CN114410531A - 降低血浆tmao及缓解、预防动脉粥样硬化的长双歧杆菌ccfm1216及其应用 - Google Patents
降低血浆tmao及缓解、预防动脉粥样硬化的长双歧杆菌ccfm1216及其应用 Download PDFInfo
- Publication number
- CN114410531A CN114410531A CN202210097915.3A CN202210097915A CN114410531A CN 114410531 A CN114410531 A CN 114410531A CN 202210097915 A CN202210097915 A CN 202210097915A CN 114410531 A CN114410531 A CN 114410531A
- Authority
- CN
- China
- Prior art keywords
- bifidobacterium longum
- ccfm1216
- reducing
- mice
- choline
- 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.)
- Granted
Links
- 241001608472 Bifidobacterium longum Species 0.000 title claims abstract description 63
- 229940009291 bifidobacterium longum Drugs 0.000 title claims abstract description 63
- UYPYRKYUKCHHIB-UHFFFAOYSA-N trimethylamine N-oxide Chemical compound C[N+](C)(C)[O-] UYPYRKYUKCHHIB-UHFFFAOYSA-N 0.000 title claims abstract description 26
- 201000001320 Atherosclerosis Diseases 0.000 title claims abstract description 14
- 210000002381 plasma Anatomy 0.000 title abstract description 26
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims abstract description 30
- 229960001231 choline Drugs 0.000 claims abstract description 29
- 241000894006 Bacteria Species 0.000 claims abstract description 20
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 17
- 230000000968 intestinal effect Effects 0.000 claims abstract description 17
- 208000008589 Obesity Diseases 0.000 claims abstract description 11
- 235000020824 obesity Nutrition 0.000 claims abstract description 11
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims abstract description 10
- 206010020772 Hypertension Diseases 0.000 claims abstract description 9
- 208000031226 Hyperlipidaemia Diseases 0.000 claims abstract description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 7
- 235000021107 fermented food Nutrition 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 9
- 230000000813 microbial effect Effects 0.000 claims description 7
- 239000006041 probiotic Substances 0.000 claims description 7
- 235000018291 probiotics Nutrition 0.000 claims description 7
- 235000012055 fruits and vegetables Nutrition 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 235000013365 dairy product Nutrition 0.000 claims description 5
- 238000004321 preservation Methods 0.000 claims description 5
- 230000000529 probiotic effect Effects 0.000 claims description 5
- 238000011160 research Methods 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 206010020751 Hypersensitivity Diseases 0.000 claims description 3
- 208000026935 allergic disease Diseases 0.000 claims description 3
- 230000007815 allergy Effects 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 208000012902 Nervous system disease Diseases 0.000 claims description 2
- 208000025966 Neurological disease Diseases 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims description 2
- 238000001727 in vivo Methods 0.000 claims description 2
- 230000001737 promoting effect Effects 0.000 claims description 2
- 208000024891 symptom Diseases 0.000 claims description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 2
- 208000002551 irritable bowel syndrome Diseases 0.000 claims 1
- 210000004534 cecum Anatomy 0.000 abstract description 15
- 241000252983 Caecum Species 0.000 abstract description 10
- 238000000034 method Methods 0.000 abstract description 9
- 241000204018 Anaeroplasma Species 0.000 abstract description 8
- 241001495171 Bilophila Species 0.000 abstract description 8
- 244000005700 microbiome Species 0.000 abstract description 5
- 241000699670 Mus sp. Species 0.000 description 32
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 30
- 239000000047 product Substances 0.000 description 13
- 239000007788 liquid Substances 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 11
- 239000001963 growth medium Substances 0.000 description 11
- 239000006228 supernatant Substances 0.000 description 11
- 239000000243 solution Substances 0.000 description 8
- 238000012258 culturing Methods 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 230000001580 bacterial effect Effects 0.000 description 6
- 239000012530 fluid Substances 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 238000012163 sequencing technique Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 230000002496 gastric effect Effects 0.000 description 4
- 238000003304 gavage Methods 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- 238000005070 sampling Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 108020004465 16S ribosomal RNA Proteins 0.000 description 3
- 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 2
- 240000007087 Apium graveolens Species 0.000 description 2
- 235000015849 Apium graveolens Dulce Group Nutrition 0.000 description 2
- 235000010591 Appio Nutrition 0.000 description 2
- 235000016068 Berberis vulgaris Nutrition 0.000 description 2
- 241000335053 Beta vulgaris Species 0.000 description 2
- 240000007124 Brassica oleracea Species 0.000 description 2
- 235000003899 Brassica oleracea var acephala Nutrition 0.000 description 2
- 235000011301 Brassica oleracea var capitata Nutrition 0.000 description 2
- 235000001169 Brassica oleracea var oleracea Nutrition 0.000 description 2
- 102000016938 Catalase Human genes 0.000 description 2
- 108010053835 Catalase Proteins 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 240000008067 Cucumis sativus Species 0.000 description 2
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 description 2
- 244000000626 Daucus carota Species 0.000 description 2
- 235000002767 Daucus carota Nutrition 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 244000174681 Michelia champaca Species 0.000 description 2
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 2
- 244000046052 Phaseolus vulgaris Species 0.000 description 2
- 241000192031 Ruminococcus Species 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 235000013351 cheese Nutrition 0.000 description 2
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 2
- 229960002327 chloral hydrate Drugs 0.000 description 2
- YTRQFSDWAXHJCC-UHFFFAOYSA-N chloroform;phenol Chemical compound ClC(Cl)Cl.OC1=CC=CC=C1 YTRQFSDWAXHJCC-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 235000015142 cultured sour cream Nutrition 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 210000003608 fece Anatomy 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000006799 invasive growth in response to glucose limitation Effects 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 238000009630 liquid culture Methods 0.000 description 2
- 235000021056 liquid food Nutrition 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 235000021055 solid food Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 238000005406 washing Methods 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
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000304886 Bacilli Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000186000 Bifidobacterium Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 208000004232 Enteritis Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 241000186660 Lactobacillus Species 0.000 description 1
- 201000010538 Lactose Intolerance Diseases 0.000 description 1
- 244000141359 Malus pumila Species 0.000 description 1
- 241000191998 Pediococcus acidilactici Species 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241001052560 Thallis Species 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- -1 Tris saturated phenol Chemical class 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- VLSOAXRVHARBEQ-UHFFFAOYSA-N [4-fluoro-2-(hydroxymethyl)phenyl]methanol Chemical compound OCC1=CC=C(F)C=C1CO VLSOAXRVHARBEQ-UHFFFAOYSA-N 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 235000021016 apples Nutrition 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 238000003287 bathing Methods 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000032770 biofilm formation Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 244000144987 brood Species 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000012154 double-distilled water Substances 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000013230 female C57BL/6J mice Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 1
- 229940039696 lactobacillus Drugs 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000007102 metabolic function Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000002068 microbial inoculum Substances 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 238000000643 oven drying Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000012070 whole genome sequencing analysis Methods 0.000 description 1
- 239000010127 yangjing Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
- A23C9/00—Milk preparations; Milk powder or milk powder preparations
- A23C9/12—Fermented milk preparations; Treatment using microorganisms or enzymes
- A23C9/123—Fermented milk preparations; Treatment using microorganisms or enzymes using only microorganisms of the genus lactobacteriaceae; Yoghurt
- A23C9/1234—Fermented milk preparations; Treatment using microorganisms or enzymes using only microorganisms of the genus lactobacteriaceae; Yoghurt characterised by using a Lactobacillus sp. other than Lactobacillus Bulgaricus, including Bificlobacterium sp.
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
- A23C13/00—Cream; Cream preparations; Making thereof
- A23C13/12—Cream preparations
- A23C13/16—Cream preparations containing, or treated with, microorganisms, enzymes, or antibiotics; Sour cream
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
- A23C19/00—Cheese; Cheese preparations; Making thereof
- A23C19/06—Treating cheese curd after whey separation; Products obtained thereby
- A23C19/063—Addition of, or treatment with, enzymes or cell-free extracts of 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
- A23L19/00—Products from fruits or vegetables; Preparation or treatment thereof
-
- 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
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/065—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
-
- 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
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- 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
-
- 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
- A23V2400/00—Lactic or propionic acid bacteria
- A23V2400/51—Bifidobacterium
- A23V2400/533—Longum
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Microbiology (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Obesity (AREA)
- Wood Science & Technology (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Zoology (AREA)
- Hematology (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- General Engineering & Computer Science (AREA)
- Urology & Nephrology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Gastroenterology & Hepatology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Child & Adolescent Psychology (AREA)
- Virology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
Abstract
本发明公开了降低血浆TMAO及缓解、预防动脉粥样硬化的长双歧杆菌CCFM1216及其应用,属于微生物技术领域。本发明的长双歧杆菌CCFM1216能够降低血浆TMAO和盲肠TMA的水平;能够改善肠道菌群的结构,恢复高胆碱造成的肠道菌群紊乱,降低有害菌的丰度(Bilophila属、Anaeroplasma属和Ruminococcaceae UCG‑009属),减少肥胖、非酒精性脂肪肝、高脂血症、高血压、心血管疾病发生的风险。因此,具有广阔的应用价值。
Description
技术领域
本发明涉及降低血浆TMAO及缓解、预防动脉粥样硬化的长双歧杆菌CCFM1216及其应用,属于微生物技术领域。
背景技术
心血管疾病是世界范围内致病率和致死率主要的原因,动脉粥样硬化(AS)是心血管的病理基础。目前,公认的AS的始动因素为动脉壁内皮损伤及脂质的沉积;危险因子为高血压,血脂升高,炎症,氧化高胆碱,肥胖,抽烟等。
有研究表明,肠道微生物主要通过细菌感染、调节胆固醇和脂质代谢、食物及微生物代谢产物三种途径对动脉粥样硬化产生影响。经膳食-肠道微生物-肝脏-氧化三甲胺(TMAO)途径产生的TMAO可以促进心血管疾病发生发展。依赖微生物的三甲胺(TMA)/TMAO途径被证明与心血管疾病的发病机制相关,是心血管疾病的重要诊断和治疗靶点。干预肠道菌群代谢,或许可以成为预防和治疗心血管疾病方法之一。
大量的科学研究和临床实验已经证明,益生菌对便秘、肠炎、乳糖不耐、抗感染、炎症、过敏、糖脂代谢紊乱均具有显著改善作用。补充益生菌能直接给人体肠道注入大量的有益菌群,帮助改善菌群的代谢功能。
发明内容
本发明提供了一种长双歧杆菌(Bifidobacterium longum)CCFM1216,其于2021年12月31日保藏于广东省微生物菌种保藏中心,保藏地址为广州市先烈中路100号大院59号楼5楼广东省微生物研究所,保藏编号为GDMCC No:62175。
本发明还提供一种发酵食品,所述发酵食品为使用长双歧杆菌CCFM1216发酵生产制得,所述发酵食品包括固态食品、液态食品、半固态食品。
在一种实施方式中,所述发酵食品包括乳制品、豆制品、果蔬制品,所述乳制品包括牛奶、酸奶油、干酪;所述果蔬制品包括黄瓜、胡萝卜、甜菜、芹菜、圆白菜制品。
本发明还提供长双歧杆菌CCFM1216在制备体内定植益生菌制剂中的应用。
在一种实施方式中,所述益生菌制剂中长双歧杆菌CCFM1216的含量≥1×109CFU/mL或≥1×109CFU/g。
本发明还提供长双歧杆菌CCFM1216在制备减少肥胖、非酒精性脂肪肝、高脂血症、高血压、心血管疾病中至少一种疾病的发病风险的药物,或缓解肠应激综合征、肥胖、过敏、神经性疾病、II型糖尿病、非酒精性脂肪肝、心血管疾病中至少一种疾病症状的保健品中的应用;所述心血管疾病包括但不限于动脉粥样硬化。
在一种实施方式中,所述应用包括如下至少一种作用:
(1)降低血浆TMAO的水平;
(2)降低盲肠TMA的水平;
(3)改善肠道菌群的结构,恢复高胆碱造成的肠道菌群紊乱。
在一种实施方式中,所述改善肠道菌群的结构包括降低有害菌的丰度。
在一种实施方式中,所述有害菌包括但不限于Bilophila属、Anaeroplasma属和Ruminococcaceae UCG-009属)。
本发明还提供所述长双歧杆菌CCFM1216在制备减少肥胖、非酒精性脂肪肝、高脂血症、高血压、动脉粥样硬化、心血管疾病的功能性食品中的应用。
本发明还提供长双歧杆菌CCFM1216在与药物联合使用时促进药物增效方面的应用。
在一种实施方式中,所述药物包括但不限于他汀类药物。
在一种实施方式中,所述药物增效物还含有药学上可接受的载体。
在一种实施方式中,所述药学上可接受的载体包括但不限于:填充剂、润湿剂、崩解剂、粘合剂或润滑剂中的一种或多种。
本发明的有益效果:
本发明提供的长双歧杆菌CCFM1216具有减少动脉粥样硬化、肥胖、非酒精性脂肪肝、高脂血症、高血压、心血管疾病等发病风险等作用,可用于制备食品、保健品或药品,具有非常广泛的应用前景。在高胆碱模型小鼠实验中,服用本发明的长双歧杆菌CCFM1216能够显著降低血浆TMAO、血浆TMA和盲肠TMA的水平,能够改善肠道菌群的结构,恢复高胆碱造成的肠道菌群紊乱,降低有害菌的丰度(Bilophila属、Anaeroplasma属和RuminococcaceaeUCG-009属),减少肥胖、非酒精性脂肪肝、高脂血症、高血压、动脉粥样硬化等心血管疾病发生的风险。
生物材料保藏
长双歧杆菌(Bifidobacterium longum)CCFM1216,分类命名为Bifidobacteriumlongum,已于2021年12月31日保藏于广东省微生物菌种保藏中心,保藏地址为广州市先烈中路100号大院59号楼5楼广东省微生物研究所,保藏编号为GDMCC No:62175。
附图说明
图1是发酵用乳酸菌长双歧杆菌CCFM1216的菌落形态;
图2是长双歧杆菌CCFM1216对胆碱饲料饲养的小鼠的血浆TMAO的影响;其中***P<0.001,****P<0.0001。
图3是长双歧杆菌CCFM1216对胆碱饲料饲养的小鼠的盲肠TMA的影响;其中**P<0.01,****P<0.0001。
图4为是长双歧杆菌CCFM1216对胆碱饲料饲养的小鼠的盲肠Bilophila属、Anaeroplasma属和Ruminococcaceae UCG-009属的影响;其中*P<0.05,**P<0.01。
图5是不同长双歧杆菌对胆碱饲料饲养的小鼠的血浆TMAO的影响;其中***P<0.001,****P<0.0001。
具体实施方式
所述长双歧杆菌CCFM1216具有以下生物学特性:
(1)菌体特征:呈革兰氏染色阳性,不形成抱子,不运动的细菌。
(2)菌落特征:菌落呈乳白色,圆形,边缘整齐,微凸起,不透明,表面湿润光滑;
(3)生长特性:该菌株的最适生长温度是35-37℃,最适生长pH为6.5,培养18h后进入稳定期;
(4)在高胆碱小鼠模型中能够显著降低血浆TMAO的水平;
(5)在高胆碱小鼠模型中能够显著降低盲肠TMA的水平;
(6)在高胆碱小鼠模型中能够显著降低Bilophila属、Anaeroplasma属和Ruminococcaceae UCG-009属的丰度,减少肥胖、非酒精性脂肪肝、高脂血症、高血压、心血管疾病的风险。
所述长双歧杆菌CCFM1216的提取方法为:
(一)长双歧杆菌的分离筛选:
(l)取1g健康人的新鲜粪便。梯度稀释后涂布于mMRS固体培养基,置于厌氧环境下37℃培养72小时;
(2)观察记录菌落形态,挑取菌落划线纯化;
(3)在MRS液体培养基中,37℃培养48小时,所得菌落进行革兰氏染色,记录菌落形态。
(4)弃除菌落中的革兰氏阴性菌菌株和革兰氏阳性球菌,挑选得到革兰氏阳性杆菌。
(5)过氧化氢酶分析后,弃除过氧化氢酶阳性菌株,保留过氧化氢酶阴性菌株。
(二)长双歧杆菌的分子生物学鉴定:
(l)单菌基因组抽提:将步骤(二)所筛选得到的乳酸片球菌培养过夜,取培养过夜的菌悬液lmL于1.5mL离心管,10000rpm离心2min,弃上清得菌体;用lmL无菌水吹洗菌体后,10000rpm离心2min,弃上清得菌体;加入200μL SDS裂解液,80℃水浴30min;加入酚-氯仿溶液200μL于菌体裂解液中,其中酚-氯仿溶液的组成成分及体积比为Tris饱和酚:氯仿:异戊醇=25:24:1,颠倒混匀后,12000rpm离心5-10min,取上清200μL;加入400μL冰乙醇或冰异丙醇于200uL上清中,﹣20℃静置1h,12000rpm离心5-10min,弃上清;加入500μL70%(体积百分数)冰乙醇重悬沉淀,12000rpm离心1-3min,弃上清;60℃烘箱烘干,或者自然晾干;50μLddH2O重溶沉淀以备PCR;
(2)16S rDNA PCR:
A.细菌16S rDNA 50μLPCR反应体系:
10×Taq buffer,5μL;dNTP,5μL;27F,0.5μL;1492R,0.5μL;Taq酶,0.5μL;模板,0.5μL;ddH2O,38μL。
B.PCR条件:
95℃5min;95℃10s;55℃30s;72℃30s;step2-4 30×;72℃5min;12℃2min;
C.制备1%琼脂糖凝胶,之后将PCR产物与10000×loading buffer混合,上样量2μL,120V跑30min,然后进行凝胶成像;
D.将得到PCR产物送专业测序公司,将得到的测序结果与使用BLAST在GeneBank中进行搜索和相似性比对,鉴定为长双歧杆菌。
(3)全基因组测序
将提取的全基因组送专业测序公司,利用二代测序仪对菌的全基因组进行测序,将得到的序列结果使用BLAST在GeneBank中进行搜索和相似性比对,测序结果鉴定为属于长双歧杆菌的一种新发现的菌株。菌株-80℃保藏备用。
实施例1:长双歧杆菌CCFM1216对模拟胃肠液的耐受性
将冷冻保存的长双歧杆菌CCFM1216接种于MRS培养基中,在温度37℃厌氧培养48h,再经MRS培养液传代培养2~3次后,取1mL长双歧杆菌CCFM1216的培养液,与9.0mLpH2.5人工模拟胃液(含1%胃蛋白酶、pH=2.5的MRS培养基)混合,并在37℃下厌氧培养,分别在0h、0.5h、1h和2h时取样,用MRS琼脂培养基浇注培养进行平板菌落计数,测定活菌数并计算其存活率。
存活率是在该培养液中在取样时的活菌数对数值与在第0h时活菌数对数值之比,以%表示。取1mL长双歧杆菌CCFM1216的培养液加入9mL人工模拟肠液(含0.3%牛胆盐、1%胰蛋白酶、pH=8.0的MRS培养基)中,在37℃下厌氧培养,分别在0h、0.5h、1h、2h、3h和4h时取样,用MRS琼脂培养基浇注培养进行平板菌落计数,测定活菌数并计算其存活率。存活率是在该培养液中在取样时的活菌数对数值与在第0h时活菌数对数值之比,以%表示。实验结果如表1和表2所示。结果表明,长双歧杆菌CCFM1216对人工胃肠液具有较好的耐受性。
表1长双歧杆菌CCFM1216在人工模拟胃液中的耐受性
表2长双歧杆菌CCFM1216在人工模拟肠液中的耐受性
实施例2:长双歧杆菌CCFM1216用于降低血浆TMAO的水平
取体重18-20g的健康雌性C57BL/6J小鼠24只,适应环境1周,随机分为4组:空白对照组(Control)、模型对照组(Choline)、长双歧杆菌CCFM1216组(CCFM1216)、长双歧杆菌FJSNT53M9对照组(按照相同方法筛选自江苏省南通市人体粪便的另一株长双歧杆菌FJSNT53M9,菌株公开于:朱如意,杭锋,张灏等.双歧杆菌生物膜形成规律及其表面性质相关性研究[J].食品与发酵工业,2020)。每组含小鼠6只,灌胃的剂量为每天每只小鼠灌胃0.2mL菌浓不低于1×109cfu/mL的菌液。
菌液的制备方法为:将长双歧杆菌CCFM1216和长双歧杆菌FJSNT53M9分别划线接种至MRS固体培养基中,在37℃条件下培养72h得到单菌落,将制备得到的单菌落分别接种至MRS液体培养基中,在37℃条件下培养24h进行活化;将活化3代后的菌液分别以2%的接种量接种至1L MRS液体培养基中,振荡混匀后于厌氧培养箱中37℃培养24h。在8000g/min,4℃的条件下离心15min,去上清后,用无菌生理盐水(含0.05%-0.1%的L-半胱氨酸盐酸盐)进行清洗2次,同样以相同条件进行离心,去上清后,用30%的甘油进行重悬,获得菌浓数量级不低于1×109CFU/mL的菌液。
将菌液于-80℃冰箱冻存一周。在进行动物实验前,将冰箱中冻存的菌液取出,将菌液以6 000r/min离心5min,再用无菌生理盐水清洗两遍,用10%脱脂乳重悬菌液,震荡均匀后用平板倾注法测定初始和冻存一周后的活菌数量。实验结果:初始活菌数分别为2.1×109CFU/mL,2.0×109CFU/mL,1周后活菌数为1.8×109CFU/mL,1.6×109CFU/mL数量级并没有产生变化,说明将菌液冻存后不会对实验产生影响,可用于动物实验。实验动物分组及处理方法见表3。
表3实验动物分组
第2-7周:正常组小鼠喂食普通饲料,其余小鼠喂食胆碱饲料。C57BL/6J小鼠(雌性,7周龄),购自于北京维通利华实验动物技术有限公司。普通饲料(LAD 3001M,胆碱含量为0.1%)和胆碱饲料(LAD 3001M,胆碱含量为1.0%),购自于南通特洛菲饲料科技有限公司。
试验结束前,小鼠禁食禁水4h,通过眼眶周围毛细管取血。血液样本4000×g、4℃条件下离心15min,取上清,冻存于-80℃冰箱,取20μL血浆样品加入80μL(V:V,1:4)乙腈沉淀血浆样品中的蛋白质,同时加入终浓度为2.0μM的d9-TMAO到血浆样品中作为内标。混匀,-80℃静置2h,在4℃条件下12000g 15分钟,吸上清至进样瓶中,保存在-80℃冰箱,通过HPLC-MS/MS测定血浆TMAO水平。
血浆TMAO实验结果如图2所示,胆碱饲料组小鼠血浆TMAO显著高于对照饲料组,大约比对照组高出5.78倍,与胆碱组小鼠相比,灌胃长双歧杆菌CCFM1216显著降低血浆TMAO的水平,与胆碱组小鼠比,灌胃长双歧杆菌CCFM1216小鼠的血浆TMAO降低了27.60%,而灌胃对照菌FJSNT53M9小鼠的血浆TMAO只降低了0.04%。
实施例3:长双歧杆菌CCFM1216用于降低盲肠TMA的水平
C57BL/6J小鼠分组、造模及处理方法同实施例2。
试验结束时,小鼠禁食禁水12h,腹腔注射10%的水合氯醛溶液麻醉后,取小鼠盲肠,冻存于-80℃冰箱,称取小鼠盲肠内容物,每mg盲肠内容物加入20μL的混合溶液(乙腈:甲醇:水以体积比40:40:20混合),同时加入终浓度为2.5μM的d9-TMA到盲肠样品中作为内标,振荡混匀,-80℃静置2h,在4℃条件下12000g15分钟,吸上清至进样瓶中,保存在-80℃冰箱,通过HPLC-MS/MS测定小鼠盲肠中TMA的含量。
盲肠TMA实验结果如图3所示,胆碱饲料组小鼠盲肠TMA显著高于对照饲料组,大约比对照组高出3.13倍,与胆碱组小鼠相比,灌胃长双歧杆菌CCFM1216显著降低盲肠TMA的水平,与胆碱组小鼠比,灌胃长双歧杆菌CCFM1216的小鼠盲肠TMA降低了50.68%,而灌胃对照菌FJSNT53M9的小鼠盲肠TMA只降低了11.45%。
实施例4:长双歧杆菌CCFM1216用于降低盲肠有害微生物的丰度
C57BL/6J小鼠分组、造模及处理方法同实施例2。
试验结束时,小鼠禁食禁水12h,腹腔注射10%的水合氯醛溶液麻醉后,取盲肠,按照粪便DNA试剂盒的方法提取盲肠DNA,利用二代测序仪对盲肠的V3-V4区进行16S rDNA菌群分析。
实验结果如图4所示。胆碱饲料组小鼠盲肠Bilophila属、Anaeroplasma属和Ruminococcaceae UCG-009属的相对丰度显著高于对照饲料组,与胆碱组小鼠相比,灌胃长双歧杆菌CCFM1216显著降低盲肠Bilophila属、Anaeroplasma属和Ruminococcaceae UCG-009属的相对丰度。
实施例5:比较不同长双歧杆菌对胆碱饲料喂养的小鼠的血浆TMAO的影响
小鼠造模及处理方法同实施例2,分别用16株不同株的长双歧杆菌灌胃胆碱饲料喂养的小鼠,检测血浆TMAO。如图5所示,只有CCFM1216具有显著的降低胆碱饲料喂养的小鼠血浆TMAO的能力,相比胆碱组下降了27.60%,其它长双歧杆菌均未显著降低胆碱饲料喂养的小鼠血浆的TMAO。
实施例6:利用本发明长双歧杆菌CCFM1216制造含该菌的发酵食品
选用新鲜苹果洗净后榨汁,接着进行高温瞬间灭菌,在温度140℃下高温热杀菌2秒后,立即降温至37℃,再接入本发明制备的长双歧杆菌CCFM1216菌剂发酵剂,使其浓度达到108CFU/mL以上,在温度4℃下冷藏保存,于是得到含有本发明长双歧杆菌CCFM1216活菌的果蔬饮料。
利用本发明能够使用长双歧杆菌CCFM1216发酵生产制备其他发酵食品,所述发酵食品包括固态食品、液态食品、半固态食品。所述发酵食品包括乳制品、豆制品、果蔬制品,所述乳制品包括牛奶、酸奶油、干酪;所述果蔬制品包括黄瓜、胡萝卜、甜菜、芹菜、圆白菜制品。
按照实施例1的方法将制备的发酵食品用于饲喂胆碱模型小鼠,结果显示本实施例制备的所述发酵食品能够降低血浆TMAO、和盲肠TMA的水平;能够改善肠道菌群的结构,恢复高胆碱造成的肠道菌群紊乱,降低有害菌的丰度(Bilophila属、Anaeroplasma属和Ruminococcaceae UCG-009属),减少肥胖、非酒精性脂肪肝、高脂血症、高血压、心血管疾病发生的风险。
虽然本发明已以较佳实施例公开如上,但其并非用以限定本发明,任何熟悉此技术的人,在不脱离本发明的精神和范围内,都可做各种的改动与修饰,因此本发明的保护范围应该以权利要求书所界定的为准。
Claims (10)
1.一种长双歧杆菌(Bifidobacterium longum)CCFM1216,其于2021年12月31日保藏于广东省微生物菌种保藏中心,保藏地址为广州市先烈中路100号大院59号楼5楼广东省微生物研究所,保藏编号为GDMCC No:62175。
2.一种发酵食品,其特征在于,所述发酵食品为使用长双歧杆菌CCFM1216发酵生产制得。
3.根据权利要求2所述的发酵食品,其特征在于,所述发酵食品包括乳制品、豆制品、或果蔬制品。
4.权利要求1所述的长双歧杆菌CCFM1216在制备体内益生菌制剂中的应用。
5.一种益生菌制剂,其特征在于,所述益生菌制剂中长双歧杆菌CCFM1216的含量≥1×109CFU/mL或≥1×109CFU/g。
6.权利要求1所述的长双歧杆菌CCFM1216在制备减少动脉粥样硬化、肥胖、非酒精性脂肪肝、高脂血症、高血压、心血管疾病中至少一种疾病的发病风险的药物,或缓解动脉粥样硬化、肠应激综合征、肥胖、过敏、神经性疾病、II型糖尿病、非酒精性脂肪肝、心血管疾病中至少一种疾病症状的保健品中的应用。
7.根据权利要求6所述的应用,其特征在于,所述应用包括如下至少一种作用:
(1)降低血浆TMAO的水平;
(2)降低盲肠TMA的水平;
(3)改善肠道菌群的结构,恢复高胆碱造成的肠道菌群紊乱。
8.根据权利要求7所述的应用,其特征在于,所述改善肠道菌群的结构包括降低有害菌的丰度。
9.含有权利要求1所述长双歧杆菌CCFM1216的药物,其特征在于,还含有药学上可接受的载体。
10.权利要求1所述的长双歧杆菌CCFM1216在与药物联合使用时促进药物增效方面的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210097915.3A CN114410531B (zh) | 2022-01-27 | 2022-01-27 | 降低血浆tmao及缓解、预防动脉粥样硬化的长双歧杆菌ccfm1216及其应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210097915.3A CN114410531B (zh) | 2022-01-27 | 2022-01-27 | 降低血浆tmao及缓解、预防动脉粥样硬化的长双歧杆菌ccfm1216及其应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114410531A true CN114410531A (zh) | 2022-04-29 |
CN114410531B CN114410531B (zh) | 2023-10-27 |
Family
ID=81278693
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210097915.3A Active CN114410531B (zh) | 2022-01-27 | 2022-01-27 | 降低血浆tmao及缓解、预防动脉粥样硬化的长双歧杆菌ccfm1216及其应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114410531B (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN117143780A (zh) * | 2023-10-23 | 2023-12-01 | 广东省科学院微生物研究所(广东省微生物分析检测中心) | 缓解动脉粥样硬化的发酵乳杆菌f356、植物乳杆菌p470和长双歧杆菌l556 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2017201983A (ja) * | 2016-05-10 | 2017-11-16 | 協同乳業株式会社 | トリメチルアミンを産生し難い腸内菌叢を形成するためのプロバイオティクス組成物および方法 |
-
2022
- 2022-01-27 CN CN202210097915.3A patent/CN114410531B/zh active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2017201983A (ja) * | 2016-05-10 | 2017-11-16 | 協同乳業株式会社 | トリメチルアミンを産生し難い腸内菌叢を形成するためのプロバイオティクス組成物および方法 |
Non-Patent Citations (1)
Title |
---|
SHUANG YAN等: "Production of exopolysaccharide by Bifidobacterium longum isolated from elderly and infant feces and analysis of priming glycosyltransferase genes" * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN117143780A (zh) * | 2023-10-23 | 2023-12-01 | 广东省科学院微生物研究所(广东省微生物分析检测中心) | 缓解动脉粥样硬化的发酵乳杆菌f356、植物乳杆菌p470和长双歧杆菌l556 |
CN117143780B (zh) * | 2023-10-23 | 2024-02-02 | 广东省科学院微生物研究所(广东省微生物分析检测中心) | 缓解动脉粥样硬化的发酵乳杆菌f356、植物乳杆菌p470和长双歧杆菌l556 |
Also Published As
Publication number | Publication date |
---|---|
CN114410531B (zh) | 2023-10-27 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN112322528B (zh) | 一株可干预代谢综合征的鼠李糖乳杆菌及应用 | |
CN112322527A (zh) | 一株可干预代谢综合征的罗伊氏乳杆菌及应用 | |
CN110079485B (zh) | 缓解抑郁的乳酸片球菌ccfm6432、其发酵食品及其应用 | |
CN110093286B (zh) | 假小链双歧杆菌ccfm1046、其组合物、发酵食品、用途、菌剂及其菌剂制备方法 | |
JP7158761B2 (ja) | 乳酸菌株の混合物を含むスターターカルチャー、そのようなスターターカルチャーを使用して製造された発酵製品、及びその発酵製品の使用 | |
CN113403231B (zh) | 一株可干预代谢综合征的罗伊氏乳杆菌ccfm1178及应用 | |
CN112574917B (zh) | 一株缓解高尿酸血症的鼠李糖乳杆菌ccfm1131 | |
CN113943681B (zh) | 一株降低炎症反应且具有缓解便秘作用的长双歧杆菌 | |
CN110106103B (zh) | 假小链双歧杆菌ccfm1047、其组合物、发酵食品、用途、菌剂及其菌剂制备方法 | |
CN113025526B (zh) | 一株减少结肠病理损伤且具有缓解便秘作用的两歧双歧杆菌 | |
CN116555076B (zh) | 一株长双歧杆菌长亚种my1及其在制备通便和护肠食品药品中的应用 | |
CN114410531A (zh) | 降低血浆tmao及缓解、预防动脉粥样硬化的长双歧杆菌ccfm1216及其应用 | |
CN114317334A (zh) | 一株能够与幽门螺杆菌共聚集的清酒乳杆菌及其应用 | |
CN114381406B (zh) | 可同时降低血浆及盲肠三甲胺的短双歧杆菌ccfm1217及其应用 | |
CN113943682A (zh) | 缓解便秘的长双歧杆菌长亚种及其制备的发酵食品与益生菌制剂 | |
CN114410532B (zh) | 一株降低血浆氧化三甲胺和盲肠三甲胺水平的长双歧杆菌及其应用 | |
CN112029676B (zh) | 一种有利于提高免疫力的益生菌组合及其应用 | |
CN114686405B (zh) | 一株具有减少脂肪和缓解高血糖,调节肠道免疫力的两歧双歧杆菌及其应用 | |
CN116064313A (zh) | 植物乳杆菌ccfm1281在缓解运动性疲劳中的应用 | |
CN112877260B (zh) | 一株缓解泻剂结肠的副干酪乳杆菌及其应用 | |
WO2021169627A1 (zh) | Blautia sp B2132菌在预防和/或治疗炎症性肠病中的应用 | |
CN113943683A (zh) | 一株缓解便秘并增加粪便总胆汁酸含量的长双歧杆菌长亚种及其应用 | |
CN113249256A (zh) | 一株缓解***相关代谢紊乱及肥胖的植物乳杆菌及应用 | |
CN116286519B (zh) | 一株副干酪乳酪杆菌ks3及其在制备抗衰老和助消化食品药品中的应用 | |
CN114517171B (zh) | 一株可促进肠道分泌IgA的发酵乳杆菌CCFM1225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 |