CN114134080A - Bacillus coagulans and application thereof in treatment of colitis - Google Patents
Bacillus coagulans and application thereof in treatment of colitis Download PDFInfo
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Abstract
The invention discloses bacillus coagulans and application thereof in treatment of colitis, and belongs to the field of microorganisms. The strain is bacillus coagulans FCYS01, is preserved in China center for type culture collection, has a preservation number of CCTCC NO of M20211273, is preserved at Wuhan university, China, and has a preservation date of 2021, 10 and 14 days, can be applied to preparation of medicaments for preventing and/or treating colitis, achieves the technical effect of preventing and treating colitis by improving the immune regulation function of colitis mice, enhancing the stability of colitis mouse intestinal flora and improving the colitis mouse intestinal barrier, and is a new probiotic strain with potential application prospect in the field of colitis prevention and treatment.
Description
Technical Field
The invention relates to the field of microorganisms, in particular to bacillus coagulans and application thereof in treatment of colitis.
Background
Inflammatory Bowel Disease (IBD) is a chronic, recurrent inflammation of the gastrointestinal tract, divided into crohn's disease, which involves the entire gastrointestinal tract, and ulcerative enteritis, which is restricted to the colon and rectum. The clinical manifestations of IBD include diarrhea, abdominal pain, rectal bleeding, weight loss, etc. the current studies show that IBD has many complications, besides causing toxic megacolon, heavy bleeding and colon cancer in the intestinal tract, it also causes extra-intestinal complications related to autoimmune reaction, similar to arthritis, oral ulcer. The incidence of inflammatory bowel inflammation is increasing in the world today and the promotion of western diets high in energy and low in dietary fiber is believed to be the primary cause of its increased incidence.
Ulcerative colitis has the characteristics of easy relapse, difficult treatment and difficult cure, and the existing treatment mainly aims at resisting inflammation and regulating immunity. The drugs used are generally classified into 6 classes: the traditional Chinese medicine composition is prepared from amino salicylic acids, glucocorticoids, immune preparations, biological preparations, probiotics and anti-infection medicines, and is combined with surgical operation, so that the colitis can be well relieved, side effects are large, the price is high, and more treatment schemes are important to find. A large number of animal experiments and clinical trials have shown that certain probiotics can be used to treat colitis. Probiotics treat colitis by regulating immune function, maintaining intestinal microbial homeostasis, and repairing intestinal barriers. The use of probiotics for treating colitis is undoubtedly a new idea which is simple, effective and free of side effects.
Bacillus coagulans (Bacillus coagulans) is a gram-positive bacterium, is facultative anaerobic, non-pathogenic, can form spores and produce lactic acid, and has the industrial characteristics of high temperature resistance, acid resistance, bile resistance and the like. Has been widely applied to the industries of medicine, food, chemical industry and the like. Research reports that bacillus coagulans can be used for treating intestinal diseases such as acute diarrhea, irritable bowel syndrome, antibiotic-associated diarrhea, constipation and the like by regulating the composition of microbiota, host immunity and metabolism. However, in the existing research, medicines such as bacillus coagulans and olsalazine are mostly adopted to treat colitis in a combined mode.
Disclosure of Invention
The invention aims to provide a bacillus coagulans strain and application thereof in treatment of colitis, so as to solve the problems in the prior art, and the bacillus coagulans strain can prevent and treat colitis and has potential application prospects in the field of colitis prevention and treatment.
In order to achieve the purpose, the invention provides the following scheme:
the invention provides application of bacillus coagulans in preparation of a medicine for preventing and/or treating colitis.
Further, the Bacillus coagulans is Bacillus coagulans (Bacillus coagulans) FCYS01, and is preserved in China center for type culture Collection with the preservation number of CCTCC NO: M20211273, the preservation address of university of Wuhan, China, and the preservation date of 2021 year, 10 months and 14 days.
Further, the active ingredient of the medicament is the bacillus coagulans FCYS 01.
Further, the effective dose of the bacillus coagulans FCYS01 in the medicament is 1.0 × 109CFU。
Further, the medicament prevents and/or treats colitis by one or more of the following routes:
(1) relieving rectal bleeding symptoms of patients with colitis;
(2) relieving diarrhea symptoms of colitis patients;
(3) restoring the body weight of a colitis patient;
(4) reducing the level of gut tissue myeloperoxidase in a colitis patient;
(5) restoring colon health in patients with colitis;
(6) reducing the content of C-reactive protein in the serum of a colitis patient;
(7) increasing the content of anti-inflammatory factor interleukin-4 in colon of a colitis patient;
(8) reducing the content of inflammatory factor interleukin-6 in colon of a colitis patient;
(9) reducing the content of inflammatory factor interleukin-8 in colon of a colitis patient;
(10) increasing the content of anti-inflammatory factor interleukin-10 in colon of a colitis patient;
(11) reducing the extent of crypt destruction in the colon of a colitis patient;
(12) reducing goblet cell loss in colon tissue in patients with colitis;
(13) reducing inflammatory cell infiltration levels in colon tissue of a colitis patient;
(14) reduce colonic atrophy in patients with colitis;
(15) increasing the abundance of beneficial bacteria in intestinal tracts of patients with colitis;
(16) reducing the abundance of harmful intestinal bacteria of patients with colitis;
(17) improving the immunoregulation capability of the colitis patient;
(18) improving the diversity of intestinal microflora of a colitis patient;
(19) enhancing intestinal microbial homeostasis in patients with colitis;
(20) can strengthen intestinal barrier of colitis patients.
Further, the medicine also comprises other medicines compatible with the bacillus coagulans FCYS01 and pharmaceutically acceptable carriers and/or auxiliary materials.
Furthermore, the other medicines comprise medicines which are compatible with the bacillus coagulans FCYS01, do not cause hydrolysis and damage failure physicochemical reaction of the bacillus coagulans FCYS01, and can improve the treatment effect of the bacillus coagulans FCYS01 after synergistic action with the bacillus coagulans FCYS 01.
Further, the medicament is a pharmaceutically acceptable dosage form.
Further, the dosage form is powder, injection, capsule, tablet or oral liquid.
The invention discloses the following technical effects:
the bacillus coagulans FCYS01 can recover the weight and the colon length of a colitis mouse, reduce the disease activity index of the colitis mouse, reduce the expression of proinflammatory factors and myeloperoxidase in colon tissues of the colitis mouse, reduce the expression of C-reactive protein in serum of the colitis mouse, improve the expression of anti-inflammatory factors in the colon of the colitis mouse, reduce inflammatory cell infiltration in the colon of the colitis mouse, repair damaged colon tissues, prevent and treat colitis by improving the immune regulation function of the colitis mouse, enhance the stability of intestinal flora of the colitis mouse and improve the intestinal barrier of the colitis mouse, and is a new probiotic strain with potential application prospects in the field of colitis prevention and treatment.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings needed in the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings without creative efforts.
FIG. 1 is the macroscopic change in colitis in mice in example 2, wherein the A-graph shows the change in body weight of mice in the normal group, DSS group and BC group; the B picture shows the change of the colitis disease index of mice in the normal group, the DSS group and the BC group; c is colon and length statistics of mice in normal group, DSS group and BC group; d is colon tissue section observation and tissue ulcer statistics of mice in normal group, DSS group and BC group (p < 0.05;. p < 0.01;. p < 0.001);
FIG. 2 shows the results of the test analysis of inflammatory cytokines in colon tissues of mice in the normal group, DSS group and BC group in example 2, including proinflammatory cytokines IL-6 and IL-10, anti-inflammatory cytokines IL-4 and IL-10, and the test of the content of myeloperoxidase in C-reactive protein and tissues in serum (p < 0.05;. p < 0.01;. p < 0.001);
FIG. 3 is the results of measurement of the abundance of microorganisms in the intestinal tracts of mice in the normal group, DSS group and BC group in example 2, wherein A is a Simpson index in the alpha diversity of intestinal microorganisms, B is a shannon index in the alpha diversity of intestinal microorganisms, and C is the result of differential classification of microorganisms analyzed by LefSe;
FIG. 4 shows the results of expression of colon Ocplus protein in mice of normal group, DSS group and BC group in example 2.
Detailed Description
Reference will now be made in detail to various exemplary embodiments of the invention, the detailed description should not be construed as limiting the invention but as a more detailed description of certain aspects, features and embodiments of the invention.
It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. Further, for numerical ranges in this disclosure, it is understood that each intervening value, between the upper and lower limit of that range, is also specifically disclosed. Every smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in a stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference herein for the purpose of disclosing and describing the methods and/or materials associated with the documents. In case of conflict with any incorporated document, the present specification will control.
It will be apparent to those skilled in the art that various modifications and variations can be made in the specific embodiments of the present disclosure without departing from the scope or spirit of the disclosure. Other embodiments will be apparent to those skilled in the art from consideration of the specification. The description and examples are intended to be illustrative only.
As used herein, the terms "comprising," "including," "having," "containing," and the like are open-ended terms that mean including, but not limited to.
The experimental procedures in the following examples are conventional unless otherwise specified. The test materials used in the following examples were purchased from a conventional biochemical reagent store unless otherwise specified. The quantitative tests in the following examples, all set up three replicates and the results averaged.
The test materials used in the present invention are not specifically described, and are all commercially available products.
Male SPF grade C57 mice 7-8 weeks old, body mass (20 ± 2) g: animal center, university of agriculture in china, animal license number: HZAUMO-2021-.
Example 1 isolation, identification and preservation of strains
First, isolation of the Strain
The method comprises the steps of taking samples from a cattle farm in Xinkamura village of Mirabo, Deyang, Sichuan province, and taking the samples as fresh cattle manure.
And repeatedly carrying out streak culture on the sample by a solid YPD medium plate, selecting a single colony which generates a yellow circle, inoculating the single colony on the solid YPD medium plate, continuously culturing, and repeatedly carrying out streak culture and purification by the solid YPD medium plate to obtain a plurality of pure culture strains.
Selecting gram-positive strain from pure cultured strains, inoculating to liquid YPD medium, adding 20% glycerol, and storing at-80 deg.C in refrigerator.
II, identification of the strains
And performing morphological identification, physiological and biochemical identification and molecular identification on each separated strain, wherein the strain FCYS01 belongs to Bacillus coagulans (Bacillus coagulans).
The results of morphological identification and physiological and biochemical identification of the strain FCYS01 are as follows: gram-positive, spore-forming, short rod-shaped thallus, two ends of which are round, and grow in single, paired or chain arrangement; spores are resistant to high temperature; the hydrolyzed starch has cellulase activity and no protease activity, and can produce acid by fermenting glucose, galactose, xylose, fructose, sorbitol, arabinose and maltose.
The strain FCYS01 shows uniform turbid growth in a liquid YPD culture medium, and the thallus is white precipitate after long-time standing.
The optimum growth temperature of the strain FCYS01 is 37-45 ℃, and the suitable pH is 6.6-7.0.
The 16S rDNA (SEQ ID NO.1) sequence of strain FCYS01 is shown below:
GCGATGCGCGTGGCTAATACTGCAGGTTCGTTGCGGACCTTTTAAAGCTTGCTTTTAAAAGGTTAGCGGCGGACGGGTGAGTAACACGTGGGCAACCTGCCTGTAAGATCGGGATAACGCCGGGAAACCGGGGCTAATACCGGATAGTTTTTTCCTCCGCATGGAGGAAAAAGGAAAGACGGCTTCTGCTGTCACTTACAGATGGGCCCGCGGCGCATTAGCTAGTTGGTGGGGTAACGGCTCACCAAGGCAACGATGCGTAGCCGACCTGAGAGGGTGATCGGCCACATTGGGACTGAGACACGGCCCAAACTCCTACGGGAGGCAGCAGTAGGGAATCTTCCGCAATGGACGAAAGTCTGACGGAGCAACGCCGCGTGAGTGAAGAAGGCCTTCGGGTCGTAAAACTCTGTTGCCGGGGAAGAACAAGTGCCGTTCGAACAGGGCGGCGCCTTGACGGTACCCGGCCAGAAAGCCACGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGTGGCAAGCGTTGTCCGGAATTATTGGGCGTAAAGCGCGCGCAGGCGGCTTCTTAAGTCTGATGTGAAATCTTGCGGCTCAACCGCAAGCGGTCATTGGAAACTGGGAGGCTTGAGTGCAGAAGAGGAGAGTGGAATTCCACGTGTAGCGGTGAAATGCGTAGAGATGTGGAGGAACACCAGTGGCGAAGGCGGCTCTCTGGTCTGTAACTGACGCTGAGGCGCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGAGTGCTAAGTGTTAGAGGGTTTCCGCCCTTTAGTGCTGCAGCTAACGCATTAAGCACTCCGCCTGGGGAGTACGGCCGCAAGGCTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAGGTCTTGACATCCTCTGACCTCCCTGGAGACAGGGCCTTCCCCTTCGGGGGACAGAGTGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTGACCTTAGTTGCCAGCATTCAGTTGGGCACTCTAAGGTGACTGCCGGTGACAAACCGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGACCTGGGCTACACACGTGCTACAATGGATGGTACAAAGGGCTGCGAGACCGCGAGGTTAAGCCAATCCCAGAAAACCATTCCCAGTTCGGATTGCAGGCTGCAACCCGCCTGCATGAAGCCGGAATCGCTAGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCACACCACGAGAGTTTGTAACACCCGAAGTCGGTGGAGGTAACCTTTACGAACCACCGCCGAAGGACAAGT。
third, preservation of the Strain
Bacillus coagulans FCYS01(Bacillus coagulans) FCYS01 which is preserved in China center for type culture Collection (CCTCC for short, address: China, Wuhan university) at 10 months and 14 days in 2021 has a preservation number of CCTCC NO: M20211273.
Example 2 therapeutic Effect of Bacillus coagulans FCYS01 on colitis in a mouse model
First, experimental design and grouping
The treatment effect of Bacillus coagulans on colitis was studied by constructing a mouse acute colitis model by supplementing 2.5% DSS solution to a C57BL/6 mouse as a test subject. Grouping tests: 30 male C57BL/6 mice, weighing about 20g, were randomly divided into 3 groups of 10 mice each. The test set-up was normal, model and experimental: (1) healthy normal group (HC group) (2) DSS-model group (DSS group for short), and (3) probiotic Bacillus coagulans (B.coagulons) FCYS01 experimental group (BC group for short). In addition to the normal daily feed, the Bacillus coagulans group was supplemented with Bacillus coagulans FCYS01 spores (10)9CFU/day/mouse), inoculating the strain into a basic sporulation culture medium according to the inoculation amount of 3%, and culturing for 48h at 37 ℃ by a shaker at 250 r/min. The whole experiment period is 19 days, the mice are firstly adapted for 3 days, then the formal experiment is started, drinking water of the other two groups except the normal group is changed into 2.5 percent DSS solution for colitis molding on the 4 th to 11 th days, and the mice freely drink water. Stopping supplying DSS solution on 12-18 days, changing into normal drinking water, adding normal feed in HC group and DSS group, and supplementing Bacillus coagulans spore in BC group feed (10)9CFU/day/mouse), the experiment was ended on day 19, by CO2The mice were sacrificed by asphyxiation.
Second, Experimental procedure
I, the adaptation period of the mice is 3 days, fresh feed, padding and weight are replaced every morning, and the mice begin to be molded when the weight is stable.
II, molding: on days 4-11, the drinking water of the bacillus coagulans group and the model group is replaced by 2.5% DSS solution, and during the period, the state of the excrement of the mice and whether the excrement or rectum is bleeding are observed, the change of the body weight is recorded, and the colitis disease index of the mice is scored.
III, probiotic supplementation: on days 12-18, the Bacillus coagulans group was supplemented with 10 per mouse per day9CFU bacillus coagulans spores, model group and healthy normal group normal diet.
Iv day 19 the mice were bled from their orbits, sacrificed and dissected, the colons collected, and the length of the colons recorded.
V blood overnight at 4 ℃ and serum was collected and the C-reactive protein content was measured according to the kit (Wuhan Gene science and technology Co., Ltd., China, JYM0563 Mo). Colon tissue homogenate was prepared by a grinder, and the contents of IL-4 (Wuhan Gene science and technology Co., Ltd., JYM0011Mo), IL-6 (Wuhan Gene science and technology Co., Ltd., JYM0012Mo), IL-8 (Wuhan Gene science and technology Co., Ltd., JYM0457Mo), IL-10 (Wuhan Gene science and technology Co., Ltd., China, JYM0005Mo) inflammatory cytokine and Myeloperoxidase (MPO) (Wuhan Gene science and technology Co., Ltd., JYM0260Mo) were measured according to the ELISA kit instructions. Colon tissue was HE stained and sectioned for histological changes. Data processing was performed according to GraphPad Prism 8.0.2 Ordinary one-way ANOVA Test: sidak.
Third, the macroscopic therapeutic effect of the bacillus coagulans on colitis model mice
As shown in fig. 1A and fig. 1B, the disease index results of evaluating the softness of feces (degree of diarrhea) and blood content of feces in mice show that, during the colitis modeling process, the weight of DSS group mice is significantly reduced and the colitis disease activity index is significantly increased compared to the normal group, indicating that DSS induced colitis modeling is successful. After treatment with bacillus coagulans, the body weight recovery of mice was better and the disease activity index decreased significantly compared to DSS group. As shown in fig. 1C, the results of colon length in mice showed that the colon was significantly atrophied in DSS group compared to normal group; the colon length of the BC group was significantly longer than that of the DSS group, tending to return to normal length. As shown in fig. 1D, colon tissue section results showed that the colon of DSS group exhibited significant histological damage including erosion or destruction of intestinal epithelium, mucosal ulceration, crypt destruction, goblet cell reduction and inflammatory cell infiltration compared to the normal group. Compared to the DSS group, the BC group had almost total recovery of colonic tissue damage, substantial retention of colonic structure, protection of crypt and goblet cells, and reduced inflammatory cell infiltration.
The above disease indices and slice staining results suggest that DSS can cause rectal bleeding, diarrhea, weight loss, colon atrophy, crypt destruction, goblet cell loss, and ultimately ulcerative colitis; the bacillus coagulans FCYS01 can reduce rectal bleeding and diarrhea, recover body weight, recover colon length, repair colon structure, and finally relieve the progress of colitis of mice.
Fourthly, bacillus coagulans improves the immunoregulation of colitis model mice
Detection of inflammatory cytokines in colon tissue demonstrates that bacillus coagulans can improve immune modulation in colitis. As shown in FIG. 2, the DSS group significantly reduced the expression of anti-inflammatory factors IL-4 and IL-10 in colon tissue, and significantly increased the expression of pro-inflammatory factors IL-6 and IL-8, myeloperoxidase MPO and C-reactive protein in serum in colon tissue, as compared to the normal group. Compared with the DSS group, the BC group can obviously improve the expression of anti-inflammatory factors IL-4 and IL-10 in colon tissues and obviously reduce the expression of proinflammatory factors IL-6 and IL-8, myeloperoxidase MPO and C-reactive protein in serum.
The results of the above immune response-related factors show that DSS can cause inflammatory reactions in the body, ultimately leading to ulcerative colitis; bacillus coagulans FCYS01 can modulate the inflammatory response in the treatment of colitis.
Fifthly, the bacillus coagulans enhances the stability of intestinal flora
16S sequencing and analysis of the mouse cecal feces showed that the Simpson index and the shannon index in the intestinal microbial alpha diversity were significantly reduced in the DSS group compared to the normal group, as shown in FIGS. 3A-B; the simpson index and shannon index were significantly increased in the intestinal microbial alpha diversity of the BC group compared to the DSS group. It was demonstrated that supplementation with bacillus coagulans FCYS01 increased the intestinal microflora diversity. The results of the microbiologic classification analysis showed that, as shown in fig. 3C, in the DSS group, harmful flora such as bacteroides, vibrio, SMB53, which may cause intestinal imbalance, were enriched compared to the normal group; in the bacillus coagulans BC group, enrichment of the flora is obviously reduced, and beneficial bacteria such as Lactobacillaceae and S24-7 are enriched.
The alpha diversity index and the microorganism classification analysis result show that the DSS can reduce the diversity of the intestinal microorganisms, enrich harmful flora and finally cause the disorder of the intestinal flora; the bacillus coagulans FCYS01 can restore the diversity of intestinal microorganisms, inhibit pathogenic bacteria enrichment, promote beneficial bacteria enrichment, and further regulate and control intestinal tract to restore steady state.
Sixthly, the bacillus coagulans strengthens intestinal barrier
After serum was taken on day 16 of the experiment, the mice were sacrificed and dissected to collect the colon, total protein was extracted according to the method of the BCA protein quantification kit instructions, and the expression of the colon Occludin protein was detected by Western Blot.
The result of Western Blot protein expression is shown in FIG. 4. Compared with a healthy normal group, the expression level of Occludin in the colon of mice in the DSS group is obviously reduced; the expression level of Occludin in the colon was significantly increased in the BC group mice compared to the DSS group.
The Western Blot detection result shows that: DSS induction can down-regulate the expression of intestinal connexin Occludin; the bacillus coagulans FCYS01 can restore the DSS-induced down-regulation of the connexin Ocplus, which indicates that the bacillus coagulans FCYS01 can repair intestinal barriers, thereby preventing and treating DSS-induced intestinal injury.
The above-described embodiments are merely illustrative of the preferred embodiments of the present invention, and do not limit the scope of the present invention, and various modifications and improvements of the technical solutions of the present invention can be made by those skilled in the art without departing from the spirit of the present invention, and the technical solutions of the present invention are within the scope of the present invention defined by the claims.
Sequence listing
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<120> a strain of bacillus coagulans and application thereof in treatment of colitis
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gcgatgcgcg tggctaatac tgcaggttcg ttgcggacct tttaaagctt gcttttaaaa 60
ggttagcggc ggacgggtga gtaacacgtg ggcaacctgc ctgtaagatc gggataacgc 120
cgggaaaccg gggctaatac cggatagttt tttcctccgc atggaggaaa aaggaaagac 180
ggcttctgct gtcacttaca gatgggcccg cggcgcatta gctagttggt ggggtaacgg 240
ctcaccaagg caacgatgcg tagccgacct gagagggtga tcggccacat tgggactgag 300
acacggccca aactcctacg ggaggcagca gtagggaatc ttccgcaatg gacgaaagtc 360
tgacggagca acgccgcgtg agtgaagaag gccttcgggt cgtaaaactc tgttgccggg 420
gaagaacaag tgccgttcga acagggcggc gccttgacgg tacccggcca gaaagccacg 480
gctaactacg tgccagcagc cgcggtaata cgtaggtggc aagcgttgtc cggaattatt 540
gggcgtaaag cgcgcgcagg cggcttctta agtctgatgt gaaatcttgc ggctcaaccg 600
caagcggtca ttggaaactg ggaggcttga gtgcagaaga ggagagtgga attccacgtg 660
tagcggtgaa atgcgtagag atgtggagga acaccagtgg cgaaggcggc tctctggtct 720
gtaactgacg ctgaggcgcg aaagcgtggg gagcaaacag gattagatac cctggtagtc 780
cacgccgtaa acgatgagtg ctaagtgtta gagggtttcc gccctttagt gctgcagcta 840
acgcattaag cactccgcct ggggagtacg gccgcaaggc tgaaactcaa aggaattgac 900
gggggcccgc acaagcggtg gagcatgtgg tttaattcga agcaacgcga agaaccttac 960
caggtcttga catcctctga cctccctgga gacagggcct tccccttcgg gggacagagt 1020
gacaggtggt gcatggttgt cgtcagctcg tgtcgtgaga tgttgggtta agtcccgcaa 1080
cgagcgcaac ccttgacctt agttgccagc attcagttgg gcactctaag gtgactgccg 1140
gtgacaaacc ggaggaaggt ggggatgacg tcaaatcatc atgcccctta tgacctgggc 1200
tacacacgtg ctacaatgga tggtacaaag ggctgcgaga ccgcgaggtt aagccaatcc 1260
cagaaaacca ttcccagttc ggattgcagg ctgcaacccg cctgcatgaa gccggaatcg 1320
ctagtaatcg cggatcagca tgccgcggtg aatacgttcc cgggccttgt acacaccgcc 1380
cgtcacacca cgagagtttg taacacccga agtcggtgga ggtaaccttt acgaaccacc 1440
gccgaaggac aagt 1454
Claims (9)
1. Application of bacillus coagulans in preparation of medicines for preventing and/or treating colitis.
2. The use according to claim 1, wherein the Bacillus coagulans is Bacillus coagulans (Bacillus coagulans) FCYS01, which is preserved in the China center for type culture Collection with the preservation number of CCTCC NO: M20211273, the preservation address of university of Wuhan, China, and the preservation date of 10 months and 14 days 2021.
3. The use according to claim 2, wherein the active ingredient of the medicament is the bacillus coagulans FCYS 01.
4. The use as claimed in claim 3, wherein the effective dose of Bacillus coagulans FCYS01 in the medicament is 1.0 x 109CFU。
5. Use according to claim 1, wherein the medicament prevents and/or treats colitis by one or more of the following routes:
(1) relieving rectal bleeding symptoms of patients with colitis;
(2) relieving diarrhea symptoms of colitis patients;
(3) restoring the body weight of a colitis patient;
(4) reducing the level of gut tissue myeloperoxidase in a colitis patient;
(5) restoring colon health in patients with colitis;
(6) reducing the content of C-reactive protein in the serum of a colitis patient;
(7) increasing the content of anti-inflammatory factor interleukin-4 in colon of a colitis patient;
(8) reducing the content of inflammatory factor interleukin-6 in colon of a colitis patient;
(9) reducing the content of inflammatory factor interleukin-8 in colon of a colitis patient;
(10) increasing the content of anti-inflammatory factor interleukin-10 in colon of a colitis patient;
(11) reducing the extent of crypt destruction in the colon of a colitis patient;
(12) reducing goblet cell loss in colon tissue in patients with colitis;
(13) reducing inflammatory cell infiltration levels in colon tissue of a colitis patient;
(14) reduce colonic atrophy in patients with colitis;
(15) increasing the abundance of beneficial bacteria in intestinal tracts of patients with colitis;
(16) reducing the abundance of harmful intestinal bacteria of patients with colitis;
(17) improving the immunoregulation capability of the colitis patient;
(18) improving the diversity of intestinal microflora of a colitis patient;
(19) enhancing intestinal microbial homeostasis in patients with colitis;
(20) can strengthen intestinal barrier of colitis patients.
6. The use according to claim 3, wherein the medicament further comprises other drugs compatible with the Bacillus coagulans FCYS01 and a pharmaceutically acceptable carrier and/or adjuvant.
7. The use of claim 6, wherein said other agents comprise agents which are compatible with said Bacillus coagulans FCYS01 and which do not hydrolyze and destroy any physicochemical reactions of said Bacillus coagulans FCYS01 and which, in combination with Bacillus coagulans FCYS01, enhance the therapeutic effect of Bacillus coagulans FCYS 01.
8. The use of claim 1, wherein the medicament is in a pharmaceutically acceptable dosage form.
9. The use according to claim 8, wherein the dosage form is a powder, injection, capsule, tablet or oral liquid.
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