CN114099554A - Application of strain containing fadD gene in preparation of medicine for reducing postprandial blood fat - Google Patents
Application of strain containing fadD gene in preparation of medicine for reducing postprandial blood fat Download PDFInfo
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- CN114099554A CN114099554A CN202111385804.4A CN202111385804A CN114099554A CN 114099554 A CN114099554 A CN 114099554A CN 202111385804 A CN202111385804 A CN 202111385804A CN 114099554 A CN114099554 A CN 114099554A
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- 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
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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Abstract
The invention relates to an application of a strain containing a fadD gene in preparing a medicine for reducing postprandial blood fat, and the synergistic effect of a probiotic formula of the strain containing the fadD gene and berberine in reducing postprandial blood fat can be used as an effective formula for treating T2D dyslipidemia.
Description
Technical Field
The invention belongs to the field of application of strains containing fadD genes, and particularly relates to application of strains containing fadD genes in preparation of a medicine for reducing postprandial blood fat.
Background
Hyperlipidemia is a major risk factor for atherosclerotic cardiovascular disease (ASCVD), and particularly when patients with hyperglycemia and type 2 diabetes (T2D) are combined with hyperlipidemia, the risk of ASCVD is significantly increased. There is increasing evidence that high levels of postprandial blood lipid levels (PL) are one of the important cardiovascular risk factors, and for measuring lipid profiles in non-fasting states to predict cardiovascular risk status, more and more countries and regions are currently changing their guidelines to reach consensus. In addition, since in the insulin resistant state, entry of free fatty acids into the intestinal tract is increased, down-regulation of intestinal insulin signaling and up-regulation of microsomal triglyceride transfer protein of the intestinal epithelium both stimulate intestinal lipoprotein production, postprandial hyperlipidemia is a common feature of diabetic patients and has been recommended as an important indicator for evaluating ASCVD associated with T2D. Unlike fasting plasma lipids (mainly from liver-derived lipoproteins), PL changes are primarily a result of intestinal lipid absorption, lipoprotein secretion, and chylomicron production.
Disclosure of Invention
The invention aims to solve the technical problem of providing an application of a strain containing a fadD gene in preparing a medicine for reducing postprandial blood fat.
The invention discloses application of a strain containing a fadD gene in preparation of a medicine for reducing postprandial blood fat, which is characterized in that the fadD gene is one or more of GL001435, GL000888, GL001247 and GL 000390.
GL001435, GL000888, GL001247 and GL000390 (all of KEGG gene numbers).
The strain containing the fadD gene is bifidobacterium.
The Bifidobacterium is Bifidobacterium breve (B.breve) CGMCC No. 6402.
The invention relates to an application of berberine and probiotics containing fadD gene strains in preparing a medicine for reducing postprandial blood fat.
The invention relates to an application of berberine and probiotics containing fadD gene strains in preparing a medicament for treating T2D dyslipidemia.
The invention relates to an application of berberine and probiotics containing bifidobacterium breve in preparing a medicine for reducing postprandial blood fat.
The invention relates to an application of berberine and probiotics containing bifidobacterium breve in preparing a medicament for treating T2D dyslipidemia.
The c-containing probiotics is (B.breve CGMCC No. 6402).
Advantageous effects
The synergistic effect of the probiotic formula (such as bifidobacterium breve) containing the bifidobacterium and the berberine in reducing the postprandial blood fat can be used as an effective formula for treating T2D dyslipidemia.
Drawings
In figure 1, (A) the abundance of lipid-related genes in 9 probiotics and (B) berberine promotes the transcription expression of B.breve CGMCC No.6402fadD gene.
FIG. 2 shows that berberine promotes B.breve CGMCC No.6402 to consume fatty acid.
Detailed Description
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Further, it should be understood that various changes or modifications of the present invention may be made by those skilled in the art after reading the teaching of the present invention, and such equivalents may fall within the scope of the present invention as defined in the appended claims.
Bifidobacterium breve (B.breve) CGMCC 6402 strain is from China general microbiological culture Collection center. ProMetS probiotics (including Lactobacillus rhamnosus, Lactobacillus salivarius, Lactobacillus crispatus, Lactobacillus casei, Lactobacillus fermentum, Lactobacillus gasseri, Bifidobacterium breve, Bifidobacterium longum, Lactobacillus plantarum, provided by Shanghai Van der Li Ltd.)
In the example, the formula of the culture medium 1 comprises 5g of tryptone, 5g of peptone, 10g of yeast extract, 40mL of L salt solution, 0.5g of cysteine hydrochloride, 2.5g of sodium carbonate, 10g of maltose, 2g of glucose, 1g of agar, 0.2mL of vitamin K1 solution and 1000mL of water. The formula of the salt solution comprises 0.25g of CaCl 2.2H2O 0.25, 0.5g of MgSO 4.7H2O 0.5, K2 HPO41.0g, KH2 PO41.0g and NaHCO 310 g; NaCl 2g, water 1000 mL. After the components are dissolved according to the formula, the sealing cover is covered. Sterilizing at 121 deg.C for 20 min.
Example 1
Bifidobacterium breve (b.breve)6402 strain was obtained from the chinese universal microorganism culture collection center and cultured in medium 1. The cultures were incubated at 37 ℃ in an anaerobic chamber (Whitley A35anaerobic work, Don Whitley Scientific, UK) with 5% hydrogen, 10% carbon dioxide and 85% nitrogen. B.breve 6402 16S rRNA gene was amplified by Polymerase Chain Reaction (PCR) and sequenced, indicating that bifidobacterium breve uniquely contains 4 fadD genes (GL001435, GL000888, GL001247, GL 000390).
As shown in fig. 1, the distribution of genes regulating bacterial lipid metabolism in the genomes of the added 9 probiotic strains (fig. 1A) is shown. Unlike e.coli strains, which are equipped with relatively intact lipid degradation and synthesis genes, these 9 probiotic strains all contain phospholipid biosynthesis genes such as glycerol-3-phosphate dehydrogenase (glycerol-3-phosphate dehydrogenase [ nad (p +) ], K00057, gspA), 1-acyl-sn-glycerol-3-phosphate acyltransferase (1-acyl-sn-glycerol-3-phosphate acyltransferase, K00655, plsC) and phosphatidyl cytidine transferase (K α zydylyltransferase, K00981, cdsA), whereas only two bifidobacterium strains uniquely express key enzymes that enhance the mobilization of bacterial FFAs, namely fadD127 (long-chain acyl-coa synthetase, K01897, EC 6.2.1.3, fig. 1A). Therefore, strains with multiple fadD genes, such as b.breve, can accelerate microbial lipid metabolism in the intestinal lumen. Breve when treated with different concentrations of BBR in vitro, the RNA expression levels of all four fadD genes were significantly increased compared to the control group (fig. 1B). The potential of BBR to activate b.breve lipid absorption and utilization therefore contributes to the postprandial lipid lowering benefits of the combination co-therapy group.
Example 2
Bifidobacterium breve 6402 was inoculated at a concentration of 10% to culture in a medium containing LA (linolenic acid, final concentration of 1mg/ml) for 1 hour, then treated with control B.breve (B) or BBR (6.25. mu.g/ml) + B.breve for 4 hours (C), and finally centrifuged at 4 degrees 3000rpm to extract the supernatant, and the NEFA content in the medium was measured by a colorimetric assay (LabAssay NEFA, Wako, Japan). Culture medium 1 containing LA (linolenic acid, final concentration 1mg/ml) without bifidobacteria as a blank.
Preparing LA mother liquor: LA (200mg/ml) was dissolved in Tween 80 (2%) in PBS and homogenized by a high speed homogenizer ULTRA-RURRAX for a maximum frequency of 30s three times at 30s intervals.
As shown in fig. 2, when b.breve was cultured in vitro, the medium fatty acid level (mean ± sd 1.02 ± 0.05VS 0.74 ± 0.02mEq/L) was significantly reduced, increasing the fatty acid consumption, while when BBR treatment was used, the fatty acid level was more significantly reduced (0.74 ± 0.02VS 0.62 ± 0.02mEq/L) compared to the control group, and thus, it was further clarified that berberine promoted the consumption and utilization of fatty acid by bifidobacterium breve 6402.
Example 3
Naive type 2 diabetic patients (20 centers, a randomized 409 subjects) were collected without drug treatment and treated with short-term (1 week) broad-spectrum antibiotics: after the oral intestinal tract of the gentamicin sulfate sustained-release tablets is cleaned, the tablets are randomly divided into four treatment groups: namely, the berberine combined ProMetS probiotic treatment group (Prob + BBR), the berberine + probiotic placebo treatment group (BBR), the berberine placebo + probiotic treatment group (Prob) and the double placebo treatment group (Plac) were subjected to interventional therapy for 12 weeks.
Postprandial blood lipid measurement
Postprandial total cholesterol (pTC), postprandial triglycerides (pTGs), postprandial high density lipoprotein cholesterol (pHDLc) and postprandial low density lipoprotein cholesterol (pLDLc) were measured by the cholesterol oxidase method, the glycerophosphate oxidase peroxidase (GPO-POD), the polyanionic polymer/detergent (PPD) method and the solubilization with autoanalyzer (SOL) method, respectively (AU 5800; Beckman Coulter, CA, USA).
TABLE 1 postprandial blood lipid changes after treatment
Data represent least squares means (LS means) and 95% Confidence Interval (CI). pTC total postprandial cholesterol; (ii) a pLDLc, postprandial low density lipoprotein; pTG (log) postprandial triglycerides; pHDLc-postprandial high density lipoprotein. Model 1, performing one-factor analysis of variance to compare differences among groups, and performing Tukey correction for multiple comparisons; model 2, analyzing and comparing differences among groups by multi-factor variance, correcting preset hierarchical factor age groups (50 years old and more than or equal to 50 years old), and performing Tukey correction for multiple times of comparison; statistical significance was defined as corrected P <0.05 corrected for multiple comparisons using the two-sided test.
BBR alone is effective in lowering fasting blood lipid levels but not postprandial cholesterol levels, and the synergistic effect of BBR and probiotics lowers postprandial blood lipid levels.
Claims (7)
1. The application of a strain containing a fadD gene in preparing a medicine for reducing postprandial blood fat is characterized in that the fadD gene is one or more of GL001435, GL000888, GL001247 and GL 000390.
2. The use according to claim 1, wherein the strain containing the fadD gene is a bifidobacterium.
3. The use according to claim 2, wherein the bifidobacterium is bifidobacterium breve (b.breve) CGMCC No. 6402.
4. Use of berberine in combination with a probiotic of a strain according to claim 1 containing the fadD gene for the manufacture of a medicament for lowering postprandial blood lipids.
5. Use of berberine in combination with a probiotic of a strain according to claim 1 containing the fadD gene for the manufacture of a medicament for the treatment of T2D dyslipidaemia.
6. Use of berberine in combination with a probiotic comprising bifidobacterium breve as claimed in claim 2 in the manufacture of a medicament for reducing postprandial blood lipid.
7. Use of berberine in combination with a probiotic comprising Bifidobacterium breve as claimed in claim 2 in the manufacture of a medicament for the treatment of T2D dyslipidaemia.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202111385804.4A CN114099554A (en) | 2021-11-22 | 2021-11-22 | Application of strain containing fadD gene in preparation of medicine for reducing postprandial blood fat |
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| CN202111385804.4A CN114099554A (en) | 2021-11-22 | 2021-11-22 | Application of strain containing fadD gene in preparation of medicine for reducing postprandial blood fat |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102670661A (en) * | 2011-03-08 | 2012-09-19 | 惠宏襄 | Drug for stimulating glucagon-like peptide 1 (GLP-1) secretion |
| CN108157973A (en) * | 2017-12-14 | 2018-06-15 | 上海交通大学医学院附属瑞金医院 | The probiotic composition and its preparation of a kind of beneficial glycolipid metabolism function and application |
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2021
- 2021-11-22 CN CN202111385804.4A patent/CN114099554A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102670661A (en) * | 2011-03-08 | 2012-09-19 | 惠宏襄 | Drug for stimulating glucagon-like peptide 1 (GLP-1) secretion |
| CN108157973A (en) * | 2017-12-14 | 2018-06-15 | 上海交通大学医学院附属瑞金医院 | The probiotic composition and its preparation of a kind of beneficial glycolipid metabolism function and application |
Non-Patent Citations (4)
| Title |
|---|
| SHUJIE WANG等: "Combined berberine and probiotic treatment as an effective regimen for improving postprandial hyperlipidemia in type 2 diabetes patients: a double blinded placebo controlled randomized study" * |
| YIFEI ZHANG等: "Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study)" * |
| 李雪琳等: "益生菌改善2 型糖尿病的相关机制" * |
| 王琰等: "肠道菌介导的PK-PD 新模式: 小檗碱药代动力学引发的思考" * |
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