TW201912171A - 戈氏副擬桿菌用於降低胰島素抗性及提升葡萄糖耐受性之用途 - Google Patents
戈氏副擬桿菌用於降低胰島素抗性及提升葡萄糖耐受性之用途 Download PDFInfo
- Publication number
- TW201912171A TW201912171A TW106128476A TW106128476A TW201912171A TW 201912171 A TW201912171 A TW 201912171A TW 106128476 A TW106128476 A TW 106128476A TW 106128476 A TW106128476 A TW 106128476A TW 201912171 A TW201912171 A TW 201912171A
- Authority
- TW
- Taiwan
- Prior art keywords
- gordonii
- insulin resistance
- item
- patent application
- glucose tolerance
- Prior art date
Links
- 208000001072 type 2 diabetes mellitus Diseases 0.000 title claims abstract description 43
- 206010022489 Insulin Resistance Diseases 0.000 title claims abstract description 30
- 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 title claims abstract description 24
- 239000008103 glucose Substances 0.000 title claims abstract description 24
- 241000606208 Campylobacter gracilis Species 0.000 title 1
- 241000030714 Parabacteroides goldsteinii Species 0.000 claims abstract description 7
- 230000037396 body weight Effects 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 9
- 241000606125 Bacteroides Species 0.000 claims description 3
- 235000013343 vitamin Nutrition 0.000 claims description 3
- 229940088594 vitamin Drugs 0.000 claims description 3
- 229930003231 vitamin Natural products 0.000 claims description 3
- 239000011782 vitamin Substances 0.000 claims description 3
- 150000001413 amino acids Chemical class 0.000 claims description 2
- 150000001720 carbohydrates Chemical class 0.000 claims description 2
- 235000014633 carbohydrates Nutrition 0.000 claims description 2
- 150000002016 disaccharides Chemical class 0.000 claims description 2
- 239000007903 gelatin capsule Substances 0.000 claims description 2
- 150000004676 glycans Chemical class 0.000 claims description 2
- 150000002632 lipids Chemical class 0.000 claims description 2
- 239000007937 lozenge Substances 0.000 claims description 2
- 150000002772 monosaccharides Chemical class 0.000 claims description 2
- 229920001542 oligosaccharide Polymers 0.000 claims description 2
- 150000002482 oligosaccharides Chemical class 0.000 claims description 2
- 229920001282 polysaccharide Polymers 0.000 claims description 2
- 239000005017 polysaccharide Substances 0.000 claims description 2
- 102000004169 proteins and genes Human genes 0.000 claims description 2
- 108090000623 proteins and genes Proteins 0.000 claims description 2
- 239000007901 soft capsule Substances 0.000 claims description 2
- 239000004615 ingredient Substances 0.000 claims 1
- 208000001145 Metabolic Syndrome Diseases 0.000 abstract description 8
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 abstract description 8
- 241000894006 Bacteria Species 0.000 abstract description 5
- 238000000034 method Methods 0.000 abstract description 4
- 239000006041 probiotic Substances 0.000 abstract description 4
- 235000018291 probiotics Nutrition 0.000 abstract description 4
- 230000000529 probiotic effect Effects 0.000 abstract description 3
- 241000699670 Mus sp. Species 0.000 description 23
- 235000009200 high fat diet Nutrition 0.000 description 22
- 239000008280 blood Substances 0.000 description 16
- 210000004369 blood Anatomy 0.000 description 16
- 230000000694 effects Effects 0.000 description 15
- 235000021590 normal diet Nutrition 0.000 description 13
- 238000007410 oral glucose tolerance test Methods 0.000 description 9
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 8
- 241000204306 Parabacteroides merdae Species 0.000 description 6
- 239000008363 phosphate buffer Substances 0.000 description 6
- 238000013218 HFD mouse model Methods 0.000 description 5
- 206010012601 diabetes mellitus Diseases 0.000 description 5
- 102000004877 Insulin Human genes 0.000 description 4
- 108090001061 Insulin Proteins 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 210000003608 fece Anatomy 0.000 description 4
- 229940125396 insulin Drugs 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- 235000015872 dietary supplement Nutrition 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000013116 obese mouse model Methods 0.000 description 3
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 2
- 108010082126 Alanine transaminase Proteins 0.000 description 2
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 2
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 2
- 230000001332 colony forming effect Effects 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000003907 kidney function Effects 0.000 description 2
- 230000003908 liver function Effects 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- DDYAPMZTJAYBOF-ZMYDTDHYSA-N (3S)-4-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S,3R)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-4-amino-1-[[(2S,3S)-1-[[(1S)-1-carboxyethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-4-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-oxobutanoic acid Chemical class [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O DDYAPMZTJAYBOF-ZMYDTDHYSA-N 0.000 description 1
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 238000010152 Bonferroni least significant difference Methods 0.000 description 1
- 208000027244 Dysbiosis Diseases 0.000 description 1
- 108010088406 Glucagon-Like Peptides Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241001236817 Paecilomyces <Clavicipitaceae> Species 0.000 description 1
- 241000178958 Paenibacillus validus Species 0.000 description 1
- 241000160321 Parabacteroides Species 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 229940127322 Sodium-Glucose Transporter 2 Inhibitors Drugs 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- 229940123464 Thiazolidinedione Drugs 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000003888 alpha glucosidase inhibitor Substances 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 230000007140 dysbiosis Effects 0.000 description 1
- 230000005584 early death Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- -1 glitazone Meglitinides Chemical class 0.000 description 1
- 244000005709 gut microbiome Species 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 230000003284 homeostatic effect Effects 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 235000020845 low-calorie diet Nutrition 0.000 description 1
- 238000013227 male C57BL/6J mice Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229950004994 meglitinide Drugs 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000015816 nutrient absorption Nutrition 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 235000017924 poor diet Nutrition 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 230000001235 sensitizing effect Effects 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 235000000891 standard diet Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000001467 thiazolidinediones Chemical class 0.000 description 1
- CWERGRDVMFNCDR-UHFFFAOYSA-M thioglycolate(1-) Chemical compound [O-]C(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-M 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Classifications
-
- 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
-
- 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
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
-
- 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
- A61P3/08—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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Diabetes (AREA)
- Engineering & Computer Science (AREA)
- Nutrition Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Organic Chemistry (AREA)
- Physiology (AREA)
- Food Science & Technology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Polymers & Plastics (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本發明提供一種使用戈氏副擬桿菌於降低胰島素抗性及提升葡萄糖耐受性之用途，故可用於第二型糖尿病與代謝症候群的治療。
Description
本發明係關於一種益生菌之用途。進一步而言，本發明係關於一種戈氏副擬桿菌用於降低胰島素抗性、提升葡萄糖耐受性、及治療第二型糖尿病與代謝症候群之用途。
依據世界衛生組織的報導，自1980年來全球第二型糖尿病患者的發生率已經增加一倍以上，達到全球性流行的標準。據估計2014年全球人口中約有8.5%(4.42億)罹患第二型糖尿病。糖尿病患者有較高風險發生失明、腎衰竭、高血壓、心臟病、及中風，大幅降低生活品質，並可能導致提早死亡。胰島素抗性(insulin resistance)是一種身體細胞對胰島素反應差的狀況，其可能發生於第二型糖尿病之前，並導致疲勞及多種代謝疾病(即代謝症候群)。儘管某些個體的胰島素抗性及糖尿病形成與老化及遺傳有關，糖尿病流行主要是起因於飲食不良、吸煙、及缺乏運動。因此，第二型糖尿病及其併發症可透過改變生活方式加以預防。
雖然多種用於治療第二型糖尿病的藥物已被核准，例如雙胍類(biguanides)、α-葡萄糖苷酶(α-glucosidase)抑制劑、類升糖素胜肽(glucagon-like peptides)、格列奈類(meglitinides)、鈉-葡萄糖轉運蛋白2(sodium glucose transporter 2)抑製劑、磺基尿素類(sulfonylureas)、格列酮類(thiazolidinediones)，這些藥物通常會產生副作用，因此降低治療效果和患者依從性。治療糖尿病及減輕體重的策略之一為低熱量飲食及規律運動，但這些方法難以執行，且其長期效果令人 失望。基於這些因素，開發安全而有效的第二型糖尿病替代治療方案實有其必要。
腸道菌群(gut microbiota)參與多種生理功能，例如能量調節、維生素生產、毒素中和、及養分吸收。先前研究發現糖尿病患者的腸道菌組成改變(gut dysbiosis)，但各種益生菌是否可用於治療胰島素抗性和第二型糖尿病仍不清楚。
緣此，本發明之一目的在提供一種戈氏副擬桿菌(Parabacteroides goldsteinii)用於製備降低胰島素抗性及提升葡萄糖耐受性之組合物之用途。
在本發明之一實施例中，戈氏副擬桿菌係為一活菌株，其係以口服方式施予一個體；戈氏副擬桿菌的有效劑量係為每日0.001菌落形成單位(colony-forming units，CFUs)/kg體重至5×1018CFUs/kg體重，而對一人類個體(平均體重為70公斤)而言，戈氏副擬桿菌的有效劑量係為每日給予一個體6.1×109CFUs。
前述由戈氏副擬桿菌所製備之降低胰島素抗性及提升葡萄糖耐受性之組合物可包含一其他成分，該其他成分係選自於由單醣、雙醣、寡醣、多醣、碳水化合物、胺基酸、蛋白質、脂質、維生素、及其任意組合所組成的群組。該組合物亦可包含一他種菌株。同時，該組合物具有一溶液、一明膠膠囊、一軟膠囊、或一錠劑之形式。
本發明證實戈氏副擬桿菌在哺乳類動物能有效降低胰島素抗性及提升葡萄糖耐受性，因此可提供治療或預防第二型糖尿病或代謝症候群的醫藥品、飲料、食品、或營養補充品。
以下將配合圖式進一步說明本發明的實施方式，下述所列舉的實施例係用以闡明本發明之發明特點及應用，而非以限定本發明之範圍，任何熟習此技藝者，在不脫離本發明之精神和範圍內，當可做些許更動與潤飾，因此本發明之保護範圍當視後附之申請專利範圍所界定者為準。
圖1顯示戈氏副擬桿菌(P.goldsteinii)對正常飲食(chow)及高脂飲食(high-fat diet，HFD)小鼠之胰島素抗性的影響；***表示P<0.001。
圖2顯示戈氏副擬桿菌(P.goldsteinii)對正常飲食(chow)及高脂飲食(HFD)小鼠之口服葡萄糖耐受性試驗結果的影響。
圖3顯示戈氏副擬桿菌(P.goldsteinii)對正常飲食(chow)及高脂飲食(HFD)小鼠之口服葡萄糖耐受性試驗結果的影響；縱軸之曲線下面積(area under the curve，AUC)係使用梯形法由圖2的結果計算而得，其值以任意單位(arbitrary units)表示；*表示P<0.05。
圖4顯示屎副擬桿菌(Parabacteroides merdae)對正常飲食(chow)及高脂飲食(HFD)小鼠之口服葡萄糖耐受性試驗結果的影響。
圖5顯示屎副擬桿菌(P.merdae)對正常飲食(chow)及高脂飲食(HFD)小鼠之口服葡萄糖耐受性試驗結果的影響；縱軸之曲線下面積係由圖4的結果計算而得。
本文所述之「有效劑量」係表示能降低動物及人類胰島素抗性(HOMA-IR)與提升葡萄糖耐受性之細菌量。該有效劑量可依施予生物體或個體的不同而有差異，但可運用如劑量遞增研究之多種實驗技術決定有效劑量。
本文中所使用數值為近似值，所有實驗數據皆表示在20%的範圍內，較佳為在10%的範圍內，最佳為在5%的範圍內。
本發明提供一種戈氏副擬桿菌用於製備降低胰島素抗性及提升葡萄糖耐受性之組合物之用途，故戈氏副擬桿菌可應用於治療第二型糖尿病與代謝症候群。以下實驗顯示將一有效劑量的戈氏副擬桿菌施予一表現胰島素抗性或第二型糖尿病的個體後，該個體的胰島素抗性明顯降低，且其葡萄糖耐受性增加。概括而言，每日施予哺乳動物或人類的戈氏副擬桿菌劑量可為0.001CFUs/kg體重至5×1018CFUs/kg體重。本發明之詳細說明如下。
本發明實施例中所用細菌包含購自美國典型培養物保藏中心(American Type Culture Collection，ATCC)之戈氏副擬桿菌(P.goldsteinii)ATCC BAA-1180菌株、及屎副擬桿菌(P.merdae)ATCC 43184菌株。該細菌培養於硫乙醇酸鹽(thioglycollate)液體培養基，培養條件為含10%二氧化碳、10%氫氣、及80%氮氣的無氧環境(DG250 Anaerobic Workstation，Don Whitley Scientific，英國)。
空腹血液中葡萄糖或血糖之測定係使用血糖機測試條(Johnson & Johnson Medical Devices，香港)在小鼠禁食6小時後進行。空腹血液中胰島素之測定係依據廠商說明書利用酵素連結免疫吸附分析(enzyme-linked immunosorbent assay，ELISA)試劑組(Mercodia，瑞典)。HOMA-IR指數之計算係使用下列公式：空腹血糖(mg/dl)×空腹血液中胰島素(μU/ml)/405
進行口服葡萄糖耐受性試驗時，以胃內灌食(intragastric gavage)方式給予禁食8小時的小鼠10%(w/v)葡萄糖溶液(劑量為1g/kg)，並每隔一段固定時間測定血糖。
實驗數據皆表示為平均值±標準偏差，其統計分析係使用單變量變異數分析(one-way ANOVA)及Bonferroni氏事後檢定(Bonferroni post hoc test)。
對8週齡的C57BL/6J雄性小鼠餵食標準飼料(能量來源13.5%為脂肪；參見Laboratory Rodent Diet 5001，LabDiet，美國)或高脂肪含量飼料(能量來源60%為脂肪；參見Laboratory Rodent Diet 5001，LabDiet，美國)，並且每天以胃內灌食方式給予200μL的戈氏副擬桿菌ATCC BAA-1180菌株(2×106CFUs)、屎副擬桿菌ATCC 43184菌株(2×106CFUs)、或磷酸鹽緩衝液，持續8週(n=6，代表每組各有6隻小鼠)。前述小鼠組別分為標示為正常飲食+磷酸鹽緩衝液、正常飲 食+P.goldsteini、高脂飲食+磷酸鹽緩衝液、高脂飲食+P.goldsteini、及高脂飲食+P.merdae。8週後，各組小鼠進行胰島素抗性平衡模式評估(HOMA-IR)及口服葡萄糖耐受性試驗(OGTT)。
圖1顯示戈氏副擬桿菌對正常飲食小鼠及高脂飲食小鼠之HOMA-IR指數的影響。依據圖1，高脂飲食小鼠相比正常飲食小鼠表現出較高的胰島素抗性。但相較於經高脂飲食+磷酸鹽緩衝液處理的小鼠，高脂飲食+P.goldsteini之處理明顯降低小鼠的胰島素抗性，顯示施予戈氏副擬桿菌可顯著降低個體的胰島素抗性。
圖2及圖3顯示戈氏副擬桿菌對正常飲食小鼠及高脂飲食小鼠之口服葡萄糖耐受性試驗結果的影響。依據圖2至圖3，在服用葡萄糖後，高脂飲食小鼠相比正常飲食小鼠有普遍較高的血液中葡萄糖濃度，但以戈氏副擬桿菌處理高脂飲食小鼠會顯著低其血液中葡萄糖濃度，顯示施予戈氏副擬桿菌可顯著提升個體的葡萄糖耐受性。
上述圖1至圖3的結果證實戈氏副擬桿菌對高脂飲食誘導肥胖小鼠有降低胰島素抗性及提升葡萄糖耐受性的功效。由該些結果可計算得戈氏副擬桿菌在8週間促進小鼠(平均體重為23g)胰島素敏感性或使其對抗糖尿病所需的劑量為8.7×107CFUs/kg體重。經由換算，可得戈氏副擬桿菌在8週間於人類個體(平均體重為70kg)產生相似的胰島素致敏功效的劑量為6.1×109CFUs/個人。
圖4及圖5顯示副擬桿菌屬中的屎副擬桿菌對正常飲食小鼠及高脂飲食小鼠之口服葡萄糖耐受性試驗結果的影響，該屎副擬桿菌之處理係作為負對照組。經過8週之飼料餵食及屎副擬桿菌處理，如圖4至圖5所示，相較於經高脂飲食+磷酸鹽緩衝液處理的小鼠，高脂飲食+P.merdae之處理未顯著改變小鼠的血糖濃度。此結果說明前述戈氏副擬桿菌促進胰島素敏感性的效果並非副擬桿菌屬細菌的共通特性，而是戈氏副擬桿菌的專有特性。
本實施例進一步檢測戈氏副擬桿菌之處理對小鼠血液生化指數的影響，其結果如表1所示。該血液生化指數包括用於評估肝功能的天冬胺酸轉氨酶(aspartate transaminase，AST)與丙胺酸轉氨酶(alanine transaminase，ALT)含量以及用於評估腎功能的血液中尿素氮(blood urea nitrogen)與肌酸酐(creatinine)含量，其測定係利用Hitachi 7080生化分析儀(Hitachi，日本)。依據表1，小鼠以正常飲食+磷酸鹽緩衝液處理或以正常飲食+P.goldsteini處理後，該二組小鼠的血液生化指數沒有顯著差異，顯示施予戈氏副擬桿菌不會影響肝功能及腎功能。
上述實驗結果顯示戈氏副擬桿菌在哺乳類動物中能有效降低胰島素抗性及提升葡萄糖耐受性，故其能應用於治療第二型糖尿病與代謝症候群。同時，本發明以P.merdae做為比較例，證實儘管戈氏副擬桿菌屬(Parabacteroides)之菌株眾多，非所有副擬桿菌屬之菌株皆具有降低胰島素抗性及提升葡萄糖耐受性的效果。戈氏副擬桿菌可添加於一個體的飲食，製成一醫藥品、一飲料、一食品、或一營養補充品，卻不影響個體的生活型態，亦不會引發不良健康狀況或毒性。因此，本發明提供了一種利用戈氏副擬桿菌治療胰島素抗性、第二型糖尿病、及代謝症候群的新策略。鑑於市場上對胰島素抗性、第二型糖尿病、及代謝症候群之治療或預防產品的迫切需求，本發明顯然具有產業上利用的價值。
Claims (9)
- 一種戈氏副擬桿菌( Parabacteroides goldsteinii)用於製備降低胰島素抗性及提升葡萄糖耐受性之組合物之用途。
- 如申請專利範圍第1項所述之用途，其中該戈氏副擬桿菌係以口服方式施予。
- 如申請專利範圍第1項所述之用途，其中該戈氏副擬桿菌係為一活菌株。
- 如申請專利範圍第1項所述之用途，其中該戈氏副擬桿菌的有效劑量係為每日給予0.001CFUs/kg體重至5×10 18CFUs/kg體重。
- 如申請專利範圍第1項所述之用途，其中該戈氏副擬桿菌的有效劑量係為每日給予一個體6.1×10 9CFUs。
- 如申請專利範圍第1項所述之用途，其中該組合物包含一其他成分。
- 如申請專利範圍第6項所述之用途，其中該其他成分係選自於由單醣、雙醣、寡醣、多醣、碳水化合物、胺基酸、蛋白質、脂質、維生素、及其任意組合所組成的群組。
- 如申請專利範圍第1項所述之用途，其中該組合物包含一他種菌株。
- 如申請專利範圍第1項所述之用途，其中該組合物具有一溶液、一明膠膠囊、一軟膠囊、或一錠劑之形式。
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TW106128476A TWI640314B (zh) | 2017-08-22 | 2017-08-22 | 戈氏副擬桿菌用於降低胰島素抗性及提升葡萄糖耐受性之用途 |
| US15/791,010 US10086019B1 (en) | 2017-08-22 | 2017-10-23 | Method to reduce insulin resistance and improve glucose tolerance using Parabacteroides goldsteinii |
| CN201711228678.5A CN109419817B (zh) | 2017-08-22 | 2017-11-29 | 戈氏副拟杆菌用于降低胰岛素抗性及提升葡萄糖耐受性的用途 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TW106128476A TWI640314B (zh) | 2017-08-22 | 2017-08-22 | 戈氏副擬桿菌用於降低胰島素抗性及提升葡萄糖耐受性之用途 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TWI640314B TWI640314B (zh) | 2018-11-11 |
| TW201912171A true TW201912171A (zh) | 2019-04-01 |
Family
ID=63639265
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW106128476A TWI640314B (zh) | 2017-08-22 | 2017-08-22 | 戈氏副擬桿菌用於降低胰島素抗性及提升葡萄糖耐受性之用途 |
Country Status (3)
| Country | Link |
|---|---|
| US (1) | US10086019B1 (zh) |
| CN (1) | CN109419817B (zh) |
| TW (1) | TWI640314B (zh) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI636788B (zh) * | 2017-08-28 | 2018-10-01 | 長庚生物科技股份有限公司 | 戈氏副擬桿菌用於抑制脂肪肝疾病之用途 |
| JP7761556B2 (ja) * | 2019-09-18 | 2025-10-28 | リサーチ ディベロップメント ファウンデーション | 代謝性疾患および障害を治療するための方法およびプロバイオティック組成物 |
| CN113862168B (zh) * | 2020-06-30 | 2023-06-30 | 中国医学科学院医药生物技术研究所 | 一种副拟杆菌及其在改善肥胖或其代谢相关疾病中的应用 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014075745A1 (en) * | 2012-11-19 | 2014-05-22 | Université Catholique de Louvain | Use of akkermansia for treating metabolic disorders |
| JP2016509003A (ja) * | 2013-02-04 | 2016-03-24 | セレス セラピューティクス インコーポレイテッド | 組成物および方法 |
| US9956282B2 (en) * | 2013-12-16 | 2018-05-01 | Seres Therapeutics, Inc. | Bacterial compositions and methods of use thereof for treatment of immune system disorders |
| MA41020A (fr) * | 2014-11-25 | 2017-10-03 | Evelo Biosciences Inc | Compositions probiotiques et prébiotiques, et leurs procédés d'utilisation pour la modulation du microbiome |
| PT3071235T (pt) * | 2015-01-26 | 2018-02-21 | Kaleido Biosciences Inc | Produtos terapêuticos de glicanos e respetivos métodos relacionados |
| WO2017083520A1 (en) * | 2015-11-13 | 2017-05-18 | Cadena Bio, Inc. | Animal therapeutic and feed compositions and methods of use |
| GB201607510D0 (en) * | 2016-04-29 | 2016-06-15 | Inst Of Food Res The | Engineering gut commensal bacteria to express heterologous proteins in their outer membrane vesicles (OMV) for delivery to the GI-tract |
| US11566238B2 (en) * | 2016-12-15 | 2023-01-31 | The Board Of Trustees Of The Leland Stanford Junior University | Compositions and methods for modulating growth of a genetically modified gut bacterial cell |
| TWI640313B (zh) * | 2017-08-18 | 2018-11-11 | 長庚生物科技股份有限公司 | 戈氏副擬桿菌用於抑制肥胖之用途 |
| TWI636788B (zh) * | 2017-08-28 | 2018-10-01 | 長庚生物科技股份有限公司 | 戈氏副擬桿菌用於抑制脂肪肝疾病之用途 |
| CN107550942A (zh) * | 2017-09-08 | 2018-01-09 | 中国科学院微生物研究所 | 副拟杆菌在治疗和预防代谢性疾病中的应用 |
| JP7761556B2 (ja) * | 2019-09-18 | 2025-10-28 | リサーチ ディベロップメント ファウンデーション | 代謝性疾患および障害を治療するための方法およびプロバイオティック組成物 |
-
2017
- 2017-08-22 TW TW106128476A patent/TWI640314B/zh active
- 2017-10-23 US US15/791,010 patent/US10086019B1/en active Active
- 2017-11-29 CN CN201711228678.5A patent/CN109419817B/zh active Active
Also Published As
| Publication number | Publication date |
|---|---|
| TWI640314B (zh) | 2018-11-11 |
| CN109419817A (zh) | 2019-03-05 |
| US10086019B1 (en) | 2018-10-02 |
| CN109419817B (zh) | 2021-11-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108541221B (zh) | Hmo的混合物 | |
| Batiha et al. | Dairy-derived and egg white proteins in enhancing immune system against COVID-19 | |
| US20210052615A1 (en) | Synthetic composition for treating metabolic disorders | |
| CN113491289A (zh) | 可提升生物体对金黄色葡萄球菌感染的抵御能力的母乳低聚糖 | |
| EP3377071B1 (en) | Human milk oligosaccharides for treating antibiotic associated complications | |
| CN109419814B (zh) | 戈氏副拟杆菌用于抑制脂肪肝疾病的用途 | |
| US11890293B2 (en) | Synthetic composition for treating metabolic disorders | |
| US9956255B1 (en) | Method to reduce body weight, fat accumulation and adipocyte size using Parabacteroides goldsteinii | |
| WO2020174386A1 (en) | Composition, food supplement and method for supporting and/or improving intestinal health | |
| TWI640314B (zh) | 戈氏副擬桿菌用於降低胰島素抗性及提升葡萄糖耐受性之用途 | |
| CN113398144B (zh) | 核苷酸混合物在制备预防或缓解老年肌少症制剂中的应用 | |
| Beikmohammadi et al. | Therapeutic potential of probiotics: A review of their role in modulating inflammation | |
| dos Santos Ferreira et al. | Immunonutrition effects on coping with COVID-19 | |
| Mason | Chlorella and Spirulina: Green supplements for balancing the body | |
| US11813238B2 (en) | Medium chain fatty acids for use in the prevention or treatment of cardiac enlargement and/or valvular heart disease | |
| JP2025505760A (ja) | 腸内微生物叢におけるブラウチア・オベウムを増加／増強させることによって下痢の発生を低減するための組成物及び方法 | |
| Holečková et al. | Effect of a 3-month nutritional intervention with a high protein omega 3-enriched oral nutritional supplement on selected anthropometric and laboratory parameters and muscle strength in oncology patients | |
| RU2772955C2 (ru) | Смесь олигосахаридов человеческого грудного молока | |
| Maggini | Vitamins and minerals: contribution to immune function and health | |
| CN120569193A (zh) | 花生四烯酸乙醇胺组合物及其应用 | |
| WO2022182220A1 (es) | Sistema de soporte nutricional para activar las rutas metabólicas alteradas | |
| WO2025183547A1 (es) | Composiciones que comprenden vitaminas y minerales | |
| EP3930482A1 (en) | Composition, food supplement and method for supporting and/or improving intestinal health | |
| Meyer et al. | Amino Acid Composition Reduces Frequency of Common Colds. Results of a Controlled Randomised Completely Masked Trial | |
| Ponomareva et al. | Phytocorrection of dysbiosis in patients with chronic nonspecific inflammatory diseases of the genitals |