-BL18, 10 parts of Bifidobacterium bifidum HH-BB27, and 10 parts of Bifidobacterium longum subsp. infantis HH-BI27.

3. Use of the probiotic composition for treating inflammatory bowel disease according to any one of claims 1 to 2 in the preparation of a product for treating inflammatory bowel disease.

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