CN113827610A - Intestinal flora regulator and application thereof - Google Patents
Intestinal flora regulator and application thereof Download PDFInfo
- Publication number
- CN113827610A CN113827610A CN202111165752.XA CN202111165752A CN113827610A CN 113827610 A CN113827610 A CN 113827610A CN 202111165752 A CN202111165752 A CN 202111165752A CN 113827610 A CN113827610 A CN 113827610A
- Authority
- CN
- China
- Prior art keywords
- intestinal
- intestinal flora
- regulator
- sargassum
- flora
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 230000000968 intestinal effect Effects 0.000 title claims abstract description 69
- 210000001035 gastrointestinal tract Anatomy 0.000 claims abstract description 25
- 208000030159 metabolic disease Diseases 0.000 claims abstract description 13
- 206010022489 Insulin Resistance Diseases 0.000 claims abstract description 12
- 239000006041 probiotic Substances 0.000 claims abstract description 11
- 235000018291 probiotics Nutrition 0.000 claims abstract description 11
- 150000004666 short chain fatty acids Chemical class 0.000 claims abstract description 11
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 11
- 241001261005 Verrucomicrobia Species 0.000 claims abstract description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 9
- 241000702462 Akkermansia muciniphila Species 0.000 claims abstract description 8
- 230000036541 health Effects 0.000 claims abstract description 8
- 208000024891 symptom Diseases 0.000 claims abstract description 7
- 241000199919 Phaeophyceae Species 0.000 claims abstract description 6
- 235000013305 food Nutrition 0.000 claims abstract description 6
- 239000003814 drug Substances 0.000 claims abstract description 5
- 210000004347 intestinal mucosa Anatomy 0.000 claims abstract description 5
- 208000031226 Hyperlipidaemia Diseases 0.000 claims abstract description 3
- 201000001421 hyperglycemia Diseases 0.000 claims abstract description 3
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims abstract description 3
- 201000010099 disease Diseases 0.000 claims description 7
- 241000192125 Firmicutes Species 0.000 claims description 6
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 5
- 241000195474 Sargassum Species 0.000 claims description 5
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 5
- 229930000044 secondary metabolite Natural products 0.000 claims description 5
- 241000512259 Ascophyllum nodosum Species 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
- 210000000582 semen Anatomy 0.000 claims description 3
- 241000980780 Cladosiphon okamuranus Species 0.000 claims description 2
- 241000209020 Cornus Species 0.000 claims description 2
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 claims description 2
- 241000968420 Dynamena pumila Species 0.000 claims description 2
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 claims description 2
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 claims description 2
- 208000008589 Obesity Diseases 0.000 claims description 2
- 241000593522 Sargassum thunbergii Species 0.000 claims description 2
- 235000020824 obesity Nutrition 0.000 claims description 2
- 241000605059 Bacteroidetes Species 0.000 claims 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims 1
- 241001475537 Sargassum integerrimum Species 0.000 claims 1
- 241000220690 Sargassum pallidum Species 0.000 claims 1
- 239000012620 biological material Substances 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 208000033679 diabetic kidney disease Diseases 0.000 claims 1
- 239000000463 material Substances 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 235000009200 high fat diet Nutrition 0.000 abstract description 31
- 210000004185 liver Anatomy 0.000 abstract description 20
- 241000699670 Mus sp. Species 0.000 abstract description 18
- 235000021391 short chain fatty acids Nutrition 0.000 abstract description 9
- 230000001603 reducing effect Effects 0.000 abstract description 5
- 241000702460 Akkermansia Species 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 4
- 230000003907 kidney function Effects 0.000 abstract description 4
- 230000003908 liver function Effects 0.000 abstract description 4
- 201000001431 Hyperuricemia Diseases 0.000 abstract description 3
- 230000028709 inflammatory response Effects 0.000 abstract description 3
- 241001465754 Metazoa Species 0.000 abstract description 2
- 101000931570 Dictyostelium discoideum Farnesyl diphosphate synthase Proteins 0.000 description 32
- 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 20
- 210000004369 blood Anatomy 0.000 description 20
- 239000008280 blood Substances 0.000 description 20
- 239000008103 glucose Substances 0.000 description 19
- 238000013218 HFD mouse model Methods 0.000 description 15
- 230000002829 reductive effect Effects 0.000 description 13
- 230000000694 effects Effects 0.000 description 12
- 241000894006 Bacteria Species 0.000 description 11
- 229920000855 Fucoidan Polymers 0.000 description 10
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 10
- 229960003105 metformin Drugs 0.000 description 9
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 8
- 108010082126 Alanine transaminase Proteins 0.000 description 8
- 238000003304 gavage Methods 0.000 description 8
- 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
- 108010023302 HDL Cholesterol Proteins 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 6
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 6
- 235000019197 fats Nutrition 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 108010028554 LDL Cholesterol Proteins 0.000 description 5
- 241000192142 Proteobacteria Species 0.000 description 5
- 210000003494 hepatocyte Anatomy 0.000 description 5
- 241000606125 Bacteroides Species 0.000 description 4
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 102000004877 Insulin Human genes 0.000 description 4
- 108090001061 Insulin Proteins 0.000 description 4
- 102000004889 Interleukin-6 Human genes 0.000 description 4
- 108090001005 Interleukin-6 Proteins 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 235000021588 free fatty acids Nutrition 0.000 description 4
- 229940125396 insulin Drugs 0.000 description 4
- 229940100601 interleukin-6 Drugs 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 3
- 102000006395 Globulins Human genes 0.000 description 3
- 108010044091 Globulins Proteins 0.000 description 3
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 3
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 210000001072 colon Anatomy 0.000 description 3
- 229940109239 creatinine Drugs 0.000 description 3
- 230000008021 deposition Effects 0.000 description 3
- 235000013325 dietary fiber Nutrition 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 244000005709 gut microbiome Species 0.000 description 3
- 230000002440 hepatic effect Effects 0.000 description 3
- 230000002218 hypoglycaemic effect Effects 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 210000000936 intestine Anatomy 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 210000005228 liver tissue Anatomy 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 229940116269 uric acid Drugs 0.000 description 3
- 210000003934 vacuole Anatomy 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- 108020004465 16S ribosomal RNA Proteins 0.000 description 2
- 241001272701 Akkermansiaceae Species 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 208000032928 Dyslipidaemia Diseases 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 206010019837 Hepatocellular injury Diseases 0.000 description 2
- 208000017170 Lipid metabolism disease Diseases 0.000 description 2
- 206010028851 Necrosis Diseases 0.000 description 2
- 241000425347 Phyla <beetle> Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- 102100040247 Tumor necrosis factor Human genes 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 230000035508 accumulation Effects 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 210000000593 adipose tissue white Anatomy 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 238000007622 bioinformatic analysis Methods 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 238000012303 cytoplasmic staining Methods 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000007405 data analysis Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 230000037149 energy metabolism Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 210000003608 fece Anatomy 0.000 description 2
- 230000002452 interceptive effect Effects 0.000 description 2
- 230000007358 intestinal barrier function Effects 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 210000005229 liver cell Anatomy 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000003607 modifier Substances 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- 231100000915 pathological change Toxicity 0.000 description 2
- 230000036285 pathological change Effects 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 230000000529 probiotic effect Effects 0.000 description 2
- 239000002096 quantum dot Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 241000186361 Actinobacteria <class> Species 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical class CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- 102000000018 Chemokine CCL2 Human genes 0.000 description 1
- 208000036649 Dysbacteriosis Diseases 0.000 description 1
- 208000027244 Dysbiosis Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241001354491 Lasthenia californica Species 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- YKTKTXKGUAMWKD-UHFFFAOYSA-N [N].NC(N)=O.NC(N)=O Chemical compound [N].NC(N)=O.NC(N)=O YKTKTXKGUAMWKD-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000003579 anti-obesity Effects 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 230000007140 dysbiosis Effects 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 230000019439 energy homeostasis Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 230000014101 glucose homeostasis Effects 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000437 hepatocellular injury Toxicity 0.000 description 1
- 244000005702 human microbiome Species 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 210000005027 intestinal barrier Anatomy 0.000 description 1
- 210000001596 intra-abdominal fat Anatomy 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 230000006372 lipid accumulation Effects 0.000 description 1
- 230000004322 lipid homeostasis Effects 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100000849 liver cell damage Toxicity 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 208000018191 liver inflammation Diseases 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000003818 metabolic dysfunction Effects 0.000 description 1
- 230000007102 metabolic function Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 238000007410 oral glucose tolerance test Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000007863 steatosis Effects 0.000 description 1
- 231100000240 steatosis hepatitis Toxicity 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 238000002137 ultrasound extraction Methods 0.000 description 1
- 229940045136 urea Drugs 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
-
- 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
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
-
- 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
- A23L33/20—Reducing nutritive value; Dietetic products with reduced nutritive value
- A23L33/21—Addition of substantially indigestible substances, e.g. dietary fibres
-
- 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
-
- 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
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- 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)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Rheumatology (AREA)
- Food Science & Technology (AREA)
- Nutrition Science (AREA)
- Mycology (AREA)
- Polymers & Plastics (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Molecular Biology (AREA)
- Endocrinology (AREA)
- Pain & Pain Management (AREA)
- Gastroenterology & Hepatology (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Urology & Nephrology (AREA)
- Physical Education & Sports Medicine (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
The invention discloses an intestinal flora regulator derived from brown algae and application thereof. The intestinal flora regulator has been verified on an animal experimental level to remarkably increase the proportion of Verrucomicrobia (Verrucomicrobia) in intestinal tracts, increase the relative abundance of intestinal probiotics Akkermansia and Akkermansia _ muciniphila, maintain the thickness of intestinal mucosa and increase the generation of short-chain fatty acids (SCFAs). The intestinal flora regulator can reduce hyperglycemia, insulin resistance and hyperlipidemia symptoms of mice with metabolic disorder induced by high fat diet; protecting liver and kidney function, and reducing hyperuricemia and non-alcoholic fatty liver; and reducing inflammatory response in the body. The intestinal flora regulator can be widely applied to preparation of medicines, foods and/or health products for treating or preventing metabolic disorder diseases.
Description
Technical Field
The invention belongs to the field of food health care, and particularly relates to an intestinal flora regulator derived from brown algae and an application thereof.
Background
The key role of the intestinal flora in maintaining health has attracted considerable interest. The human microbiota is mainly composed of four phyla: actinomycetes (Actinobacillia), Firmicutes (Firmicutes), Proteobacteria (Proteobacteria) and Bacteroides (Bacteroides). It is estimated that there are up to 1000 different bacteria in the intestine, including nearly 200 million genes. In fact, the number of bacteria in the gastrointestinal tract is about 10 times the total cell number of the human body, which makes the total genome of bacteria much larger than the human genes. Thus, humans are also referred to as "super organisms". Based on the symbiotic relationship between intestinal bacteria and human, the intestinal flora is closely related to the physiological state of human body. Among them, the intestinal flora plays a crucial role in metabolic diseases, and may become a potential drug target for preventing and treating the diseases. The intestinal flora is an important environmental factor for regulating weight and energy homeostasis, and plays an important role in aspects of blood glucose homeostasis, impaired fasting blood glucose, type 2 diabetes, insulin resistance and the like. This "external" organ regulates the intake and storage of energy in the body through various metabolic functions and different control regimes.
Algal polysaccharides have been proposed as supplements for health enhancement and disease management. In recent years, fucoidan has become a potential adjuvant for the treatment of metabolic syndrome due to its broad activities of anti-oxidation, immunomodulation, anti-inflammation and anti-obesity. In addition, as a dietary fiber of marine origin, the regulation effect of fucoidan on intestinal flora is also gradually attracting attention. Fucoidan has been shown to alleviate metabolic disorders including lowering blood glucose, lowering blood lipid, and resisting obesity by altering the intestinal microbiota. It is contemplated that there may be structural dependence of fucoidan on the regulation of gut flora. Fucoidan with different structures also has different effects on intestinal flora. The invention discloses application of fucoidin serving as an intestinal tract regulator for specifically increasing probiotics Akkermansia _ muciniphila in improving the structure of intestinal tract flora, improving the relative abundance of intestinal tract probiotics, maintaining the thickness of intestinal mucosa and increasing secondary metabolites of the intestinal tract flora and application of the fucoidin in foods, medicines and health-care products for treating and preventing symptoms/diseases related to metabolic disorder.
Disclosure of Invention
The invention aims to provide an intestinal tract flora regulator derived from brown algae and application thereof. Animal experiments show that the intestinal flora regulator can improve intestinal flora disorder and metabolic disorder induced by high fat diet.
Further, the content of fucoidin in the intestinal flora regulator is 30% -40%, the content of sulfate group is 25% -35%, and the molecular weight range is 3kDa-9kDa, wherein the optimal value is 7 kDa. The intestinal tract regulator is prepared from one or more of brown algae such as sea brown algae including herba Zosterae Marinae, thallus laminariae, Sargassum, sea oak, cornu Cervi, Ascophyllum nodosum, thallus laminariae, Cladosiphon okamuranus, Sargassum thunbergii, Sargassum integrifolium, Cyrtymenia Sparsa, Sargassum salmias, semen Panici Miliacei, and semen Artemisiae Annuae.
The intestinal flora regulator can improve the structure of intestinal flora, improve the relative abundance of intestinal probiotics, maintain the thickness of intestinal mucosa and increase secondary metabolites of the intestinal flora.
The further intestinal flora regulator can improve the structure of intestinal flora, specifically increase the proportion of Verrucomicrobia (Verrucomicrobia) in intestinal tract and increase the ratio of Bacteroides to firmicnobia.
Further gut flora modulators are able to increase the relative abundance of gut probiotics, in particular of the probiotics Akkermansia and/or a.
Wherein, Akkermansiaceae can prevent weight gain caused by high fat diet, repair damaged intestinal barrier integrity, reduce endotoxin level in blood, and improve insulin resistance. Oral Akkermansia was shown to reverse the metabolic syndrome induced by high fat diet in mice, suggesting a potential approach to treat metabolic syndrome by manipulating Akkermansia abundance in the gut flora. Muciniphila is a widely regarded intestinal probiotic. The specific degradation of mucin makes it a key microorganism for maintaining the barrier function of intestinal mucosa. The A.muciniphila in intestinal tract can protect intestinal barrier function, reduce endotoxin level in blood plasma, and improve low-grade inflammation and metabolic disorder of organism.
The further intestinal flora regulator can increase the secondary metabolite of the intestinal flora, in particular to improve the generation of short-chain fatty acid in the intestinal tract. Short chain fatty acids are short chain organic acids containing less than 6 carbon atoms, particularly acetic, propionic, and butyric acids, produced by the digestion of dietary fiber by some intestinal bacteria. There is evidence that short chain fatty acids can reduce appetite and/or alter energy metabolism to promote health.
The intestinal flora regulator can reduce hyperglycemia, insulin resistance and hyperlipidemia symptoms of mice with metabolic disorder induced by high fat diet; protecting liver and kidney function, reducing hyperuricemia and non-alcoholic fatty liver, and reducing inflammatory reaction of organism.
The intestinal flora regulator of the invention has wide application in foods, medicines and health products for treating and preventing symptoms/diseases related to metabolic disorder.
Drawings
Figure 1. effect of fucoidan of different molecular weight on blood glucose (a) and abundance of a. muciniphila in the gut of HFD mice (b).
Fig. 2 intestinal flora modulators may improve HFD-induced intestinal microbial dysregulation. Species distribution plots, with different colors representing different phylum classification levels.
Figure 3 LEFse analyses bacterial populations with significant differences among groups.
Figure 4 level of short chain fatty acids in colon contents. Data are mean ± sd (n-8). Significance is expressed as p<0.05,**p<0.01, vs negative group;#p<0.05or##p<0.01, vs control group.
FIG. 5 intestinal flora modulators improve insulin resistance and increase insulin sensitivity in HFD mice. (a) The method comprises the following steps The intestinal flora regulator reduces the fasting blood glucose level of HFD mice; (b) the method comprises the following steps The intestinal flora regulator reduces the fasting insulin level of HFD mice; (c) the method comprises the following steps A plot of blood glucose over time; (d) the method comprises the following steps The intestinal flora regulator reduces fasting glucose tolerance of HFD mice and increases insulin 0 high fat diet; DFPS1.0-L, 100 mg/kg/d; DFPS 1.0-H200 mg/kg/d; the dose of Met to metformin is 200 mg/kg/d. Data are mean ± sd. Significance is expressed as p<0.05,**p<0.01, vs negative group;#p<0.05or##p<0.01, vs control group
FIG. 6 is a graph of the effect of gut flora modulators on the biochemical indices of the liver and kidney of HFD mice. (a) The method comprises the following steps The intestinal flora regulator reduces the liver index of the HFD mice; (b) the method comprises the following steps Effects of gut flora regulators on alanine Aminotransferase (ALT) and alanine Aminotransferase (AST); (c) the method comprises the following steps Effects of gut flora modulators on Albumin (ALB) and Globulin (GLOB). Gut flora modulators can significantly reduce urea nitrogen (urea) (d), Uric Acid (UA) (e), and Creatinine (CRE) (f) levels in HFD mice.
FIG. 7 intestinal flora modulators reduce liver cell steatosis, lipid deposition, reduce liver inflammatory response and oxidative stress. (a) Histological analysis was performed using hematoxylin and eosin staining (H & E staining). White fat vacuoles (red arrows); cell balloon-like changes (black arrows); uneven cytoplasmic staining of hepatocytes (green arrows); (b) western blot results show that the intestinal flora regulator reduces the expression of TNF alpha, IL-6 and MCP-1 and reduces the inflammatory reaction of the liver.
Detailed Description
The invention is further illustrated by the following examples, but the scope of the invention as claimed is not limited to the examples.
Example 1: regulation of blood glucose and intestinal flora in High Fat Diet (HFD) -induced mice by fucoidan of different molecular weights
Selecting male mice of C57BL/6J with kelp-derived fucoidan FL (1030Da), FM (6000Da), and FH (10kDa) of four weeks old, weighing 20 + -2 g, dividing into 4 groups of 6 mice, feeding 60% fat-powered high fat feed, and molding for 7 weeks before administration. FL (1.3Da), FM (7.2kDa), FH (10kDa) were gavaged at 200 mg/kg/day, and the blank group was gavaged with saline of the same volume. High-fat diet was continuously fed during the gavage period and blood glucose changes were monitored. After 8 weeks of dosing, mice were blood glucose measured and mouse feces were collected using sterile metabolic cages for analysis of intestinal microbes.
(1) Intestinal flora modifier for improving intestinal flora structure
The V3+ V4 region of the 16s rDNA of the enteric bacteria was amplified using primers 341F (5'-CCTAYGGGRBGCASCAG-3') and 806R (5'-GGACTACNNGGGTATCTAAT-3') (341-806). The amplification products were then pooled, purified and quantified by a fluorescence quantifier Qubit 3.0(Thermo fisher technology co., New York, USA). A new generation of sequencing was performed by Illumina Hiseq 2500PE250(Illumina, Inc, California, USA) in midio biotechnology, ltd. Bioinformatic analysis was performed using the real-time interactive data analysis online platform, Omicsmart (http:// www.omicsmart.com).
Figure 1 shows that FM and FH significantly reduced fasting blood glucose levels in HFD mice after 8 weeks of gavage, with FM showing better hypoglycemic activity than FH. Intestinal bacteria were identified and the relative abundance of probiotic a. muciniphila was found to be significantly increased in the intestines of FM group mice.
Example 2: gut flora modulator improves High Fat Diet (HFD) -induced disturbances of the gut flora in mice
The experiment was carried out using an intestinal flora regulator extracted from kelp, wherein the fucose content was 33.2%, the sulfate group content was 29.3%, and the weight average molecular weight was 7.2kDa.
Four-week-old C57BL/6J male mice were selected, and the mice were divided into 5 groups (blank group-CK group, high fat diet group-HFD group, fucoidan low dose group-DFPS-L group, fucoidan high dose group-DFPS-H group, metformin group-Met group) with a body weight of 20. + -.2 g, and 12 mice per group. The blank group was fed with 10% fat-powered normal feed. The remaining 4 groups were fed with 60% fat-energized high-fat diet, and administration was started 7 weeks after molding. The gavage normal saline is gavage 100 mg/kg/day in the high-fat diet group, the gavage 200 mg/kg/day in the high-dose group, the metformin (sigma aldrich Shanghai trade Co., Ltd.) is selected as the positive drug, and the gavage dose is 200 mg/kg/day. During the gavage period, high-fat diet was continuously fed and changes in body weight, diet, and blood sugar were monitored. After 8 weeks of dosing, mouse feces were collected in sterile metabolic cages for analysis of intestinal microbes. The mouse is dissected, and liquid nitrogen treatment is carried out on serum, liver, colon content and the like, and then the mouse is placed in a refrigerator at the temperature of-80 ℃ for standby application, and the mouse is used for biochemical determination and tissue morphology observation.
(1) Intestinal flora modifier for improving intestinal flora structure
The V3+ V4 region of the 16s rDNA of the enteric bacteria was amplified using primers 341F (5'-CCTAYGGGRBGCASCAG-3') and 806R (5'-GGACTACNNGGGTATCTAAT-3') (341-806). The amplification products were then pooled, purified and quantified by a fluorescence quantifier Qubit 3.0(Thermo fisher technology co., New York, USA). A new generation of sequencing was performed by Illumina Hiseq 2500PE250(Illumina, Inc, California, USA) in midio biotechnology, ltd. Bioinformatic analysis was performed using the real-time interactive data analysis online platform, Omicsmart (http:// www.omicsmart.com).
Fig. 1 shows that the ratio of Firmicutes to bacteroides in the HFD group is reversed (HFD: CK 0.18/2.95) and the relative abundance of Proteobacteria is significantly higher than that in the CK group (1.98%) by 13.62%. And proteobacteria are the hallmark of intestinal dysbacteriosis. DFPS significantly reduced the proportion of proteobacteria, especially in the high dose group (2.95%). The firmicutes of the DFPS group were dose-dependent decreased from 23.02% to 16.97% compared to HFD mice (61.73%). The changes described above result in a reduction in the proportion of both phyla (Firmicutes and bacterioides) in the overall gut microbiota. The relative abundance of Verrucomicrobia in HFD mice (1.92%) was significantly lower than that of CK group (15.28%). DFPS, in turn, increased the proportion of Microwartia bacteria from 40.93% to 67.65% and was dose-dependent. These changes are similar to the effect of metformin on gut microbiota.
(2) Intestinal flora regulator for increasing content of intestinal probiotics
LEFse analyzed groups of bacteria with significant differences among groups. Compared to the HFD mouse intestinal flora, the addition of DFPS and the addition of metformin showed similar differences in specific genera, with Verrucomicrobia specificity increased. The intestinal microorganism, Akkermansiaceae, which is the most representative of Verrucomicrobia, was significantly elevated in the intestine of mice supplemented with DFPS and metformin. In addition, Akkermansia _ muciniphila outbreaks also occurred in the high dose group and the metformin group. DFPS predisposes the gut flora structure to metformin on the gut level as well as on species composition. Functional prediction of picrusst 2 shows that DFPS significantly reduces the metabolic levels of three nutrients (carbohydrate, fat and protein), reducing the energy metabolism level of the body.
(3) Intestinal flora modulator for increasing production of short chain fatty acids
The colon contents (25mg) were suspended in 1.5mL of water and adjusted to pH 2-3 with 1M HCl solution. Ultrasonic extraction was carried out in an ice bath for 20 minutes, and centrifugation was carried out at 12000rpm for 15 minutes. The supernatant was added with 1ml of ethyl acetate, centrifuged at 12000rpm for 15min by vortexing, and the ethyl acetate layer was subjected to gas chromatography (Agilent 7890a, Agilent Technologies, Ca, USA). SCFAs standards were purchased from Sigma (Shanghai Sigma Aldrich training co., Shanghai, China).
Short chain fatty acids are short chain organic acids, containing less than six carbon atoms, produced by the digestion of dietary fiber by some intestinal bacteria. The effect of DFPS on intestinal flora has led us to focus on its effect on short chain fatty acids. Figure 3 shows that DFPS significantly increased intestinal short chain fatty acid levels in both low and high dose groups.
Example 3: intestinal flora modulators ameliorate High Fat Diet (HFD) -induced metabolic disorders in mice
At the end of week 8, mice were fasted for 12h and gavaged with 2g/kg of D-glucose solution. Blood glucose determination of mice blood glucose was determined 0, 30, 90 and 120min after gavage using a Roche Diagnostics GmbH (ACCU-CHEK Performa) glucometer (Roche Diagnostics GmbH, Basel, Switzerland). Glucose change curves were plotted and oral glucose tolerance (OGTT) was assessed by calculating the area under the curve. The steady state model evaluation index (HOMA-IR) was used to evaluate insulin resistance in mice according to the following formula:
HOMA-IR index ═ fasting blood glucose (mmol/L) × fasting insulin (mU/mL) ]/22.5.
At the end of 8 weeks, mouse serum was collected and biochemical indicators of blood lipid were determined using a fully automatic biochemical analyzer (laborpt 008AS, hitachi high-tech limited, tokyo, japan) of the china Qingdao gold domain detection center.
High Fat Diet (HFD) significantly increased fasting blood glucose and fasting insulin levels (fig. 4a, b), increased glucose tolerance, and decreased insulin sensitivity. The hypoglycemic effect of DFPS is dose-dependent. Low doses of DFPS significantly reduced fasting glucose and glucose tolerance, restored insulin sensitivity, and improved insulin resistance (fig. 4 e). The HOMA-IR model also showed that DFPS was effective in improving insulin resistance in HFD mice (FIG. 4 f). In particular, large doses of DFPS have the same hypoglycemic effect as metformin.
Dyslipidemia is an important feature of metabolic syndrome, including elevation of TC, CHOL, HDL-C and lowering of HDL-C. Table 1 shows that HFD causes significant increases in TG, CHOL and LDL-C and abnormal increases in HDL-C. The low dose of DFPS significantly reduced CHOL, LDL-C and HDL-C levels, and the high dose significantly reduced TG levels. The reduction of Free Fatty Acids (FFA) by DFPS was not significant. Among them, DFPS is superior to metformin in lowering CHOL, LDL-C and HDL-C, suggesting that DFPS contributes to restoration of lipid homeostasis.
Table 1. biochemical index of blood fat
And Note is biochemical index of blood fat. TG, CHOL, LDL-C, HDL-C, TG, CHOL, LDL-C, HDL-C, Free Fatty Acids (FFA) and Visceral Fat Index (VFI). Data are presented as mean ± SD (n ═ 8).abcGroups that are not identical letters in a row are indicated as significantly different groups, at a level of p < 0.05 by one-way ANOVA test.
Example 4: intestinal flora regulator for improving High Fat Diet (HFD) -induced liver and kidney function injury of mice
A full-automatic biochemical analyzer (LABOSPECT 008AS, Hitachi high-tech limited company, Tokyo, Japan) of the detection center of Qingdao gold field in China is adopted to measure biochemical indexes of liver function and kidney function.
The liver is the largest organ of the body and is the central organ that regulates lipid metabolism. Dyslipidemia and accumulation of hepatic triglycerides cause liver disease, thereby affecting the normal function of the liver. The biochemical index of the serum liver can reflect the pathological changes of the liver. DFPS reduced liver lipid accumulation, manifested as a decrease in liver index (fig. 5 a). ALT and AST are sensitive indicators of liver cell damage. When cells are damaged and cell membrane permeability increases, the levels of both enzymes in serum rise. As shown in fig. 5b, HFD doubled ALT and AST levels and significant damage to hepatocytes. DFPS significantly reduced AST levels, but low doses had no significant effect on ALT levels. At high doses, levels of alanine Aminotransferase (ALT) and aspartate Aminotransferase (AST) were both significantly reduced, suggesting that DFPS may reduce hepatocellular injury. In addition, DFPS also significantly reduced GLOB, suggesting that DFPS may reduce liver inflammation and infection (fig. 5 c). In conclusion, supplementation with DFPS can ameliorate the metabolic dysfunction caused by HFD. The protective effect of DFPS on the kidney of HFD mice was further observed. DFPS significantly reduced UA, CRE and urea even to normal levels (fig. 5d, e, f), indicating that DFPS reduced the incidence of renal insufficiency and hyperuricemia in HFD mice.
Fresh liver tissue was taken for histological analysis. The tissue was soaked in 4% paraformaldehyde for 24h, dehydrated and embedded in paraffin. The fixed tissues were cut into 5 μm thick sections and stained with hematoxylin and eosin (H & E). The slices were scanned by a digital pathology scanner (Leica Aperio CS2, Leica biological Systems inc., Nussloch, Germany) to generate representative images.
The effect of DFPS on liver was further analyzed by histological analysis. As can be seen in fig. 6a, HFD increases liver fat deposition, altering liver morphology. The hepatic lobular margin of HFD mice was unclear. Intrahepatic fat deposits form white fat vacuoles (red arrows) and intrahepatic fat pushes the nucleus to the edge, making the hepatocytes balloon-like (black arrows). Meanwhile, uneven cytoplasmic staining of hepatocytes (green arrows) may indicate hepatocyte deformation or necrosis. DFPS reduced the number of fat vacuoles and no significant cell deformation or necrosis was seen. In particular, high doses of DFPS can even restore liver morphology to normal levels. Histological observation shows that DFPS can effectively reduce liver fat deposition and reduce liver cell pathological changes caused by HFD.
Extracting the hepatic protein to carry out western blot. Liver tissue (20mg) was washed twice with cold PBS and lysis buffer (containing 0.1mM PMSF and protease inhibitor) was dissolved. Protein concentration was determined using BCA kit (Solaibao Technology co., Beijing, China). Proteins were separated by polyacrylamide gel electrophoresis (SDS-PAGE), transferred to PVDF membrane, blotted with each antibody, and detected with ECL reagent. Tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein 1(MCP-1), and interleukin-6 (IL-6) (Santa Cruz Biotechnology, Santa Cruz, Calif., USA) were determined.
It is well known that chronic inflammation plays an important role in the development of T2DM and MetS 21. Accumulation of liver fat leads to an increase in inflammatory cytokines and oxidative stress. Western blot was used to detect the expression of inflammatory cytokines (TNF. alpha., IL-6, MCP-1) in liver tissues. As shown in fig. 6b, DFPS effectively reduced inflammatory factor levels, attenuating HFD-induced inflammatory responses. The above examples are only intended to illustrate the technical solution of the present invention, but not to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof; such modifications and substitutions do not depart from the spirit and scope of the corresponding technical solutions.
Claims (10)
1. An intestinal flora modulator, characterized in that: the main component of the product is low molecular weight fucoidin.
2. The modulator of claim 1, wherein: the intestinal flora regulator is prepared from one or more of marine brown algae including herba Zosterae Marinae, thallus laminariae, Sargassum, sea oak, cornu Cervi, Ascophyllum nodosum, thallus laminariae, Cladosiphon okamuranus, Sargassum thunbergii, Sargassum integerrimum, Cyrtymenia Sparsa, Sargassum Ammoniacus, semen Panici Miliacei, and Sargassum pallidum.
3. The modulator of claim 1, wherein: the intestinal flora regulator contains fucose 30-40%, sulfate 25-35%, and molecular weight of 3-9 kDa.
4. Use of a modulator according to claims 1-3 for improving the structure of the intestinal flora, characterized in that: the application of improving the structure of the intestinal flora, namely increasing the relative abundance of specific probiotics Akkermansia _ muciniphila, maintaining the thickness of intestinal mucosa and increasing secondary metabolites of the intestinal flora.
5. Use according to claim 4, characterized in that: the structure for improving the intestinal flora is to increase the proportion of Verrucomicrobia (Verrucomicrobia) in the intestinal tract and increase the ratio of bacteroidetes to firmicutes.
6. Use according to claim 4, characterized in that: the intestinal probiotics are Akkermanspiaceae and Akkermansia _ muciniphila.
7. Use according to claim 4, characterized in that: the secondary metabolite of the intestinal flora is short-chain fatty acid.
8. Use of the intestinal flora modulator according to claims 1-3 in food, pharmaceutical, health care products for the treatment and prevention of symptoms/diseases associated with metabolic disorders.
9. The symptoms/diseases associated with metabolic disorders according to claim 8 include obesity, hyperglycemia, insulin resistance, hyperlipidemia, diabetic nephropathy, non-alcoholic fatty liver disease, inflammatory bowel disease, metabolic syndrome and the like.
10. Use according to claim 8, characterized in that: the food, medicine, health product and biological material for treating and preventing metabolic disorder related symptoms/diseases can be added with pharmaceutically and biologically acceptable carriers or auxiliary materials.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111165752.XA CN113827610A (en) | 2021-09-30 | 2021-09-30 | Intestinal flora regulator and application thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111165752.XA CN113827610A (en) | 2021-09-30 | 2021-09-30 | Intestinal flora regulator and application thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
CN113827610A true CN113827610A (en) | 2021-12-24 |
Family
ID=78968126
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202111165752.XA Pending CN113827610A (en) | 2021-09-30 | 2021-09-30 | Intestinal flora regulator and application thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN113827610A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115590865A (en) * | 2022-10-19 | 2023-01-13 | 中国海洋大学(Cn) | Application of brown algae oligosaccharide in preparation of product for improving intestinal flora disorder |
Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1616494A (en) * | 2004-10-18 | 2005-05-18 | 中国科学院海洋研究所 | Method for preparing low molecular weight seaweed polysaccharide sulfate |
JP2006087393A (en) * | 2004-09-27 | 2006-04-06 | Global Science:Kk | Health food and medicine |
CN101152208A (en) * | 2006-09-27 | 2008-04-02 | 中国科学院海洋研究所 | Application of brown seaweed polyoses sulfate in preparing medicament for treating senile dementia |
CN101301310A (en) * | 2007-05-08 | 2008-11-12 | 首都医科大学 | Use of brown alga polysaccharide sulfate in preventing and treating Parkinson's disease |
CN104586878A (en) * | 2015-01-14 | 2015-05-06 | 青岛海洋生物医药研究院股份有限公司 | Fucoidan sulfate and application of low-molecular-weight fucoidan sulfate in preparation of metabolic syndrome resistant medicines and health products |
CN108904524A (en) * | 2018-06-22 | 2018-11-30 | 中国海洋大学 | Low molecular weight fucoidan is preventing and treating the application in enteritis |
CN109091496A (en) * | 2018-08-06 | 2018-12-28 | 大连工业大学 | The application and pharmaceutical composition of sea cucumber sulfated polysaccharide and its oligomer |
WO2019211442A1 (en) * | 2018-05-04 | 2019-11-07 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Fucoidans from diatoms |
CN111499770A (en) * | 2020-04-20 | 2020-08-07 | 大连工业大学 | Brown algae fucoidin, preparation method thereof and application of brown algae fucoidin in improving intestinal flora |
CN111728976A (en) * | 2020-07-15 | 2020-10-02 | 西南大学 | Application of fucooligosaccharide in preparation of intestinal prebiotics |
-
2021
- 2021-09-30 CN CN202111165752.XA patent/CN113827610A/en active Pending
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006087393A (en) * | 2004-09-27 | 2006-04-06 | Global Science:Kk | Health food and medicine |
CN1616494A (en) * | 2004-10-18 | 2005-05-18 | 中国科学院海洋研究所 | Method for preparing low molecular weight seaweed polysaccharide sulfate |
CN101152208A (en) * | 2006-09-27 | 2008-04-02 | 中国科学院海洋研究所 | Application of brown seaweed polyoses sulfate in preparing medicament for treating senile dementia |
CN101301310A (en) * | 2007-05-08 | 2008-11-12 | 首都医科大学 | Use of brown alga polysaccharide sulfate in preventing and treating Parkinson's disease |
CN104586878A (en) * | 2015-01-14 | 2015-05-06 | 青岛海洋生物医药研究院股份有限公司 | Fucoidan sulfate and application of low-molecular-weight fucoidan sulfate in preparation of metabolic syndrome resistant medicines and health products |
WO2019211442A1 (en) * | 2018-05-04 | 2019-11-07 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Fucoidans from diatoms |
CN108904524A (en) * | 2018-06-22 | 2018-11-30 | 中国海洋大学 | Low molecular weight fucoidan is preventing and treating the application in enteritis |
CN109091496A (en) * | 2018-08-06 | 2018-12-28 | 大连工业大学 | The application and pharmaceutical composition of sea cucumber sulfated polysaccharide and its oligomer |
CN111499770A (en) * | 2020-04-20 | 2020-08-07 | 大连工业大学 | Brown algae fucoidin, preparation method thereof and application of brown algae fucoidin in improving intestinal flora |
CN111728976A (en) * | 2020-07-15 | 2020-10-02 | 西南大学 | Application of fucooligosaccharide in preparation of intestinal prebiotics |
Non-Patent Citations (3)
Title |
---|
DENG Z,等: "Low molecular weight fucoidan fraction LF2 improves metabolic syndrome via up-regulating PI3K-AKT-mTOR axis and increasing the abundance of Akkermansia muciniphila in the gut microbiota", INT J BIOL MACROMOL * |
XU Y,等: "Low molecular weight fucoidan ameliorates the inflammation and glomerular filtration function of diabetic nephropathy", J APPL PHYCOL * |
黄金莉,等: "岩藻多糖对代谢性疾病及肠道菌群调节作用研究进展", 现代预防医学 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115590865A (en) * | 2022-10-19 | 2023-01-13 | 中国海洋大学(Cn) | Application of brown algae oligosaccharide in preparation of product for improving intestinal flora disorder |
CN115590865B (en) * | 2022-10-19 | 2024-02-02 | 中国海洋大学 | Application of brown alginate oligosaccharides in preparation of product for improving intestinal flora disorder |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Gaudier et al. | Butyrate specifically modulates MUC gene expression in intestinal epithelial goblet cells deprived of glucose | |
Chen et al. | Bamboo-shaving polysaccharide protects against high-diet induced obesity and modulates the gut microbiota of mice | |
Qu et al. | Kiwifruit seed oil prevents obesity by regulating inflammation, thermogenesis, and gut microbiota in high-fat diet-induced obese C57BL/6 mice | |
CN108367030B (en) | Use of fecal bacillus prodigiosus and Desulfovibrio inerticus for treating or preventing diabetes and intestinal diseases | |
Zhang et al. | Evaluation of the efficacy of chlorogenic acid in reducing small intestine injury, oxidative stress, and inflammation in chickens challenged with Clostridium perfringens type A | |
CN110150669B (en) | Probiotic composition suitable for diabetic patients and application thereof | |
CN110248646A (en) | Slow releasing composition comprising pirfenidone is used to treat and reverse the medicinal usage of people's steatohepatitis (NAFLD/NASH) | |
CN113197921B (en) | Application of bifidobacterium lactis MN-Gup and microbial inoculum thereof in treating type 2 diabetes | |
Wang et al. | Nanoparticles isolated from porcine bone soup ameliorated dextran sulfate sodium-induced colitis and regulated gut microbiota in mice | |
WO2020006663A1 (en) | Novel lactobacillus paracasei gks6 for mitigating metabolic syndrome, culture medium thereof, culture method, use, pharmaceutical composition, and edible composition | |
Feng et al. | Effects of β-carotin and green tea powder diets on alleviating the symptoms of gouty arthritis and improving gut microbiota in C57BL/6 mice | |
Zhang et al. | Ameliorative effect of tuna elastin peptides on AIA mice by regulating the composition of intestinal microorganisms and SCFAs | |
Li et al. | d-Arabitol Ameliorates Obesity and Metabolic Disorders via the Gut Microbiota–SCFAs–WAT Browning Axis | |
CN101897687B (en) | New application of sodium valproate in treating liver inflammation related disease | |
CN111493325A (en) | Application of plant selenium peptide in preparation of composition for improving obesity and metabolic syndrome | |
CN115887485A (en) | Application of pachyman in regulating intestinal microbial structure and metabolite of obese organism | |
CN113827610A (en) | Intestinal flora regulator and application thereof | |
Wang et al. | Anti‐diabetic effect of banana peel dietary fibers on type 2 diabetic mellitus mice induced by streptozotocin and high‐sugar and high‐fat diet | |
Liao et al. | Flavonoids from Lycium barbarum leaves attenuate obesity through modulating glycolipid levels, oxidative stress, and gut bacterial composition in high-fat diet-fed mice | |
Wang et al. | Pretreatment with lactobacillus fermentum XY18 relieves gastric injury induced by HCl/ethanol in mice via antioxidant and anti-inflammatory mechanisms | |
CN110123824B (en) | Ilicis Pubescentis saponin A1New use of | |
CN112457423A (en) | Natural extracted compound polysaccharide with function of improving insulin resistance and application thereof | |
Wang et al. | Foxtail millet (Setaria italica) alleviates non-alcoholic fatty liver disease in high-fat diet/streptozotocin-induced diabetic mice through gut microbiota modulation | |
CN110771769A (en) | Chitosan oligosaccharide composite solid beverage for adjuvant therapy of type II diabetes | |
CN110420270A (en) | A kind of functional composition containing camellia oil and fish oil and its application |
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 | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20211224 |
|
RJ01 | Rejection of invention patent application after publication |