CN116836880B - 一种普氏梭杆菌及其应用 - Google Patents
一种普氏梭杆菌及其应用 Download PDFInfo
- Publication number
- CN116836880B CN116836880B CN202310906490.0A CN202310906490A CN116836880B CN 116836880 B CN116836880 B CN 116836880B CN 202310906490 A CN202310906490 A CN 202310906490A CN 116836880 B CN116836880 B CN 116836880B
- Authority
- CN
- China
- Prior art keywords
- mice
- strain
- praecox
- composition
- fusobacterium
- 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.)
- Active
Links
- 241000605909 Fusobacterium Species 0.000 title claims abstract description 14
- 239000000203 mixture Substances 0.000 claims abstract description 35
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 33
- 241000894006 Bacteria Species 0.000 claims description 49
- 238000009472 formulation Methods 0.000 claims description 7
- 239000000243 solution Substances 0.000 claims description 7
- 230000002265 prevention Effects 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 4
- 235000009508 confectionery Nutrition 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 2
- 238000001802 infusion Methods 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 239000008176 lyophilized powder Substances 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 230000000055 hyoplipidemic effect Effects 0.000 claims 1
- 210000004369 blood Anatomy 0.000 abstract description 16
- 239000008280 blood Substances 0.000 abstract description 16
- 150000002632 lipids Chemical class 0.000 abstract description 16
- 241001465754 Metazoa Species 0.000 abstract description 10
- 230000000694 effects Effects 0.000 abstract description 10
- 241000193403 Clostridium Species 0.000 abstract description 6
- 230000015572 biosynthetic process Effects 0.000 abstract description 6
- 230000004060 metabolic process Effects 0.000 abstract description 6
- 230000003907 kidney function Effects 0.000 abstract description 5
- 206010061218 Inflammation Diseases 0.000 abstract description 4
- 239000001963 growth medium Substances 0.000 abstract description 4
- 230000004054 inflammatory process Effects 0.000 abstract description 4
- 230000003908 liver function Effects 0.000 abstract description 4
- 238000002474 experimental method Methods 0.000 abstract description 3
- 230000006378 damage Effects 0.000 abstract description 2
- 230000000813 microbial effect Effects 0.000 abstract description 2
- 241000699670 Mus sp. Species 0.000 description 53
- 239000002207 metabolite Substances 0.000 description 17
- 230000002829 reductive effect Effects 0.000 description 16
- 108010028554 LDL Cholesterol Proteins 0.000 description 9
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 210000003291 sinus of valsalva Anatomy 0.000 description 8
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 7
- 235000013305 food Nutrition 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 230000001580 bacterial effect Effects 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 208000024172 Cardiovascular disease Diseases 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 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 4
- 210000004185 liver Anatomy 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 3
- 108010082126 Alanine transaminase Proteins 0.000 description 3
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 3
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 3
- 108010023302 HDL Cholesterol Proteins 0.000 description 3
- KXGVEGMKQFWNSR-WFTUMUMQSA-N allodeoxycholic acid Chemical compound C([C@@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-WFTUMUMQSA-N 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 239000000419 plant extract Substances 0.000 description 3
- 239000006041 probiotic Substances 0.000 description 3
- 235000018291 probiotics Nutrition 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 3
- 101150037123 APOE gene Proteins 0.000 description 2
- 102000013918 Apolipoproteins E Human genes 0.000 description 2
- 108010025628 Apolipoproteins E Proteins 0.000 description 2
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 2
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 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 2
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- 208000032382 Ischaemic stroke Diseases 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- 108010007622 LDL Lipoproteins Proteins 0.000 description 2
- 102000007330 LDL Lipoproteins Human genes 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- 206010067125 Liver injury Diseases 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- 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 2
- 229930003451 Vitamin B1 Natural products 0.000 description 2
- 210000000577 adipose tissue Anatomy 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 210000000709 aorta Anatomy 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 235000013325 dietary fiber Nutrition 0.000 description 2
- 201000010063 epididymitis Diseases 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- -1 fat) Chemical class 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 230000004153 glucose metabolism Effects 0.000 description 2
- 239000002955 immunomodulating agent Substances 0.000 description 2
- 229940121354 immunomodulator Drugs 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 235000013384 milk substitute Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 230000007505 plaque formation Effects 0.000 description 2
- 235000013406 prebiotics Nutrition 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 229960003495 thiamine Drugs 0.000 description 2
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- 239000011691 vitamin B1 Substances 0.000 description 2
- 235000010374 vitamin B1 Nutrition 0.000 description 2
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 1
- KXGVEGMKQFWNSR-OFYXWCICSA-N 3beta,12alpha-dihydroxy-5beta-cholan-24-oic acid Chemical compound C([C@H]1CC2)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-OFYXWCICSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 108010062877 Bacteriocins Proteins 0.000 description 1
- 101100216294 Danio rerio apoeb gene Proteins 0.000 description 1
- 241001134569 Flavonifractor plautii Species 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 241000581650 Ivesia Species 0.000 description 1
- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 1
- 206010000059 abdominal discomfort Diseases 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003674 animal food additive Substances 0.000 description 1
- 230000000879 anti-atherosclerotic effect Effects 0.000 description 1
- 239000003524 antilipemic agent Substances 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 235000020934 caloric restriction Nutrition 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 235000015140 cultured milk Nutrition 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 230000002550 fecal effect Effects 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000003209 gene knockout Methods 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000005976 liver dysfunction Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 230000000291 postprandial effect Effects 0.000 description 1
- 230000000529 probiotic effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 235000013618 yogurt Nutrition 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
- C12N1/205—Bacterial isolates
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K10/00—Animal feeding-stuffs
- A23K10/10—Animal feeding-stuffs obtained by microbiological or biochemical processes
- A23K10/16—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions
- A23K10/18—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions of live microorganisms
-
- 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
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Organic Chemistry (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Biochemistry (AREA)
- Polymers & Plastics (AREA)
- Biomedical Technology (AREA)
- Veterinary Medicine (AREA)
- Mycology (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Virology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Nutrition Science (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Physiology (AREA)
- Animal Husbandry (AREA)
Abstract
本申请属于微生物治疗的技术领域,尤其涉及一种普氏梭杆菌及其应用。本申请第一方面提供了普氏梭杆菌Flavonifractor plautii Xia‑2菌株,其保藏编号为GDMCC No:62984。实验证明,所述普氏梭杆菌菌株及其衍生物、培养基或组合物具有预防、改善或治疗动脉粥样硬化的作用。本申请公开的菌株能有效降低血脂水平,抑制动脉粥样硬化斑块形成,降低斑块局部炎症水平,且对动物的体重和糖代谢无显著影响,同时不会对动物的肝功能和肾功能造成损伤,具有较好的安全性。
Description
技术领域
本申请属于微生物治疗的技术领域,尤其涉及一种普氏梭杆菌及其应用。
背景技术
在不同类型的心血管病中,动脉粥样硬化性心血管病(主要包括冠心病和缺血性卒中)的疾病负担在我国人群中快速增长,已占心血管病死亡的60%以上。因此,控制心血管病,尤其是动脉粥样硬化性心血管病负担的增长是一项严峻挑战。
动脉粥样硬化(atherosclerosis,AS)是指中等动脉或大动脉的动脉壁形成脂质斑片状沉积物(粥样斑或粥样硬化斑块),导致血流量减少或阻塞血液流出的一种疾病,也是诱发冠心病和缺血性卒中的共同病理基础。糖脂代谢紊乱是促进AS进展的关键环节,其中血脂中的低密度脂蛋白胆固醇(LDL-C)是粥样脂质斑块的主要组成成分,血液中LDL-C含量升高是动脉粥样硬化最明确的危险因素和目前临床最关键的治疗靶标之一。
目前AS的防治主要包括药物干预和生活方式调节。生活方式干预的依从性往往不好,如长期热量限制、规律运动或少盐少油饮食等,患者通常无法适应生活方式的巨大改变,从而中断治疗的过程。长期药物治疗可能造成不良反应,如他汀类药物不耐受引起肝功能异常、血糖升高或胃肠道不适等症状,部分具有禁忌症的患者需要更换治疗方法。即使遵循药物治疗,部分患者的血脂水平仍无法降低到预期目标值,依然存在较大的残留风险。因此,急需寻找依从性好、防治效果明显的早期干预措施。
发明内容
鉴于此,本申请公开了一种普氏梭杆菌及其应用,该普氏梭杆菌能有效降低血脂水平,抑制动脉粥样硬化斑块形成,同时具有较好的安全性。
本申请第一方面提供了普氏梭杆菌Flavonifractor plautii Xia-2菌株,其保藏编号为GDMCC No: 62984。
需要说明的是,所述普氏梭杆菌菌株保藏在广东省微生物菌种保藏中心,命名为Flavonifractor plautiiXia-2。
具体的,所述普氏梭杆菌菌株可采用GAM培养基或常见的GAM改良培养基进行培养。
本申请第二方面提供了所述菌株的衍生物。
作为优选,所述衍生物为活细菌、死细菌、细菌细胞成分、培养物、裂解物、提取物、灭活产物或其组合。
本申请第三方面提供了一种培养基,包含所述的菌株或所述的衍生物。
具体的,所述培养物包括Flavonifractor plautiiXia-2及其后代的无细胞培养滤液。
本申请第四方面提供了一种组合物,包括所述的菌株、所述的衍生物或所述的培养基。
具体的,所述组合物为用于预防、改善或治疗动脉粥样硬化的组合物或制剂。
作为优选,所述组合物为食品组合物、膳食补充组合物、营养组合物、保健食品组合物、药物组合物、特殊医学用途食品组合物、化妆品组合物或饲料组合物。
具体的,所述食品组合物可以为固体饮料、糖果或果汁、乳制品(如酸奶,风味发酵乳,乳酸菌饮料,奶酪)。
作为优选,所述组合物以丸剂、片剂、冻干粉剂、颗粒剂、胶囊剂、水溶液、醇溶液、油溶液、糖浆剂、乳液、悬浮液、栓剂、注射或输注用溶液、凝胶糖果的形式存在。
作为优选,所述组合物还包括益生菌、后生元、益生元、抗菌剂、免疫调节剂、矿物质、维生素、膳食纤维、蛋白质、碳水化合物、脂类物质、植物提取物、氨基酸和乳汁替代物中的一种或多种。
具体的,所述组合物为用于口服或注射用的固体物、半固体物或液体物。
作为优选,所述组合物还包括药学上可接受的辅料、食品上可接受的辅料和代谢产物中的一种或多种。
更优选的,所述药学上可接受的辅料选自赋形剂、崩解剂、润滑剂、甜味剂和粘合剂中的一种或多种;
所述代谢产物为所述肠道菌株代谢产生的酶、细胞结构成分、胞外多糖和细菌素中的一种或多种。
更优选的,所述食品上可接受的辅料选自矿物质、维生素、膳食纤维、益生元、蛋白质(例如酶)、碳水化合物、脂类物质(例如脂肪)、植物提取物(例如植物提取物)、氨基酸、免疫调节剂和乳汁替代物中的一种或多种。
具体的,所述药学上可接受的辅料和所述食品上可接受的辅料均为现有常规的成分,本申请不作具体赘述。
作为优选,所述普氏梭杆菌以106至1012cfu/天的量的存在。
具体的,所述普氏梭杆菌以5×108cfu/天的量的存在。
本申请第五方面公开了所述的菌株、所述的衍生物、所述的培养基或所述的组合物在制备用于预防、改善或治疗动脉粥样硬化制剂中的用途。
具体的,所述制剂可以为药物制剂、益生菌制剂或食品和/或饲料添加剂制剂。
本申请第六方面公开了所述的菌株、所述的衍生物、所述的培养基或所述的组合物在制备降低血脂制剂中的用途。
本申请针对目前缺少依从性好、防治效果佳的动脉粥样硬化早期干预措施的缺陷,提供了一种新型的普氏梭杆菌Flavonifractor plautii Xia-2,其保藏编号为GDMCCNo: 62984。实验数据可知,该普氏梭杆菌及其衍生物、培养基和组合物具有抑制动脉粥样硬化进展的作用,能有效降低血脂水平,抑制动脉粥样硬化斑块形成,同时具有较好的安全性。
附图说明
为了更清楚地说明本申请实施例或现有技术中的技术方案,下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍。
图1示本申请实施例提供的动物实验的示意图;
图2示本申请实施例提供了普氏梭杆菌Flavonifractor plautiiXia-2的定值情况;
图3示本申请实施例提供了普氏梭杆菌Flavonifractor plautiiXia-2抑制小鼠动脉粥样硬化斑块形成的结果;
图4示本申请实施例提供了普氏梭杆菌Flavonifractor plautiiXia-2降低小鼠斑块内炎症水平的结果;
图5示本申请实施例提供了普氏梭杆菌Flavonifractor plautiiXia-2干预小鼠后对小鼠体重和糖代谢影响;
图6示本申请实施例提供了普氏梭杆菌Flavonifractor plautiiXia-2干预小鼠后对小鼠血脂的影响;
图7示本申请实施例提供了普氏梭杆菌Flavonifractor plautiiXia-2干预小鼠后对小鼠肝肾的影响;
图8示本申请实施例提供了普氏梭杆菌Flavonifractor plautiiXia-2灭活菌干预小鼠后对小鼠主动脉和主动脉窦的影响;
图9示本申请实施例提供了普氏梭杆菌Flavonifractor plautiiXia-2的关键代谢产物(别脱氧胆酸)干预小鼠后对小鼠主动脉和主动脉窦的影响。
具体实施方式
本申请提供了及一种普氏梭杆菌及其应用,有效解决现有技术中缺少依从性好、防治效果佳的动脉粥样硬化早期干预措施的技术缺陷。
下面将对本申请实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例仅仅是本申请一部分实施例,而不是全部的实施例。基于本申请中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本申请保护的范围。
其中,以下实施例的动物造模(AS模型小鼠):
Apoe-/-高脂高胆固醇饲料喂养模型: ApoE基因敲除小鼠因ApoE失效使得LDL、VLDL/IDL等不能与相关受体识别结合,以致这些脂蛋白清除延缓而出现高脂血症。血脂过高诱发脂蛋白的氧化修饰,促使AS病变形成。普通饲料和高脂高胆固醇饲料均可进行造模,造模时间约为8-12周。
以下实施例所用的普氏梭杆菌(Flavonifractor plautiiXia-2,以下简称FP菌)是申请人团队从健康人群中分离鉴定出的菌株,经鉴定后,归属于Flavonifractor plautii。其活性和基因序列通过了广东省微生物保藏中心的鉴定,并获得了保藏号(GDMCCNo: 62984)。
具体的,普氏梭杆菌Flavonifractor plautiiXia-2保藏信息如下:
保藏中心:广东省微生物菌种保藏中心(GDMCC);
保藏中心地址:广东省广州市先烈中路100号大院59号楼5楼;
保藏号:GDMCC No: 62984;
保藏单位:中山大学;
保藏单位地址:广东省广州市越秀区中山二路74号中山大学北校区公卫楼;
分类学名称:Flavonifractor plautii ;
保藏时间:2022年11月17日;
菌种存活检测时间:2022年11月17日,检测结果为存活。以下实施例的HFHC为高脂高胆固醇饲料。
以下实施例的FP活菌菌液:采用海博生物的GAM改良培养基进行厌氧培养,将培养获得的菌体以每5×108菌落总数/天的剂量重悬于终浓度为10%甘油的无菌PBS(添加半胱氨酸和维生素B1)维持厌氧环境。
以下实施例的FP灭活菌菌液:按上述方式获得的活菌,在121℃条件下高压灭菌15分钟,获得灭活菌株后以每5×108菌落总数/天的剂量重悬于终浓度为10%甘油的无菌PBS(添加半胱氨酸和维生素B1)重悬。
以下实施例的FP关键代谢产物为别脱氧胆酸(Isodeoxycholic acid),通过宏基因组与靶向代谢组联合分析发现别脱氧胆酸是FP菌发挥AS保护作用的关键代谢产物。
上述FP活菌,FP灭活菌和FP活性代谢产物用于干预AS模型小鼠,干预周期均为12周。
实施例1
本申请实施例提供了动物实验,以验证普氏梭杆菌Flavonifractor plautiiXia-2的预防、改善或治疗动脉粥样硬化作用,具体包括:
1、动物的分组与干预设计
研究方案如图1所示,使用8周龄的雄性SPF级ApoE-/-小鼠32只,随机分为4组,每组8只,分别为动脉粥样硬化模型组(HFHC+无菌PBS,记为PBS);FP活菌干预组(HFHC+FP活菌菌液,记为FP);FP灭活菌干预组(HFHC+FP灭活菌菌液,记为灭活FP)和FP关键代谢产物组(HFHC+别脱氧胆酸,记为FP代谢物)。四组均采用高脂高胆固醇饲料HFHC喂养12周建立动脉粥样硬化模型,高脂高胆固醇饲料HFHC的配方为39.9%脂肪、40%碳水化合物、20%蛋白质,添加1.25%胆固醇。HFHC+PBS组每天灌胃无菌PBS溶液,灌胃体积为200μL;FP活菌组小鼠每天灌胃5×108CFU的普氏梭杆菌FP,灌胃体积为200μL;FP灭活干预组小鼠每天灌胃5×108CFU的灭活菌液,灌胃体积为200μL;FP活性代谢物组小鼠每天灌胃200μL别脱氧胆酸。小鼠连续干预12周,动物房室内温度为(22±2)℃,湿度为(45±15)%,采用12小时昼夜轮替(光照时间为早上8点至晚上8点),自由饮食,垫料保持干燥每隔3-4天更换一次。
2、菌定植情况
提取上一步骤两组小鼠的粪便DNA,用荧光定量PCR检测FP的含量。结果如图2所示,图2的PBS为PBS组,FP为FP活菌干预组,FP活菌干预组小鼠粪便中的FP菌含量显著升高,表明FP活菌在小鼠肠道内定植成功,具有成为新型益生菌的潜质。
3、FP活菌抑制小鼠动脉粥样硬化斑块形成
测定两组小鼠主动脉和主动脉窦进行油红O染色,结果如图3A和3B,图3的PBS为PBS组,FP为FP活菌干预组,FP活菌干预组小鼠主动脉大体标本阳性面积减少36.7%(图3A),主动脉窦斑块面积减小27.4%(图3B),差异具有统计学意义,说明FP活菌干预有利于降低小鼠动脉粥样硬化斑块面积。
4、FP活菌降低小鼠动脉粥样硬化斑块内炎症水平
测定两组小鼠AS斑块内促炎因子MCP-1表达情况和巨噬细胞浸润浸润情况,结果如图4,图4的PBS为PBS组,FP为FP活菌干预组,说明:FP活菌干预能显著降低小鼠AS斑块内促炎因子MCP-1表达(图4A)和巨噬细胞浸润浸润(图4B),从而降低小鼠斑块局部炎症水平。以上结果表明FP活菌干预可有效延缓AS进展,降低AS严重程度。
5、FP活菌干预小鼠后,测定FP活菌对小鼠体重和糖代谢的影响
FP菌干预结束后取小鼠尾静脉血液测量小鼠血糖,评估小鼠糖代谢情况。小鼠处死前,称量体重并检测体成分,处死后收集附睾脂肪组织用于评估小鼠的肥胖情况。如图5A-C所示,图5的PBS为PBS组,FP为FP活菌干预组,FP菌干预组小鼠的体重、体脂率和附睾脂肪含量有所下降。小鼠糖代谢情况如图5D-E所示,FP菌干预组小鼠的餐后血糖和空腹血糖略有下降,小鼠体重和糖代谢没有显著改善。结果表明FP菌对小鼠的肥胖和糖代谢的作用并不显著。
6、FP活菌干预小鼠后,测定FP活菌对小鼠血脂的影响
采用商品化试剂盒检测PBS组小鼠和FP组小鼠的血清中甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-c)和低密度脂蛋白胆固醇(LDL-c)的含量,用于评估小鼠脂代谢情况。结果如图6A-D所示,图6的PBS为PBS组,FP为FP活菌干预组,FP活菌干预组小鼠血清中的LDL-c含量显著降低,血清TC和TG含量略有下降,HDL-c含量升高,表明FP活菌干预后显著降低小鼠血脂水平,FP活菌是通过调节LDL-c水平发挥其抗动脉粥样硬化的效应。
7、FP活菌干预小鼠后,测定FP活菌对小鼠肝肾的影响
通过体重变化情况、肝肾功能是否发生损伤这三个方面来衡量FP菌的安全性。采用试剂盒检测PBS组小鼠和FP组小鼠血清中的肌酐(Scr)、尿素氮(BUN)、丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)含量。结果如图7所示,图7的PBS为PBS组,FP为FP活菌干预组,FP活菌干预组和PBS对照组小鼠的体重,以及血清中的肾功能相关指标如Scr、BUN,以及肝脏损伤相关指标如ALT和AST含量均无显著差异,且均在正常值范围内。表明FP活菌的干预对小鼠的肝功能和肾功能不会造成损伤,在有效抗动脉粥样硬化作用的同时仍具有一定的安全性,FP活菌干预具有良好的肝肾安全性。
8、FP灭活菌干预小鼠后动脉粥样硬化斑块面积减小,血脂水平降低
对两组小鼠主动脉和主动脉窦进行油红O染色,结果如图8A和8B,图8的PBS为PBS组,灭活FP为FP灭活菌干预组,FP灭活菌干预组小鼠主动脉大体标本阳性面积减少35%(图8A),主动脉窦斑块面积减小25%(图8B),差异具有统计学意义,说明FP灭活菌干预也能够有效降低小鼠动脉粥样硬化斑块面积。此外,FP灭活菌干预后,小鼠LDL-c水平显著降低,其他脂质水平没有显著改变,说明FP灭活菌具有降低低密度脂蛋白的作用(图8C)。
9、FP关键代谢产物(别脱氧胆酸)干预小鼠后动脉粥样硬化斑块面积减小,血脂水平降低
对两组小鼠主动脉和主动脉窦进行油红O染色,结果如图9A和9B,图9的PBS为PBS组,FP代谢产物为FP关键代谢产物组,FP关键代谢产物(别脱氧胆酸)干预小鼠主动脉大体标本阳性面积减少42%(图9A),主动脉窦斑块面积减小30%(图9B),差异具有统计学意义,说明FP关键代谢产物(别脱氧胆酸)干预也能够有效降低小鼠动脉粥样硬化斑块面积。此外,FP活性代谢产物(别脱氧胆酸)干预后,小鼠LDL-c水平显著降低,其他脂质水平没有显著改变,说明FP关键代谢产物(别脱氧胆酸)具有降低低密度脂蛋白的作用(图9C)。
综上所述,本申请发现Flavonifractor plautiiXia-2菌株活菌、灭活菌群及其关键代谢产物均能有效降低血脂水平,抑制动脉粥样硬化斑块形成,降低斑块局部炎症水平,且对动物的体重和糖代谢无显著影响,同时不会对动物的肝功能和肾功能造成损伤,具有较好的安全性。
以上所述仅是本申请的优选实施方式,应当指出,对于本技术领域的普通技术人员来说,在不脱离本申请原理的前提下,还可以做出若干改进和润饰,这些改进和润饰也应视为本申请的保护范围。
Claims (7)
1.一种普氏梭杆菌(Flavonifractor plautii)Xia-2菌株,
其保藏编号为GDMCC No: 62984。
2.一种如权利要求1所述菌株的衍生物;所述衍生物为活细菌、死细菌或其组合。
3.一种组合物,其特征在于,包括如权利要求1所述的菌株或如权利要求2所述的衍生物。
4.根据权利要求3所述的组合物,其特征在于,所述组合物为药物组合物。
5.根据权利要求3所述的组合物,其特征在于,所述组合物以丸剂、片剂、冻干粉剂、胶囊剂、注射或输注用溶液、凝胶糖果的形式存在。
6.权利要求1所述的菌株、权利要求2所述的衍生物或权利要求3-5中任一项所述的组合物在制备用于预防、改善或治疗动脉粥样硬化制剂中的用途。
7.权利要求1所述的菌株、权利要求2所述的衍生物或权利要求3-5中任一项所述的组合物在制备降低血脂制剂中的用途。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310906490.0A CN116836880B (zh) | 2023-07-24 | 2023-07-24 | 一种普氏梭杆菌及其应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310906490.0A CN116836880B (zh) | 2023-07-24 | 2023-07-24 | 一种普氏梭杆菌及其应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN116836880A CN116836880A (zh) | 2023-10-03 |
CN116836880B true CN116836880B (zh) | 2023-11-28 |
Family
ID=88163402
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202310906490.0A Active CN116836880B (zh) | 2023-07-24 | 2023-07-24 | 一种普氏梭杆菌及其应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN116836880B (zh) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107949391A (zh) * | 2015-05-14 | 2018-04-20 | 克雷斯顿沃控股公司 | 用于粪便菌群移植的组合物以及用于制备和使用它们的方法和用于递送它们的装置 |
CN108712906A (zh) * | 2016-02-04 | 2018-10-26 | 根特大学 | 微生物群落用于人类和动物健康的用途 |
CN116004481A (zh) * | 2023-02-27 | 2023-04-25 | 中山大学 | 一种肠道菌株及其应用 |
-
2023
- 2023-07-24 CN CN202310906490.0A patent/CN116836880B/zh active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107949391A (zh) * | 2015-05-14 | 2018-04-20 | 克雷斯顿沃控股公司 | 用于粪便菌群移植的组合物以及用于制备和使用它们的方法和用于递送它们的装置 |
CN108712906A (zh) * | 2016-02-04 | 2018-10-26 | 根特大学 | 微生物群落用于人类和动物健康的用途 |
CN116004481A (zh) * | 2023-02-27 | 2023-04-25 | 中山大学 | 一种肠道菌株及其应用 |
Non-Patent Citations (1)
Title |
---|
Flavonifractor plautii Protects Against Elevated Arterial Stiffness;Shiyun Luo等;《Circulation Research》;第132卷(第2期);摘要,图1 * |
Also Published As
Publication number | Publication date |
---|---|
CN116836880A (zh) | 2023-10-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6954563B2 (ja) | 代謝障害を処置するための低温殺菌アッカーマンシアの使用 | |
JP6608047B2 (ja) | 多様な機能性を有する新規乳酸菌およびその用途 | |
Delgado et al. | The putative effects of prebiotics as immunomodulatory agents | |
CN114317353B (zh) | 一种植物乳杆菌zjufyj7及其应用 | |
JP6630388B2 (ja) | ラクトバチルスプランタルムtci378、およびそれを用いた脂肪の減少および胃腸機能の改善における使用 | |
JP6684966B2 (ja) | 新規なラクトバチルス・サケイ及びそれを含む組成物 | |
TW200944215A (en) | Lactobacillus isolates having anti-inflammatory activities and uses of the same | |
BR112012008005B1 (pt) | composição compreendendo cepas de lactobacillus plantarum | |
US11147843B2 (en) | Method of preventing or treating obesity using a novel strain of Parabacteroides goldsteinii | |
CN109481510A (zh) | 一种有助于改善2型糖尿病及其并发症的合生元复方制剂及其制备方法 | |
WO2001085186A1 (fr) | Composition nutritive renfermant une culture-fermentation de bacteries benefiques mortes | |
CN109593678B (zh) | 长双歧杆菌yh295及其在制备降低腹型肥胖风险产品中的应用 | |
CN113322216B (zh) | 一种副干酪乳杆菌b111h及其在代谢综合征中的应用 | |
KR102397916B1 (ko) | 건강한 임산부 모유 유래 혐기성 인체 균주 및 이를 이용한 대사성 질환의 예방 또는 치료방법 | |
CN116286551B (zh) | 长双歧杆菌婴儿亚种在调节体内脂肪代谢、塑形减脂改善肥胖方面的应用 | |
CN115089619A (zh) | 植物乳杆菌zdy2013在具有缓解非酒精性脂肪肝功能的制剂中的应用 | |
TW201705969A (zh) | 新穎馬利乳酸桿菌aps1及其用途 | |
CN105853467B (zh) | 罗伊氏乳杆菌gmnl-263用于制备降血脂组合物的用途 | |
JP2013147457A (ja) | メタボリックシンドローム予防改善剤 | |
JP2020533008A (ja) | Megamonas funiformis及びその適用 | |
CN103228143A (zh) | 用于增强肾功能的组合物和方法 | |
CN113812634A (zh) | 一种合生元组合物及其制备方法与应用 | |
WO2023237067A1 (zh) | 嗜粘蛋白阿克曼菌在制备改善代谢综合征的药物组合物或保健品组合物中的应用 | |
KR101238836B1 (ko) | 혼합 유산균을 포함하는 비만 또는 비만 관련 질환 치료 또는 예방용 약제학적 조성물 또는 식품 조성물 | |
CN116004481B (zh) | 一种肠道菌株及其应用 |
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 | ||
GR01 | Patent grant | ||
GR01 | Patent grant |