CN113116936A - Application of akkermansia muciniphila in preparation of beta-chenodeoxycholic acid inhibitor - Google Patents
Application of akkermansia muciniphila in preparation of beta-chenodeoxycholic acid inhibitor Download PDFInfo
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- CN113116936A CN113116936A CN202110361343.0A CN202110361343A CN113116936A CN 113116936 A CN113116936 A CN 113116936A CN 202110361343 A CN202110361343 A CN 202110361343A CN 113116936 A CN113116936 A CN 113116936A
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- CN
- China
- Prior art keywords
- chenodeoxycholic acid
- akkermansia muciniphila
- acid inhibitor
- beta
- muciniphila
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
Abstract
The invention relates to an application of akkermansia muciniphila in preparation of a beta-chenodeoxycholic acid inhibitor. The research shows that the akkermansia muciniphila can increase the insulin secretion capacity, improve the expression level of FGF15/19, promote glycogen synthesis, reduce gluconeogenesis and improve sugar tolerance by reducing the level of serum bile acid beta chenodeoxycholic acid, and is a microorganism normally existing in healthy intestinal tracts, can be ingested for a long time and has high safety. Therefore, the akkermansia muciniphila can be used as a chenodeoxycholic acid inhibitor and can be used for developing a medicine or a health-care product with high safety and capability of improving the sugar tolerance.
Description
Technical Field
The invention relates to the technical field of biological medicines, and particularly relates to an application of Ekermansia muciniphila in preparation of a beta-chenodeoxycholic acid inhibitor.
Background
Akkermansia muciniphila (Akkermansia muciniphila) is a species isolated in 2004 in the human intestinal tract and is ubiquitous in the human digestive tract, accounting for approximately 3% to 5%. Unlike other enterobacteria, akkermansia muciniphila can store mucin and flourish even when there are no nutrients in the intestine (particularly during fasting). Researches show that the akkermansia muciniphila has the effects of delaying senescence and inhibiting neurodegenerative diseases.
Disclosure of Invention
According to the invention, through research, the Akkermansia muciniphila (Akkermansia muciniphila) can reduce the level of serum bile acid beta-chenodeoxycholic acid (beta CDCA), increase the insulin secretion capacity, improve the expression level of small intestine fibroblast growth factor 15/19(FGF15/19) (human FGF19 is homologous with mouse FGF 15), promote glycogen synthesis, reduce gluconeogenesis and improve sugar tolerance, and is a microorganism normally existing in a healthy intestinal tract, can be taken in for a long time and has high safety. Therefore, the akkermansia muciniphila can be used as a chenodeoxycholic acid inhibitor and can be used for developing a medicine or a health-care product with high safety and capability of improving the sugar tolerance.
Based on the application, the invention provides the application of the Ekermansia muciniphila in the preparation of the beta-chenodeoxycholic acid inhibitor.
In addition, the application of the beta-chenodeoxycholic acid inhibitor in preparing a mouse FGF15 gene expression promoter or a human FGF19 gene expression promoter is also provided.
In one embodiment, the Exkermanella muciniphila is deposited under accession number DSM 22959.
In one embodiment, the β -chenodeoxycholic acid inhibitor comprises an active ingredient comprising the akkermansia muciniphila.
In one embodiment, the beta-chenodeoxycholic acid inhibitor further comprises an auxiliary material, wherein the auxiliary material comprises a stabilizer selected from at least one of sodium metabisulfite, sodium bisulfite, vitamin C, cysteine, sodium ascorbate, sodium erythorbate, L-cysteine hydrochloride and edetate.
In one embodiment, the adjuvant further comprises a filler selected from at least one of microcrystalline cellulose, lactose, starch, pregelatinized starch, mannitol, and sorbitol.
In one embodiment, the excipient further comprises a binder selected from at least one of hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, povidone, and crospovidone.
In one embodiment, the excipient further comprises a disintegrant selected from at least one of sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, crospovidone, sodium cross-linked carboxymethyl cellulose, and dry starch.
In one embodiment, the excipient further comprises a lubricant selected from at least one of magnesium stearate, talc, micronized silica gel, and sodium stearyl fumarate.
An application of beta-chenodeoxycholic acid inhibitor in preparing insulin secretion promoter or human FGF19 gene expression promoter is disclosed.
In one embodiment, the β -chenodeoxycholic acid inhibitor comprises akkermansia muciniphila.
Application of akkermansia muciniphila in preparing insulin secretion promoter is provided.
Drawings
FIG. 1 shows the statistical results of the body weights of mice in the control group, HS-water group, HS-hk AKK group and HS-AKK group;
FIG. 2 is a statistical result of the content of Ichmanella enterocolitica in mice in a control group, an HS-water group, an HS-hk AKK group and an HS-AKK group;
FIG. 3 shows glucose tolerance in mice in the control, HS-water, HS-hk AKK and HS-AKK groups;
FIG. 4 shows insulin secretion after glucose stimulation in control, HS-water, HS-hk AKK and HS-AKK mice;
FIG. 5 is a graph showing the statistical results of insulin secretion of islet cells of mice in the control group, HS-water group, HS-hk AKK group and HS-AKK group after stimulation with glucose at different concentrations in vitro;
FIG. 6 shows insulin tolerance in mice of control, HS-water, HS-hk AKK and HS-AKK groups;
FIG. 7 is a statistical result of the levels of β CDCA in the serum of mice in the control group, HS-water group, HS-hk AKK group and HS-AKK group;
FIG. 8 is a statistical result of insulin secretion stimulated by the islet cell line MIN6 cells after treatment with β CDCA for different concentrations of glucose;
FIG. 9 shows the expression of FGF15 gene mRNA in small intestine tissue of mice in the control group, HS-water group, HS-hk AKK group and HS-AKK group after administration of Exmannheimia muciniphila;
FIG. 10 is a graph showing statistics of hepatic glycogen content of mice in the control group, HS-water group, HS-hk AKK group and HS-AKK group after administration of Ichmanella muciniphila;
FIG. 11 shows the expression of gluconeogenesis-associated gene mRNA in mice of the control group, HS-water group, HS-hk AKK group and HS-AKK group after administration of Exmannheimia muciniphila;
FIG. 12 shows the expression of mRNA of FGF19 gene in cells of the intestinal cell line LS174T treated with different concentrations of β CDCA.
Detailed Description
The present invention will now be described more fully hereinafter for purposes of facilitating an understanding thereof, and may be embodied in many different forms and are not limited to the embodiments described herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
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. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.
The liver is the organ where bile acids are synthesized from cholesterol in the liver, the synthetic pathways including the classical pathway mediated by cholesterol 7 alpha-hydroxylase (CYP7a1) and the alternative pathway mediated by sterol 27-hydroxylase (CYP27a 1). Under normal conditions at least 75% of bile acids are produced by classical pathways, the classical pathway producing mainly chenodeoxycholic acid (CDCA) and Cholic Acid (CA), while the alternative pathway produces mainly CDCA. Bile acids are divided into primary and secondary bile acids according to source: the CA and CDCA produced from cholesterol in the liver and their products bound to glycine or taurine are primary bile acids which are converted to deoxycholic acid (DCA) and lithocholic acid (LCA) as secondary bile acids under the action of intestinal bacteria.
Beta CDCA and CDCA are both primary bile acids existing in human bodies, but the structures of beta CDCA and CDCA are different, specifically, the stereo configurations of chiral carbons at positions 3 of steroid rings of the beta CDCA and CDCA are different, the carbon at position 3 of the steroid ring of the beta CDCA is S configuration, the carbon at position 3 of the steroid ring of the CDCA is R configuration, and the beta CDCA and CDCA are diastereoisomers, so that the research on the beta CDCA is less, and the functions are not known.
The inventor of the application finds that the akkermansia muciniphila (Akkermansia muciniphila) can reduce the level of primary bile acid beta-chenodeoxycholic acid (beta CDCA) in serum, and the beta CDCA can inhibit the insulin secretion level. Therefore, the akkermansia muciniphila can increase the insulin secretion capacity, promote glycogen synthesis, reduce gluconeogenesis and improve sugar tolerance by reducing the content of beta CDCA. Based on the above, one embodiment of the invention provides an application of Ekermansia muciniphila in preparation of a beta-chenodeoxycholic acid inhibitor.
In this embodiment, the akkermansia muciniphila is a strain of the german collection of microorganisms and cell cultures (DSMZ) deposit number DSM 22959. The akkermansia muciniphila is a probiotic isolated from the intestinal tract of healthy adults, is a microorganism normally present in the healthy intestinal tract, is highly safe and can be ingested for a long period of time, and has a strong colonization ability in the intestinal tract. Proved by verification, the level of beta CDCA in serum can be reduced and the insulin secretion can be increased by supplementing the akkermansia muciniphila.
Specifically, the beta-chenodeoxycholic acid inhibitor comprises an active ingredient, and the active ingredient comprises akkermansia muciniphila. It is understood that in other embodiments, the active ingredient may also include other substances other than akkermansia muciniphila.
Optionally, the beta-chenodeoxycholic acid inhibitor further comprises an auxiliary material. Such as stabilizers, fillers, binders, disintegrants, lubricants, flavoring agents, and the like.
In some embodiments, the excipient comprises at least one of a stabilizer, a filler, a binder, a disintegrant, a lubricant, and a flavoring agent. Specifically, the stabilizer is used for maintaining the stability of the beta-chenodeoxycholic acid inhibitor and keeping the effectiveness of the active ingredients of the beta-chenodeoxycholic acid inhibitor. Specifically, the stabilizer is at least one selected from sodium metabisulfite, sodium bisulfite, vitamin C, cysteine, sodium ascorbate, sodium erythorbate, L-cysteine hydrochloride and edetate. In one optional specific example, the stabilizer is selected from sodium metabisulfite, sodium bisulfite, vitamin C, cysteine, sodium ascorbate, sodium erythorbate, L-cysteine hydrochloride, or edetate. Of course, in other embodiments, the stabilizer is not limited to the above, and may be other stabilizer capable of stabilizing the β -chenodeoxycholic acid inhibitor to make the activity thereof effective.
Specifically, the filler is used for increasing the weight of the beta-chenodeoxycholic acid inhibitor, and is beneficial to reagent forming. Optionally, the filler is selected from at least one of microcrystalline cellulose, lactose, starch, pre-crosslinked starch, mannitol, and sorbitol. In an alternative specific example, the filler is microcrystalline cellulose, lactose, starch, pre-crosslinked starch, mannitol, or sorbitol. Of course, in other embodiments, the bulking agent is not limited to the above, and may be other edible bulking agents.
In particular, the adhesive functions as an adhesive. Optionally, the binder is selected from at least one of hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, povidone, and crospovidone. In a specific example, the binder is hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, povidone, or crospovidone. Of course, in other embodiments, the adhesive is not limited to the above, but may be other edible substances having an adhesive effect.
Specifically, the disintegrant enables the β -chenodeoxycholic acid inhibitor to be rapidly disintegrated into fine particles in gastrointestinal fluids, thereby enabling the active ingredient to be rapidly dissolved and absorbed. Optionally, the disintegrant is selected from at least one of sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, cross-linked polyvinyl pyrrolidone, cross-linked sodium carboxymethyl cellulose, and dry starch. It will be appreciated that in other embodiments, the disintegrant is not limited to the above but may be other edible materials having a disintegrating effect.
Specifically, the lubricant has the functions of glidant, anti-adhesion and lubrication, and is beneficial to the preparation of the beta-chenodeoxycholic acid inhibitor. Optionally, the lubricant is selected from at least one of magnesium stearate, talc, micronized silica gel, and sodium stearyl fumarate. In a specific example, the lubricant is magnesium stearate, talc, aerosil or sodium stearyl fumarate. It will be appreciated that in other embodiments, the lubricant is not limited to the above, but may be other edible substances having a lubricating effect.
In particular, the flavoring agent is used for improving the taste of the beta-chenodeoxycholic acid inhibitor. Optionally, the flavoring agent is selected from at least one of a sweetener and an aroma. Optionally, the sweetener is selected from at least one of sorbose, xylose, xylitol, glycerol, disodium glycyrrhizinate, mannitol, mannose, galactose, maltose, lactose, fructose, cyclamate, saccharin sodium, stevioside, cyclamate, glucose, sucrose, and aspartame; the aromatic is at least one of fennel oil, rose essence, lemon oil, lemon essence, vanilla essence, vanillin, banana essence, pineapple essence, papaya essence, peppermint oil, orange peel oil, apple essence, orange essence and apricot essence. It will be appreciated that in other embodiments, the flavouring agent is not limited to the above but may be other substances that may have an improved mouthfeel.
Of course, in other embodiments, the auxiliary materials are not limited to the above, and may be other edible auxiliary materials.
Of course, the dosage form of the above-mentioned β -chenodeoxycholic acid inhibitor is not particularly limited. Optionally, the dosage form of the beta-chenodeoxycholic acid inhibitor is granules, capsules or tablets.
In addition, an embodiment of the present invention provides a method of treating type 2 diabetes by administering to a subject in need thereof an effective amount of akkermansia muciniphila, wherein the amount of akkermansia muciniphila is not less than 1 x 1013CFU/kg*d。
In addition, FGF15/19 (which refers to the expression product of mouse FGF15 gene or human FGF19 gene) is a bile acid-induced, late-fed gut hormone that acts to reduce hepatic lipogenesis and promote metabolic conversion from fed to fasted state. Studies have shown that FGF15/19 stimulates glycogen synthesis and inhibits gluconeogenesis through an insulin-independent pathway. The research of the inventor of the application finds that the beta-chenodeoxycholic acid inhibitor can also promote the expression of mouse FGF15 gene or human FGF19 gene by inhibiting the beta-chenodeoxycholic acid, thereby stimulating glycogen synthesis and inhibiting gluconeogenesis.
Therefore, an embodiment of the invention also provides application of the beta-chenodeoxycholic acid inhibitor in preparing an insulin secretion promoter, a mouse FGF15 gene expression promoter or a human FGF19 gene expression promoter. In particular, the β -chenodeoxycholic acid inhibitor is a β -chenodeoxycholic acid inhibitor of any one of the embodiments described above.
In addition, the invention also provides application of the beta-chenodeoxycholic acid inhibitor in preparing a product which stimulates glycogen synthesis and inhibits gluconeogenesis in a non-insulin pathway.
In addition, based on the effect of the akkermansia muciniphila on promoting insulin secretion, the embodiment of the invention also provides application of the akkermansia muciniphila in preparation of the insulin secretion promoter.
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
The following detailed description is given with reference to specific examples. The following examples are not specifically described, and other components except inevitable impurities are not included. Reagents and instruments used in the examples are all conventional in the art and are not specifically described. The experimental procedures, in which specific conditions are not indicated in the examples, were carried out according to conventional conditions, such as those described in the literature, in books, or as recommended by the manufacturer. The major instruments used in the following examples include an animal balance, an anaerobic incubator, a centrifuge, a Roche LightCycler480 fluorescent quantitative PCR instrument, a general optical microscope (Olympus Co., Japan). The akkermansia muciniphila in the following examples was purchased from the german collection of microorganisms and cell cultures (DSMZ) under the accession number DSM 22959. In the drawings, "+" indicates "P < 0.05", "+" indicates "P < 0.01", "+" "," P <0.001 "; the "control" in the figure represents the control group.
Example 1
(1) Preparation of akkermansia muciniphila
Akkermansia muciniphila (catalog No.22959, Type strain, DSMZ, germany) was cultured anaerobically in brain-heart infusion broth medium (BD Bioscience, San Jose, CA) supplemented with 0.5% (w/v, i.e. 100mL of medium containing 0.5g of pig mucin) pig mucin (Sigma-Aldrich, st. louis, MO) and 0.05% (w/v, i.e. 100mL of medium containing 0.5g of cysteine) cysteine (Sigma-Aldrich). The density of the culture was calculated by measuring the absorbance at a wavelength of 600 nm. Culture purity was checked by gram stain and Colony Forming Units (CFU) were counted by serial dilution on agar plates. Exkermanella muciniphila was centrifuged at 3000rpm for 30min at 4 ℃, washed 2 times with sterile PBS, resuspended to 5X 10 with 2mL anaerobic sterile PBS containing 20% glycerol by volume10CFU/mL, storage at-80 ℃.
(2) Intervention of common feed or high-sucrose feed and akkermansia muciniphila of mice
Mice of strain C57BL/J6 (8 weeks old, male, almost undifferentiated in body weight) (nanjing biomedical research institute, university of south kyo, china) at 8 weeks of age were housed in a specific pathogen-free barrier facility in individually ventilated cages of 5 mice per cage. The mice were fed normal feed or high sucrose feed (HS) (containing 42% sucrose by mass). Mice fed with HS feed were randomly divided into 3 groups, namely, high-sucrose live-mucin Ackermansia (HS-AKK), high-sucrose heat-inactivated-mucin Ackermansia (HS-hk AKK) and high-sucrose ordinary drinking water (HS-water). Wherein:
HS-AKK group: feeding the high-sucrose feed, and adding the akkermansia muciniphila into drinking water of mice. The method specifically comprises the following steps: recovering the cryopreserved bacteria obtained in the step (1), performing amplification culture, and harvesting 1mL of the cryopreserved bacteria with the concentration of 5 × 1012CFU/mL suspension of Ichmansia muciniphila was diluted in 100mL of drinking water (i.e., 5X 10 concentration in water)10CFU/mL), the mice were allowed free access to water only (calculated as 6mL water per day for 30g mice per body weight, 3X 10 bacteria per day for each mouse11CFU)。
HS-hk AKK group: height ofThe mice are fed with the sucrose feed, the high-temperature inactivated akkermansia muciniphila with the same amount as that of the HS-AKK group is added into drinking water of the mice, and the water feeding mode of the HS-hk AKK group mice is the same as that of the HS-AKK group. High-temperature inactivation of akkermansia muciniphila (hk-AKK) is carried out by the bacteria concentration in the step (1) being 5 multiplied by 1010The preparation method comprises sterilizing a CFU/mL suspension of Ikemanella mucronatum at 121 deg.C and 225kPa for 15 min.
HS-water group: the high sucrose feed is used for feeding, no substance is added into drinking water of the mice, and the feeding mode of water feeding of the HS-water group mice is the same as that of the HS-AKK group.
Control group: the feed is used for feeding, and no substance is added into drinking water.
The four groups of mice were raised in the manner described above for 15 weeks with daily replacement of drinking water.
(3) Study of the Effect of Ekermanella muciniphila on insulin secretion
After 15 weeks of raising each group of mice, the following tests were performed:
1) the body weights of the mice in each group were measured, and the results are shown in fig. 1.
As can be seen from FIG. 1, the weight of the control group mice was higher than that of the HS-water group, and the weight of the HS-AKK group mice was significantly higher than that of the HS-water group mice, while no weight increase was observed in the HS-hk AKK group.
2) The number of Ichmanella muciniphila in feces of each group of mice was determined by RT-PCR, and the results are shown in FIG. 2.
As can be seen from FIG. 2, the number of Ichmansia muciniphila in the feces of the mice fed with the high-sugar diet was significantly reduced compared to the control group of mice fed with the normal diet; treatment with live akkermansia muciniphila for 15 weeks restored the reduction in akkermansia muciniphila caused by the high-sugar diet.
3) Glucose tolerance of each group of mice was measured by an intraperitoneal glucose tolerance test, and the results are shown in fig. 3.
As can be seen from fig. 3, the glucose tolerance was impaired by the high-glucose diet, the glucose tolerance could be significantly improved by the intervention of live bacteria of akkermansia muciniphila, whereas the glucose tolerance could not be improved by heat-inactivated akmansia muciniphila.
4) The effects of akkermansia muciniphila on insulin secretion in vivo and in vitro and insulin tolerance were studied by a glucose-stimulated insulin secretion test, and the results are shown in fig. 4 to 6.
As can be seen from FIG. 4, there was no significant difference in fasting insulin secretion in the four groups in the in vivo experiment. In the HS-AKK group, insulin secretion was restored after glucose stimulation, whereas insulin secretion was not improved in the HS-hk AKK group and insulin secretion was disturbed after glucose stimulation.
As can be seen from FIG. 5, in the in vitro experiment, islets were isolated from four groups of mice, and the high glucose treatment resulted in a significant increase in insulin release, while the HS-water group isolated islets showed impaired insulin release compared to the control group. Consistent with the results of the in vivo experiments, islets isolated from the HS-AKK group showed improved insulin secretion following glucose stimulation, whereas islets isolated from the HS-hk AKK group did not show such changes.
As can be seen from FIG. 6, there was no significant difference in insulin sensitivity between the four groups.
As can be seen from fig. 1 to 6, the mouse model with impaired insulin secretion in hyperglycomic group but no insulin resistance shows a decrease in the number of akkermansia muciniphila, and the supplementation of live akkermansia muciniphila can restore insulin secretion and improve glucose tolerance.
(4) Research on the relationship between the effect of Ichmanella muciniphila on mouse serum bile acid and insulin secretion
1) The amount of β CDCA in serum of each group of mice was examined to investigate the effect of akkermansia muciniphila on bile acids in serum of mice, and the results are shown in fig. 7.
As can be seen from FIG. 7, the serum β CDCA level in the HS-water group was significantly higher than that in the control group, while the serum β CDCA level in the HS-AKK group was significantly reduced. However, no significant decrease in β CDCA levels was observed in the HS-hk AKK group.
2) To further investigate the effect of β CDCA on insulin secretion, β CDCA treatment was performed on mouse islet cell line MIN6 cells, and the level of insulin secretion was measured, as shown in fig. 8.
As can be seen from fig. 8, stimulation of MIN6 cells with glucose significantly induced increased insulin levels, and treatment of MIN6 cells with glucose in combination with β CDCA inhibited glucose-induced insulin secretion, indicating that akkermansia muciniphila can stimulate insulin secretion by reducing β CDCA levels in the intestine.
(5) Study of the Effect of Ichmanella muciniphila on FGF15/19 Gene
Human fibroblast growth factor 19(FGF19) stimulates glycogen synthesis and inhibits gluconeogenesis through an insulin-independent pathway. To investigate the effect of Ichmansia muciniphila on the FGF15/19 gene, glycogen synthesis, expression of FGF15 gene and expression of gluconeogenesis-associated genes in liver tissue, ileum, were determined in each group of mice, and the results are shown in FIGS. 9 to 11.
As can be seen from fig. 9 and 10, the mRNA level of FGF15 gene in mice fed with high-sugar diet was significantly decreased, and the decrease in FGF15 gene level caused by the high-sugar diet was restored by the treatment with live akkermansia muciniphila compared to the control mice fed with normal diet. At the same time, a high-sugar diet significantly reduced hepatic glycogen content, but increased hepatic glycogen content after treatment with live Engramansia muciniphila. As can be seen from FIG. 11, Exkermannheimia muciniphila can significantly inhibit gluconeogenesis.
From FIGS. 9 to 11, it can be seen that the expression of mouse FGF15 gene can be up-regulated by Ekermansia muciniphila.
To investigate the effect of β CDCA on the expression of FGF19 gene, we administered the intestinal cell line LS174T cell β CDCA treatment and then examined the mRNA expression level of FGF19 gene, the results of which are shown in fig. 12.
As can be seen from FIG. 12, the mRNA expression level of FGF19 gene decreased with increasing concentration of β CDCA, indicating that β CDCA can inhibit FGF19 gene expression.
The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (10)
1. Application of Akkermansia muciniphila (Akkermansia muciniphila) in preparation of beta-chenodeoxycholic acid inhibitor.
2. Use of akkermansia muciniphila according to claim 1 for the production of a β -chenodeoxycholic acid inhibitor, wherein the akkermansia muciniphila is deposited under the accession number DSM 22959.
3. Use of akkermansia muciniphila according to claim 1 or 2 for the preparation of a β -chenodeoxycholic acid inhibitor, wherein the β -chenodeoxycholic acid inhibitor comprises an active ingredient comprising the akkermansia muciniphila.
4. The use of akkermansia muciniphila according to claim 3 for the preparation of a β -chenodeoxycholic acid inhibitor, wherein the β -chenodeoxycholic acid inhibitor further comprises an auxiliary material comprising a stabilizer selected from at least one of sodium metabisulfite, sodium bisulfite, vitamin C, cysteine, sodium ascorbate, sodium erythorbate, L-cysteine hydrochloride and edetate.
5. The use of Ekermannheimia muciniphila according to claim 4, wherein said excipient further comprises a filler, and said filler is at least one selected from the group consisting of microcrystalline cellulose, lactose, starch, pregelatinized starch, mannitol, and sorbitol.
6. The use of akkermansia muciniphila in the preparation of a beta-chenodeoxycholic acid inhibitor according to claim 4, wherein the auxiliary material further comprises a binder, and the binder is at least one selected from hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, povidone and crospovidone.
7. The use of Ekermannheimia muciniphila according to any one of claims 4 to 6, wherein the excipient further comprises a disintegrant selected from at least one of sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, crospovidone, sodium croscarmellose and dry starch;
and/or the auxiliary materials also comprise a lubricant, and the lubricant is selected from at least one of magnesium stearate, talcum powder, micro-powder silica gel and sodium fumarate stearate.
8. Application of beta-chenodeoxycholic acid inhibitor in preparing human FGF19 gene expression promoter or insulin secretion promoter.
9. The use of a β -chenodeoxycholic acid inhibitor according to claim 8 for the preparation of an FGF19 gene expression promoter or an insulin secretion promoter, wherein the β -chenodeoxycholic acid inhibitor comprises akkermansia muciniphila.
10. Application of akkermansia muciniphila in preparing insulin secretion promoter is provided.
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