CN113476472A - 一种用于缓解肠道紊乱的益生元组合物 - Google Patents
一种用于缓解肠道紊乱的益生元组合物 Download PDFInfo
- Publication number
- CN113476472A CN113476472A CN202110831275.XA CN202110831275A CN113476472A CN 113476472 A CN113476472 A CN 113476472A CN 202110831275 A CN202110831275 A CN 202110831275A CN 113476472 A CN113476472 A CN 113476472A
- Authority
- CN
- China
- Prior art keywords
- composition
- intestinal
- genus
- prebiotic
- group
- 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
- 239000000203 mixture Substances 0.000 title claims abstract description 90
- 235000013406 prebiotics Nutrition 0.000 title claims abstract description 35
- 208000028774 intestinal disease Diseases 0.000 title claims abstract description 23
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 claims abstract description 36
- 229960004099 azithromycin Drugs 0.000 claims abstract description 36
- 229920001542 oligosaccharide Polymers 0.000 claims abstract description 33
- 230000000968 intestinal effect Effects 0.000 claims abstract description 29
- 150000002482 oligosaccharides Chemical class 0.000 claims abstract description 27
- OKBVVJOGVLARMR-QSWIMTSFSA-N cefixime Chemical compound S1C(N)=NC(C(=N\OCC(O)=O)\C(=O)N[C@@H]2C(N3C(=C(C=C)CS[C@@H]32)C(O)=O)=O)=C1 OKBVVJOGVLARMR-QSWIMTSFSA-N 0.000 claims abstract description 22
- 229960002129 cefixime Drugs 0.000 claims abstract description 21
- 241000199919 Phaeophyceae Species 0.000 claims abstract description 19
- 230000003115 biocidal effect Effects 0.000 claims abstract description 19
- 229920001202 Inulin Polymers 0.000 claims abstract description 16
- JYJIGFIDKWBXDU-MNNPPOADSA-N inulin Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@]1(OC[C@]2(OC[C@]3(OC[C@]4(OC[C@]5(OC[C@]6(OC[C@]7(OC[C@]8(OC[C@]9(OC[C@]%10(OC[C@]%11(OC[C@]%12(OC[C@]%13(OC[C@]%14(OC[C@]%15(OC[C@]%16(OC[C@]%17(OC[C@]%18(OC[C@]%19(OC[C@]%20(OC[C@]%21(OC[C@]%22(OC[C@]%23(OC[C@]%24(OC[C@]%25(OC[C@]%26(OC[C@]%27(OC[C@]%28(OC[C@]%29(OC[C@]%30(OC[C@]%31(OC[C@]%32(OC[C@]%33(OC[C@]%34(OC[C@]%35(OC[C@]%36(O[C@@H]%37[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O%37)O)[C@H]([C@H](O)[C@@H](CO)O%36)O)[C@H]([C@H](O)[C@@H](CO)O%35)O)[C@H]([C@H](O)[C@@H](CO)O%34)O)[C@H]([C@H](O)[C@@H](CO)O%33)O)[C@H]([C@H](O)[C@@H](CO)O%32)O)[C@H]([C@H](O)[C@@H](CO)O%31)O)[C@H]([C@H](O)[C@@H](CO)O%30)O)[C@H]([C@H](O)[C@@H](CO)O%29)O)[C@H]([C@H](O)[C@@H](CO)O%28)O)[C@H]([C@H](O)[C@@H](CO)O%27)O)[C@H]([C@H](O)[C@@H](CO)O%26)O)[C@H]([C@H](O)[C@@H](CO)O%25)O)[C@H]([C@H](O)[C@@H](CO)O%24)O)[C@H]([C@H](O)[C@@H](CO)O%23)O)[C@H]([C@H](O)[C@@H](CO)O%22)O)[C@H]([C@H](O)[C@@H](CO)O%21)O)[C@H]([C@H](O)[C@@H](CO)O%20)O)[C@H]([C@H](O)[C@@H](CO)O%19)O)[C@H]([C@H](O)[C@@H](CO)O%18)O)[C@H]([C@H](O)[C@@H](CO)O%17)O)[C@H]([C@H](O)[C@@H](CO)O%16)O)[C@H]([C@H](O)[C@@H](CO)O%15)O)[C@H]([C@H](O)[C@@H](CO)O%14)O)[C@H]([C@H](O)[C@@H](CO)O%13)O)[C@H]([C@H](O)[C@@H](CO)O%12)O)[C@H]([C@H](O)[C@@H](CO)O%11)O)[C@H]([C@H](O)[C@@H](CO)O%10)O)[C@H]([C@H](O)[C@@H](CO)O9)O)[C@H]([C@H](O)[C@@H](CO)O8)O)[C@H]([C@H](O)[C@@H](CO)O7)O)[C@H]([C@H](O)[C@@H](CO)O6)O)[C@H]([C@H](O)[C@@H](CO)O5)O)[C@H]([C@H](O)[C@@H](CO)O4)O)[C@H]([C@H](O)[C@@H](CO)O3)O)[C@H]([C@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 JYJIGFIDKWBXDU-MNNPPOADSA-N 0.000 claims abstract description 16
- 229940029339 inulin Drugs 0.000 claims abstract description 16
- 229920000294 Resistant starch Polymers 0.000 claims abstract description 12
- 235000021254 resistant starch Nutrition 0.000 claims abstract description 12
- JCQLYHFGKNRPGE-FCVZTGTOSA-N lactulose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 JCQLYHFGKNRPGE-FCVZTGTOSA-N 0.000 claims abstract description 10
- 229960000511 lactulose Drugs 0.000 claims abstract description 10
- PFCRQPBOOFTZGQ-UHFFFAOYSA-N lactulose keto form Natural products OCC(=O)C(O)C(C(O)CO)OC1OC(CO)C(O)C(O)C1O PFCRQPBOOFTZGQ-UHFFFAOYSA-N 0.000 claims abstract description 10
- 208000024891 symptom Diseases 0.000 claims abstract description 6
- 150000004676 glycans Chemical class 0.000 claims description 14
- 229920001282 polysaccharide Polymers 0.000 claims description 14
- 239000005017 polysaccharide Substances 0.000 claims description 14
- 230000000813 microbial effect Effects 0.000 claims description 9
- 238000002156 mixing Methods 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 238000006116 polymerization reaction Methods 0.000 claims description 2
- 244000005700 microbiome Species 0.000 abstract description 20
- 230000000694 effects Effects 0.000 abstract description 12
- 239000003242 anti bacterial agent Substances 0.000 abstract description 11
- 229940088710 antibiotic agent Drugs 0.000 abstract description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 7
- 241000124008 Mammalia Species 0.000 abstract description 5
- 150000001720 carbohydrates Chemical class 0.000 abstract description 5
- 230000001105 regulatory effect Effects 0.000 abstract description 5
- 230000007413 intestinal health Effects 0.000 abstract description 3
- 230000002708 enhancing effect Effects 0.000 abstract description 2
- 210000000987 immune system Anatomy 0.000 abstract description 2
- 241000699670 Mus sp. Species 0.000 description 14
- 239000003651 drinking water Substances 0.000 description 12
- 235000020188 drinking water Nutrition 0.000 description 12
- 239000002207 metabolite Substances 0.000 description 12
- 241000894006 Bacteria Species 0.000 description 11
- 241000702460 Akkermansia Species 0.000 description 10
- 241000186000 Bifidobacterium Species 0.000 description 10
- -1 NC: control group Chemical compound 0.000 description 10
- 241000194033 Enterococcus Species 0.000 description 9
- 241000589989 Helicobacter Species 0.000 description 9
- 241000186660 Lactobacillus Species 0.000 description 9
- 241000160321 Parabacteroides Species 0.000 description 9
- 229940072056 alginate Drugs 0.000 description 9
- 229920000615 alginic acid Polymers 0.000 description 9
- 235000010443 alginic acid Nutrition 0.000 description 9
- 229940039696 lactobacillus Drugs 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 8
- 210000003608 fece Anatomy 0.000 description 8
- 150000002500 ions Chemical class 0.000 description 8
- 241000606125 Bacteroides Species 0.000 description 7
- 206010012735 Diarrhoea Diseases 0.000 description 6
- 241000076839 Dubosiella Species 0.000 description 6
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- JRLGPAXAGHMNOL-LURJTMIESA-N N(2)-acetyl-L-ornithine Chemical compound CC(=O)N[C@H](C([O-])=O)CCC[NH3+] JRLGPAXAGHMNOL-LURJTMIESA-N 0.000 description 6
- 241000191940 Staphylococcus Species 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 6
- 241001267951 Parasutterella Species 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 241001202853 Blautia Species 0.000 description 4
- 241000193403 Clostridium Species 0.000 description 4
- 241000089032 Erysipelatoclostridium Species 0.000 description 4
- 241001304190 Hungatella Species 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- RFMMMVDNIPUKGG-YFKPBYRVSA-N N-acetyl-L-glutamic acid Chemical compound CC(=O)N[C@H](C(O)=O)CCC(O)=O RFMMMVDNIPUKGG-YFKPBYRVSA-N 0.000 description 4
- 241000605861 Prevotella Species 0.000 description 4
- 241000095588 Ruminococcaceae Species 0.000 description 4
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- ZQSIJRDFPHDXIC-UHFFFAOYSA-N daidzein Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(O)=CC=C2C1=O ZQSIJRDFPHDXIC-UHFFFAOYSA-N 0.000 description 4
- 230000002550 fecal effect Effects 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- BTNMPGBKDVTSJY-UHFFFAOYSA-N keto-phenylpyruvic acid Chemical compound OC(=O)C(=O)CC1=CC=CC=C1 BTNMPGBKDVTSJY-UHFFFAOYSA-N 0.000 description 4
- 239000006041 probiotic Substances 0.000 description 4
- 235000018291 probiotics Nutrition 0.000 description 4
- 238000004393 prognosis Methods 0.000 description 4
- 241000589291 Acinetobacter Species 0.000 description 3
- 241000193798 Aerococcus Species 0.000 description 3
- 241000701474 Alistipes Species 0.000 description 3
- 241000521092 Alloprevotella Species 0.000 description 3
- 241000186063 Arthrobacter Species 0.000 description 3
- 229930186147 Cephalosporin Natural products 0.000 description 3
- 241000605716 Desulfovibrio Species 0.000 description 3
- 241000316163 Jeotgalicoccus Species 0.000 description 3
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 3
- 241000566145 Otus Species 0.000 description 3
- 241000605947 Roseburia Species 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 229940124587 cephalosporin Drugs 0.000 description 3
- 150000001780 cephalosporins Chemical class 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 229960003638 dopamine Drugs 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 229960003104 ornithine Drugs 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 2
- 108020004465 16S ribosomal RNA Proteins 0.000 description 2
- 239000001903 2-oxo-3-phenylpropanoic acid Substances 0.000 description 2
- KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 description 2
- OLXZPDWKRNYJJZ-UHFFFAOYSA-N 5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol Chemical compound C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(CO)O1 OLXZPDWKRNYJJZ-UHFFFAOYSA-N 0.000 description 2
- 241000204018 Anaeroplasma Species 0.000 description 2
- 241001227086 Anaerostipes Species 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 2
- 229920000855 Fucoidan Polymers 0.000 description 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- 241000148146 Ileibacterium <Mailhe et al. 2017> Species 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 2
- 241000785902 Odoribacter Species 0.000 description 2
- 241000607768 Shigella Species 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- 229960005305 adenosine Drugs 0.000 description 2
- DEDGUGJNLNLJSR-UHFFFAOYSA-N alpha-hydroxycinnamic acid Natural products OC(=O)C(O)=CC1=CC=CC=C1 DEDGUGJNLNLJSR-UHFFFAOYSA-N 0.000 description 2
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 2
- 244000052616 bacterial pathogen Species 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 229960004106 citric acid Drugs 0.000 description 2
- 235000007240 daidzein Nutrition 0.000 description 2
- MYFMARDICOWMQP-YUMQZZPRSA-N gamma-Glu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CC[C@H](N)C(O)=O MYFMARDICOWMQP-YUMQZZPRSA-N 0.000 description 2
- 108010064169 gamma-glutamyl-leucine Proteins 0.000 description 2
- 229940097043 glucuronic acid Drugs 0.000 description 2
- BPMFZUMJYQTVII-UHFFFAOYSA-N guanidinoacetic acid Chemical compound NC(=N)NCC(O)=O BPMFZUMJYQTVII-UHFFFAOYSA-N 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 239000003120 macrolide antibiotic agent Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- BITYXLXUCSKTJS-ZETCQYMHSA-N (2S)-2-isopropylmalic acid Chemical compound CC(C)[C@](O)(C(O)=O)CC(O)=O BITYXLXUCSKTJS-ZETCQYMHSA-N 0.000 description 1
- RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 description 1
- MXHRCPNRJAMMIM-ULQXZJNLSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-tritiopyrimidine-2,4-dione Chemical compound O=C1NC(=O)C([3H])=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 MXHRCPNRJAMMIM-ULQXZJNLSA-N 0.000 description 1
- YKBGVTZYEHREMT-KVQBGUIXSA-N 2'-deoxyguanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 YKBGVTZYEHREMT-KVQBGUIXSA-N 0.000 description 1
- YKBGVTZYEHREMT-UHFFFAOYSA-N 2'-deoxyguanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1CC(O)C(CO)O1 YKBGVTZYEHREMT-UHFFFAOYSA-N 0.000 description 1
- QDGAVODICPCDMU-UHFFFAOYSA-N 2-amino-3-[3-[bis(2-chloroethyl)amino]phenyl]propanoic acid Chemical compound OC(=O)C(N)CC1=CC=CC(N(CCCl)CCCl)=C1 QDGAVODICPCDMU-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 1
- 241000071140 Candidatus Saccharimonas Species 0.000 description 1
- 241001234090 Candidatus Stoquefichus Species 0.000 description 1
- 241000148145 Colidextribacter Species 0.000 description 1
- 238000007400 DNA extraction Methods 0.000 description 1
- QAGGICSUEVNSGH-UHFFFAOYSA-N Diosmetin Natural products C1=C(O)C(OC)=CC=C1C1=CC(=O)C2=CC=C(O)C=C2O1 QAGGICSUEVNSGH-UHFFFAOYSA-N 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 241000588722 Escherichia Species 0.000 description 1
- 101100508576 Gallus gallus CXCL8 gene Proteins 0.000 description 1
- 206010018612 Gonorrhoea Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 229930010555 Inosine Natural products 0.000 description 1
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 1
- 241001112693 Lachnospiraceae Species 0.000 description 1
- 241000097097 Laurella Species 0.000 description 1
- 238000000585 Mann–Whitney U test Methods 0.000 description 1
- 241000736262 Microbiota Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 1
- RDHQFKQIGNGIED-MRVPVSSYSA-N O-acetyl-L-carnitine Chemical compound CC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C RDHQFKQIGNGIED-MRVPVSSYSA-N 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 201000007100 Pharyngitis Diseases 0.000 description 1
- 241000692844 Prevotellaceae Species 0.000 description 1
- 241000232299 Ralstonia Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 241000193996 Streptococcus pyogenes Species 0.000 description 1
- WBWWGRHZICKQGZ-UHFFFAOYSA-N Taurocholic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCCS(O)(=O)=O)C)C1(C)C(O)C2 WBWWGRHZICKQGZ-UHFFFAOYSA-N 0.000 description 1
- HDYANYHVCAPMJV-LXQIFKJMSA-N UDP-alpha-D-glucuronic acid Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C(NC(=O)C=C1)=O)O)O)OP(O)(=O)OP(O)(=O)O[C@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O HDYANYHVCAPMJV-LXQIFKJMSA-N 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 description 1
- XBJFCYDKBDVADW-UHFFFAOYSA-N acetonitrile;formic acid Chemical compound CC#N.OC=O XBJFCYDKBDVADW-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- HWXBTNAVRSUOJR-UHFFFAOYSA-N alpha-hydroxyglutaric acid Natural products OC(=O)C(O)CCC(O)=O HWXBTNAVRSUOJR-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229940009533 alpha-ketoglutaric acid Drugs 0.000 description 1
- 229960003022 amoxicillin Drugs 0.000 description 1
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- KKTCWAXMXADOBB-UHFFFAOYSA-N azanium;hydrogen carbonate;hydrate Chemical compound [NH4+].O.OC([O-])=O KKTCWAXMXADOBB-UHFFFAOYSA-N 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229960002173 citrulline Drugs 0.000 description 1
- 235000013477 citrulline Nutrition 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 238000010219 correlation analysis Methods 0.000 description 1
- 230000013872 defecation Effects 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- VGONTNSXDCQUGY-UHFFFAOYSA-N desoxyinosine Natural products C1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 VGONTNSXDCQUGY-UHFFFAOYSA-N 0.000 description 1
- 230000000741 diarrhetic effect Effects 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- MBNGWHIJMBWFHU-UHFFFAOYSA-N diosmetin Chemical compound C1=C(O)C(OC)=CC=C1C1=CC(=O)C2=C(O)C=C(O)C=C2O1 MBNGWHIJMBWFHU-UHFFFAOYSA-N 0.000 description 1
- 229960001876 diosmetin Drugs 0.000 description 1
- 235000015428 diosmetin Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- HQVFCQRVQFYGRJ-UHFFFAOYSA-N formic acid;hydrate Chemical compound O.OC=O HQVFCQRVQFYGRJ-UHFFFAOYSA-N 0.000 description 1
- 208000001786 gonorrhea Diseases 0.000 description 1
- 244000005709 gut microbiome Species 0.000 description 1
- 208000035861 hematochezia Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229960002885 histidine Drugs 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000007366 host health Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 229960003786 inosine Drugs 0.000 description 1
- 210000005027 intestinal barrier Anatomy 0.000 description 1
- 230000007358 intestinal barrier function Effects 0.000 description 1
- 210000002490 intestinal epithelial cell Anatomy 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000002705 metabolomic analysis Methods 0.000 description 1
- 230000001431 metabolomic effect Effects 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 238000002552 multiple reaction monitoring Methods 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 1
- 229960005190 phenylalanine Drugs 0.000 description 1
- 208000022131 polyp of large intestine Diseases 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000000529 probiotic effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- JDTUMPKOJBQPKX-GBNDHIKLSA-N sedoheptulose 7-phosphate Chemical compound OCC(=O)[C@@H](O)[C@H](O)[C@H](O)[C@H](O)COP(O)(O)=O JDTUMPKOJBQPKX-GBNDHIKLSA-N 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 235000021391 short chain fatty acids Nutrition 0.000 description 1
- 150000004666 short chain fatty acids Chemical class 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- WBWWGRHZICKQGZ-GIHLXUJPSA-N taurocholic acid Chemical compound C([C@@H]1C[C@H]2O)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)[C@H](O)C1 WBWWGRHZICKQGZ-GIHLXUJPSA-N 0.000 description 1
- AWDRATDZQPNJFN-VAYUFCLWSA-N taurodeoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)[C@@H](O)C1 AWDRATDZQPNJFN-VAYUFCLWSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 206010044008 tonsillitis Diseases 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 description 1
- 229960001661 ursodiol Drugs 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- A61K31/733—Fructosans, e.g. inulin
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7016—Disaccharides, e.g. lactose, lactulose
-
- 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
- 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
- A61K31/716—Glucans
- A61K31/718—Starch or degraded starch, e.g. amylose, amylopectin
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- 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)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Immunology (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及益生元的组合物，具体的说是一种用于修复、缓解哺乳动物由于阿奇霉素或头孢克肟抗生素使用导致肠道紊乱的症状的益生元组合物。组合物为褐藻寡糖、菊粉、抗性淀粉和乳果糖中的一种或几种。本发明组合物适用于哺乳动物的组合物，以缓解由于抗生素引起的肠道紊乱，该组合物通过调配剂量，对抗生素诱导的肠道紊乱的调节效果较单一糖类更佳；进而使得组合物能够增强针对特异性肠道微生物紊乱缓解的效果，具有恢复肠道健康，改善免疫***，增强肠道舒适度等作用。
Description
技术领域
本发明涉及益生元的组合物，具体的说是一种用于修复、缓解哺乳动物由于阿奇霉素或头孢克肟抗生素使用导致肠道紊乱的症状的益生元组合物。
背景技术
益生元是一种常见的膳食补充剂，在啮齿动物和人类研究中已被证明可以影响肠道健康益生元在肠道中不被宿主吸收，由肠道细菌发酵，刺激特定微生物类群的生长，产生如短链脂肪酸等代谢物，对宿主有改善代谢，调节免疫，修复肠道屏壁等积极作用。
肠道微生物群是一个复杂的微生物生态***，肠道内的稳态对宿主健康至关重要。同时引起不同程度肠道微生物紊乱的因素有多种，抗生素是影响肠道微生物的因素之一，许多研究证明即使通过短期或低剂量的抗生素治疗，可能会降低肠道微生物物种丰富度和生物多样性，导致某一微生物物种消失，并且这种变化可能对健康产生长期影响，如增加结直肠息肉风险，肠道微生物产生耐药性，促进炎症等。阿奇霉素是一种大环内酯类抗生素，被用来治疗细菌感染，头孢克肟是一种第三代头孢菌素抗生素，通常用于治疗淋病、扁桃腺炎和咽炎，但是滥用也有可能引起腹泻、恶心、腹痛、稀便、呕吐等反应，造成肠道菌群紊乱，对人体带来负面影响。
避免抗生素治疗引起的肠道微生物失调，可采用益生菌、益生元、粪菌移植等方法。例如，Elinav等最近发现，某些益生菌的使用，自体粪便移植有助于恢复微生物组。为施用阿莫西林的3-6岁健康儿童提供菊粉发现，菊粉选择性的改善了肠道菌群组成，恢复了抗生素治疗降低的双歧杆菌丰度，减轻了抗生素对肠道微生物组成造成的干扰。但由于单一来源的糖类缓解效果往往较弱，同时其也仅是对某种特定抗生素存在效果，因此需要提供一种更全面的即本发明的组合物。
发明内容
本发明目的在于提供一种用于修复、缓解哺乳动物由于抗生素阿奇霉素或头孢克肟使用导致肠道紊乱的症状的益生元组合物。
为实现上述目的，本发明采用技术方案为：
一种用于缓解抗生素使用导致肠道紊乱的益生元组合物，组合物为褐藻寡糖、菊粉、抗性淀粉和乳果糖中的一种或几种。
组合物为褐藻寡糖、菊粉、抗性淀粉和乳果糖中至少两种多糖的混合。
所述组合物为两种多糖时，按质量比为20-80：10-30混合；
所述组合物为三种多糖时，按质量比为20-50：20-50：10-30混合；
所述组合物为四种多糖时，按质量比为20-40：20-40：10-20：10-20混合。
所述褐藻寡糖为聚合度1-4。
所述抗生素为阿奇霉素或头孢克肟。
一种益生元组合物的应用，所述组合物在制备用于缓解抗生素使用导致肠道紊乱的益生元中的应用。
所述组合物在制备用于缓解抗生素使用导致肠道微生物紊乱的益生元中的应用。
一种缓解阿奇霉素或头孢克肟干扰肠道紊乱症状的方法，所述方法包括向受试者给予有效剂量的所述益生元组合物。
将有效剂量的权利要求1所述益生元组合物连续或间歇向受试者给予；其中，有效剂量为2g/kg/d-15g/kg/d。
本发明所具有的优点：
本发明组合物适用于哺乳动物的组合物，以缓解由于抗生素引起的肠道紊乱，该组合物通过调配剂量，对抗生素诱导的肠道紊乱的调节效果较单一糖类更佳；进而使得组合物能够增强针对特异性肠道微生物紊乱缓解的效果，具有恢复肠道健康，改善免疫***，增强肠道舒适度等作用。
附图说明
图1为本发明实施例提供的阿奇霉素及不同组合物（即，AZ1：阿奇霉素干预组，AZ2：阿奇霉素干预＋褐藻寡糖添加组，AZ3：阿奇霉素干预＋组合物添加组）添加后属水平肠道微生物变化图。
图2为本发明实施例提供的头孢克肟及不同组合物（即，NC：对照组，AZ1：头孢克肟干预组，AZ2：头孢克肟干预＋褐藻寡糖添加组，AZ3：头孢克肟干预＋组合物添加组）添加后属水平肠道微生物变化图。
图3为本发明实施例提供的阿奇霉素及不同组合物（即，AZ1：阿奇霉素干预组，AZ2：阿奇霉素干预＋褐藻寡糖添加组，AZ3：阿奇霉素干预＋组合物添加组）添加后粪便代谢物变化图。
具体实施方式
本发明实施例中所使用的方法无特殊说明均为本领域常规方法。本发明实施例中所使用的物料均可通过商业途径获得。
实施例1
一种用于缓解阿奇霉素使用导致肠道紊乱的益生元为褐藻寡糖。
实施例2
一种用于缓解阿奇霉素使用导致肠道紊乱的益生元组合物，其由如下组分混合而成：褐藻寡糖和菊粉。褐藻寡糖在组合物种的重量份为50份，菊粉在组合物中的重量份为50份。
实施例3
一种用于缓解阿奇霉素使用导致肠道紊乱的益生元组合物，其由如下组分混合而成：褐藻寡糖、菊粉和抗性淀粉。褐藻寡糖在组合物种的重量份为40份，菊粉在组合物中的重量份为40份，抗性淀粉在组合物中的重量份为20份。
实施例4
一种用于缓解头孢克肟使用导致肠道紊乱的益生元组合物，其由如下组分混合而成：褐藻寡糖、菊粉、抗性淀粉和乳果糖。褐藻寡糖在组合物种的重量份为37.5份，菊粉在组合物中的重量份为37.5份，抗性淀粉在组合物中的重量份为12.5份，乳果糖在组合中的重量份为12.5份。
应用例
实验方法
选取77只六周龄SPF级C57BL/6J小鼠，正常饲料饲喂一周后，随机分组，对照组（NC组），阿奇霉素组（仅阿奇霉素干预，AZ1），褐藻寡糖组（阿奇霉素+褐藻寡糖干预，AZ2），益生元组合物组（阿奇霉素+实施例4组合物干预AZ3）。头孢克肟组（仅头孢克肟干预CEF4），褐藻寡糖组（头孢克肟+褐藻寡糖干预CEF5），益生元组合物组（头孢克肟+实施例4组合物干预CEF6）；小鼠饲喂于25℃，湿度50%的可控环境中，光照黑暗周期均为12 h，期间自由饮食及饮水。实验组0-7 d均在饮用水中添加上述各干预物质，即，每组中抗生素添加量为10 g/kg/d，组合物或褐藻寡糖中添加量为3.75 g/kg/d，对照组为正常饮水。干预周期为15天。
在干预期结束收集小鼠的粪便，对其获得粪便进行评价参见表1，干预结束后，处死小鼠，并对小鼠的粪便进行微生物组和代谢组分析（参见图1、图2和图3）。
表1 添加糖类后各组小鼠粪便评分表
注：粪便形态评分，a 正常，b 便软，c 便血。
由上述表1可见在糖类物质添加一周后收集粪便发现，抗生素诱导后无褐藻寡糖和组合物干预的小鼠有便软症状（AZ1，CEF4组），但抗生素诱导后组合物干预（AZ3，CEF6）后小鼠的粪便状况整体上优于正常饮水对照组（AZ1，CEF4）和褐藻寡糖单独添加组（AZ2，CEF5），均能体现对抗生素造成腹泻状况调节的效果更佳。
对收集小鼠的粪便进行微生物组和代谢组分析（参见图1、图2和图3）：
1）DNA提取和PCR扩增：粪便中细菌总DNA的提取与分析：参照试剂盒QIAamp DNA试剂盒按照说明书提取粪便中细菌的总DNA。利用特异性引物（16S V4: 515F-806R）扩增16SrRNA基因。所有PCR反应均使用Phusion®高保真PCR Master Mix（New England Biolabs）进行，在Illumina HiSeq 2500平台上对文库进行测序。16S rRNA测序数据采用微生物生态学平台（Quantitative Insights Into Microbial Ecology platform，QIIME）定量分析（V.1.9.1）。以97%的相似性临界值选择操作分类学单位（OTUs）。OTUs丰度信息采用与序列最小样本对应的序列号标准进行归一化。对每个有代表性的序列，根据RDP分类器算法（Version 2.2，http://sourceforge.net/projects/rdp-classifier/）的GreenGene数据库（http://greengenes.lbl.gov/cgi-bin/nph-index.cgi）进行分类信息标注。利用Wilcoxon秩和检验评价组间类群的丰度差异。相关分析采用Spearman相关性检验。采用R包对所有菌群数据进行统计分析（V.2.15.3）。通过PICRUSt（通过重建未观测状态对群落进行***发育研究）进一步利用OTUs对菌群进行基因组预测（参见图1和图2）。
2）代谢物检测
用80%（v/v）甲醇和0.1%（v/v）甲酸提取代谢产物。冰上孵育5 min后，4℃15000 g离心10 min。收集上清液，稀释至终浓度为60%（v/v）甲醇。然后用0.22 μm滤器过滤样品，在4℃下15000g离心10分钟后进行检测。采用高效液相色谱（Exrion LC，SCIEX）和MS/MS（QTRAP6500+，SCIEX）联用分析代谢产物。正离子模式，流动相为0.1%甲酸-水（v/v；A）和0.1%甲酸-乙腈（v/v；B），负离子模式6.5 mmol/L碳酸氢铵-水（A）和6.5 mmol/L碳酸氢铵-95%甲醇-水（v/v；B）。在正离子模式下，用BEH C8柱（100 mm×2.1 mm，Waters）梯度洗脱代谢产物（表2A）。在负离子模式下，用HSS T3柱（100 mm×2.1 mm，Waters）梯度洗脱代谢产物（表2B）。根据Wu等人描述的方法，采用多反应监测模式检测代谢物，用离子（Q3）定量分析（参见图3）。
表2 代谢组学分析的色谱条件
（A）正离子模式
（B）负离子模式
阿奇霉素会引发肠道微生物在门、纲、目、科、属、种水平的紊乱，甚至肠道炎症。褐藻寡糖和组合物干预都对肠道微生物的紊乱有一定的缓解作用，但是组合物会对某些特定的微生物菌属有调节作用。对阿奇霉素干预的微生物群落结构热图属水平分析表明（图1），阿奇霉素干预后（AZ1组），螺杆菌属（Helicobacter）、拟普雷沃菌属（Alloprevotella）、阿克曼氏菌属（Akkermansia）、双歧杆菌属（Bifidobacterium）、Anaerostipes、Candidatus Stoquefichus、脱硫弧菌属（Desulfovibrio）、Parasutterella、Unidentified Ruminococcaceae、Odoribacter、劳尔氏菌属（Ralstonia）、Ileibacterium 、Erysipelatoclostridium和Robinsoniella等相对丰度相较与空白对照组（NC）显著下降，拟杆菌属（Bacteroides）、副拟杆菌（Parabacteroides）、杜氏杆菌属（Dubosiella）、咸海鲜球菌属（Jeotgalicoccus）、罗氏菌属（Roseburia）、葡萄球菌属（Staphylococcus）和气球菌属（Aerococcus）等相对丰度相较与空白对照组（NC）显著上升；经褐藻寡糖干预后（AZ2组），乳杆菌属（Lactobacillus）和杜氏杆菌属（Dubosiella）等相对丰度相较对照组阿奇霉素添加饮水组（AZ1组）显著下降，拟普雷沃菌属（Alloprevotella）、Parasutterella、Unidentified Ruminococcaceae、Odoribacter、Ileibacterium、Erysipelatoclostridium、不动杆菌属（Acinetobacter）属等的相对丰度相较对照组阿奇霉素添加饮水组（AZ1组）显著上升；而经组合物添加后（AZ3组），乳杆菌属（Lactobacillus）、杜氏杆菌属（Dubosiella）、咸海鲜球菌属（Jeotgalicoccus）、罗氏菌属（Roseburia）、Candidatus Saccharimonas、葡萄球菌属（Staphylococcus）和气球菌属（Aerococcus）等相对丰度相较对照组阿奇霉素添加饮水组（AZ1组）显著下降，螺杆菌属（Helicobacter）、拟普雷沃菌属（Alloprevotella）、阿克曼氏菌属（Akkermansia）、Candidatus Stoquefichus、脱硫弧菌属（Desulfovibrio）、Parasutterella、Unidentified Ruminococcaceae、Odoribacter、拟杆菌属（Bacteroides）、副拟杆菌属（Parabacteroides）、Anaeroplasma、Erysipelatoclostridium和Robinsoniella等相对丰度相较对照组阿奇霉素添加饮水组（CEF4）显著上升，进而可见组合物处理组相较于褐藻寡糖处理组提高了对肠道上皮细胞及黏液层的完整性有保护作用的阿克曼氏菌属，降低了常见的化脓性球菌属葡萄球菌属丰度。进一步分析和表1结合可见，阿奇霉素为大环内酯类抗生素，主要作用于细菌引起的感染性疾病。组合物添加后（AZ3组），乳杆菌属（Lactobacillus）、杜氏杆菌属（Dubosiella）、咸海鲜球菌属（Jeotgalicoccus）、罗氏菌属（Roseburia）、Candidatus Saccharimonas、葡萄球菌属（Staphylococcus）和气球菌属（Aerococcus）等相对丰度相较对照组阿奇霉素添加饮水组（AZ1组）显著下降；螺杆菌属（Helicobacter）、拟普雷沃菌属（Alloprevotella）、阿克曼氏菌属（Akkermansia）、Candidatus Stoquefichus、脱硫弧菌属（Desulfovibrio）、Parasutterella、Unidentified Ruminococcaceae、Odoribacter、拟杆菌属（Bacteroides）、副拟杆菌属（Parabacteroides）、Anaeroplasma、Erysipelatoclostridium和Robinsoniella等相对丰度相较对照组阿奇霉素添加饮水组（AZ1组）显著上升。添加组合物后由于菊粉、抗性淀粉、乳果糖对褐藻寡糖的协同作用，其调节小鼠肠道中特异性的肠道微生物，进而使得阿克曼氏菌属（Akkermansia）等菌属的丰度增加，葡萄球菌属等的丰度降低，可以进一步缓解由该抗生素引发的小鼠肠道微生物的紊乱甚至结肠炎症，使得干预后腹泻便软情况改善。
头孢克肟会引发肠道微生物在门、纲、目、科、属、种水平的紊乱，甚至肠道炎症。褐藻寡糖和组合物干预都对肠道微生物的紊乱有一定的缓解作用，但是组合物会对某些特定的微生物菌属有调节作用。由图2对头孢克肟干预的微生物群落结构热图属水平分析表明，头孢克肟干预后（CEF4组）拟普雷沃菌属（Alloprevotella）、另枝菌属（Alistipes）、Colidextribacter、Candidatus Stoquefichus、Candidatus Saccharimonas、Anaerostipes、Lachnospiraceae NK4A136group、Odoribacter、Dubosiella、Prevotellaceae NK3B31 group、Enterorhabdus、乳杆菌属（Lactobacillus）和Eubacterium xylanophilum group相对丰度较对照组（NC）显著性降低；拟杆菌属（Bacteroides）、粪芽孢菌属（Coprobacillus）、Robinsoniella、布劳特氏菌属（Blautia）、Lachnoclostridium、埃希氏-志贺菌属（Escherichia Shigella）、Parasutterella、Hungatella、Erysipelatoclostridium、unidentified Mitochondria、Clostridium sensu stricto 1、肠球菌属（Enterococcus）、阿克曼氏菌属（Akkermansia）、Bifidobacterium、Parabacteroides、Muribaculum和Mucispirillum的相对丰度较对照组（NC组）显著性升高。添加褐藻寡糖（CEF5组）与对照组头孢克肟添加饮水组（CEF4组）相比，Robinsoniella、布劳特氏菌属（Blautia）、Lachnoclostridium、埃希氏菌属（EscherichiaShigella）、Parasutterella、粪芽孢菌属（Coprobacillus）、Hungatella、Erysipelatoclostridium、Clostridium sensu stricto 1和Anaerostipes菌属丰度显著下降；褐藻寡糖干预组（CEF5组）的双歧杆菌属（Bifidobacterium）、副拟杆菌属（Parabacteroides）、Alloprevotella、另枝菌属（Alistipes）、不动杆菌属（Acinetobacter）、杜氏杆菌属（Dubosiella）、Prevotellaceae NK3B31 group和乳杆菌属（Lactobacillus）菌属丰度显著上升。添加组合物（CEF6组）与对照组头孢克肟添加饮水组（CEF4）组相比，组合物组中Robinsoniella、布劳特氏菌属（Blautia）、Lachnoclostridium、粪芽孢菌属（Coprobacillus）、Hungatella、Erysipelatoclostridium、unidentified Mitochondria、螺杆菌属（Helicobacter）、Clostridium sensu stricto 1、肠球菌属（Enterococcus）和阿克曼氏菌属（Akkermansia）菌属丰度显著下降；双歧杆菌属（Bifidobacterium）、Parabacteroides、Alloprevotella、另枝菌属（Alistipes）、Dubosiella菌属丰度显著上升。进而可见组合物通过上调双歧杆菌属（Bifidobacterium）等有益菌的丰度，又降低了褐藻寡糖处理组中增加的肠球菌属（Enterococcus）等致病菌的丰度对小鼠肠道微生物起到选择性的调节作用。
进一步分析和表1结合可见，头孢克肟为头孢菌素类抗生素，主要作用于细菌引起的感染性疾病。组合物添加后，Robinsoniella、布劳特氏菌属（Blautia）、Lachnoclostridium、粪芽孢菌属（Coprobacillus）、Hungatella、Erysipelatoclostridium、unidentified Mitochondria、螺杆菌属（Helicobacter）、Clostridium sensu stricto 1、肠球菌属（Enterococcus）和阿克曼氏菌属（Akkermansia）等相对丰度相较阿奇霉素添加饮水组显著下降。添加组合物后由于菊粉、抗性淀粉、乳果糖对褐藻寡糖的协同作用，其调剂小鼠肠道中肠道微生物，进而使得粪芽孢菌属（Coprobacillus）、unidentified Mitochondria、螺杆菌属（Helicobacter）、肠球菌属（Enterococcus）和阿克曼氏菌属（Akkermansia）菌属丰度降低，可以进一步缓解由该抗生素引发的小鼠肠道微生物的紊乱甚至结肠炎症，使得干预后腹泻便软情况改善。
由图3代谢物检测可见，阿奇霉素干预后，多巴胺和戊二酸浓度降低，葡萄糖醛酸、γ-谷氨酰-亮氨酸、N2-乙酰-L-鸟氨酸、N-乙酰鸟氨酸、L-鸟氨酸、L-鸟氨酸、L-苯丙氨酸、牛磺脱氧胆酸、乙酰左旋肉碱、烟酰胺、大豆苷元浓度增加，褐藻寡糖处理后，小鼠粪便中苯基丙酮酸、N2-乙酰-L-鸟氨酸、N-乙酰鸟氨酸、柠檬酸、D-景天庚酮糖 7-磷酸，葡萄糖醛酸、D-糖酸、抗坏血酸，苯基丙酮酸、γ-谷氨酰-亮氨酸、N2-乙酰-L-鸟氨酸、N-乙酰鸟氨酸、柠檬酸，α-酮戊二酸、L-鸟氨酸，L-鸟氨酸和L-苯丙氨酸物质浓度显著性增加。异丙基苹果酸、瓜氨酸、UDP-D-葡萄糖醛酸、2-异丙基苹果酸、N-乙酰-L-谷氨酸、N-乙酰-L-谷氨酸浓度显著性降低。组合物处理后，粪便中牛磺胆酸、熊去氧胆酸、戊二酸、2’-脱氧尿苷、尿苷、丙二酸、腺苷、多巴胺、肌苷、鸟嘌呤、2’-脱氧鸟苷，2’-脱氧腺苷，黄豆苷元和L-组氨酸等物质浓度显著性增加。牛磺酸脱氧胆酸、烟酰胺、3-甲基色氨盐酸盐、香叶木素和胍基乙酸浓度显著降低。相较于褐藻寡糖处理，组合物恢复了益于健康的多巴胺、L-鸟氨酸等代谢物的水平，并增加腺苷等这类对免疫有益的代谢物浓度。
综上所述有菌群和代谢物两方面的检测采用本发明的益生元均能在不同程度上对特定抗生素引起的肠道紊乱的缓解，并且益生元为褐藻寡糖、菊粉、抗性淀粉和乳果糖组合时，可实现进一步的对可使更广泛的致病菌丰度降低，并且增加益生菌丰度，同时还会增加益于健康的代谢物的水平，从而改善抗生素对宿主的影响。
Claims (9)
1.一种用于缓解肠道紊乱的益生元组合物，其特征在于：组合物为褐藻寡糖、菊粉、抗性淀粉和乳果糖中的一种或几种。
2.按权利要求1所述用于缓解肠道紊乱的益生元组合物，其特征在于：组合物为褐藻寡糖、菊粉、抗性淀粉和乳果糖中至少两种多糖的混合。
3.按权利要求2所述用于缓解肠道紊乱的益生元组合物，其特征在于：所述组合物为两种多糖时，按质量比为20-80：10-30混合；
所述组合物为三种多糖时，按质量比为20-50：20-50：10-30混合；
所述组合物为四种多糖时，按质量比为20-40：20-40：10-20：10-20混合。
4.按权利要求1-3任意一项所述用于缓解肠道紊乱的益生元组合物，其特征在于：所述褐藻寡糖为聚合度1-4。
5.按权利要求1-3任意一项所述用于缓解肠道紊乱的益生元组合物，其特征在于：所述抗生素为阿奇霉素或头孢克肟。
6.一种权利要求1所述益生元组合物的应用，其特征在于：所述组合物在制备用于缓解抗生素使用导致肠道紊乱的益生元中的应用。
7.按权利要求6所述益生元组合物的应用，其特征在于：所述组合物在制备用于缓解抗生素使用导致肠道微生物紊乱的益生元中的应用。
8.一种缓解阿奇霉素或头孢克肟干扰肠道紊乱症状的方法，其特征在于：所述方法包括向受试者给予有效剂量的权利要求1所述益生元组合物。
9.按权利要求8所述的方法，其特征在于：将有效剂量的权利要求1所述益生元组合物连续或间歇向受试者给予；其中，有效剂量为2g/kg/d-15g/kg/d。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110831275.XA CN113476472A (zh) | 2021-07-22 | 2021-07-22 | 一种用于缓解肠道紊乱的益生元组合物 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110831275.XA CN113476472A (zh) | 2021-07-22 | 2021-07-22 | 一种用于缓解肠道紊乱的益生元组合物 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113476472A true CN113476472A (zh) | 2021-10-08 |
Family
ID=77942040
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110831275.XA Pending CN113476472A (zh) | 2021-07-22 | 2021-07-22 | 一种用于缓解肠道紊乱的益生元组合物 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113476472A (zh) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1562071A (zh) * | 2004-04-16 | 2005-01-12 | 中国海洋大学 | 褐藻胶低聚糖作为益生元的应用 |
| WO2005056023A1 (en) * | 2003-12-12 | 2005-06-23 | Nova Biotics As | Prebiotic combination products |
| US20070254023A1 (en) * | 2004-08-30 | 2007-11-01 | Kiselev Nikolai A | Perorally Administrable Antimicrobial Composition |
| CN101998858A (zh) * | 2008-03-18 | 2011-03-30 | 亚历山大·弗拉基米罗维奇·季科夫斯基 | 抗生素和益生元的药物组合物用于预防和治疗抗生素治疗中的微生态失调 |
| US20200360418A1 (en) * | 2019-05-15 | 2020-11-19 | Axcess Global Sciences, Llc | Autobiotic compositions and method for promoting healthy gut microbiome |
-
2021
- 2021-07-22 CN CN202110831275.XA patent/CN113476472A/zh active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005056023A1 (en) * | 2003-12-12 | 2005-06-23 | Nova Biotics As | Prebiotic combination products |
| CN1562071A (zh) * | 2004-04-16 | 2005-01-12 | 中国海洋大学 | 褐藻胶低聚糖作为益生元的应用 |
| US20070254023A1 (en) * | 2004-08-30 | 2007-11-01 | Kiselev Nikolai A | Perorally Administrable Antimicrobial Composition |
| CN101998858A (zh) * | 2008-03-18 | 2011-03-30 | 亚历山大·弗拉基米罗维奇·季科夫斯基 | 抗生素和益生元的药物组合物用于预防和治疗抗生素治疗中的微生态失调 |
| US20200360418A1 (en) * | 2019-05-15 | 2020-11-19 | Axcess Global Sciences, Llc | Autobiotic compositions and method for promoting healthy gut microbiome |
Non-Patent Citations (3)
| Title |
|---|
| "褐藻寡糖可缓解肠道炎症", 《食品工业》 * |
| NIKOLAOU E等: "Intestinal microbiome analysis demonstrates azithromycin post treatment effects improve when combined with lactulose", 《WORLD JOURNAL OF PEDIATRICS》 * |
| 傅政等: "褐藻胶寡糖生物活性研究进展", 《中国海洋药物》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Li et al. | Probiotics, prebiotics, and synbiotics regulate the intestinal microbiota differentially and restore the relative abundance of specific gut microorganisms | |
| Cheng et al. | Effect of functional oligosaccharides and ordinary dietary fiber on intestinal microbiota diversity | |
| Tao et al. | Polysaccharides from Chrysanthemum morifolium Ramat ameliorate colitis rats by modulating the intestinal microbiota community | |
| Yu et al. | Dietary high zinc oxide modulates the microbiome of ileum and colon in weaned piglets | |
| You et al. | Commensal-derived metabolites govern Vibrio cholerae pathogenesis in host intestine | |
| Sivieri et al. | Lactobacillus acidophilus CRL 1014 improved “gut health” in the SHIME® reactor | |
| Zheng et al. | Impact and consequences of polyphenols and fructooligosaccharide interplay on gut microbiota in rats | |
| Yu et al. | Microbiome-metabolomics analysis investigating the impacts of dietary starch types on the composition and metabolism of colonic microbiota in finishing pigs | |
| Xie et al. | Effects of phycocyanin in modulating the intestinal microbiota of mice | |
| Yu et al. | Low-molecular-weight chitosan supplementation increases the population of Prevotella in the cecal contents of weanling pigs | |
| Lin et al. | The prolonged disruption of a single-course amoxicillin on mice gut microbiota and resistome, and recovery by inulin, Bifidobacterium longum and fecal microbiota transplantation | |
| Ni et al. | Characteristics of gut microbiota and its response to a Chinese Herbal Formula in elder patients with metabolic syndrome | |
| Tian et al. | Moringa oleifera polysaccharides regulates caecal microbiota and small intestinal metabolic profile in C57BL/6 mice | |
| Sulek et al. | A combined metabolomic and phylogenetic study reveals putatively prebiotic effects of high molecular weight arabino-oligosaccharides when assessed by in vitro fermentation in bacterial communities derived from humans | |
| Xie et al. | Bacterial diversity in intestinal mucosa of antibiotic-associated diarrhea mice | |
| KR20200138333A (ko) | 염증성 장 질환을 치료하는 조성물 및 방법 | |
| US20220160797A1 (en) | Probiotic bacteria capable of adaptive response to pomegranate extract and methods of production and use thereof | |
| Li et al. | Apple polysaccharide could promote the growth of Bifidobacterium longum | |
| Bao et al. | Regulatory effect of Lactiplantibacillus plantarum 2-33 on intestinal microbiota of mice with antibiotic-associated diarrhea | |
| Yuan et al. | Restoration of cefixime-induced gut microbiota changes by a prebiotic blend in a mouse model | |
| Tang et al. | Bifidobacterium lactis TY-S01 prevents loperamide-induced constipation by modulating gut microbiota and its metabolites in mice | |
| Wu et al. | Broccoli seed extract rich in polysaccharides and glucoraphanin ameliorates DSS‐induced colitis via intestinal barrier protection and gut microbiota modulation in mice | |
| Xiang et al. | Isolation and purification of Tartary buckwheat polysaccharides and their effect on gut microbiota | |
| JP2016502983A (ja) | 硫酸化ポリアニオン性多糖及び非硫酸化ポリアニオン性多糖を含む藻類抽出物及びその使用 | |
| Xue et al. | Neuroprotective effect of fucoidan by regulating gut-microbiota-brain axis in alcohol withdrawal mice |
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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20211008 |