CN117982540A - Use of Muribaculum intestinal in the preparation of a medicament for the prophylaxis and/or treatment of intestinal diseases - Google Patents
Use of Muribaculum intestinal in the preparation of a medicament for the prophylaxis and/or treatment of intestinal diseases Download PDFInfo
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- CN117982540A CN117982540A CN202410034720.3A CN202410034720A CN117982540A CN 117982540 A CN117982540 A CN 117982540A CN 202410034720 A CN202410034720 A CN 202410034720A CN 117982540 A CN117982540 A CN 117982540A
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- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The invention provides the application of Muribaculum intestinal in preparing the medicine for preventing and/or treating the intestinal diseases, the Muribaculum intestinal is safe to use, the application prospect is good, and a new thought is provided for preventing and treating the intestinal diseases clinically.
Description
Technical Field
The invention relates to the field of biological medicine. In particular, the invention relates to the use of Muribaculum intestinal in the manufacture of a medicament for the prophylaxis and/or treatment of intestinal diseases.
Background
Inflammatory bowel disease (Inflammatory bowel disease, IBD) is a chronic inflammatory disease of the gastrointestinal tract, including ulcerative colitis (Ulcerative colitis, UC) and Crohn's Disease (CD). The etiology and pathogenesis of IBD are complex, and so far it is widely believed that the disease is mainly affected by environmental, genetic, immune, stress, and other factors. In recent years, the incidence of IBD has increased year by year, and chronic inflammatory diseases have become a major issue to be resolved. IBD patients often experience serious complications such as fibrosis, stenosis, fistulae, and perforation. In addition, long-term inflammation of the colon is also associated with the development of colorectal cancer, severely affecting the quality of life of the patient. Colorectal cancer is one of the common digestive tract tumors, mainly a multifactorial disease caused by lifestyle, genetic genes and environmental factors, and external factors are the release of pro-inflammatory cytokines of immune cells and intestinal dysbiosis.
At present, medicines for treating inflammatory bowel diseases are still to be studied.
Disclosure of Invention
The present invention aims to solve at least one of the technical problems existing in the prior art to at least some extent.
The invention provides an application of Muribaculum intestinal in preparing medicines. According to an embodiment of the invention, the medicament is for use in the prevention and/or treatment of intestinal diseases.
Muribaculum intestinal belongs to the Muribaculum genus, isolated from the cecal content of C57BL/6J wild-type mice. The inventors found that when studying the intestinal flora of colon cancer mice, the abundance of the bacteria in the intestinal tract of colon cancer mice is lower than that in the intestinal tract of normal mice, and concluded that the bacteria may have anti-inflammatory and anticancer effects. Further, by administering Muribaculum intestinal to colon cancer mice, colon cancer disorders can be effectively alleviated. Therefore, muribaculum intestinal has the curative effect of preventing and/or treating intestinal diseases, is safe to use, has good application prospect, and clinically provides a new idea for preventing and treating intestinal diseases.
According to an embodiment of the present invention, the use of Muribaculum intestinal in the preparation of a medicament may further have the following additional technical features:
according to an embodiment of the invention, the intestinal disease comprises a colon-related disease.
According to an embodiment of the invention, the colon-related diseases include colitis and colon cancer. The colitis may specifically be ulcerative colitis, and the colon cancer may be colon cancer induced by long-term inflammation.
According to an embodiment of the invention, the medicament is for alleviating weight loss due to suffering from colitis.
According to an embodiment of the invention, the medicament is for alleviating the elevation of DAI score due to suffering from colitis.
According to an embodiment of the invention, the medicament is for alleviating colonic tissue damage caused by suffering from colitis.
According to an embodiment of the invention, the medicament is used for alleviating spleen tissue enlargement due to suffering from colitis.
According to an embodiment of the invention, the medicament is for alleviating an increase in colon cancer tumors.
According to an embodiment of the invention, the medicament is used for alleviating spleen tissue enlargement caused by colon cancer.
According to an embodiment of the present invention, the drug is administered orally, by lavage or by enema.
According to an embodiment of the invention, the drug is administered in a dose of 0.5 to 1.5MCF Muribaculum intestinal/kg person/day.
Additional aspects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention.
Drawings
The foregoing and/or additional aspects and advantages of the invention will become apparent and may be better understood from the following description of embodiments taken in conjunction with the accompanying drawings in which:
FIG. 1 shows a graph of the analysis of the changes in body weight and DAI score of the mice of example 1;
FIG. 2 shows a real image of the colon and a colon length analysis image of the mouse of example 1;
FIG. 3 shows a sample of the spleen of the mouse of example 1, and a spleen length and weight analysis;
FIG. 4 shows a colon physical map and a tumor number and size analysis map of example 2;
FIG. 5 shows a sample of the spleen of the mouse of example 2, and a map of the spleen length and weight analysis.
Detailed Description
The scheme of the present invention will be explained below with reference to examples. It will be appreciated by those skilled in the art that the following examples are illustrative of the present invention and should not be construed as limiting the scope of the invention. The examples are not to be construed as limiting the specific techniques or conditions described in the literature in this field or as per the specifications of the product. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
The bacteria used in the experiments described below were Muribaculum INTESTINALE DSM 28989, purchased from German collection of microorganisms and bacteria DSMZ (Deutsche Sammlung von Mikroorganismen und Zellkulturen).
Example 1
1. Male C57BL/6 mice with the age of 5-6 weeks are adopted, the weight is 18-22 g, and 20 mice are randomly divided into 2 groups: model group (DSS group), muribaculum intestinale intervention group (Muri group). The feeding mode of the mice in the DSS group is as follows: free water diet for one to five weeks, two to three times per week with 0.2mL of PBS buffer, and water with 2% dss (ulcerative colitis) for the fifth week; the Muri groups of mice are fed by the following modes: antibiotic water (0.2 g/L ampicillin, metronidazole, neomycin, 0.1g/L vancomycin for the purpose of eliminating most of the microorganisms in the intestinal tract) was consumed on the first two weeks of free diet, three to five weeks of free diet and two to three times a week of 0.2mL Muribaculum intestinale (1 MCF) was infused, and water containing 2% DSS was consumed starting the fifth week.
Daily observations of mouse behavior and health status, recording mouse weight changes, evaluating disease activity index (DISEASE ACTIVITY index, DAI) scores, and the results are shown in fig. 1; after the experiment is finished, the mice are sacrificed, the colon is taken out, and the colon length is measured, and the result is shown in fig. 2; the spleens of the mice were taken, and the length and weight were measured, and the results are shown in fig. 3.
2. Male C57BL/6 mice with the age of 5-6 weeks are adopted, the weight is 18-22 g, and 24 mice are randomly divided into 2 groups: model group (M group), muribaculum intestinale intervention group (Muri group). The feeding mode of the M groups of mice is as follows: two to three times per week of gastric lavage with 0.2mL of PBS buffer, the first four weeks of free drinking diet, one week of intraperitoneal injection of azomethane AOM (10 mg/kg, colon cancer), one week of drinking water containing 2% DSS for the fourth, seventh and tenth weeks, and the rest of the time with normal drinking water, experiment for 13 weeks; the Muri groups of mice are fed by the following modes: two to three times per week of gastric lavage 0.2mL Muribaculum intestinale (1 MCF), two weeks of antibiotic water (0.2 g/L ampicillin, metronidazole, neomycin, 0.1g/L vancomycin for removal of most of the micro-organisms in the intestinal tract), one intraperitoneal injection of azomethane AOM (10 mg/kg) in the third week, one week of water containing 2% DSS for the fourth, seventh and tenth weeks, and normal water for the remaining time, experiment for 13 weeks.
After the experiment is finished, the mice are sacrificed, the colon is taken out, and the number and the size of colon tumors are counted, and the result is shown in figure 4; the spleens of the mice were taken, and the length and weight were measured, and the results are shown in fig. 5.
Experimental results:
The results in FIG. 1 show that the weight change rate of mice in the DSS group decreased from 5 days, and the weight decrease rate of mice on day 7 was about 4.9%; the mice weight loss phenomenon (P < 0.05) caused by colonitis can be obviously relieved after Muribaculum intestinale stem prognosis. The DAI score is an important index for evaluating the severity of IBD, and is calculated from the comprehensive evaluation of the weight loss percentage, fecal color and hardness, and fecal bloody conditions of mice. On day 5, the model group mice had loose stool, had a reddish brown color, had a tendency to lay down and had a tendency to lose weight, had a tendency to be progressively unshaped, had a tendency to adhere around the anus, and had macroscopic bloody stools with a gradual rise in DAI score. After Muribaculum intestinale colonization, muribaculum intestinale-intervention mice had reduced disease symptoms and a slower trend of increasing DAI scores compared to DSS mice.
The results in fig. 2 show that: congestion of feces in intestinal tracts of mice in the DSS group is not formed, muribaculum intestinale is used for intervening in reduction of purulent stool in blood samples in colon intestinal tracts of the mice in the group, and normal feces of the mice exist; in addition, the colon of DSS mice was significantly shortened, with a more severe inflammatory response, and after Muribaculum intestinale stem prognosis, the colon length shortening tended to be alleviated for Muribaculum intestinale mice, with a significant difference from DSS mice (P < 0.01).
The results in fig. 3 show that: spleen is the largest lymphoid organ of the organism, can reflect the inflammatory reaction of the organism to a certain extent, and can generate phenomena such as splenomegaly when the organism has inflammation. Both spleen length (P < 0.001) and weight (P < 0.0001) were significantly higher for DSS group mice than for Muribaculum intestinale groups.
The results in fig. 4 show that: the phenotypes of the M groups of mice and the Muribaculum intestinale groups have no obvious difference during the modeling period, and after dissection, the tumors of the M groups of mice are obvious, the protrusions in the colon are more, the tumors of the Muribaculum intestinale groups are less, and the colon is smoother. The number of tumors (P < 0.001), tumor size (P < 0.01) and average tumor size (P < 0.05) were significantly higher in group M than in group Muribaculum intestinale.
The results in fig. 5 show that: the spleen weights (P < 0.05) were significantly higher for group M mice than for group Muribaculum intestinale, with no significant difference in spleen length.
In conclusion, muribaculum intestinale colonization effectively relieves the phenomena of weight loss, DAI score increase, colon tissue destruction and spleen tissue enlargement of mice caused by DSS; the method also effectively prevents the phenomena of tumor increase, spleen tissue enlargement and the like caused by colon cancer, and provides theoretical basis for Muribaculum intestinale serving as probiotics for preventing and treating colonitis and colon cancer.
In the description of the present specification, a description referring to terms "one embodiment," "some embodiments," "examples," "specific examples," or "some examples," etc., means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the present invention. In this specification, schematic representations of the above terms are not necessarily directed to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Furthermore, the different embodiments or examples described in this specification and the features of the different embodiments or examples may be combined and combined by those skilled in the art without contradiction.
While embodiments of the present invention have been shown and described above, it will be understood that the above embodiments are illustrative and not to be construed as limiting the invention, and that variations, modifications, alternatives and variations may be made to the above embodiments by one of ordinary skill in the art within the scope of the invention.
Claims (10)
- Use of muribaculumin for the preparation of a medicament, characterized in that the medicament is for the prevention and/or treatment of intestinal diseases.
- 2. The use according to claim 1, wherein the intestinal disease comprises a colon-related disease;Optionally, the colon-related disease includes colitis and colon cancer.
- 3. The use according to claim 1, wherein the medicament is for alleviating weight loss due to suffering from colitis.
- 4. The use according to claim 1, wherein the medicament is for alleviating the elevation of DAI score due to suffering from colitis.
- 5. The use according to claim 1, wherein the medicament is for alleviating colonic tissue damage due to suffering from colitis.
- 6. The use according to claim 1, wherein the medicament is for alleviating enlargement of spleen tissue due to suffering from colitis.
- 7. The use according to claim 1, wherein the medicament is for alleviating an increase in colon cancer tumors.
- 8. The use according to claim 1, wherein the medicament is for alleviating enlargement of spleen tissue due to colon cancer.
- 9. The use according to claim 1, wherein the medicament is administered orally, by lavage or by enema.
- 10. The use according to claim 1, wherein the medicament is administered in a dose of 0.5 to 1.5MCF Muribaculumintestinal/kg person/day.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410034720.3A CN117982540A (en) | 2024-01-09 | 2024-01-09 | Use of Muribaculum intestinal in the preparation of a medicament for the prophylaxis and/or treatment of intestinal diseases |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202410034720.3A CN117982540A (en) | 2024-01-09 | 2024-01-09 | Use of Muribaculum intestinal in the preparation of a medicament for the prophylaxis and/or treatment of intestinal diseases |
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| CN117982540A true CN117982540A (en) | 2024-05-07 |
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- 2024-01-09 CN CN202410034720.3A patent/CN117982540A/en active Pending
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