CN117281839A - Application of bacteroides sally CSP6 in preparing medicine and/or food for treating and/or preventing inflammatory bowel disease - Google Patents
Application of bacteroides sally CSP6 in preparing medicine and/or food for treating and/or preventing inflammatory bowel disease Download PDFInfo
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- CN117281839A CN117281839A CN202311326218.1A CN202311326218A CN117281839A CN 117281839 A CN117281839 A CN 117281839A CN 202311326218 A CN202311326218 A CN 202311326218A CN 117281839 A CN117281839 A CN 117281839A
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- bacteroides
- csp6
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- inflammatory bowel
- salesii
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- 241000606125 Bacteroides Species 0.000 title claims abstract description 55
- 208000022559 Inflammatory bowel disease Diseases 0.000 title claims abstract description 32
- 239000003814 drug Substances 0.000 title claims abstract description 29
- 235000013305 food Nutrition 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 claims abstract description 19
- 230000000968 intestinal effect Effects 0.000 claims abstract description 17
- 230000006378 damage Effects 0.000 claims abstract description 14
- 229940079593 drug Drugs 0.000 claims abstract description 9
- 230000004580 weight loss Effects 0.000 claims abstract description 9
- 206010061218 Inflammation Diseases 0.000 claims abstract description 7
- 230000004054 inflammatory process Effects 0.000 claims abstract description 7
- 238000011282 treatment Methods 0.000 claims abstract description 6
- 229920003045 dextran sodium sulfate Polymers 0.000 claims description 16
- 239000007788 liquid Substances 0.000 claims description 16
- 239000007787 solid Substances 0.000 claims description 11
- 241000894006 Bacteria Species 0.000 claims description 8
- 241001236817 Paecilomyces <Clavicipitaceae> Species 0.000 claims description 3
- 241000201895 Salicornia Species 0.000 claims description 2
- 238000011321 prophylaxis Methods 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 208000012671 Gastrointestinal haemorrhages Diseases 0.000 abstract description 10
- 208000035861 hematochezia Diseases 0.000 abstract description 10
- 208000024891 symptom Diseases 0.000 abstract description 8
- 206010012735 Diarrhoea Diseases 0.000 abstract description 7
- 210000004347 intestinal mucosa Anatomy 0.000 abstract description 7
- 238000004904 shortening Methods 0.000 abstract description 5
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000606123 Bacteroides thetaiotaomicron Species 0.000 description 2
- 208000031648 Body Weight Changes Diseases 0.000 description 2
- 229920001287 Chondroitin sulfate Polymers 0.000 description 2
- 208000011231 Crohn disease Diseases 0.000 description 2
- 208000004232 Enteritis Diseases 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 description 1
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- 241000588807 Bordetella Species 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
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- 230000002262 irrigation Effects 0.000 description 1
- 238000003973 irrigation Methods 0.000 description 1
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- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
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- 235000019319 peptone Nutrition 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000006041 probiotic Substances 0.000 description 1
- 235000018291 probiotics Nutrition 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
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- 150000004666 short chain fatty acids Chemical class 0.000 description 1
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- 229920001221 xylan Polymers 0.000 description 1
- 150000004823 xylans Chemical class 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Mycology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Microbiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The invention belongs to the technical field of intestinal microorganisms, and particularly relates to application of a bacteroides salesii CSP6 in preparation of medicines and foods for treating and/or preventing inflammatory bowel diseases. The bacteroides salesii is bacteroides salesii @Bacteroides salyersiae) CSP6, the strain is separated from intestinal tracts of healthy human bodies and preserved in China Center for Type Culture Collection (CCTCC) NO: m20221993. The strain can protect colorectal mucosa from damage, repair damaged intestinal mucosa, improve symptoms such as loose stool, hematochezia and colorectal shortening, relieve weight loss caused by intestinal injury and inflammation,finally, the treatment of inflammatory bowel disease is realized.
Description
Technical Field
The invention belongs to the technical field of intestinal microorganisms, and particularly relates to application of a bacteroides salesii CSP6 in preparation of medicines and foods for treating and/or preventing inflammatory bowel diseases.
Background
Inflammatory Bowel Disease (IBD) is a complex chronic inflammatory bowel disease (PMID: 26323879). Inflammatory bowel disease clinics mainly include Ulcerative Colitis (UC) and Crohn's Disease (CD) (PMID: 31648971). Currently, about 680 tens of thousands of people worldwide are affected by inflammatory bowel disease (PMID: 31648971). The pathogenesis of inflammatory bowel disease is complex and currently unknown, but it is related to various factors such as genetics, environment, diet, lifestyle and the like. Recent studies have shown that intestinal flora disorders are a key factor in the induction of inflammatory bowel disease (PMID: 32913180). The disturbance of intestinal flora can lead to a decrease in beneficial bacteria and an increase in harmful bacteria, which in turn destroy the intestinal mucosal barrier and induce abnormal inflammatory reactions in intestinal tissues (PMID: 32913180). Thus, by targeting the regulatory flora, the correction of intestinal flora disorders can be achieved for the purpose of treating inflammatory bowel disease (PMID: 32076145).
Bacteroides (wall.) HarmoniousBacteroidesspp.) is an important symbiotic bacterium in the human intestinal tract (PMID: 33535896). The bacteroides are a new generation of probiotics in human intestinal tracts, can help human bodies digest and absorb dietary fibers, polysaccharides and other nutrient substances, can ferment to generate short-chain fatty acids beneficial to human health, and has important development value (PMID: 30716990). At present, 34 species of Bacteroides isolated from human intestinal tracts (PMID: 30716990) have been reported. Research shows that Bacteroides thetaiotaomicron isBacteroides thetaiotaomicron) Bacteroides oval shapeBacteroides ovatus) Bacteroides thetaiotaomicron (L.) BretBacteroides vulgatus) And xylan bacteroides of the present inventionBacteroides xylanisolvens) All have the function of relieving ulcerative colitis (PMID: 30215718; chinese invention patent, patent No.: ZL 202210548538.0).
Salicornia species of Paecilomyces salesiiBacteroides salyersiae) Is a new species of bacteroides, which is an obligate anaerobic gram-negative bacterium, isolated for the first time from human fecal samples by y.l. Song et al in 2004 (PMID: 15583282). The bacteroides salesii is extremely difficult to separate and culture, is sensitive to oxygen, and has few activity researches on the bacteroides salesii at present. In 2023, shang Qingsen et al separated from a healthy human intestinal fecal sample to obtain a strain of bacteroides salvinsis CSP6, which can degrade chondroitin sulfate and hyaluronic acid and has a good application prospect in the preparation of functional oligosaccharides (Chinese patent application No. 202310238846.8). However, there are still few functional studies on bacteroides salvinsis at present, and no reports on the treatment of inflammatory bowel disease by bacteroides salvinsis have been made yet.
Disclosure of Invention
Based on the fact that the functions of the bacteroides salesii are not systematically researched in the prior art, the invention provides application of the bacteroides salesii CSP6 in preparation of medicines and foods for treating and/or preventing inflammatory bowel diseases.
In a first aspect, the invention provides application of bacteroides sally CSP6 in preparing medicines and foods for treating and/or preventing inflammatory bowel diseases.
Further, the bacteroides salesii CSP6 is preserved in China Center for Type Culture Collection (CCTCC) with a preservation number of NO: m20221993.
Further, the inflammatory bowel disease is induced by dextran sodium sulfate.
In a second aspect, the invention provides a medicament for treating and/or preventing inflammatory bowel disease, characterized in that the medicament comprises an effective amount of bacteroides salvinsis CSP6.
Further, the medicament is in a liquid preparation or a solid preparation, and the concentration of the live bacteria of the bacteroides salesii CSP6 in the medicament is (1-9) multiplied by 10 9 CFU/mL, the administration dosage of the medicine is (1-9) multiplied by 10 10 CFU/kg/day。
In a third aspect, the invention provides an application of the bacteroides salesii CSP6 in preparing food.
Further, the application of the bacteroides sally CSP6 in preparing food for relieving weight loss.
Further, the weight loss is a weight loss caused by intestinal inflammation and intestinal damage.
Compared with the prior art, the invention has the following beneficial effects: the invention provides a strain of bacteroides sallyBacteroides salyersiae) CSP6, the strain can protect colorectal mucosa from damage, repair the damaged intestinal mucosa, improve symptoms such as loose stool, hematochezia, colorectal shortening and the like, relieve weight loss caused by intestinal damage and inflammation, and finally treat inflammatory bowel disease.
Drawings
Fig. 1 is the rate of change of body weight of mice, NC: a control group of natural growth; MD: dextran Sodium Sulfate (DSS) feeding the disease model group; BS: the arillus salsi CSP6 intragastric treatment group, which represents a significant difference (P < 0.05) compared to NC group; * Represents a very significant difference compared to NC group (P < 0.01); # represents a significant difference (P < 0.05) compared to MD group; # represents a very significant difference (P < 0.01) compared to MD group; statistical tests were performed using Student t-test and data were presented as mean.+ -. Standard Error (SEM).
Fig. 2 is a graph comparing colorectal length of mice in each group, showing significant differences (P < 0.05) compared to NC groups; * Represents a very significant difference compared to NC group (P < 0.01); # represents a significant difference (P < 0.05) compared to MD group; # represents a very significant difference (P < 0.01) compared to MD group; statistical tests were performed using Student t-test and data were presented as mean.+ -. Standard Error (SEM).
FIG. 3 is a comparison of the morphology of colorectal tissue of each group of mice, with 5 colorectal tissues selected for each group for display.
Fig. 4 is a graph comparing disease activity index (Disease activity index, DAI) and Total of mice in each group: total score; stool consistence: fecal consistency score; occult/gross feed: a concealing or total bleeding amount score; body weight: scoring body weight; * Indicating significant differences (P < 0.05) compared to NC group; * Represents a very significant difference compared to NC group (P < 0.01); # represents a significant difference (P < 0.05) compared to MD group; # indicates a very significant difference (P < 0.01) compared to the MD group. Scoring was performed according to the literature (PMID: 34973740) method, statistical examination was performed using Student t-test, and the data was presented as mean.+ -. Standard Error (SEM).
Fig. 5 is a hematoxylin-eosin (HE) staining chart of the colorectal of each group of mice, bar=100 μm, and HE staining of colorectal tissue of 5 mice per group was selected for display.
Fig. 6 is a graph of colorectal tissue injury scores for mice in each group, representing significant differences (P < 0.05) compared to NC groups; * Represents a very significant difference compared to NC group (P < 0.01); # represents a significant difference (P < 0.05) compared to MD group; # indicates a very significant difference (P < 0.01) compared to the MD group. Scoring was performed according to the literature (PMID: 34973740) method, statistical examination was performed using Student t-test, and the data was presented as mean.+ -. Standard Error (SEM).
Biological preservation description:
the invention provides a strain of bacteroides sallyBacteroides salyersiae) CSP6, preserved in China Center for Type Culture Collection (CCTCC) NO: m20221993, the preservation date is 2022, 12 and 19 days, and the preservation address is in the eight-path 299-No. Wuhan university school in Wuchang district of Wuhan, hubei province, china center for type culture collection。
Detailed Description
The invention provides an application of a strain of bacteroides sally CSP6 in preparing a medicament and/or food for treating and/or preventing inflammatory bowel disease. The Bacteroides sally is @Bacteroides salyersiae) CSP6, preserved in China Center for Type Culture Collection (CCTCC) NO: m20221993.
In the present invention, the inflammatory bowel disease is induced by dextran sodium sulfate, and the inflammatory bowel disease also includes inflammatory bowel disease induced by other factors.
The invention also provides a medicament for treating and/or preventing inflammatory bowel disease, which comprises the bacteroides salvinsis CSP6.
In the present invention, the dosage form of the drug is preferably a liquid formulation or a solid formulation, and more preferably a liquid formulation. In the invention, when the dosage form of the medicine is a solid microbial inoculum, the medicine is prepared by freeze-drying bacterial liquid of the bacteroides salvinsis CSP6. In the invention, the concentration of the live bacteria of the bacteroides salesii CSP6 in the medicament is preferably (1-9) multiplied by 10 9 CFU/mL. The solvent for the drug is preferably Phosphate Buffered Saline (PBS). In the invention, the medicine is preferably taken by stomach irrigation, and the dosage of the medicine is preferably (1-9) multiplied by 10 10 CFU/kg/day。
The invention also provides application of the bacteroides sally CSP6 in preparing food. The formulation of the food is not particularly limited in the present invention, and conventional food formulations in the art, such as solid formulations or liquid formulations, may be employed. In the invention, when the food is a solid microbial inoculum, the food is prepared by freeze-drying a bacterial liquid of bacteroides salesii CSP6. In the invention, the food also comprises food acceptable auxiliary materials, and the type and the dosage of the auxiliary materials are not particularly limited.
The technical solutions provided by the present invention are described in detail below with reference to examples, but they should not be construed as limiting the scope of the present invention.
Example 1
Culture of bacteroides sally CSP6
The fermentation culture of the bacteroides salesii CSP6 is carried out by referring to the method of Chinese invention patent (application number: CN 202310238846.8).
(1) Preparation of culture Medium
Preparing VI liquid culture medium, which comprises the following specific components: chondroitin sulfate (molecular weight of 24 kDa) 8g/L, tryptone 3g/L, peptone 3g/L, yeast extract 3g/L, mucin 0.5g/L, bile salt number 3 0.4g/L, cysteine hydrochloride 0.8g/L, heme 0.05g/L, tween 80 1mL/L, sodium chloride 4.5g/L, potassium chloride 2.5g/L, magnesium chloride 4.5g/L, calcium chloride 0.2g/L, potassium dihydrogen phosphate 0.4g/L, and compound trace element 2mL/L, distilled water as solvent, pH 6.4, and filling the culture medium into an anaerobic vial, sealing and preserving after filling nitrogen, and sterilizing under high pressure steam at 121deg.C for 30min.
In the invention, the concentration composition of the compound trace elements is as follows: mgSO (MgSO) 4 •7H 2 0 3.0g/L、CaCl 2 •2H 2 0 0.1g/L、MnCl 2 •4H 2 0 0.32g/L、FeSO 4 •7H 2 0 0.1g/L、CoSO 4 •7H 2 0 0.18g/L、ZnSO 4 •7H 2 0 0.18g/L、CuSO 4 •5H 2 0 0.01g/L、NiCl 2 •6H 2 0 0.092g/L。
(2) Inoculating culture
The Paecilomyces salsi CSP6 was inoculated into an anaerobic vial (volume 20 mL) containing the above-mentioned sterilized medium at an inoculum size of 1% (v/v). Wherein the anaerobic gas composition in the anaerobic bottle is 80% (v/v) N 2 , 10%（v/v）H 2 And 10% (v/v) CO 2 . And (5) placing the obtained bacterial liquid in enrichment culture at 37 ℃ for 36 hours to obtain seed liquid. The seed solution was inoculated in an inoculum size of 5% (v/v) into a large anaerobic flask (100 mL) containing the sterilized medium at 37℃for fermentation culture. And collecting bacterial liquid after 48 hours.
Example 2
Application of bacteroides sally CSP6 in treating inflammatory bowel disease
1. Experimental materials: 30C 57BL/6J mice (seven weeks old, male) purchased from Vitrehua laboratory animal science and technology Co., ltd (Beijing) (certificate number SCXK (Beijing)) 2016-0011; dextran sodium sulfate (DSS, cat No. 1601110), available from MP Biomedicals, usa.
Experiment main equipment: microscope (olympus CKX41 SF).
Experimental strain sources: obtained as in example 1.
2. The experimental method comprises the following steps:
(1) Experimental animal grouping and model establishment
30 male C57BL/6 mice (body weight of about 25 g) were randomly divided into 3 groups, namely, a normal control group (NC, n=10), a model control group (MD, n=10) and a Torulopsis salvinsis CSP6 administration group (BS, n=10). All mice were kept in an environment at approximately 23 ℃ with a light cycle of 12 h alternating day and night, and were free to eat standard feed and water. After a one week adaptation period, mice began molding and were dosed simultaneously. Wherein NC group mice were normally drinking water and were gavaged with 150 μl of PBS daily for 9 consecutive days; MD group mice were drinking water to add 2.2% (wt/vol) DSS solution and were gavaged with 150 μl of PBS daily for 9 consecutive days; BS group mice were drinking water to add 2.2% (wt/vol) DSS solution and 6.72×10 per mouse 10 CFU/kg/day dose of the suspension of the CSP6 strain of bordetella gastrosis was continued for 9 days. Wherein, the stomach filling volume of the daily bacterial liquid of each mouse is 150 mu L, and the concentration of the bacterial liquid of the bacteroides sally CSP6 is 1.68x10 9 The CFU/mL original fermentation broth is added into PBS for resuspension in a centrifugal way to prepare the culture medium. On day 10, all mice were sacrificed and colorectal tissue was collected for further experiments. Wherein, if the symptoms of weight reduction, hematochezia, loose stool, colorectal shortening and the like of the mice in the MD group are more obvious than those of the mice in the NC group, and the pathological score of the intestinal section is obviously higher than that of the mice in the NC group, the model establishment is successful.
(2) Histopathological examination
After mice were sacrificed, the posterior colorectal was taken at 0.5 cm and fixed with 4% paraformaldehyde solution. Then, the paraffin-embedded samples were washed with absolute ethanol, and HE stained after 5 μm section to examine the damage of colorectal mucosa. The slice samples were observed under a microscope (olympus CKX41 SF) and recorded by photographing.
3. Experimental results and analysis
Step 1, the body weight of the mice was weighed daily, and the calculated and drawn body weight change chart was shown in fig. 1 and table 2.
TABLE 2 mice weight change profile
| Group of | Body weight change Rate (%) | Significance (day 7) | Significance (day 8) | Significance (day 9) | Significance (day 10) |
| NC | 5.18±0.95 | - | - | - | - |
| MD | -12.4±1.9 | ** | ** | ** | ** |
| BS | -5.27±1.59 | - | # | **# | **## |
The results of fig. 1 and table 2 show that: the NC group mice had relatively stable body weight during the experiment, and the MD group mice had slightly increased body weight during the first 3 days of 2.2% (wt/vol) DSS induction. After day 4, mice in each group induced by DSS showed a significant decrease in body weight, with the appearance of fecal softening, runny stool, and even hematochezia symptoms. The body weight was continuously reduced after stopping DSS induction, with a minimum reduction of about 12.4%. The weight change ratio of NC mice and MD mice is significantly different. The BS group mice had a slow weight loss compared to the MD group mice, while the stool was thin and the hematochezia condition was markedly improved. The BS group mice showed significant differences in body weight (P < 0.05) on days 8 and 9 and very significant differences (P < 0.01) on day 10 compared to MD group mice, indicating that BS group mice were significantly recovered in body weight, approaching the growth status of normal mice.
Step 2, dissecting the whole cecum and colorectal, measuring the length thereof, and drawing the image, and the results are shown in fig. 2 and table 3.
The results of fig. 2 and table 3 show that: the colorectal length of the MD mice was significantly reduced (P < 0.01) compared to NC mice. The colorectal length of BS mice was significantly increased compared to MD mice, and there was a significant difference (P < 0.05) between the colorectal length of BS mice and the colorectal length of MD mice, indicating that the colorectal shortening and damage of BS mice was significantly improved.
Table 3 colorectal length comparison of mice in each group
| Group of | Colorectal length (cm) | Significance of the invention |
| NC | 7.28±0.11 | |
| MD | 5.75±0.16 | ** |
| BS | 6.63±0.13 | **## |
Step 3, after the measurement in step 2, the whole cecum of each group representing the mice was photographed with colorectal, and combined.
FIG. 3 is a graph of colorectal morphology of mice in each group, and it can be seen that the colorectal of the MD group mice is significantly shortened and engorged, while the colorectal length of the BS group mice is significantly increased, consistent with the colorectal length statistics of Table 3.
Step 4, in combination with the weight change of the mice in step 1, and daily observation of the stool viscosity and hematochezia detected, disease Activity Index (DAI) of the mice was measured according to the literature method and the image was drawn (PMID: 36986080).
As shown in FIG. 4 and Table 4, the DAI values of the NC group mice were kept around 0-1, and the mice showed little decrease in body weight, normal stool hardness, and no loose stool or hematochezia. Compared with NC mice, the MD mice have obviously increased DAI scores, the weight of the MD mice is greatly reduced, the condition of loose stool and hematochezia is serious, and the DAI scores of various disease indexes of the MD mice are extremely obviously different from those of the NC mice. Compared with the MD group mice, the BS group mice have more gentle weight drop, and the loose stool and hematochezia symptoms are obviously improved. The DAI scores were significantly reduced for BS group mice compared to MD group mice and both achieved significant or very significant differences. The above results further demonstrate that the bacteroides sally CSP6 can alleviate DSS-induced inflammatory bowel disease and improve enteritis symptoms.
Table 4 comparison of disease Activity index (Disease activity index, DAI) for mice of groups
| Group of | Total score | Significance of the invention | Latent or total bleeding scoring | Significance of the invention | Fecal consistency score | Significance of the invention | Weight scoring | Significance of the invention |
| NC | 0.1±0.1 | - | 0 | - | 0 | - | 0.1±0.1 | - |
| MD | 9.7±0.93 | ** | 3.2±0.36 | ** | 3.5±0.22 | ** | 3±0.37 | ** |
| BS | 3.5±1.04 | *## | 1.4±0.43 | **## | 0.8±0.33 | ## | 1.3±0.33 | **## |
Step 5, distal colorectal tissue of each group of mice was taken about 0.5. 0.5 cm and fixed in 4% (wt/vol) paraformaldehyde solution. The fixed tissues were washed with absolute ethanol and paraffin-embedded and tissue-sectioned (5 μm). The sectioned tissue was HE stained, placed under a microscope, and images were acquired.
As shown in fig. 5, NC group mice have a complete intestinal epithelial structure, clear crypt, obvious goblet cells and complete morphology, without inflammatory cell infiltration and intestinal mucosa injury phenomena. The MD group mice have obvious colorectal inflammatory reaction and intestinal mucosa injury phenomena due to the toxic effect of DSS. Compared with NC mice, MD mice have lost intestinal epithelial cell integrity, and obvious inflammatory cell infiltration, goblet cell deficiency, intestinal crypt damage and other phenomena can be seen. Compared with the MD group mice, the BS group mice have obviously improved inflammatory cell infiltration and intestinal mucosa injury symptoms, more complete intestinal epithelial cell morphology and obvious intestinal goblet cell and crypt formation. The above results further demonstrate that the bacteroides sally CSP6 can alleviate and treat DSS-induced inflammatory bowel disease.
And 6, calculating a mouse colorectal tissue damage score according to the HE staining result in the step 5, and drawing an image.
As shown in fig. 6 and table 5, NC group mice had the lowest colorectal tissue damage score, indicating that the mice had good colorectal tissue morphology and no damage. The MD group mice showed a significant increase in colorectal tissue damage score compared to NC group mice, indicating severe colorectal tissue damage. Compared with the MD group mice, the BS group mice have obviously reduced colorectal tissue injury scores, which indicates that oral administration of the Bacteroides salvinsis CSP6 can protect intestinal mucosa and reduce colorectal tissue injury of the mice. There was a very significant difference in colorectal tissue damage score for BS group mice compared to MD group mice (P < 0.01).
Table 5 colorectal tissue injury score for each group of mice
| Group of | Colorectal tissue injury scoring | Significance of the invention |
| NC | 0.13±0.13 | - |
| MD | 3.5±0.27 | ** |
| BS | 1.2±0.44 | ## |
In conclusion, the bacteroides sally CSP6 provided by the invention can obviously improve DSS-induced inflammatory bowel disease in a mouse model. The strain can protect colorectal mucosa from damage, repair the damaged intestinal mucosa, improve symptoms such as loose stool, hematochezia, colorectal shortening and the like, relieve weight loss caused by intestinal damage and inflammation, and finally realize the treatment of inflammatory bowel disease.
The preparation of the live bacteria of the bacteroides sally CSP6 is tested, and the dosage form of the medicine is preferably liquid or solid. When the preparation is a liquid preparation, the bacteroides sally CSP6 is dissolved into the liquid preparation by adopting a proper solvent; when the bacteroides salvinsis CSP6 is prepared into a solid microbial inoculum, the preparation process is a conventional freeze drying technology, and the bacterial liquid of the bacteroides salvinsis CSP6 is prepared by freeze drying, wherein the living bacterial concentration of the bacteroides salvinsis CSP6 is preferably (1-9) multiplied by 10 9 CFU/mL. The formulation solvent is preferably Phosphate Buffered Saline (PBS). The liquid preparation or solid preparation is preferably administered orally, and the dosage of the medicine is preferably (1-9) ×10 10 CFU/kg/day. The preparation method can use acceptable auxiliary materials when preparing the pharmaceutical preparation, and can also be combined with other enteritis therapeutic drugs.
The above-mentioned Bacteroides sally CSP6 can be prepared into food. The food prepared from the bacteroides salesii CSP6 has no specific dosage form requirement, and can be prepared into conventional food dosage forms in the field, and is usually solid or liquid. When the food is a solid microbial inoculum, the food is prepared by freeze-drying bacterial liquid of the bacteroides salesii CSP6. In preparing the food, acceptable auxiliary materials and additives are used, and the types and the amounts of the auxiliary materials and the additives are not particularly limited.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (8)
1. Salicornia species of Paecilomyces salesiiBacteroides salyersiae) Use of CSP6 in the manufacture of a medicament for the treatment and/or prophylaxis of inflammatory bowel disease.
2. The bacteroides salesii CSP6 of claim 1, wherein the collection is at the collection center of chinese typical cultures, with the collection number cctccc NO: m20221993.
3. The use according to claim 1, wherein the inflammatory bowel disease is induced by dextran sodium sulfate.
4. A medicament for the treatment and/or prophylaxis of inflammatory bowel disease, wherein the medicament comprises bacteroides salvinsis CSP6.
5. The drug according to claim 4, wherein the drug is in the form of a liquid preparation or a solid preparation, and the concentration of viable bacteria of the bacteroides salvinsis CSP6 in the drug is (1-9) x 10 9 CFU/mL, the administration dosage of the medicine is (1-9) multiplied by 10 10 CFU/kg/day.
6. Use of bacteroides salesii CSP6 of claim 1 in the preparation of a food product.
7. The use according to claim 6, characterized in that it is the use of bacteroides salesii CSP6 for the preparation of a food product for reducing weight.
8. The use according to claim 7, wherein the weight loss is a weight loss caused by intestinal inflammation, intestinal damage.
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