CN116942685A - Application of acidic goat milk oligosaccharide composition in preparation of antiallergic drugs or foods - Google Patents
Application of acidic goat milk oligosaccharide composition in preparation of antiallergic drugs or foods Download PDFInfo
- Publication number
- CN116942685A CN116942685A CN202310998230.0A CN202310998230A CN116942685A CN 116942685 A CN116942685 A CN 116942685A CN 202310998230 A CN202310998230 A CN 202310998230A CN 116942685 A CN116942685 A CN 116942685A
- Authority
- CN
- China
- Prior art keywords
- sugar chains
- composition
- goat milk
- acidic
- sialylated
- 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
- 150000002482 oligosaccharides Chemical class 0.000 title claims abstract description 50
- 235000020251 goat milk Nutrition 0.000 title claims abstract description 49
- 239000000203 mixture Substances 0.000 title claims abstract description 46
- 229920001542 oligosaccharide Polymers 0.000 title claims abstract description 46
- 230000002378 acidificating effect Effects 0.000 title claims abstract description 35
- 235000013305 food Nutrition 0.000 title claims abstract description 7
- 239000000043 antiallergic agent Substances 0.000 title claims abstract description 6
- 238000002360 preparation method Methods 0.000 title claims abstract description 6
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 claims abstract description 26
- 125000005630 sialyl group Chemical group 0.000 claims abstract description 24
- SQVRNKJHWKZAKO-LUWBGTNYSA-N N-acetylneuraminic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)CC(O)(C(O)=O)O[C@H]1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-LUWBGTNYSA-N 0.000 claims abstract description 14
- FDJKUWYYUZCUJX-AJKRCSPLSA-N N-glycoloyl-beta-neuraminic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@@H]1O[C@](O)(C(O)=O)C[C@H](O)[C@H]1NC(=O)CO FDJKUWYYUZCUJX-AJKRCSPLSA-N 0.000 claims abstract description 12
- FDJKUWYYUZCUJX-UHFFFAOYSA-N N-glycolyl-beta-neuraminic acid Natural products OCC(O)C(O)C1OC(O)(C(O)=O)CC(O)C1NC(=O)CO FDJKUWYYUZCUJX-UHFFFAOYSA-N 0.000 claims abstract description 12
- 230000004048 modification Effects 0.000 claims abstract description 11
- 238000012986 modification Methods 0.000 claims abstract description 11
- 230000000968 intestinal effect Effects 0.000 claims description 21
- 230000007935 neutral effect Effects 0.000 claims description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 18
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
- 210000003289 regulatory T cell Anatomy 0.000 claims description 16
- 206010061218 Inflammation Diseases 0.000 claims description 14
- 230000004054 inflammatory process Effects 0.000 claims description 14
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 12
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 claims description 12
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 claims description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
- 210000002966 serum Anatomy 0.000 claims description 10
- 241000986886 Marinifilaceae Species 0.000 claims description 9
- 230000009286 beneficial effect Effects 0.000 claims description 9
- 239000012154 double-distilled water Substances 0.000 claims description 9
- 229960001340 histamine Drugs 0.000 claims description 9
- 241001112693 Lachnospiraceae Species 0.000 claims description 8
- 108010078777 Colistin Proteins 0.000 claims description 7
- 241001468155 Lactobacillaceae Species 0.000 claims description 7
- 229960003346 colistin Drugs 0.000 claims description 7
- JORAUNFTUVJTNG-BSTBCYLQSA-N n-[(2s)-4-amino-1-[[(2s,3r)-1-[[(2s)-4-amino-1-oxo-1-[[(3s,6s,9s,12s,15r,18s,21s)-6,9,18-tris(2-aminoethyl)-3-[(1r)-1-hydroxyethyl]-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-h Chemical compound CC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@H]([C@@H](C)O)CN[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O.CCC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@H]([C@@H](C)O)CN[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O JORAUNFTUVJTNG-BSTBCYLQSA-N 0.000 claims description 7
- XDJYMJULXQKGMM-UHFFFAOYSA-N polymyxin E1 Natural products CCC(C)CCCCC(=O)NC(CCN)C(=O)NC(C(C)O)C(=O)NC(CCN)C(=O)NC1CCNC(=O)C(C(C)O)NC(=O)C(CCN)NC(=O)C(CCN)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(CCN)NC1=O XDJYMJULXQKGMM-UHFFFAOYSA-N 0.000 claims description 7
- KNIWPHSUTGNZST-UHFFFAOYSA-N polymyxin E2 Natural products CC(C)CCCCC(=O)NC(CCN)C(=O)NC(C(C)O)C(=O)NC(CCN)C(=O)NC1CCNC(=O)C(C(C)O)NC(=O)C(CCN)NC(=O)C(CCN)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(CCN)NC1=O KNIWPHSUTGNZST-UHFFFAOYSA-N 0.000 claims description 7
- 108090000978 Interleukin-4 Proteins 0.000 claims description 6
- 241000692844 Prevotellaceae Species 0.000 claims description 6
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 6
- 230000035755 proliferation Effects 0.000 claims description 6
- 235000019260 propionic acid Nutrition 0.000 claims description 6
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 6
- 241000609971 Erysipelotrichaceae Species 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 239000001913 cellulose Substances 0.000 claims description 4
- 229920002678 cellulose Polymers 0.000 claims description 4
- 230000004069 differentiation Effects 0.000 claims description 4
- 230000006378 damage Effects 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 229910002804 graphite Inorganic materials 0.000 claims description 3
- 239000010439 graphite Substances 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 239000006228 supernatant Substances 0.000 claims description 3
- 238000010257 thawing Methods 0.000 claims description 3
- 241000606126 Bacteroidaceae Species 0.000 claims description 2
- 235000020254 sheep milk Nutrition 0.000 claims description 2
- 125000005629 sialic acid group Chemical group 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 2
- 241000193403 Clostridium Species 0.000 claims 1
- 241001467894 Desulfovibrionaceae Species 0.000 claims 1
- 239000011780 sodium chloride Substances 0.000 claims 1
- 230000003266 anti-allergic effect Effects 0.000 abstract description 17
- 239000000126 substance Substances 0.000 abstract description 5
- 108010058846 Ovalbumin Proteins 0.000 description 39
- 229940092253 ovalbumin Drugs 0.000 description 39
- 241000699670 Mus sp. Species 0.000 description 36
- 230000002829 reductive effect Effects 0.000 description 16
- 208000010668 atopic eczema Diseases 0.000 description 12
- QVFWZNCVPCJQOP-UHFFFAOYSA-N chloralodol Chemical compound CC(O)(C)CC(C)OC(O)C(Cl)(Cl)Cl QVFWZNCVPCJQOP-UHFFFAOYSA-N 0.000 description 12
- 230000000052 comparative effect Effects 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 241000699666 Mus <mouse, genus> Species 0.000 description 11
- 230000000172 allergic effect Effects 0.000 description 11
- 235000020247 cow milk Nutrition 0.000 description 11
- 102000015728 Mucins Human genes 0.000 description 10
- 108010063954 Mucins Proteins 0.000 description 10
- 108090000695 Cytokines Proteins 0.000 description 8
- 102000004127 Cytokines Human genes 0.000 description 8
- 208000004262 Food Hypersensitivity Diseases 0.000 description 8
- 206010016946 Food allergy Diseases 0.000 description 8
- 235000020932 food allergy Nutrition 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- 235000013336 milk Nutrition 0.000 description 7
- 239000008267 milk Substances 0.000 description 7
- 210000004080 milk Anatomy 0.000 description 7
- 241000894006 Bacteria Species 0.000 description 6
- 210000001072 colon Anatomy 0.000 description 6
- 230000004989 O-glycosylation Effects 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 230000033581 fucosylation Effects 0.000 description 5
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 4
- 241001112696 Clostridia Species 0.000 description 4
- 102100037850 Interferon gamma Human genes 0.000 description 4
- 108010074328 Interferon-gamma Proteins 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 235000021255 galacto-oligosaccharides Nutrition 0.000 description 4
- 150000003271 galactooligosaccharides Chemical class 0.000 description 4
- 208000037817 intestinal injury Diseases 0.000 description 4
- 229960003088 loratadine Drugs 0.000 description 4
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 description 4
- 210000001165 lymph node Anatomy 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 230000009450 sialylation Effects 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 3
- 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 description 3
- 241001607451 Oscillospiraceae Species 0.000 description 3
- 206010070834 Sensitisation Diseases 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 208000026935 allergic disease Diseases 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000024245 cell differentiation Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 210000003608 fece Anatomy 0.000 description 3
- 210000002865 immune cell Anatomy 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000008313 sensitization Effects 0.000 description 3
- 150000004666 short chain fatty acids Chemical class 0.000 description 3
- 235000021391 short chain fatty acids Nutrition 0.000 description 3
- 230000019635 sulfation Effects 0.000 description 3
- 238000005670 sulfation reaction Methods 0.000 description 3
- 210000001541 thymus gland Anatomy 0.000 description 3
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 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 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
- 241000186660 Lactobacillus Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 239000013566 allergen Substances 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 239000003613 bile acid Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 238000006206 glycosylation reaction Methods 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- 210000004347 intestinal mucosa Anatomy 0.000 description 2
- 244000005700 microbiome Species 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
- 239000000047 product Substances 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000004451 qualitative analysis Methods 0.000 description 2
- 238000004445 quantitative analysis Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- 230000001018 virulence Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- XYHKNCXZYYTLRG-UHFFFAOYSA-N 1h-imidazole-2-carbaldehyde Chemical compound O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-M 3-Methylbutanoic acid Natural products CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 206010002199 Anaphylactic shock Diseases 0.000 description 1
- 241001538513 Caerulea Species 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 1
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 1
- 238000004977 Hueckel calculation Methods 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 101001002703 Mus musculus Interleukin-4 Proteins 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 241000192142 Proteobacteria Species 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 210000004241 Th2 cell Anatomy 0.000 description 1
- 241001122767 Theaceae Species 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 210000004082 barrier epithelial cell Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N beta-methyl-butyric acid Natural products CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 238000010835 comparative analysis Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 235000013325 dietary fiber Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 238000005265 energy consumption Methods 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
- 229960005139 epinephrine Drugs 0.000 description 1
- 230000004890 epithelial barrier function Effects 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000002550 fecal effect Effects 0.000 description 1
- 239000000834 fixative Substances 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 210000002175 goblet cell Anatomy 0.000 description 1
- 230000007412 host metabolism Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 210000002490 intestinal epithelial cell Anatomy 0.000 description 1
- 230000009856 intestinal mucosal lesion Effects 0.000 description 1
- 230000003870 intestinal permeability Effects 0.000 description 1
- 210000001630 jejunum Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 230000007373 microbial translocation Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000006041 probiotic Substances 0.000 description 1
- 235000018291 probiotics Nutrition 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 229940043517 specific immunoglobulins Drugs 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- -1 sulfated Chemical compound 0.000 description 1
- 235000019722 synbiotics Nutrition 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 229940005605 valeric acid Drugs 0.000 description 1
- 230000008673 vomiting Effects 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
-
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to the use of an acidic goat milk oligosaccharide composition for the preparation of an antiallergic drug or food, said composition comprising 24 acidic sugar chains 24SMAOs, said 24SMAOs comprising 12 Neu5Ac modified sialylated sugar chains, 10 Neu5Gc modified sialylated sugar chains and 2 sialylated sugar chains having both Neu5Ac and Neu5Gc modifications, classified according to the sialyl linkage, comprising 11 alpha 2,3 linked sialyl sugar chains, 10 alpha 2,6 linked sialyl sugar chains and 3 sialyl sugar chains having both alpha 2,3 and alpha 2,6 linkages, classified according to the sialyl structure. The composition belongs to natural antiallergic substances, has safety and effectiveness, and realizes excellent antiallergic performance.
Description
Technical Field
The invention belongs to the field of biological preparations, and particularly relates to application of an acidic goat milk oligosaccharide composition in preparation of antiallergic drugs or foods.
Background
Food Allergy (FA) is an abnormal immune response characterized by the involvement of allergen-specific immunoglobulins E (IgE) and Th2 cells. Research shows that the development of immune cells and cytokines (interleukin (IL) -4), active medium (beta-Hex and histamine) and the like produced by the immune cells can cause a series of allergic symptoms such as vomiting, diarrhea, anaphylactic shock and death and the like of organisms, and the development of immune cells and the cytokines (beta-Hex and histamine) and the like cause great threat to public health safety. Currently, therapeutic drugs for food allergy (epinephrine, antihistamine or glucocorticoid) do not fundamentally eliminate the sensitivity of the allergen to the patient, and may cause drug dependence or even adverse reaction. Therefore, it is important to find safe and effective natural antiallergic substances to reduce the risk of food allergy.
Disclosure of Invention
The invention provides an application of an acidic goat milk oligosaccharide composition in preparing antiallergic drugs or foods, solves the technical problem that natural antiallergic substances are lacking in the prior art, can relieve intestinal injury and inflammation, and has excellent antiallergic activity.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:
use of an acidic goat milk oligosaccharide composition comprising 24 acidic sugar chains 24SMAOS, said 24SMAOS comprising 12 Neu5Ac modified sialylated sugar chains, 10 Neu5Gc modified sialylated sugar chains and 2 sialylated sugar chains having both Neu5Ac and Neu5Gc modifications, classified according to sialic acid linkage, comprising 11 α2,3 linked sialyl sugar chains, 10 α2,6 linked sialyl sugar chains and 3 sialyl sugar chains having both α2,3 and α2,6 linkages, in the manufacture of an antiallergic medicament or food.
Further, the content of the 12 kinds of Neu5Ac modified sialylated sugar chains was 52%, the content of the 10 kinds of Neu5Gc modified sialylated sugar chains was 45%, and the content of the 2 kinds of sialylated sugar chains having both Neu5Ac modification and Neu5Gc modification was 3%.
Further, the content of the 11 kinds of α2, 3-linked sialyl sugar chains was 28%, the content of the 10 kinds of α2, 6-linked sialyl sugar chains was 68%, and the content of the 3 kinds of α2, 3-and α2, 6-linked sialyl sugar chains was 4%.
Further, the composition alleviates intestinal damage and inflammation.
Further, the composition reduces sIgE, histamine, igG2a, IFN-gamma, IL-4 in serum.
Further, the composition induces differentiation of Treg cells.
Further, the composition not only regulates the relative abundance of Lachnospiraceae, erysipelotrichaceae and Bactoidaceae to return to normal levels, but also promotes proliferation of beneficial bacteria Lactobacillaceae, marinifilaceae and Clostridia caerulea, reduces the relative abundance of Desulfovibrionaeae, and promotes the relative abundance of Prevotellaceae, marinifilaceae and Lactobacilli.
Further, the composition increases the concentration of acetic acid, propionic acid, and isobutyric acid in the intestinal tract.
Further, the composition restores the expression of the O-sugar chain of colistin.
Further, the composition is prepared by the following method: taking a certain amount of sheep milk, thawing at normal temperature, and centrifuging to remove fat; adding ethanol with the volume of 2 times of the goat milk, fully and uniformly mixing, centrifuging, collecting supernatant, and freeze-concentrating and drying to obtain freeze-dried goat milk crude oligosaccharide; dissolving the freeze-dried crude goat milk oligosaccharide in double distilled water, slowly adding the double distilled water into a DEAE-52 cellulose chromatographic column, eluting neutral goat milk oligosaccharide by double distilled water, and continuously adding 0.25MNaCl solution to elute acidic goat milk oligosaccharide; washing the acidic goat milk oligosaccharide with graphite carbon column to remove salt, and obtaining the composition.
Further, the conditions of both centrifugation processes include: 3-5 ℃,8000-13000rpm,15-30min.
Compared with the prior art, the technical scheme of the invention has the following beneficial effects:
1. the acidic goat milk oligosaccharide composition is derived from goat milk, belongs to natural antiallergic substances, and has safety and effectiveness;
2. the acidic goat milk oligosaccharide composition provided by the invention maximally retains the antiallergic active ingredients in goat milk, and obtains excellent antiallergic performance;
3. the acidic goat milk oligosaccharide composition disclosed by the invention can relieve intestinal injury and inflammation, reduce sIgE, histamine, igG2a, IFN-gamma and IL-4 in serum, induce Treg cell differentiation to inhibit Th2 reaction, regulate the relative abundance of Lachnospiraceae, erysipelotrichaceae and Bactoidaceae to be recovered to a normal level, promote the proliferation of beneficial bacteria Lactobacillaceae, marinifilaceae and Clostridia acede, reduce the relative abundance of Desulfovineiganaceae, promote the relative abundance of Prevotellaceae, marinifilaceae and Lactobacteriaceae, improve the concentration of acetic acid, propionic acid and isobutyric acid in intestinal tracts, recover the expression of mucin O-sugar chains and realize an antiallergic function.
Drawings
FIG. 1 is an antiallergic activity evaluation of example 1 and comparative example 1 of the present invention;
FIG. 2 shows the effect of example 1 and comparative example 1 of the invention on antibodies, allergic mediators and cytokines in mouse serum;
FIG. 3 is the effect of example 1 and comparative example 1 of the invention on the differentiation of mouse mesenteric lymph node cell Treg cells;
FIG. 4 shows the effect of example 1 and comparative example 1 of the present invention on intestinal microorganisms in mice;
FIG. 5 shows the effect of example 1 and comparative example 1 of the present invention on short chain fatty acids in mouse feces;
FIG. 6 is the effect of example 1 and comparative example 1 of the present invention on the O-glycosylation level of colistin;
FIG. 7 shows qualitative and quantitative analyses of example 1 and comparative example 1 of the present invention.
Detailed Description
The principles and features of the present invention are described below in connection with the following examples, which are set forth to illustrate, but are not to be construed as limiting the scope of the invention. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
Materials:
goat milk (Shaneng milk goat, mature milk, 30 mixed samples) was provided by the milk goat breeding base of the red star meiling stock company. Cow's milk (Hestent cow, mature milk, 30 mixed samples in China) is supplied from the Yan Liangou sea pasture of Sian, shaanxi, so the samples are transferred to a-80℃refrigerator for storage within 2 hours. Aniline, deuterated (d 5-) aniline, activated carbon, ovalbumin (OVA), aluminum adjuvant, protease inhibitor (PMSF) were all purchased from Sigma-Aldrich, usa; loratadine (Lora) was purchased from Cinnan Possen pharmaceutical Co., ltd; sep-PakC18 (200 mg/3 mL) and Porous Graphitic Carbon (PGC) (150 mg/3 mL) solid phase extraction cartridges are products of Simonaldrich, germany. DEAE-52 cellulose was purchased from Synbiotics Biotech Inc. The other reagents were all analytically pure. The water used in the experiments was purified by the Milli-Q ultra pure water system of Millipore, U.S.A..
Example 1:
thawing 2L of goat milk at normal temperature, centrifuging to remove fat (8000 rpm,20 min), adding 2 times volume of ethanol respectively, mixing completely, centrifuging (10000 rpm,30 min), collecting supernatant, and freeze concentrating and drying to obtain lyophilized goat milk crude oligosaccharide. Dissolving the freeze-dried crude goat milk oligosaccharide in double distilled water, slowly adding the double distilled water into a DEAE-52 cellulose chromatographic column, eluting the neutral goat milk oligosaccharide by using 3 times of column volume double distilled water, and continuously adding 3 times of column volume 0.25MNaCl solution to elute the acidic goat milk oligosaccharide. The acidic goat milk oligosaccharide obtained above was washed with water using a graphite carbon column to remove salt, to obtain the acidic goat milk oligosaccharide composition of example 1. The above neutral goat milk oligosaccharide was loaded on an activated carbon column, lactose was removed by 10 times of 8% ethanol in the column volume, and then eluted by 3 times of 70% ethanol in the column volume, to obtain a lactose-removed neutral goat milk oligosaccharide composition of example 1.
Comparative example 1:
the difference from example 1 is that: the acidic milk oligosaccharide composition and the neutral milk oligosaccharide composition of comparative example 1 were obtained by substituting the goat milk of example 1 with cow milk.
Test experiment:
1. evaluation of antiallergic Activity in mice
Female Balb/c mice (body weight 20.+ -.2 g) of the 6 week old clean class were offered by the university of Western An traffic medical college animal center. Balb/c mice were kept in SPF-grade environment, at standard temperature (21-23 ℃) and humidity (45-55%), and after one week of adaptive feeding, subsequent experiments were performed. All animal experiments were approved for animal management and ethics at university of northwest (ethical approval No. NWU-AWC-20210903M).
Mice were randomly divided into 7 groups (control group (blank group), OVA group (model group), lora group (loratadine drug group), SGMOs group (acid galactooligosaccharide composition of example 1), NGMOs group (neutral galactooligosaccharide composition of example 1), SBMOs group (acid galactooligosaccharide composition of comparative example 1), and NBMOs group (neutral galactooligosaccharide composition of comparative example 1)), 6 each. All other groups except the control group were intraperitoneally injected with 200 μl of sensitization solution (OVA: aluminum adjuvant: pbs=1:1:1 (v: v)) on day 0 and day 14 for 2 induction sensitization. From 27 to 40 days, control and OVA mice were gavaged with PBS, lora with loratadine (0.2 mg/kg), and the other mice were gavaged daily with SGMOs, NGMOs, SBMOs and NBMOs (100 mg/kg), respectively. Meanwhile, on days 28-, 30-, 32-, 34-, 36-and 38-, mice were challenged with 50mgOVA solution (except for the control group), and allergic symptoms and body weights of the mice were recorded. On day 40 of the experiment, fresh stool samples were collected for 16SrRNA sequencing. At day 41, the rectal temperature and organ weight of the mice were measured and the blood, colon and fecal content was collected. Jejunal tissue from each group of mice was collected, placed in 4% paraformaldehyde fixative, dehydrated in graded ethanol solution, and embedded in paraffin. The tissue samples were then sectioned and stained with hematoxylin and eosin (H & E), respectively. The sections were sealed with neutral gel, the sections were observed with a microscope and images were collected.
Construction of OVA-sensitized mouse model As shown in FIG. 1A, balb/c mice were subjected to 6 OVA shots (50 mg/kg), and after 2 weeks of oligosaccharide sample feeding, allergic symptoms of the mice were analyzed (FIGS. 1B-1I). Compared with the control group, the colon of the OVA group mice showed obvious loose stool (figure 1B), severe allergic symptoms such as the symptoms of the flexible cheeks of the gripping ears and the rash of the tails (figure 1C), the weight of the mice (figure 1D) and the rectal temperature of the mice were significantly increased (figure 1E) (p < 0.05), which indicates that the allergic model construction was successful. Compared with OVA group, the gastric lavage oligosaccharide sample and the loratadine (Lora) positive medicament can restore the form of the mouse feces to be normal, and obviously reduce the score of the allergic symptoms (p is less than 0.05). Furthermore, SGMOs, NGMOs and Lora significantly alleviated weight loss in mice (p < 0.05), SGMOs, NGMOs, SBMOs and Lora significantly raised rectal temperature in mice, with the change in rectal temperature in mice of the SGMOs and Lora groups being significantly higher than that of the NGMOs, SBMOs and NBMOs groups (p < 0.05). The thymus index (fig. 1F) and spleen index (fig. 1G) were significantly elevated in OVA mice compared to control, and both the oligosaccharide treated mice and the Lora mice significantly reduced the thymus index (p < 0.05) compared to OVA, wherein the SGMOs thymus index was significantly lower than that of NBMOs (p < 0.05). Although OVA, lora and oligosaccharides had no effect on the length of the colon of the mice (fig. 1H), the results of tissue sections of jejunum showed that oligosaccharides were able to alleviate OVA-induced intestinal injury and inflammation (fig. 1I).
2. Effects of antibodies, allergic Medium and cytokines in mouse serum
As shown in FIG. 2, by detecting the expression of specific antibodies, allergic mediators and cytokines in the mouse serum, it was found that the levels of sIgE, igG2a, histamine, IFN-gamma, IL-4 in the serum of the OVA group of mice were significantly increased (p < 0.05) compared to control, indicating that the food allergy model of the OVA-induced Balb/c mice was successfully constructed. The level of ige (fig. 2A) and histamine (fig. 2B) was significantly reduced (p < 0.05) in serum from mice in the Lora group versus all oligosaccharide groups compared to OVA group, demonstrating that oligosaccharides have antiallergic activity. Food allergy is a type I allergic disease, associated with a shift in Th1 and Th2 balance towards Th 2. The Lora and oligosaccharide groups significantly reduced production of the Th 1-type cytokines IgG2a (fig. 2C) and IFN- γ (fig. 2D) (p < 0.05) compared to OVA groups, wherein the SGMOs group mice had significantly higher expression levels of IFN- γ than SBMOs and NBMOs groups, indicating that SGMOs induced a Th 1-type response that was stronger than BMOs. The Lora and oligosaccharide groups significantly reduced production of the Th 2-type cytokine IL-4 (fig. 2E) (p < 0.05) compared to OVA groups, with the expression level of mouse IL-4 in SGMOs groups significantly lower than NGMOs groups, indicating that SGMOs inhibit Th 2-type responses more strongly than NGMOs. The levels of anti-inflammatory factor IL-10 (FIG. 2F) were significantly increased (p < 0.05) in the serum of mice from the SGMOs, NGMOs and NBMOs groups compared to the OVA group. In conclusion, the milk oligosaccharides can inhibit Th2 reaction by reducing Th2 cytokines, reduce the production of sIgE and histamine, relieve allergic symptoms, and in addition, compared with neutral NGMOs, acidic SGMOs significantly inhibit Th2 reaction; goat milk SGMOs significantly promoted Th1 cytokine production compared to cow milk SBMOs.
3. Mouse mesenteric lymph node CD4 + Foxp3 + Effect of Treg cell differentiation
Regulatory T cells (Tregs) as immunosuppressive CD4 + T cells, CD4 + CD25 + Foxp3 + Is the main phenotype of Treg cells, mainly secretes cytokines such as IL-10 in vivo, inhibits the activation of T cells, and plays an immunosuppressive role. As shown in fig. 3, treg cell specific antibodies (CD 4) were detected in mouse mesenteric lymph node cells by employing flow cytometry + Foxp3 + ) As shown in fig. 3A, the cells in the R3 region were a cd4+foxp3+ Treg cell population. The ratio of Treg cells to cd4+ T cells is shown in figure 3B. Compared with the control group, the level of Treg cells in mesenteric lymph node cells of the OVA group mice is obviously reduced by 0.5 times. All oligosaccharide groups showed a significant increase in Treg cell fraction compared to OVA group (p<0.01 The proportion of Treg cells in the SGMOs group was increased 3.8-fold, significantly higher than in the NGMOs group, the SBMOs group and the NBMOs group (p)<0.05). The research results show that the SGMOs have remarkable advantages in the aspects of inducing differentiation of Treg cells, inhibiting Th2 reaction, relieving food allergy symptoms induced by OVA and the like compared with neutral/acidic cow milk oligosaccharides and neutral goat milk oligosaccharides.
4. Effects of intestinal microorganisms in mice
As shown in fig. 4, by 16SrRNA sequencing, it was found that, at the portal level, the intestinal flora of OVA mice was significantly increased (p < 0.05) and the relative abundance of probiotics was significantly decreased (p < 0.05) compared to Control group (fig. 4A), and these results were consistent with literature reports. It was found that some strains of these symbiotic bacteria of the genus Bacteroidota and Proteobacteria are involved in the occurrence of intestinal inflammation. The relative abundance of intestinal flora was restored to normal levels after SGMOs treatment compared to OVA group, with the relative proportion of firmics significantly higher than that of Control group (p < 0.05). Firmics is the main bacterial gate of the intestinal tract of a healthy human body, and dietary fibers can increase the abundance of certain thick-walled bacteria in the intestinal tract and relieve related diseases by changing the intestinal permeability, inflammation, sugar metabolism, oxidation/synthesis of fatty acids, energy consumption and the like. At the family level, the relative abundance of the OVA group Lachnospiraceae and Oscillospiraceae beneficial bacteria was significantly reduced (p < 0.05), the relative abundance of the erysiplotrichaceae harmful bacteria and the Bacteroidaceae symbiotic bacteria was significantly increased (p < 0.05) compared to the control group (fig. 4B). OVA-induced changes in intestinal flora have been shown to be consistent with food allergy sufferers. The research shows that the reduction of Lachnospiraceae is related to allergic diseases of children, and pectin and tea polysaccharide can promote the proliferation of Lachnospiraceae and has the function of reducing intestinal inflammation. Oscillospiraceae can produce short chain fatty acids such as butyrate and propionate, stimulate goblet cells to increase and mucus expression, and maintain intestinal epithelial integrity, thereby reducing injury and inflammation of colon tissue. Studies have shown that oligosaccharides (FOS, FUC, GOS, HMOs) increase the abundance of Oscillospiraceae. Recently, it has been reported that Erysipelotorich acid has the activity of converting primary bile acid into secondary bile acid, affecting host metabolism and thus triggering intestinal inflammation. Compared with OVA group, SGMOs treated not only regulate the relative abundance of Lachnospiraceae, erysipelotrichaceae and Bactoidaceae to return to normal levels, but also promote proliferation of beneficial bacteria Lactobacillus, marinifilaceae and Clostridia eae, reducing the relative abundance of Desulfovinationaceae. Furthermore, intestinal flora significantly promoted the relative abundance of Prevotellaceae, marifilaceae and Lactobacillaceae (p < 0.05) compared to the control group, where Prevotellaceae and Lactobacillaceae were able to reduce the incidence of allergy in infants.
5. Influence of short chain fatty acids in mouse faeces
SCFA are the most abundant metabolites of the intestinal flora, they play a vital role as important nutrient sources for intestinal epithelial cells and have an impact on intestinal morphology and function. As shown in fig. 4, SCFA content in the cecal content was measured by GC (fig. 4C), and the concentrations of acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid and isovaleric acid were significantly reduced in OVA group compared to control group (p < 0.05). Compared with OVA group, SGMOs treated the concentration of acetic acid, propionic acid and isobutyric acid was significantly increased. Acetate, propionate and butyrate can improve the effect of allergic intestinal inflammation development, thereby helping to restore abnormal intestinal mucosa and barrier function.
6. Influence of the O-glycosylation level of colomucin
The intestinal mucosa is the biggest immune site of the organism, and as shown in fig. 5, comparing the colon mucin O-sugar chains of the mice in the Control group, the OVA group and the SGMOs group by qualitative and quantitative analysis, the colon mucin O-sugar chains of the mice in different groups are similar in species, but the glycosylation level is significantly different (fig. 5). Compared with the Control group, the total O-glycosylation level of the colon mucin of the OVA group mice is obviously reduced by 0.4 times (p is less than 0.05), wherein the expression quantity of the total neutral O-sugar chain is reduced by 0.7 times, and the expression quantity of the total acid O-sugar chain is reduced by 0.4 times; compared with OVA group, SGMOs group mice showed a significant increase in total O-glycosylation level by 0.7-fold (p < 0.05) (fig. 5A), wherein the expression level of total neutral O-sugar chains was significantly increased by 2.2-fold (p < 0.05) (fig. 5B), and the expression level of total acidic O-sugar chains was significantly increased by 0.6-fold (p < 0.05) (fig. 5C). It was found that differences in sialylation and fucosylation modified intestinal glycosylation levels correlated with the severity of inflammation. Neutral O-sugar chains can be classified into fucosylated and nonfucosylated, and the expression level of fucosylated O-sugar chains in the OVA group was significantly reduced by 0.8-fold (FIG. 5D) compared to that in the Control group, with no significant difference in the expression level of nonfucosylated O-sugar chains. Compared with the expression quantity of the fucosylation neutral O-sugar chains in the OVA group, the expression quantity of the O-sugar chains in the SGMOs treatment group is obviously improved by 3 times (p is less than 0.05). It was found that fucose at the end of the O-sugar chain of colistin can be utilized by the intestinal flora, affecting the expression of the metabolic pathways of the flora and reducing the expression of bacterial virulence genes. In addition, the fucose can inhibit the expression of colonitis related intestinal epithelial virulence genes. When intestinal fucosylation is absent, pathogenic bacteria increase, beneficial bacteria decrease, resulting in microbial translocation (microbialltransduction), disruption of the epithelial barrier and intestinal inflammation. The acidic sugar is modified by sialic acid, sulfated, sialic acid and sulfuric acid, compared with the Control group, the sialylated O-sugar chain expression level of the OVA group is reduced by 0.3 times (figure 5E), the sulfated O-sugar chain expression level is reduced by 0.4 times, and the O-sugar chain expression level of the sialic acid and sialic acid are modified together without obvious difference. The SGMOs treatment significantly increased the expression levels (p < 0.05) of sialylated O-sugar chains (0.7 fold) and sulfated O-sugar chains (0.5 fold), respectively, compared to the OVA group of acidic O-sugar chains. Studies have shown that mucin sulfation can enhance the mucous barrier and has the property of combating pathogenic infections and intestinal inflammation.
As shown in FIG. 6, the effect of SGMOs on each O-sugar chain of colistin was further analyzed, and it was found that the O-sugar chains of colistin were classified into two types of acidic (FIG. 6A) and neutral O-sugar chains (FIG. 6B). Compared to the Control group, the OVA group significantly reduced the 7 acid O-sugar chain levels, comprising 4 sulfation modifications (S1F 2H2N2, S1H1N1, S1F1H3N3 and S1H2N 2), 2 sialylation modifications (A1F 2H3N3 and A1F1H2N 2) and 1 sulfation and sialylation simultaneous modification O-sugar chain (S1 A1F1H2N 2), significantly increased the O-sugar chain level of glycoform composition A1H2N4 by a factor of 1.7; in addition, the level of neutral fucosylated O-sugar chains of 3 glycoforms consisting of F1H1N3, F1H2N2 and F2H2N2 was significantly reduced. Compared with the OVA group, the SGMOs group obviously increases the level of two acidic O-sugar chains with the glycoform composition of S1F2H2N2 (0.8 times) and A1F1H2N2 (1 times), obviously reduces the level of the O-sugar chains with the glycoform composition of A1H2N4 by 0.4 times, and shows that 3 acidic O-sugar chains with the glycoform composition of S1F2H2N2, A1F1H2N2 and A1H2N4 probably play a key role in restoring the expression of the colistin O-sugar chains by the SGMOs; in addition, the level of neutral O-sugar chains of the glycoform compositions F1H2N2, F2H2N3, F1H1N2 and F2H2N2 was significantly increased.
OVA sensitization results in a general decrease in the levels of mouse coliform mucin fucosylation, sialylation, and sulfated O-glycosylation, SGMOs treatment can significantly alter mucin O-sugar chain expression, restoring mouse coliform mucin fucosylation (F1H 2N2 and F2H2N 2), sialic acid, and sulfated (A1F 1H2N2 and S1F2H2N 2) O-sugar chain expression. Recovery of SGMOs from OVA-induced food-allergic intestinal mucosal lesions in mice was associated with significant changes in mucin O-glycoprotein.
7. Qualitative and quantitative analysis of acidic goat milk/cow milk oligosaccharide compositions
As shown in FIG. 7, the structure of SGMOs of example 1 and SBMOs sialylated oligosaccharides of comparative example 1 were analyzed using the "sugar cohort" analysis strategy developed in this laboratory (FIGS. 7A, 7B). Wherein, the goat milk has 24 sialylated sugar chains, 18 monosialates and 6 bissialates according to the number of sialic acid; cow milk has 10 sialylated sugar chains, 8 monosiales, and 2 bissialates. Compared with SGMOs, the number of SBMOs is reduced by 58%. According to the sialic acid structure classification, there are 12 kinds of sialylated sugar chains modified by Neu5Ac of SGMOs, 10 kinds of sialylated sugar chains modified by Neu5Gc, and 2 kinds of sialylated sugar chains modified by both Neu5Ac and Neu5 Gc; 8 sialylated sugar chains modified by Neu5Ac in SBMOs, and 2 sialylated sugar chains modified by Neu5 Gc; according to the sialic acid linkage mode, 11 kinds of alpha 2,3 linked sialic acid sugar chains in SGMOs, 10 kinds of alpha 2,6 linked sialic acid sugar chains, 3 kinds of alpha 2,3 and alpha 2,6 linked sialic acid sugar chains are classified; there are 6 kinds of α2, 3-linked sialyl sugar chains in SBMOs, 3 kinds of α2, 6-linked sialyl sugar chains, and 1 kind of α2, 3-linked sialyl sugar chains. As shown in fig. 7C, further quantitative comparative analysis was performed on acidic goat milk and acidic cow milk oligosaccharides, respectively, the relative proportion (95%) of the sialylated sugar chain content of the cow milk Neu5Ac modification was 1.8 times that of goat milk (52%), and the relative proportion (45%) of the sialylated sugar chain modified by goat milk Neu5Gc was 56 times that of cow milk (0.8%). In addition, the sialyl sugar chains (68%) linked to goat milk α2,6 were 1.9 times that of cow milk (36%), and the sialyl sugar chains (60%) linked to cow milk α2,3 were 2.1 times that of goat milk (28%). Thus, SBMOs are mainly composed of α2, 3-linked sialyl sugar chains, and SGMOs are mainly composed of α2, 6-linked sialyl sugar chains.
Compared with the prior art, the method has the following beneficial effects:
1. the acidic goat milk oligosaccharide composition is derived from goat milk, belongs to natural antiallergic substances, and has safety and effectiveness;
2. the acidic goat milk oligosaccharide composition provided by the invention maximally retains the antiallergic active ingredients in goat milk, and obtains excellent antiallergic performance;
3. the acidic goat milk oligosaccharide composition disclosed by the invention can relieve intestinal injury and inflammation, reduce sIgE, histamine, igG2a, IFN-gamma and IL-4 in serum, induce Treg cell differentiation to inhibit Th2 reaction, regulate the relative abundance of Lachnospiraceae, erysipelotrichaceae and Bactoidaceae to be recovered to a normal level, promote the proliferation of beneficial bacteria Lactobacillaceae, marinifilaceae and Clostridia acede, reduce the relative abundance of Desulfovineiganaceae, promote the relative abundance of Prevotellaceae, marinifilaceae and Lactobacteriaceae, improve the concentration of acetic acid, propionic acid and isobutyric acid in intestinal tracts, recover the expression of mucin O-sugar chains and realize an antiallergic function.
While embodiments of the present invention have been shown and described, it will be understood by those of ordinary skill in the art that: many changes, modifications, substitutions and variations may be made to the embodiments without departing from the spirit and principles of the invention, the scope of which is defined by the claims and their equivalents.
Claims (10)
1. Use of an acidic goat milk oligosaccharide composition for the preparation of an antiallergic drug or food, characterized in that the composition comprises 24 acidic sugar chains 24SMAOs, of which 24SMAOs, comprising 12 Neu5Ac modified sialylated sugar chains, 10 Neu5Gc modified sialylated sugar chains and 2 sialylated sugar chains having both Neu5Ac and Neu5Gc modifications, classified according to sialic acid linkage, comprising 11 α2,3 linked sialyl sugar chains, 10 α2,6 linked sialyl sugar chains and 3 sialyl sugar chains having both α2,3 and α2,6 linkages, classified according to sialic acid structure.
2. The use according to claim 1, wherein the content of 12 Neu5Ac modified sialylated sugar chains is 52%, the content of 10 Neu5Gc modified sialylated sugar chains is 45%, and the content of 2 sialylated sugar chains with both Neu5Ac and Neu5Gc modifications is 3%.
3. The use according to claim 1, wherein the 11 kinds of α2, 3-linked sialyl sugar chains have a content of 28%, the 10 kinds of α2, 6-linked sialyl sugar chains have a content of 68%, and the 3 kinds of α2, 3-and α2, 6-linked sialyl sugar chains have a content of 4%.
4. The use according to claim 1, wherein the composition alleviates intestinal damage and inflammation.
5. The use according to claim 1, wherein the composition reduces sIgE, histamine, igG2a, IFN- γ, IL-4 in serum.
6. The use of claim 1, wherein the composition induces differentiation of Treg cells.
7. The use according to claim 1, wherein the composition not only modulates the relative abundance of Lachnospiraceae, erysipelotrichaceae and Bacteroidaceae back to normal levels, but also promotes proliferation of beneficial bacteria Lactobacillaceae, marinifilaceae and clostridium acedeed, reduces the relative abundance of Desulfovibrionaceae, and promotes the relative abundance of Prevotellaceae, marinifilaceae and Lactobacillaceae.
8. The use according to claim 1, wherein the composition increases the concentration of acetic acid, propionic acid and isobutyric acid in the intestinal tract.
9. The use according to claim 1, wherein the composition restores the expression of the O-sugar chain of colistin.
10. The use according to claim 1, wherein the composition is prepared by the following method: taking a certain amount of sheep milk, thawing at normal temperature, and centrifuging to remove fat; adding ethanol with the volume of 2 times of the goat milk, fully and uniformly mixing, centrifuging, collecting supernatant, and freeze-concentrating and drying to obtain freeze-dried goat milk crude oligosaccharide; dissolving the freeze-dried crude goat milk oligosaccharide in double distilled water, slowly adding the double distilled water into a DEAE-52 cellulose chromatographic column, eluting neutral goat milk oligosaccharide by double distilled water, and continuously adding 0.25M NaCl solution to elute acidic goat milk oligosaccharide; washing the acidic goat milk oligosaccharide with graphite carbon column to remove salt, and obtaining the composition.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310998230.0A CN116942685A (en) | 2023-08-09 | 2023-08-09 | Application of acidic goat milk oligosaccharide composition in preparation of antiallergic drugs or foods |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310998230.0A CN116942685A (en) | 2023-08-09 | 2023-08-09 | Application of acidic goat milk oligosaccharide composition in preparation of antiallergic drugs or foods |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116942685A true CN116942685A (en) | 2023-10-27 |
Family
ID=88449145
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310998230.0A Pending CN116942685A (en) | 2023-08-09 | 2023-08-09 | Application of acidic goat milk oligosaccharide composition in preparation of antiallergic drugs or foods |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116942685A (en) |
-
2023
- 2023-08-09 CN CN202310998230.0A patent/CN116942685A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101730607B1 (en) | Composition comprising extracellular vesicles derived from fermented food, and use thereof | |
| US9737575B2 (en) | Use of lactic acid bacteria to treat or prevent eczema | |
| CN105832774B (en) | Use of LGG in the manufacture of a medicament for the prevention or treatment of respiratory allergies | |
| US20110217402A1 (en) | Probiotic Derived Non-Viable Material For Allergy Prevention And Treatment | |
| RU2671209C2 (en) | Lactobacillus rhamnosus rht-3201 conjugated with polysaccharide polymer binder, and use thereof for prevention or treatment of atopic diseases | |
| Rajput et al. | Potential role of probiotics in mechanism of intestinal immunity. | |
| O’Doherty et al. | Novel marine polysaccharides and maternal nutrition to stimulate gut health and performance in post-weaned pigs | |
| Zhou et al. | Effect of fecal microbiota transplantation on experimental colitis in mice | |
| US20060233772A1 (en) | Method for preventing or treating the development of respiratory allergies | |
| Vilahur et al. | Lactobacillus plantarum CECT 7315/7316 intake modulates the acute and chronic innate inflammatory response | |
| Yang et al. | Effects of fenugreek seed extracts on growth performance and intestinal health of broilers | |
| CN117887643B (en) | Antiallergic probiotic and application thereof | |
| JP5531321B2 (en) | Immunostimulatory composition having IL-10 production promoting action | |
| CA2531261A1 (en) | Control of intestinal inflammatory syndromes with a preparation of killed or non infectious bacteria | |
| JP2008231094A (en) | Antiallergic agent | |
| WO2011099875A1 (en) | Use of lactic acid bacteria to treat or prevent rhinitis | |
| JPWO2016136624A1 (en) | Immunomodulators and uses thereof | |
| CN116942685A (en) | Application of acidic goat milk oligosaccharide composition in preparation of antiallergic drugs or foods | |
| US20230074301A1 (en) | Compositions comprising pig stomach mucins and uses thereof | |
| CN111195298A (en) | Composition for regulating intestinal flora and preventing and treating food allergy and preparation method thereof | |
| JP2007054081A (en) | Antiallergic food including ground lotus and/or lotus extract and lactic bacteria | |
| Crane | Pro and anti: the biotics of allergic disease | |
| JP3947778B2 (en) | Anti-allergic agent containing crushed lotus and / or extract and lactic acid bacteria | |
| CN115252638B (en) | Preparation method and application of quinoa dietary fiber for improving intestinal inflammation | |
| CN110237101B (en) | Composition of bacillus licheniformis and xylo-oligosaccharide and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |