CN117264810A - Probiotic composition with metabolism syndrome improving function and application thereof - Google Patents
Probiotic composition with metabolism syndrome improving function and application thereof Download PDFInfo
- Publication number
- CN117264810A CN117264810A CN202311027414.9A CN202311027414A CN117264810A CN 117264810 A CN117264810 A CN 117264810A CN 202311027414 A CN202311027414 A CN 202311027414A CN 117264810 A CN117264810 A CN 117264810A
- Authority
- CN
- China
- Prior art keywords
- lactobacillus
- probiotic composition
- metabolic syndrome
- genes
- expression
- 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.)
- Pending
Links
- 239000006041 probiotic Substances 0.000 title claims abstract description 100
- 235000018291 probiotics Nutrition 0.000 title claims abstract description 100
- 230000000529 probiotic effect Effects 0.000 title claims abstract description 91
- 239000000203 mixture Substances 0.000 title claims abstract description 84
- 230000004060 metabolic process Effects 0.000 title description 7
- 208000011580 syndromic disease Diseases 0.000 title description 5
- 208000001145 Metabolic Syndrome Diseases 0.000 claims abstract description 54
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims abstract description 54
- 230000014509 gene expression Effects 0.000 claims abstract description 39
- 210000001035 gastrointestinal tract Anatomy 0.000 claims abstract description 38
- 241000186840 Lactobacillus fermentum Species 0.000 claims abstract description 34
- 229940012969 lactobacillus fermentum Drugs 0.000 claims abstract description 32
- 210000004185 liver Anatomy 0.000 claims abstract description 31
- 150000004666 short chain fatty acids Chemical class 0.000 claims abstract description 25
- 101000978937 Homo sapiens Nuclear receptor subfamily 0 group B member 2 Proteins 0.000 claims abstract description 23
- 101001082043 Sulfolobus acidocaldarius (strain ATCC 33909 / DSM 639 / JCM 8929 / NBRC 15157 / NCIMB 11770) Translation initiation factor 5A Proteins 0.000 claims abstract description 23
- 240000006024 Lactobacillus plantarum Species 0.000 claims abstract description 21
- 241001608472 Bifidobacterium longum Species 0.000 claims abstract description 19
- 235000013965 Lactobacillus plantarum Nutrition 0.000 claims abstract description 19
- 229940072205 lactobacillus plantarum Drugs 0.000 claims abstract description 19
- 241001134770 Bifidobacterium animalis Species 0.000 claims abstract description 18
- 241000218588 Lactobacillus rhamnosus Species 0.000 claims abstract description 18
- 229940009291 bifidobacterium longum Drugs 0.000 claims abstract description 17
- 229940118852 bifidobacterium animalis Drugs 0.000 claims abstract description 16
- 101150018468 Abcg5 gene Proteins 0.000 claims abstract description 10
- 102100027844 Fibroblast growth factor receptor 4 Human genes 0.000 claims abstract description 10
- 101000957672 Homo sapiens Cytochrome P450 7A1 Proteins 0.000 claims abstract description 10
- 101000917134 Homo sapiens Fibroblast growth factor receptor 4 Proteins 0.000 claims abstract description 10
- 210000004369 blood Anatomy 0.000 claims description 59
- 239000008280 blood Substances 0.000 claims description 59
- 244000005700 microbiome Species 0.000 claims description 25
- 230000001603 reducing effect Effects 0.000 claims description 20
- 108090000623 proteins and genes Proteins 0.000 claims description 18
- 235000021391 short chain fatty acids Nutrition 0.000 claims description 17
- 241000186660 Lactobacillus Species 0.000 claims description 16
- 229940039696 lactobacillus Drugs 0.000 claims description 16
- 230000001737 promoting effect Effects 0.000 claims description 14
- 150000002632 lipids Chemical class 0.000 claims description 13
- 230000015572 biosynthetic process Effects 0.000 claims description 12
- 238000004321 preservation Methods 0.000 claims description 12
- 238000003786 synthesis reaction Methods 0.000 claims description 12
- 239000003613 bile acid Substances 0.000 claims description 11
- 238000009472 formulation Methods 0.000 claims description 11
- 208000008589 Obesity Diseases 0.000 claims description 10
- 235000020824 obesity Nutrition 0.000 claims description 10
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 claims description 8
- 238000009629 microbiological culture Methods 0.000 claims description 7
- 230000001105 regulatory effect Effects 0.000 claims description 7
- 101100390675 Mus musculus Fgf15 gene Proteins 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 101150075266 CYP7A1 gene Proteins 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 241000186000 Bifidobacterium Species 0.000 claims 2
- 230000000694 effects Effects 0.000 abstract description 33
- 230000002195 synergetic effect Effects 0.000 abstract description 17
- 230000000968 intestinal effect Effects 0.000 abstract description 12
- 102100038637 Cytochrome P450 7A1 Human genes 0.000 abstract description 5
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 32
- 241000700159 Rattus Species 0.000 description 27
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 22
- 239000008103 glucose Substances 0.000 description 22
- 235000009200 high fat diet Nutrition 0.000 description 21
- 241000252212 Danio rerio Species 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- 230000006870 function Effects 0.000 description 17
- 102100023172 Nuclear receptor subfamily 0 group B member 2 Human genes 0.000 description 16
- 230000002354 daily effect Effects 0.000 description 15
- 235000012000 cholesterol Nutrition 0.000 description 14
- 238000002474 experimental method Methods 0.000 description 13
- 239000003814 drug Substances 0.000 description 12
- 238000011282 treatment Methods 0.000 description 10
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 108010028554 LDL Cholesterol Proteins 0.000 description 6
- GHUUBYQTCDQWRA-UHFFFAOYSA-N Pioglitazone hydrochloride Chemical compound Cl.N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 GHUUBYQTCDQWRA-UHFFFAOYSA-N 0.000 description 6
- 238000013401 experimental design Methods 0.000 description 6
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 6
- 229960002827 pioglitazone hydrochloride Drugs 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 238000007619 statistical method Methods 0.000 description 6
- 150000003626 triacylglycerols Chemical class 0.000 description 6
- 235000005911 diet Nutrition 0.000 description 5
- 230000037213 diet Effects 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 230000002906 microbiologic effect Effects 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 208000017170 Lipid metabolism disease Diseases 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 210000002969 egg yolk Anatomy 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 229960005095 pioglitazone Drugs 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 208000032928 Dyslipidaemia Diseases 0.000 description 2
- 108010023302 HDL Cholesterol Proteins 0.000 description 2
- 102000016267 Leptin Human genes 0.000 description 2
- 108010092277 Leptin Proteins 0.000 description 2
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 2
- 230000035508 accumulation Effects 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000004043 dyeing Methods 0.000 description 2
- 210000003608 fece Anatomy 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 2
- 229940039781 leptin Drugs 0.000 description 2
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 2
- 238000007410 oral glucose tolerance test Methods 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- 108700028369 Alleles Proteins 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 208000002705 Glucose Intolerance Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- NPGIHFRTRXVWOY-UHFFFAOYSA-N Oil red O Chemical compound Cc1ccc(C)c(c1)N=Nc1cc(C)c(cc1C)N=Nc1c(O)ccc2ccccc12 NPGIHFRTRXVWOY-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000023852 carbohydrate metabolic process Effects 0.000 description 1
- 208000020450 carbohydrate metabolism disease Diseases 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 201000011529 cardiovascular cancer Diseases 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000004136 fatty acid synthesis Effects 0.000 description 1
- 230000002550 fecal effect Effects 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 208000017745 inborn carbohydrate metabolic disease Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000006372 lipid accumulation Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000006371 metabolic abnormality Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229960003105 metformin Drugs 0.000 description 1
- 229960004329 metformin hydrochloride Drugs 0.000 description 1
- OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 201000009104 prediabetes syndrome Diseases 0.000 description 1
- REQCZEXYDRLIBE-UHFFFAOYSA-N procainamide Chemical compound CCN(CC)CCNC(=O)C1=CC=C(N)C=C1 REQCZEXYDRLIBE-UHFFFAOYSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
-
- 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
- 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
- A61K35/745—Bifidobacteria
-
- 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
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
-
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
- A61P3/06—Antihyperlipidemics
-
- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
- C12R2001/225—Lactobacillus
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
- C12R2001/225—Lactobacillus
- C12R2001/25—Lactobacillus plantarum
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Diabetes (AREA)
- Organic Chemistry (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Epidemiology (AREA)
- Food Science & Technology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Biomedical Technology (AREA)
- Polymers & Plastics (AREA)
- Biochemistry (AREA)
- Nutrition Science (AREA)
- General Engineering & Computer Science (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Child & Adolescent Psychology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The invention relates to the technical field of probiotic compositions, in particular to a probiotic composition with a function of improving metabolic syndrome and application thereof. The probiotic composition comprises bifidobacterium animalis WHH2276, lactobacillus fermentum WHH3906, lactobacillus fermentum 2644, bifidobacterium longum WHH2270, lactobacillus plantarum 1701 and lactobacillus rhamnosus 1155. In the probiotic composition, 6 strains can generate better synergistic effect in improving metabolic syndrome, so that the probiotic composition can effectively stimulate intestinal flora to generate short chain fatty acid, promote the expression of FXR, SHP, FGF genes in intestinal tracts and FGFR4, SHP and Abcg5 genes in livers, inhibit the expression of CYP7A1 in livers, have more comprehensive effect and obviously improve compared with single strain.
Description
Technical Field
The invention relates to the technical field of probiotic compositions, in particular to a probiotic composition with a function of improving metabolic syndrome and application thereof.
Background
Metabolic syndrome (Metabolic syndrome, MS) is one of the most prominent problems in medicine today, often accompanied by carbohydrate and lipid metabolism disorders, often occurring simultaneously with obesity, dyslipidemia and glycometabolism disorders (type 2 diabetes or impaired glucose tolerance), and also pathologically interacting, with increased risk of cardiovascular disease, cancer and nonalcoholic fatty liver in patients suffering from metabolic syndrome. It is counted that metabolic syndrome patients spend more than $4000 on treatment each year, and the prevalence is growing at a striking rate and is showing a trend towards younger age. The metabolic syndrome seriously affects the physical health of people, and brings trouble to the life of people and also brings heavy burden to the development of national economy.
It has been reported that the occurrence of metabolic syndrome is closely related to the imbalance of intestinal flora, while probiotics are commonly used intestinal flora modulators. Patent CN202211588301.1 filed before the applicant relates to a bifidobacterium longum strain with blood sugar reducing effect and application thereof, wherein lactobacillus fermentum WHH3906 is found to be capable of regulating intestinal microenvironment, stimulating G protein coupled receptor expression of intestinal and pancreatic mediated short chain fatty acids, relieving insulin resistance and reducing blood sugar; patent CN202010953587.3 relates to a fermented lactobacillus plantarum with a weight-losing function and application thereof, wherein it is disclosed that the fermented lactobacillus plantarum WHH3906 can effectively reduce the level of leptin to restore the leptin sensitivity of the body, and effectively prevent and treat obesity.
The above patents all use a single strain to relieve metabolic diseases, and have single effect and limited relieving degree. By utilizing the synergistic effect among different strains, the effect of relieving the metabolic syndrome is expected to be improved, but the research on a plurality of strains in the aspect of improving the metabolic syndrome is very little at present, the interaction mechanism among the strains and the mechanism for improving the metabolic syndrome are not clear, and therefore, the difficulty for obtaining the probiotic composition with ideal effect is very great. In patent CN202011448810.5 filed before the applicant, lactobacillus plantarum 1701 and lactobacillus mucilaginosus WHH3906 are compounded, and the two strains show a synergistic effect on weight loss, but the effect is still single for improving metabolic syndrome.
Disclosure of Invention
The invention provides a probiotic composition with a function of improving metabolic syndrome and application thereof, and aims to solve the technical problems that an existing probiotic bacterial agent for improving metabolic syndrome is limited in improvement range and single in action effect. The probiotic composition has better synergistic effect in improving metabolic syndrome, can effectively stimulate intestinal flora to generate short-chain fatty acid, regulate and control the expression of related genes in intestinal tracts and livers, reduce blood sugar and blood fat, improve obesity, has more comprehensive effect and is superior to a single strain.
The specific technical scheme of the invention is as follows:
in a first aspect, the present invention provides a probiotic composition having a function of improving metabolic syndrome, comprising bifidobacterium animalis WHH2276, lactobacillus fermentum WHH3906, lactobacillus fermentum 2644, bifidobacterium longum WHH2270, lactobacillus plantarum 1701 and lactobacillus rhamnosus 1155;
the bifidobacterium animalis WHH2276 has been deposited at the microorganism strain collection center of Guangdong province (address: guangzhou Mitsui No. 100 university, guangzhou, md. 100, building No. 5, guangdong province academy of sciences of China) on 10 months 18 of 2022, with deposit number of GDMCC No. 62901, and the microorganism classification named as bifidobacterium animalis Bifidobacterium animalis subsp.
The fermented lactobacillus mucilaginosus WH3906 is preserved in China general microbiological center (the address is China academy of sciences of microbiology, national academy of sciences, 1 st da, 3 rd da, beijing, chaoyang area) at 3 months 13 days in 2020, the preservation number is CGMCC No.19472, and the microorganism classification is named fermented lactobacillus mucilaginosus Limosilactobacillus fermentun;
the fermented lactobacillus mucilaginosus 2644 is preserved in China general microbiological center (the address is China academy of sciences of microbiology, national academy of sciences, 1 st da, 3 rd da, beijing, the city of korea) at 11 months and 19 days in 2018, with a preservation number of CGMCC No.16754, and the microorganism classification is named fermented lactobacillus mucilaginosus Limosilactobacillus fermentun;
the bifidobacterium longum WH 2270 has been deposited at the microorganism strain collection center of Guangdong province (address: guangzhou Mitsui No. 100, ming's 100, building No. 5, guangdong province academy of sciences of China) on 10-month 18 of 2022, with deposit number of GDMCC No. 62900, and the microorganism classification named as bifidobacterium longum Bifidobacterium longum subsp.
The lactobacillus plantarum 1701 has been preserved in the China general microbiological center (the address is China center for microbiological study, including national academy of sciences of China, including national institute of sciences, including national center for passage 1, national center for use in the morning, as seen in Beijing, and having a preservation number of CGMCC No.18728, and the microorganism classification is named lactobacillus plantarum Lactobacillus plantarum;
lactobacillus rhamnosus 1155 has been preserved in the China general microbiological center (the institute of microbiology, national academy of sciences of China, no. 3, north Chen, lu 1, beijing, kogyo) at 1, 4, and has a preservation number of CGMCC No.11955, and the microorganism classification is named lactobacillus rhamnosus Lactobacillus rhamnosus.
Regarding lactobacillus fermentum WHH3906 and lactobacillus fermentum 2644: the "lactobacillus fermentum Lactobacillus fermentum" was more named as "lactobacillus fermentum Limosilactobacillus fermentun" in 2021, lactobacillus fermentum wh 3906 and lactobacillus fermentum 2644 were preserved before the renaming, so that the classification in the preservation certificate was named as "lactobacillus fermentum Lactobacillus fermentum", and the present name "lactobacillus fermentum Limosilactobacillus fermentun" was used in the present invention.
In the probiotic composition, complex interaction relation exists between all strains, the metabolic products of one strain can influence the growth and metabolism of other strains, meanwhile, resource competition exists between the strains, the growth and the metabolism of the strains can be influenced, and further, the synergistic or antagonistic effect is shown, so that the functions of the probiotic composition are not simple superposition of all the strains. Because of the intricate interactions between strains, the mechanism of interactions between strains in improving metabolic syndrome is not yet defined; also, for synergy or antagonism between strains, even between fixed several species, the interactions exhibited between different strains are not fixed, and may even be completely reversed. These present significant difficulties in the development of probiotic compositions with desirable synergistic effects.
According to the invention, after the specific 6 strains of bifidobacterium animalis WHH2276, lactobacillus fermentum WHH3906, lactobacillus fermentum 2644, bifidobacterium longum WHH2270, lactobacillus plantarum 1701 and lactobacillus rhamnosus 1155 are compounded, the synergistic effect can be better played in the aspect of improving metabolic syndrome, and the effect is more comprehensive and better than that of a single strain. In particular, in improving the metabolic syndrome, the probiotic composition of the invention has the following effects:
(1) Has better synergistic effect in reducing blood sugar: through experiments, the probiotic composition provided by the invention can obviously reduce the blood sugar rise induced by a high-calorie diet, and the effect is better than that of a single strain of 6 strains.
(2) Has better synergistic effect in reducing blood fat: through experiments, the probiotic composition can obviously reduce cholesterol and triglyceride rise induced by high calorie diet, and the effect is better than that of a single strain of 6 strains.
(3) Has better effect in improving obesity: through experiments, the probiotic composition disclosed by the invention can be used for remarkably improving obesity induced by high-fat diet.
(4) Has better synergistic effect in promoting the synthesis of Short Chain Fatty Acids (SCFAs) of intestinal nutrient factors: through experiments, the probiotic composition can obviously increase the content of SCFAs in intestinal tracts and blood, and the effect is better than that of a single strain of 6 strains.
(5) Has better effects in regulating the expression of genes related to metabolic syndrome and restricting the synthesis of bile acid: through experiments, the probiotic composition provided by the invention can effectively promote the expression of FXR, SHP, FGF genes in intestinal tracts and FGFR4, SHP and Abcg5 genes in livers, and inhibit the expression of CYP7A1 genes in livers. Since CYP7A1 is a rate-limiting enzyme in the bile acid synthesis pathway, inhibition of expression of the CYP7A1 gene in the liver can limit bile acid synthesis, thereby promoting lipid excretion from feces and reducing lipid accumulation in the host.
Preferably, the ratio of viable count of bifidobacterium animalis WHH2276, lactobacillus fermentum WHH3906, lactobacillus fermentum 2644, bifidobacterium longum WHH2270, lactobacillus plantarum 1701 and lactobacillus rhamnosus 1155 is 1: (1-10): (1-10): (1-10): (1-10): (1-10).
In a second aspect, the present invention provides the use of said probiotic composition in a formulation having a function of improving metabolic syndrome.
Preferably, the preparation having the function of improving metabolic syndrome is used for reducing blood lipid or blood sugar, or for improving obesity, or for promoting the production of short chain fatty acids in the intestinal tract, or for regulating the expression of metabolic syndrome-related genes in the intestinal tract and liver, or for limiting the synthesis of bile acids.
Further, the regulation of expression of genes associated with metabolic syndrome in the gut and liver includes promoting expression of FXR, SHP and FGF15 genes in the gut, promoting expression of FGFR4, SHP and Abcg5 genes in the liver, and inhibiting expression of CYP7A1 gene in the liver.
In a third aspect, the invention provides the use of said probiotic composition in a regulator of expression of a gene associated with metabolic syndrome.
Preferably, the metabolic syndrome related genes include FXR, SHP and FGF15 genes in the gut, and FGFR4, SHP, abcg5 and CYP7A1 genes in the liver.
In a fourth aspect, the present invention provides the use of the probiotic composition in a formulation having the function of promoting the production of short chain fatty acids in the intestinal tract.
In a fifth aspect, the present invention provides the use of the probiotic composition in a formulation having a function of limiting bile acid synthesis.
In a sixth aspect, the present invention provides the use of said probiotic composition in a formulation having a blood glucose and blood lipid lowering function.
Compared with the prior art, the invention has the following advantages:
(1) In the probiotic composition, 6 strains can generate better synergistic effect in improving metabolic syndrome, so that the probiotic composition can effectively stimulate intestinal flora to generate short chain fatty acid, promote the expression of FXR, SHP, FGF genes in intestinal tracts and FGFR4, SHP and Abcg5 genes in livers, inhibit the expression of CYP7A1 in livers, have more comprehensive effect and obviously improve compared with single strain.
(2) The probiotic composition provided by the invention can generate remarkable synergistic effect in reducing blood sugar and blood fat. In zebra fish experiments, the concentration of probiotics is 10 8 When CFU/mL is carried out, the reduction amplitude of blood sugar is improved by 20-77% different than that of a single strain, the reduction amplitude of total cholesterol is improved by 62-150% different than that of a single strain, and the reduction amplitude of triglyceride is improved by 44-132% different than that of a single strain; in the metabolism syndrome model rat experiment, 6×10 medicine is taken 9 The CFU/kg BW probiotic composition can remarkably improve hyperglycemia and hyperlipidemia induced by high-fat diet, and the blood sugar and the blood lipid are reduced to the normal level of a normal control group.
(3) The probiotic composition provided by the invention has good weight-losing efficacy. In the metabolism syndrome model rat experiment, 6×10 medicine is taken 9 The CFU/kg BW probiotic composition can remarkably improve obesity induced by high-fat diet, and the weight is reduced by 15% compared with that of a model group.
(4) The probiotic composition provided by the invention has good short-chain fatty acid synthesis capability. In the metabolism syndrome model rat experiment, 6×10 medicine is taken 9 CFU/kg BW probiotic composition can be significantly increasedThe content of SCFAs in intestinal tract is improved by 38% compared with model group, and the content of acetic acid in blood is increased.
(5) The probiotic composition provided by the invention can effectively promote the expression of FXR, SHP, FGF and Abcg5 genes in intestinal tracts and FGFR4, SHP and Abcg5 genes in livers; inhibit the expression of CYP7A1 gene, limit the synthesis of bile acid, promote the discharge of lipid from feces, reduce the accumulation of lipid in a host body, and obviously improve metabolic syndrome.
Drawings
Figure 1 shows the effect of different interventions on blood glucose and blood lipid in blood of high fat diet zebra fish. Wherein, figures 1A-1C are the effects of different interventions on blood glucose, total blood cholesterol (TC), blood Triglycerides (TG) of high-fat diet zebra fish, respectively; different letters indicate significant differences, P <0.05.
Figure 2 is the effect of different interventions on the body weight of high fat diet rats. Wherein the different letters represent significant differences, P <0.05.
Figure 3 is the effect of different interventions on blood glucose and blood lipid in high fat diet rats. Wherein, fig. 3A to 3F are the effects of different interventions on Fasting Blood Glucose (FBG), blood Glucose (BG), oral glucose tolerance (OGTT), blood low density lipoprotein cholesterol (LDL-C), blood Triglycerides (TG), blood Total Cholesterol (TC) of high fat diet rats, respectively; different letters indicate significant differences, P <0.05.
Figure 4 shows the effect of different interventions on SCFAs concentration in the intestinal tract and blood of high fat diet rats. Among them, figure 4A is the effect of different interventions on SCFAs (including acetic acid, propionic acid and butyric acid) concentration in the intestinal tract of high fat diet rats; FIG. 4B is the effect of different interventions on acetic acid concentration in blood of high fat diet rats; different letters indicate significant differences, P <0.05.
FIG. 5 is a graph showing the effect of different interventions on the expression of genes associated with metabolic syndrome in the intestinal tract and liver of high fat diet rats; wherein # represents significant difference compared to control group, P <0.05; * Indicating significant differences compared to the model group, P <0.05.
FIG. 6 is a schematic diagram of the effect of the probiotic composition of the invention on improving metabolic syndrome.
Fig. 7 is a zebra fish experimental design. Wherein, "HFD-Y" means administration of a high fat diet, and "HCD-G" means a high sugar-based diet.
FIG. 8 is a diagram of a rat experimental design.
Detailed Description
The invention is further described below with reference to examples. It is to be understood that these embodiments are merely for illustrating the present invention and are not to be construed as limiting the scope of the present invention, and that variations and advantages which can be conceived by those skilled in the art are included therein without departing from the spirit and scope of the inventive concept, and the appended claims and any equivalents thereof are intended to be protected by the present invention.
General examples
A probiotic composition with a function of improving metabolic syndrome, comprising bifidobacterium animalis WHH2276, lactobacillus fermentum WHH3906, lactobacillus fermentum 2644, bifidobacterium longum WHH2270, lactobacillus plantarum 1701 and lactobacillus rhamnosus 1155;
the bifidobacterium animalis WHH2276 has been deposited in the microorganism strain collection of Guangdong province at 10 and 18 of 2022, and the deposited number is GDMCC No. 62901, and the microorganism classification is named as bifidobacterium animalis Bifidobacterium animalis subsp.
The fermented lactobacillus mucilaginosus WH3906 is preserved in China general microbiological culture Collection center (CGMCC) with the preservation number of CGMCC No.19472 and the microorganism classification is named fermented lactobacillus mucilaginosus Limosilactobacillus fermentun in 3 months and 13 days of 2020;
the fermented lactobacillus mucilaginosus 2644 is preserved in China general microbiological culture collection center (CGMCC) in 11 and 19 months of 2018, and the preservation number is CGMCC No.16754, and the microorganism classification is named as fermented lactobacillus mucilaginosus Limosilactobacillus fermentun;
the bifidobacterium longum WHH2270 has been deposited in the microorganism strain collection of Guangdong province at 10 and 18 of 2022, and the deposited number is GDMCC No. 62900, and the microorganism classification is named as bifidobacterium longum Bifidobacterium longum subsp.
The lactobacillus plantarum 1701 has been preserved in China general microbiological culture collection center (CGMCC) with the preservation number of CGMCC No.18728 in the 10 month 23 days of 2019, and the microorganism classification is named as lactobacillus plantarum Lactobacillus plantarum;
lactobacillus rhamnosus 1155 has been preserved in China general microbiological culture collection center (CGMCC) with a preservation number of CGMCC No.11955 in the year 1 and 4 of 2016, and the microorganism classification is named lactobacillus rhamnosus Lactobacillus rhamnosus.
As a specific embodiment, the ratio of the viable count of the bifidobacterium animalis WHH2276, lactobacillus fermentum WHH3906, lactobacillus fermentum 2644, bifidobacterium longum WHH2270, lactobacillus plantarum 1701 and lactobacillus rhamnosus 1155 is 1: (1-10): (1-10): (1-10): (1-10): (1-10).
The use of said probiotic composition in a formulation having a function of improving metabolic syndrome.
As a specific embodiment, the agent having a function of improving metabolic syndrome is used for reducing blood lipid or blood glucose, or for improving obesity, or for promoting the production of short chain fatty acids in the intestinal tract, or for regulating the expression of metabolic syndrome-related genes in the intestinal tract and liver, or for limiting the synthesis of bile acids.
As a specific embodiment, the modulating expression of genes associated with metabolic syndrome in the gut and liver includes promoting expression of FXR, SHP and FGF15 genes in the gut, promoting expression of FGFR4, SHP and Abcg5 genes in the liver, and inhibiting expression of CYP7A1 gene in the liver.
The application of the probiotic composition in the metabolic syndrome related gene expression regulator.
As a specific embodiment, the metabolic syndrome related genes include FXR, SHP and FGF15 genes in the gut, and FGFR4, SHP and CYP7A1 genes in the liver.
Use of the probiotic composition in a formulation having the function of promoting the production of short chain fatty acids in the intestinal tract.
The use of said probiotic composition in a formulation having a function of limiting bile acid synthesis.
The probiotic composition is applied to a preparation with the function of reducing blood sugar and blood fat.
Example 1: evaluation of synergistic hypoglycemic efficacy of probiotic composition
Zebra fish of the 5dpf wild type AB strain were bred in beakers, and 30 zebra fish were treated per cup (experimental group). The probiotic bacteria and the positive sample of the present invention are respectively administered in a water-soluble manner, wherein the probiotic bacteria samples comprise single strains of 6 strains of bifidobacterium animalis WHH2276, lactobacillus fermentum WHH3906, lactobacillus fermentum 2644, bifidobacterium longum WHH2270, lactobacillus plantarum 1701 and lactobacillus rhamnosus 1155 (respectively, "WHH2276", "WHH3906", "WHH2644", "WHH2270", "WHH1701", "wh 1155" in fig. 1) and a probiotic composition (Pro "in fig. 1) formulated according to a viable count of 1:1:1:1:1:1:1, positive control (Pioglitazone" in fig. 1) Pioglitazone hydrochloride of 20.0 μg/mL; a normal Control group (FIG. 1, "Control") and a Model Control group (FIG. 1, "Model") were simultaneously set, with a capacity of 25mL per cup. Except for the normal control group, the rest experimental groups were given high-fat feed (yolk powder) in water in the daytime (7.5 h daily) and high-sugar (glucose) in water in the evening (16.5 h daily) to establish a zebra fish high-sugar high-fat model. The probiotics (final concentration of single strain and probiotic composition is 10 8 CFU/mL) and high-fat feed were co-treated for 15h (7.5 h daily) and glucose for 33h (16.5 h daily), and the experimental design is shown in fig. 7.
Processing at 28deg.C for 48 hr, collecting data with glucometer, analyzing blood sugar value in zebra fish, and evaluating blood sugar lowering effect of sample with the statistical analysis result of the index. Statistical treatment results are expressed in mean+ -SE. Statistical analysis was performed with SPSS26.0 software, p <0.05 indicated that the differences were statistically significant.
The results are shown in FIG. 1A: compared with a normal control group, the blood sugar of a model group is obviously increased, and the blood sugar of the medicament pioglitazone hydrochloride, each single strain and the probiotic composition Pro group can be obviously reduced after being treated, wherein the probiotic composition Pro group has the best reducing effect, and the reducing amplitude is improved by 20-77% compared with the effect of the single strain, so that the probiotic composition provided by the invention can generate obvious synergistic effect in reducing the blood sugar.
Example 2: efficacy evaluation of probiotic composition for synergistically reducing total cholesterol
Zebra fish of the 5dpf wild type AB strain were bred in beakers, and 30 zebra fish were treated per cup (experimental group). The probiotics of the present invention and the positive samples were administered in water, respectively, wherein the probiotic samples included individual strains of 6 strains of bifidobacterium animalis WHH2276, lactobacillus fermentum WHH3906, lactobacillus fermentum 2644, bifidobacterium longum WHH2270, lactobacillus plantarum 1701 and lactobacillus rhamnosus 1155 ("WHH 2276", "WHH3906", "WHH2644", "WHH2270", "WHH1701", "wh 1155", respectively, in fig. 1) and probiotic compositions (Pro "in fig. 1) formulated in a viable count of 1:1:1:1:1:1:1 were prepared, and the positive Control (Pioglitazone" in fig. 1) Pioglitazone hydrochloride was 20.0 μg/mL, while setting the normal Control group (Control "in fig. 1) and the Model Control group (Model" in fig. 1) at a capacity of 25mL per cup. Except for the normal control group, the rest experimental groups were given high-fat feed (yolk powder) in water in the daytime (7.5 h daily) and high-sugar (glucose) in water in the evening (16.5 h daily) to establish a zebra fish high-sugar high-fat model. The probiotics (final concentration of single strain and probiotic composition is 10 8 CFU/mL) and high fat feed were co-treated for 15h (7.5 h daily) and glucose for 33h (16.5 h daily), cholesterol probe was injected at 32h, and the experimental design is shown in fig. 7.
And (3) processing at 28 ℃ for 48 hours, randomly picking 10 zebra fish from each experimental group, photographing under a fluorescence microscope, analyzing and collecting data by using NIS-ElementsD3.20 advanced image processing software, analyzing the fluorescence intensity of blood vessel cholesterol at the tail of the zebra fish, and evaluating the cholesterol reducing effect of the sample according to the statistical analysis result of the index. Statistical treatment results are expressed in mean+ -SE. Statistical analysis was performed with SPSS26.0 software, p <0.05 indicated that the differences were statistically significant.
The results are shown in FIG. 1B: compared with a normal control group, the total cholesterol content of a model group is obviously increased, and after the treatment of the medicines pioglitazone hydrochloride, the WH 2270, the WH 2644, the WH 2276, the WH 3906 and the probiotic compound Pro group, the total cholesterol increase induced by high calorie diet can be obviously reduced, wherein the reduction effect of the probiotic compound Pro group is best, and the reduction amplitude is improved by 62% -150% compared with that of a single strain, so that the probiotic composition provided by the invention can generate obvious synergistic effect in the aspect of reducing the total cholesterol.
Example 3: evaluation of synergistic triglyceride lowering efficacy of probiotic compositions
Zebra fish of the melanin allele mutant Albino strain were used, and the zebra fish were kept in beakers, and 30 zebra fish were treated per cup (experimental group). The probiotics of the present invention and the positive samples were administered in water, respectively, wherein the probiotic samples included individual strains of 6 strains of bifidobacterium animalis WHH2276, lactobacillus fermentum WHH3906, lactobacillus fermentum 2644, bifidobacterium longum WHH2270, lactobacillus plantarum 1701 and lactobacillus rhamnosus 1155 ("WHH 2276", "WHH3906", "WHH2644", "WHH2270", "WHH1701", "wh 1155", respectively, in fig. 1) and probiotic compositions formulated in a viable count of 1:1:1:1:1:1:1 ("Pro" in fig. 1), positive controls ("Pioglitazone" in fig. 1) Pioglitazone hydrochloride of 20.0 μg/mL, while setting a normal Control group ("Control" in fig. 1) and a Model Control group ("Model" in fig. 1) at 25mL per cup. Except for the normal control group, the rest experimental groups were given high-fat feed (yolk powder) in water in the daytime (7.5 h daily) and high-sugar (glucose) in water in the evening (16.5 h daily) to establish a zebra fish high-sugar high-fat model. The probiotics (final concentration of single strain and probiotic composition is 10 8 CFU/mL) and high-fat feed were co-treated for 15h (7.5 h daily) and glucose for 33h (16.5 h daily), and the experimental design is shown in fig. 7.
Treatment was carried out at 28℃for 48h, and oil red O was given to carry out mass fat staining. After the dyeing is finished, 10 zebra fish are randomly selected from each experimental group, photographed under an dissecting microscope, analyzed and data are collected by Image-Pro Plus advanced Image processing software, the intestinal tract and tail blood vessel dyeing intensity of the zebra fish is analyzed, and the triglyceride reducing efficacy (intestinal tract and tail blood vessel) of the sample is evaluated by the statistical analysis result of the index. Statistical treatment results are expressed in mean+ -SE. Statistical analysis was performed with SPSS26.0 software, p <0.05 indicated that the differences were statistically significant.
The results are shown in FIG. 1C: compared with a control group, the content of triglyceride in the model group is obviously increased, and the triglyceride increase induced by high-calorie diet can be obviously reduced after the treatments of the medicaments pioglitazone hydrochloride, the WH 2644, the WH 2276, the WH 3906, the WH 1155 and the probiotic compound Pro, wherein the effect of reducing the probiotic compound Pro group is best, and the effect of reducing the probiotic compound Pro group is improved by 44-132% compared with that of a single strain, so that the probiotic composition provided by the invention can generate obvious synergistic effect in reducing the triglyceride.
Example 4: probiotic composition for improving rat metabolic syndrome efficacy
The invention adopts SD male rats (5 weeks old) and is fed into a clean environment with room temperature of 26+/-0.5 ℃ and humidity of 50-60% and day-night light-shade alternation time (12/12 h). During the feeding period, the mice can eat and drink water freely. The experiment was divided into 4 groups, namely, a Control group (Control in FIGS. 2 to 5), a Model group (Model in FIGS. 2 to 5), a positive drug group (Metformin in FIGS. 2 to 5), and Pro (probiotic composition composed of bifidobacterium animalis WHH2276, lactobacillus fermentum WHH3906, lactobacillus fermentum 2644, bifidobacterium longum WH 2270, lactobacillus plantarum 1701 and lactobacillus rhamnosus 1155 compounded in a viable count of 1:1:1:1:1:1). The control group is normally eaten, and 2mL of sterile physiological saline is infused every day; model group high fat diet, 2mL of sterile physiological saline is infused daily; positive drug group high fat diet, 2mL Metformin hydrochloride (metaformin) (150 mg/kg BW) was infused daily; pro group high fat diet, 2mL of probiotic solution (6×10) was infused daily 9 CFU/kg BW), 8 rats per group, 12 weeks for the trial, see fig. 8 for the experimental design.
Rats were recorded for weight change during the experiment, fasted overnight after 11 weeks, tail vein blood was taken, and fasting glycemia (FBG) and oral glucose tolerance (OGTT) were measured; fresh fecal tissue was taken for detection of short chain fatty acid content and for flora analysis. After 12 weeks, the blood was taken after the sacrifice and analyzed for Triglyceride (TG), total Cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) levels using an LW C400 autoanalyzer.
The change in rat body weight is shown in fig. 2: there was no difference in body weight between groups before the start of the experiment. With the extension of the experimental time, compared with a blank control group, the weight of the model group is obviously increased faster, and the probiotic compound Pro group can obviously inhibit the weight increase, and the effect is equivalent to that of a positive medicament. The test result shows that the probiotic composition provided by the invention can obviously improve obesity of rats with metabolic syndrome induced by high-fat diet.
The rat blood glucose levels are shown in figures 3A-C: compared with a blank control group, the fasting blood glucose and the oral glucose tolerance of a model group are obviously increased, and after the probiotic compound Pro is interfered, the fasting blood glucose and the oral glucose tolerance of rats can be obviously reduced, the reduction effect is equivalent to that of a positive medicament, and the blood glucose is reduced to the normal level of the control group. The test result shows that the probiotic composition provided by the invention can obviously improve the blood sugar and oral glucose tolerance increase of the high-fat diet-induced metabolic syndrome rats.
Rat blood lipid levels are shown in figures 3D-F: compared with the blank control group, the low density lipoprotein cholesterol (LDL-C), triglyceride (TG) and total blood cholesterol (TC) of the model group are all obviously increased, and after the probiotic compound Pro is interfered, the probiotic compound Pro can be obviously improved to be reduced to the normal level of the control group. The test result shows that the probiotic composition provided by the invention can obviously improve the dyslipidemia of the high-fat diet-induced metabolic syndrome rats.
The levels of short chain fatty acids in the rat intestinal tract are shown in fig. 4A (where "WHH2276", "WHH3906", "WHH2644", "WHH2270", "WHH1701", "WHH1155" are single strain treatments using 6 strains of bifidobacterium animalis WHH2276, lactobacillus mucilaginosus WHH3906, lactobacillus mucilaginosus 2644, bifidobacterium longum WHH2270, lactobacillus plantarum 1701 and lactobacillus rhamnosus 1155, respectively), and the amounts of probiotics and treatments were the same as those of Pro group except for the differences in the probiotic composition, and the acetic acid content in blood is shown in fig. 4B: compared with a blank control group, the content of SCFAs in the intestinal tract and blood of a rat in a model group is obviously reduced, the content of acetic acid and propionic acid in the intestinal tract can be obviously improved after the probiotic compound Pro intervenes, the content of acetic acid in the blood is obviously improved, the content of SCFAs after improvement reaches the normal level of a normal control group, and the effect of single strain treatment is poor (the content of SCFAs in the intestinal tract is not obviously improved). The test result shows that the probiotic composition provided by the invention can obviously improve the metabolic abnormality of short-chain fatty acid in the fermentation product of the intestinal flora of the rats with the metabolic syndrome induced by high-fat diet, and regulate the intestinal microenvironment and the content of the short-chain fatty acid in blood.
The expression of the genes associated with metabolic syndrome in the intestinal tract and liver of rats is shown in FIG. 5: compared with a control group, the expression of SHP, FXR, FGF and Abcg5 genes in the intestinal tract and FGFGR4 and SHP genes in the liver of a model group mouse are obviously reduced, and the expression of the genes can be obviously improved after the intervention of a probiotic compound Pro; the expression of CYP7A1 in the liver is obviously increased, and after the intervention of the probiotic compound Pro, the expression of CYP7A1 genes can be obviously reduced, and similar change trends are also observed for other genes except SHP in the intestinal tract in the positive medicament group. The test result shows that the probiotic composition provided by the invention can obviously improve the expression of related genes in the intestinal tract and liver of the rat with metabolic syndrome induced by high-fat diet.
Based on the above experimental results, the action mechanism of the probiotic composition provided by the invention for improving the metabolic syndrome is shown in fig. 6: probiotics regulate intestinal flora to synthesize short chain fatty acid, inhibit the expression of liver CYP7A1 by activating intestinal FXR-FGF15 signal pathway, and limit bile acid synthesis; simultaneously, the expression of a cholesterol transport related protein Abcg5 is regulated, the absorption of cholesterol is inhibited, and the discharge of cholesterol is promoted, so that the accumulation of lipid in the liver is reduced, and the metabolic syndrome is obviously improved.
In the present invention, unless otherwise indicated, scientific and technical terms used herein have the meanings commonly understood by one of ordinary skill in the art. In addition, the experimental methods used in the invention are all conventional methods unless specified otherwise; the reagents, biological materials and apparatus used, unless otherwise indicated, are all commercially available.
The foregoing description is only a preferred embodiment of the present invention, and is not intended to limit the present invention, and any simple modification, variation and equivalent transformation of the above embodiment according to the technical substance of the present invention still fall within the scope of the technical solution of the present invention.
Claims (10)
1. A probiotic composition having a function of improving metabolic syndrome, comprising bifidobacterium animalis WHH2276, lactobacillus fermentum WHH3906, lactobacillus fermentum 2644, bifidobacterium longum WHH2270, lactobacillus plantarum 1701 and lactobacillus rhamnosus 1155;
the bifidobacterium animalis WHH2276 has been deposited at the collection of microorganism strains of Guangdong province at 10 and 18 of 2022 under the accession number GDMCC No. 62901, and the microorganism classification is named as bifidobacterium animalisBifidobacterium animalis subsp. lactis；
The Lactobacillus fermentum WH3906 has been preserved in China general microbiological culture Collection center (CGMCC) with the preservation number of CGMCC No.19472 at 13/3/2020, and the microorganism classification is named Lactobacillus fermentumLimosilactobacillus fermentun；
The fermented lactobacillus mucilaginosus 2644 has been preserved in China general microbiological culture Collection center (CGMCC) with the preservation number of CGMCC No.16754 and the microorganism classification of the fermented lactobacillus mucilaginosus in 11 and 19 days of 2018Limosilactobacillus fermentun；
The Bifidobacterium longum WHH2270 has been deposited at the microorganism strain collection of Cantonese province at 10 and 18 of 2022 under the accession number GDMCC No. 62900, and the microorganism classification was designated as Bifidobacterium longumBifidobacterium longum subsp. longum；
The lactobacillus plantarum 1701 has been preserved in China with the protection of microorganism strain in the year 10, 23 of 2019The collection number is CGMCC No.18728, and the microorganism classification is named as Lactobacillus plantarumLactobacillus plantarum；
The lactobacillus rhamnosus 1155 has been preserved in China general microbiological culture Collection center (CGMCC) with a preservation number of CGMCC No.11955 in the year 1 and 4 of 2016, and the microorganism classification is named lactobacillus rhamnosusLactobacillus rhamnosus。
2. The probiotic composition according to claim 1, characterized in that the ratio of the viable count of bifidobacterium animalis WHH2276, lactobacillus fermentum WHH3906, lactobacillus fermentum 2644, bifidobacterium longum WHH2270, lactobacillus plantarum 1701 and lactobacillus rhamnosus 1155 is 1: (1-10): (1-10): (1-10): (1-10): (1-10).
3. Use of a probiotic composition according to claim 1 or 2 in a formulation with a function of improving the metabolic syndrome.
4. The use according to claim 3, wherein the agent having a metabolic syndrome-improving function is for reducing blood lipid or blood sugar, or for improving obesity, or for promoting the production of short chain fatty acids in the intestinal tract, or for regulating the expression of metabolic syndrome-related genes in the intestinal tract and liver, or for limiting the synthesis of bile acids.
5. The use according to claim 4, wherein regulating expression of genes associated with metabolic syndrome in the gut and liver comprises promoting expression of FXR, SHP and FGF15 genes in the gut, promoting expression of FGFR4, SHP and Abcg5 genes in the liver, and inhibiting expression of CYP7A1 gene in the liver.
6. Use of a probiotic composition according to claim 1 or 2 in a regulator of expression of genes associated with metabolic syndrome.
7. The use according to claim 6, wherein the metabolic syndrome related genes comprise FXR, SHP and FGF15 genes in the gut, and FGFR4, SHP, abcg5 and CYP7A1 genes in the liver.
8. Use of a probiotic composition according to claim 1 or 2 in a formulation having the function of promoting the production of short chain fatty acids in the intestinal tract.
9. Use of a probiotic composition according to claim 1 or 2 in a formulation having a function of limiting bile acid synthesis.
10. Use of a probiotic composition according to claim 1 or 2 in a formulation having a function of lowering blood sugar and blood lipid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311027414.9A CN117264810A (en) | 2023-08-16 | 2023-08-16 | Probiotic composition with metabolism syndrome improving function and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311027414.9A CN117264810A (en) | 2023-08-16 | 2023-08-16 | Probiotic composition with metabolism syndrome improving function and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117264810A true CN117264810A (en) | 2023-12-22 |
Family
ID=89207090
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311027414.9A Pending CN117264810A (en) | 2023-08-16 | 2023-08-16 | Probiotic composition with metabolism syndrome improving function and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117264810A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117899125A (en) * | 2024-01-19 | 2024-04-19 | 吉林省农业科学院(中国农业科技东北创新中心) | A preparation for preventing and/or treating hyperglycemia |
-
2023
- 2023-08-16 CN CN202311027414.9A patent/CN117264810A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117899125A (en) * | 2024-01-19 | 2024-04-19 | 吉林省农业科学院(中国农业科技东北创新中心) | A preparation for preventing and/or treating hyperglycemia |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE60125529T2 (en) | MICRO-ORGANISMS FOR THE TREATMENT OR PREVENTION OF FATIBILITY AND DIABETES MELLITUS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM | |
| CN113293113B (en) | Bifidobacterium longum MI-186 and application thereof | |
| CN110150669B (en) | Probiotic composition suitable for diabetic patients and application thereof | |
| US11273189B2 (en) | Lactobacillus plantarum TCI378 and its uses in losing fat and improving gastrointestinal functions | |
| CN113308421B (en) | Lactobacillus plantarum BUFX and application thereof in metabolic syndrome | |
| CN113444668B (en) | Bacillus coagulans with blood sugar reducing effect and application thereof | |
| AU2020444464B2 (en) | Novel Faecalibacterium prausnitzii strain EB-FPDK11 and use thereof | |
| CN116555076B (en) | Bifidobacterium longum subspecies longum MY1 and application thereof in preparation of food and medicine for relaxing bowels and protecting intestines | |
| CN116115647A (en) | Application of akkermansia muciniphila in preparation of pharmaceutical composition or health-care product composition for improving metabolic syndrome | |
| CN117264810A (en) | Probiotic composition with metabolism syndrome improving function and application thereof | |
| JP6793380B2 (en) | Evaluation method, screening method and manufacturing method of substances that suppress the rise in blood glucose level due to sucrose intake | |
| CN113197921A (en) | Application of bifidobacterium lactis MN-Gup and microbial inoculum thereof in treating type 2 diabetes | |
| CN116410887A (en) | Microorganism strain of chaetoviridae, medicament for preventing or treating metabolic diseases and application thereof | |
| CN106389478B (en) | Application of bacteroides fragilis in treatment and/or prevention of obesity or diabetes | |
| CN113337440B (en) | Lactobacillus salivarius MG-587 and application thereof | |
| CN109045070A (en) | A kind of composition for preventing and treating non-alcoholic fatty liver disease | |
| CN111603489A (en) | Microbial inoculum for improving constipation and preparation method thereof | |
| CN118384186A (en) | AKKERMANSIA MUCINIPHILA and its use in anti-infective | |
| CN109965290B (en) | Meal replacement powder for improving intestinal flora and application thereof | |
| CN115337327B (en) | Preparation method and application of probiotic preparation with lipid-lowering, anti-inflammatory and antioxidant functions | |
| CN115044507B (en) | Microbial composition for treating and/or preventing abnormal glycolipid metabolism and application thereof | |
| CN116211956A (en) | Composition for regulating intestinal tract and/or improving obesity, preparation method, chewable tablet and application thereof | |
| CN105343132B (en) | Composition, the drug and preparation method thereof for treating colitis | |
| CN113215020B (en) | Roseburia MGB-2 and application thereof | |
| CN117965391B (en) | Acremonium muciniphilum Amuci-1 and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |