JP2013509204A - ビフィズス菌株 - Google Patents
ビフィズス菌株 Download PDFInfo
- Publication number
- JP2013509204A JP2013509204A JP2012537479A JP2012537479A JP2013509204A JP 2013509204 A JP2013509204 A JP 2013509204A JP 2012537479 A JP2012537479 A JP 2012537479A JP 2012537479 A JP2012537479 A JP 2012537479A JP 2013509204 A JP2013509204 A JP 2013509204A
- Authority
- JP
- Japan
- Prior art keywords
- food
- bifidobacteria
- cells
- strain
- formulation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 241000186000 Bifidobacterium Species 0.000 title claims description 68
- 230000037406 food intake Effects 0.000 claims abstract description 14
- 230000004957 immunoregulator effect Effects 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims description 76
- 241001465754 Metazoa Species 0.000 claims description 64
- 235000013305 food Nutrition 0.000 claims description 58
- 230000000529 probiotic effect Effects 0.000 claims description 44
- 239000006041 probiotic Substances 0.000 claims description 39
- 235000018291 probiotics Nutrition 0.000 claims description 39
- 238000011282 treatment Methods 0.000 claims description 36
- 241000282324 Felis Species 0.000 claims description 27
- 238000009472 formulation Methods 0.000 claims description 23
- 230000002265 prevention Effects 0.000 claims description 23
- 230000002757 inflammatory effect Effects 0.000 claims description 20
- 239000000463 material Substances 0.000 claims description 19
- 235000013406 prebiotics Nutrition 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 11
- 230000001105 regulatory effect Effects 0.000 claims description 11
- 210000000987 immune system Anatomy 0.000 claims description 10
- 230000002496 gastric effect Effects 0.000 claims description 9
- 208000023275 Autoimmune disease Diseases 0.000 claims description 8
- 239000000843 powder Substances 0.000 claims description 6
- 206010012735 Diarrhoea Diseases 0.000 claims description 5
- 206010061218 Inflammation Diseases 0.000 claims description 5
- 210000001072 colon Anatomy 0.000 claims description 5
- 235000013882 gravy Nutrition 0.000 claims description 5
- 230000004054 inflammatory process Effects 0.000 claims description 5
- 239000000725 suspension Substances 0.000 claims description 5
- 235000013618 yogurt Nutrition 0.000 claims description 5
- 239000002775 capsule Substances 0.000 claims description 4
- 235000013336 milk Nutrition 0.000 claims description 4
- 239000008267 milk Substances 0.000 claims description 4
- 210000004080 milk Anatomy 0.000 claims description 4
- 235000013351 cheese Nutrition 0.000 claims description 3
- 235000019868 cocoa butter Nutrition 0.000 claims description 3
- 229940110456 cocoa butter Drugs 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 239000012053 oil suspension Substances 0.000 claims description 3
- 238000001574 biopsy Methods 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000004064 dysfunction Effects 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 230000001363 autoimmune Effects 0.000 claims 1
- 230000002519 immonomodulatory effect Effects 0.000 abstract description 8
- 241001655328 Bifidobacteriales Species 0.000 abstract description 6
- 210000004027 cell Anatomy 0.000 description 104
- 241000894006 Bacteria Species 0.000 description 66
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 44
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical class CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 42
- 102000003814 Interleukin-10 Human genes 0.000 description 39
- 108090000174 Interleukin-10 Proteins 0.000 description 39
- 238000000338 in vitro Methods 0.000 description 38
- 238000000034 method Methods 0.000 description 37
- 210000001035 gastrointestinal tract Anatomy 0.000 description 32
- 230000000694 effects Effects 0.000 description 28
- 230000006698 induction Effects 0.000 description 28
- 244000005700 microbiome Species 0.000 description 26
- 210000003289 regulatory T cell Anatomy 0.000 description 25
- 230000001580 bacterial effect Effects 0.000 description 24
- 210000001744 T-lymphocyte Anatomy 0.000 description 21
- 210000000941 bile Anatomy 0.000 description 21
- 239000004310 lactic acid Substances 0.000 description 21
- 235000014655 lactic acid Nutrition 0.000 description 21
- 102000004127 Cytokines Human genes 0.000 description 20
- 108090000695 Cytokines Proteins 0.000 description 20
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 18
- 230000001965 increasing effect Effects 0.000 description 18
- 230000000638 stimulation Effects 0.000 description 17
- 206010020751 Hypersensitivity Diseases 0.000 description 16
- 108010065805 Interleukin-12 Proteins 0.000 description 16
- 102000013462 Interleukin-12 Human genes 0.000 description 16
- 238000011534 incubation Methods 0.000 description 16
- 241001608472 Bifidobacterium longum Species 0.000 description 15
- 230000007815 allergy Effects 0.000 description 15
- 229940009291 bifidobacterium longum Drugs 0.000 description 15
- 210000004443 dendritic cell Anatomy 0.000 description 15
- 239000013566 allergen Substances 0.000 description 14
- 208000026935 allergic disease Diseases 0.000 description 13
- 239000000427 antigen Substances 0.000 description 13
- 102000036639 antigens Human genes 0.000 description 13
- 108091007433 antigens Proteins 0.000 description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 13
- 238000002955 isolation Methods 0.000 description 13
- 108091023242 Internal transcribed spacer Proteins 0.000 description 12
- 201000010099 disease Diseases 0.000 description 12
- 238000001727 in vivo Methods 0.000 description 12
- 230000004044 response Effects 0.000 description 12
- 230000028327 secretion Effects 0.000 description 12
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 12
- 229960005486 vaccine Drugs 0.000 description 12
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 11
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 11
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 11
- 230000036541 health Effects 0.000 description 11
- 230000028993 immune response Effects 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- 229920001817 Agar Polymers 0.000 description 10
- 239000008272 agar Substances 0.000 description 10
- 238000000855 fermentation Methods 0.000 description 10
- 230000004151 fermentation Effects 0.000 description 10
- 230000012010 growth Effects 0.000 description 10
- 230000001717 pathogenic effect Effects 0.000 description 10
- 108090000623 proteins and genes Proteins 0.000 description 10
- 238000011161 development Methods 0.000 description 9
- 230000018109 developmental process Effects 0.000 description 9
- 239000000835 fiber Substances 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 244000052769 pathogen Species 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 210000003491 skin Anatomy 0.000 description 9
- 239000013589 supplement Substances 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 8
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 230000009286 beneficial effect Effects 0.000 description 8
- 231100000673 dose–response relationship Toxicity 0.000 description 8
- 230000000813 microbial effect Effects 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 239000006228 supernatant Substances 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 230000035899 viability Effects 0.000 description 8
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 7
- 229920001202 Inulin Polymers 0.000 description 7
- 206010009887 colitis Diseases 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 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 description 7
- 229940029339 inulin Drugs 0.000 description 7
- 235000013372 meat Nutrition 0.000 description 7
- 210000000822 natural killer cell Anatomy 0.000 description 7
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 6
- 241000282412 Homo Species 0.000 description 6
- 108090001005 Interleukin-6 Proteins 0.000 description 6
- 102000004889 Interleukin-6 Human genes 0.000 description 6
- 102000004890 Interleukin-8 Human genes 0.000 description 6
- 108090001007 Interleukin-8 Proteins 0.000 description 6
- 108091028043 Nucleic acid sequence Proteins 0.000 description 6
- 229930182555 Penicillin Natural products 0.000 description 6
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 230000001939 inductive effect Effects 0.000 description 6
- 230000000968 intestinal effect Effects 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 210000004877 mucosa Anatomy 0.000 description 6
- 235000006408 oxalic acid Nutrition 0.000 description 6
- 229940049954 penicillin Drugs 0.000 description 6
- 235000018102 proteins Nutrition 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 239000011550 stock solution Substances 0.000 description 6
- 229960005322 streptomycin Drugs 0.000 description 6
- 230000001629 suppression Effects 0.000 description 6
- 235000019750 Crude protein Nutrition 0.000 description 5
- 241000282326 Felis catus Species 0.000 description 5
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical class OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 5
- 241000287828 Gallus gallus Species 0.000 description 5
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 5
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 5
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 5
- 206010003246 arthritis Diseases 0.000 description 5
- 208000006673 asthma Diseases 0.000 description 5
- 239000006227 byproduct Substances 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 235000013330 chicken meat Nutrition 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 5
- 239000012636 effector Substances 0.000 description 5
- 230000007613 environmental effect Effects 0.000 description 5
- 208000027866 inflammatory disease Diseases 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 239000002953 phosphate buffered saline Substances 0.000 description 5
- 230000001681 protective effect Effects 0.000 description 5
- 230000003248 secreting effect Effects 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 4
- 241000196324 Embryophyta Species 0.000 description 4
- 206010015150 Erythema Diseases 0.000 description 4
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 4
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 4
- 239000012980 RPMI-1640 medium Substances 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 235000015278 beef Nutrition 0.000 description 4
- 230000033228 biological regulation Effects 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 4
- 235000019197 fats Nutrition 0.000 description 4
- 239000012894 fetal calf serum Substances 0.000 description 4
- 230000006058 immune tolerance Effects 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 229940076144 interleukin-10 Drugs 0.000 description 4
- 230000006799 invasive growth in response to glucose limitation Effects 0.000 description 4
- 210000002429 large intestine Anatomy 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 244000000010 microbial pathogen Species 0.000 description 4
- 244000005706 microflora Species 0.000 description 4
- 239000003226 mitogen Substances 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 description 4
- 210000000813 small intestine Anatomy 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 210000002700 urine Anatomy 0.000 description 4
- 201000004384 Alopecia Diseases 0.000 description 3
- 241000606125 Bacteroides Species 0.000 description 3
- 241000186015 Bifidobacterium longum subsp. infantis Species 0.000 description 3
- 244000298479 Cichorium intybus Species 0.000 description 3
- 235000007542 Cichorium intybus Nutrition 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 230000005526 G1 to G0 transition Effects 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 101000946889 Homo sapiens Monocyte differentiation antigen CD14 Proteins 0.000 description 3
- 244000035744 Hura crepitans Species 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 241000186660 Lactobacillus Species 0.000 description 3
- 241000186604 Lactobacillus reuteri Species 0.000 description 3
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 3
- 102100035877 Monocyte differentiation antigen CD14 Human genes 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 108010047620 Phytohemagglutinins Proteins 0.000 description 3
- 235000021307 Triticum Nutrition 0.000 description 3
- 244000098338 Triticum aestivum Species 0.000 description 3
- 240000008042 Zea mays Species 0.000 description 3
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 3
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 230000000172 allergic effect Effects 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 230000000845 anti-microbial effect Effects 0.000 description 3
- 208000010668 atopic eczema Diseases 0.000 description 3
- 230000004888 barrier function Effects 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 238000003501 co-culture Methods 0.000 description 3
- 235000005822 corn Nutrition 0.000 description 3
- 230000016396 cytokine production Effects 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000007123 defense Effects 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 210000003979 eosinophil Anatomy 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 150000004665 fatty acids Chemical class 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 239000003862 glucocorticoid Substances 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 208000024963 hair loss Diseases 0.000 description 3
- 230000003676 hair loss Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 229940039696 lactobacillus Drugs 0.000 description 3
- 229940001882 lactobacillus reuteri Drugs 0.000 description 3
- 229960004232 linoleic acid Drugs 0.000 description 3
- -1 low stomach pH Chemical class 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- 239000006872 mrs medium Substances 0.000 description 3
- 210000004400 mucous membrane Anatomy 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 229920001542 oligosaccharide Polymers 0.000 description 3
- 230000001885 phytohemagglutinin Effects 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 230000010287 polarization Effects 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 230000035882 stress Effects 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 229940037128 systemic glucocorticoids Drugs 0.000 description 3
- 230000036572 transepidermal water loss Effects 0.000 description 3
- 210000001635 urinary tract Anatomy 0.000 description 3
- 208000019206 urinary tract infection Diseases 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- 229910052725 zinc Inorganic materials 0.000 description 3
- AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 2
- 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 2
- HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 102100035882 Catalase Human genes 0.000 description 2
- 108010053835 Catalase Proteins 0.000 description 2
- GSXOAOHZAIYLCY-UHFFFAOYSA-N D-F6P Natural products OCC(=O)C(O)C(O)C(O)COP(O)(O)=O GSXOAOHZAIYLCY-UHFFFAOYSA-N 0.000 description 2
- 206010014950 Eosinophilia Diseases 0.000 description 2
- 229920001917 Ficoll Polymers 0.000 description 2
- 235000019733 Fish meal Nutrition 0.000 description 2
- 102100027581 Forkhead box protein P3 Human genes 0.000 description 2
- 108010068370 Glutens Proteins 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 101000861452 Homo sapiens Forkhead box protein P3 Proteins 0.000 description 2
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- 102100037850 Interferon gamma Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- 229930182816 L-glutamine Natural products 0.000 description 2
- 244000199866 Lactobacillus casei Species 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 240000007594 Oryza sativa Species 0.000 description 2
- 235000007164 Oryza sativa Nutrition 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 2
- 241000219061 Rheum Species 0.000 description 2
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 2
- 240000006394 Sorghum bicolor Species 0.000 description 2
- 235000011684 Sorghum saccharatum Nutrition 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 2
- 210000000662 T-lymphocyte subset Anatomy 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 210000000577 adipose tissue Anatomy 0.000 description 2
- 229940072056 alginate Drugs 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- JAZBEHYOTPTENJ-JLNKQSITSA-N all-cis-5,8,11,14,17-icosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O JAZBEHYOTPTENJ-JLNKQSITSA-N 0.000 description 2
- MBMBGCFOFBJSGT-KUBAVDMBSA-N all-cis-docosa-4,7,10,13,16,19-hexaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCC(O)=O MBMBGCFOFBJSGT-KUBAVDMBSA-N 0.000 description 2
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000005875 antibody response Effects 0.000 description 2
- 238000009341 apiculture Methods 0.000 description 2
- 238000003149 assay kit Methods 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 244000052616 bacterial pathogen Species 0.000 description 2
- BGWGXPAPYGQALX-ARQDHWQXSA-N beta-D-fructofuranose 6-phosphate Chemical compound OC[C@@]1(O)O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O BGWGXPAPYGQALX-ARQDHWQXSA-N 0.000 description 2
- 229940004120 bifidobacterium infantis Drugs 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 235000015895 biscuits Nutrition 0.000 description 2
- 230000035584 blastogenesis Effects 0.000 description 2
- 235000013339 cereals Nutrition 0.000 description 2
- 238000010411 cooking Methods 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 229960002433 cysteine Drugs 0.000 description 2
- 230000008260 defense mechanism Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 235000018823 dietary intake Nutrition 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- JAZBEHYOTPTENJ-UHFFFAOYSA-N eicosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O JAZBEHYOTPTENJ-UHFFFAOYSA-N 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 230000017214 establishment of T cell polarity Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000001125 extrusion Methods 0.000 description 2
- 239000004467 fishmeal Substances 0.000 description 2
- VZCCETWTMQHEPK-UHFFFAOYSA-N gamma-Linolensaeure Natural products CCCCCC=CCC=CCC=CCCCCC(O)=O VZCCETWTMQHEPK-UHFFFAOYSA-N 0.000 description 2
- VZCCETWTMQHEPK-QNEBEIHSSA-N gamma-linolenic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/CCCCC(O)=O VZCCETWTMQHEPK-QNEBEIHSSA-N 0.000 description 2
- 235000020664 gamma-linolenic acid Nutrition 0.000 description 2
- 229960002733 gamolenic acid Drugs 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 235000021312 gluten Nutrition 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 244000005709 gut microbiome Species 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000036737 immune function Effects 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 239000002955 immunomodulating agent Substances 0.000 description 2
- 229940121354 immunomodulator Drugs 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 208000002551 irritable bowel syndrome Diseases 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- 238000011813 knockout mouse model Methods 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 235000020778 linoleic acid Nutrition 0.000 description 2
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 2
- 150000004668 long chain fatty acids Chemical class 0.000 description 2
- 210000001165 lymph node Anatomy 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 235000012054 meals Nutrition 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 150000002482 oligosaccharides Chemical class 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000001044 red dye Substances 0.000 description 2
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 2
- 230000004043 responsiveness Effects 0.000 description 2
- 229930002330 retinoic acid Natural products 0.000 description 2
- 235000009566 rice Nutrition 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000008591 skin barrier function Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 235000012424 soybean oil Nutrition 0.000 description 2
- 239000003549 soybean oil Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 210000004003 subcutaneous fat Anatomy 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 229960001727 tretinoin Drugs 0.000 description 2
- 239000002435 venom Substances 0.000 description 2
- 210000001048 venom Anatomy 0.000 description 2
- 231100000611 venom Toxicity 0.000 description 2
- 208000016261 weight loss Diseases 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- 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
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 208000020053 Abnormal inflammatory response Diseases 0.000 description 1
- 108010062271 Acute-Phase Proteins Proteins 0.000 description 1
- 102000011767 Acute-Phase Proteins Human genes 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 244000291564 Allium cepa Species 0.000 description 1
- 235000002732 Allium cepa var. cepa Nutrition 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 206010003011 Appendicitis Diseases 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 244000003416 Asparagus officinalis Species 0.000 description 1
- 235000005340 Asparagus officinalis Nutrition 0.000 description 1
- 208000012657 Atopic disease Diseases 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 241000304886 Bacilli Species 0.000 description 1
- 108010077805 Bacterial Proteins Proteins 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 235000016068 Berberis vulgaris Nutrition 0.000 description 1
- 241000335053 Beta vulgaris Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 238000009631 Broth culture Methods 0.000 description 1
- 108010074051 C-Reactive Protein Proteins 0.000 description 1
- 102100032752 C-reactive protein Human genes 0.000 description 1
- 206010006895 Cachexia Diseases 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 241000193163 Clostridioides difficile Species 0.000 description 1
- 241000193403 Clostridium Species 0.000 description 1
- 241000193468 Clostridium perfringens Species 0.000 description 1
- 108010062580 Concanavalin A Proteins 0.000 description 1
- 108010043471 Core Binding Factor Alpha 2 Subunit Proteins 0.000 description 1
- 108010079362 Core Binding Factor Alpha 3 Subunit Proteins 0.000 description 1
- 241000711573 Coronaviridae Species 0.000 description 1
- 244000019459 Cynara cardunculus Species 0.000 description 1
- 235000019106 Cynara scolymus Nutrition 0.000 description 1
- 230000009946 DNA mutation Effects 0.000 description 1
- 238000012270 DNA recombination Methods 0.000 description 1
- 208000001840 Dandruff Diseases 0.000 description 1
- 208000006313 Delayed Hypersensitivity Diseases 0.000 description 1
- 108010082495 Dietary Plant Proteins Proteins 0.000 description 1
- 208000002699 Digestive System Neoplasms Diseases 0.000 description 1
- 208000000655 Distemper Diseases 0.000 description 1
- 208000017701 Endocrine disease Diseases 0.000 description 1
- 208000004232 Enteritis Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000588722 Escherichia Species 0.000 description 1
- 241001302654 Escherichia coli Nissle 1917 Species 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 206010017964 Gastrointestinal infection Diseases 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 101100005713 Homo sapiens CD4 gene Proteins 0.000 description 1
- 101000746367 Homo sapiens Granulocyte colony-stimulating factor Proteins 0.000 description 1
- 101001033249 Homo sapiens Interleukin-1 beta Proteins 0.000 description 1
- 101001033233 Homo sapiens Interleukin-10 Proteins 0.000 description 1
- 101001076408 Homo sapiens Interleukin-6 Proteins 0.000 description 1
- 101001055222 Homo sapiens Interleukin-8 Proteins 0.000 description 1
- 101000695838 Homo sapiens Receptor-type tyrosine-protein phosphatase U Proteins 0.000 description 1
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 1
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 1
- 240000005979 Hordeum vulgare Species 0.000 description 1
- 235000007340 Hordeum vulgare Nutrition 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 241000442132 Lactarius lactarius Species 0.000 description 1
- 235000013958 Lactobacillus casei Nutrition 0.000 description 1
- 235000019687 Lamb Nutrition 0.000 description 1
- 240000006240 Linum usitatissimum Species 0.000 description 1
- 235000004431 Linum usitatissimum Nutrition 0.000 description 1
- 241000186781 Listeria Species 0.000 description 1
- 241000186779 Listeria monocytogenes Species 0.000 description 1
- 206010025327 Lymphopenia Diseases 0.000 description 1
- 240000002129 Malva sylvestris Species 0.000 description 1
- 235000006770 Malva sylvestris Nutrition 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 240000004658 Medicago sativa Species 0.000 description 1
- 235000017587 Medicago sativa ssp. sativa Nutrition 0.000 description 1
- 241000736262 Microbiota Species 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 241001504654 Mustela nivalis Species 0.000 description 1
- 241000187644 Mycobacterium vaccae Species 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- 108010057466 NF-kappa B Proteins 0.000 description 1
- 102000003945 NF-kappa B Human genes 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 208000002606 Paramyxoviridae Infections Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 241001085205 Prenanthella exigua Species 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 102100028516 Receptor-type tyrosine-protein phosphatase U Human genes 0.000 description 1
- 208000002200 Respiratory Hypersensitivity Diseases 0.000 description 1
- 102100025369 Runt-related transcription factor 3 Human genes 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 235000019485 Safflower oil Nutrition 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 235000019486 Sunflower oil Nutrition 0.000 description 1
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 1
- 210000000447 Th1 cell Anatomy 0.000 description 1
- 210000000068 Th17 cell Anatomy 0.000 description 1
- 210000004241 Th2 cell Anatomy 0.000 description 1
- 235000009430 Thespesia populnea Nutrition 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 102000008233 Toll-Like Receptor 4 Human genes 0.000 description 1
- 108010060804 Toll-Like Receptor 4 Proteins 0.000 description 1
- 102000002689 Toll-like receptor Human genes 0.000 description 1
- 108020000411 Toll-like receptor Proteins 0.000 description 1
- 108010048999 Transcription Factor 3 Proteins 0.000 description 1
- 102100038313 Transcription factor E2-alpha Human genes 0.000 description 1
- 206010054094 Tumour necrosis Diseases 0.000 description 1
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 1
- 230000028654 Type IV pili-dependent aggregation Effects 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 208000009911 Urinary Calculi Diseases 0.000 description 1
- 208000025609 Urogenital disease Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 208000021017 Weight Gain Diseases 0.000 description 1
- 239000005862 Whey Substances 0.000 description 1
- 102000007544 Whey Proteins Human genes 0.000 description 1
- 108010046377 Whey Proteins Proteins 0.000 description 1
- 229960003697 abatacept Drugs 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000035508 accumulation Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- LIPOUNRJVLNBCD-UHFFFAOYSA-N acetyl dihydrogen phosphate Chemical compound CC(=O)OP(O)(O)=O LIPOUNRJVLNBCD-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 239000000048 adrenergic agonist Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 230000003679 aging effect Effects 0.000 description 1
- 230000010085 airway hyperresponsiveness Effects 0.000 description 1
- 230000008369 airway response Effects 0.000 description 1
- 230000009285 allergic inflammation Effects 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 230000000961 alloantigen Effects 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 206010002022 amyloidosis Diseases 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 235000021120 animal protein Nutrition 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 235000016520 artichoke thistle Nutrition 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 210000000649 b-lymphocyte subset Anatomy 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 239000003659 bee venom Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 229940093761 bile salts Drugs 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000037182 bone density Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 229940036811 bone meal Drugs 0.000 description 1
- 239000002374 bone meal Substances 0.000 description 1
- 235000021324 borage oil Nutrition 0.000 description 1
- 230000001680 brushing effect Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000004534 cecum Anatomy 0.000 description 1
- 230000011712 cell development Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000010307 cell transformation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 235000015111 chews Nutrition 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 238000013170 computed tomography imaging Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 235000020940 control diet Nutrition 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000011443 conventional therapy Methods 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 230000000139 costimulatory effect Effects 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 235000019784 crude fat Nutrition 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 201000003146 cystitis Diseases 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000013325 dietary fiber Nutrition 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 208000024558 digestive system cancer Diseases 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 210000003162 effector t lymphocyte Anatomy 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 235000008524 evening primrose extract Nutrition 0.000 description 1
- 239000010475 evening primrose oil Substances 0.000 description 1
- 229940089020 evening primrose oil Drugs 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 230000002550 fecal effect Effects 0.000 description 1
- 235000021323 fish oil Nutrition 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 235000021255 galacto-oligosaccharides Nutrition 0.000 description 1
- 150000003271 galactooligosaccharides Chemical class 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 201000010231 gastrointestinal system cancer Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000004478 grain bait Substances 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000007407 health benefit Effects 0.000 description 1
- 230000008821 health effect Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 229960001660 histamine phosphate Drugs 0.000 description 1
- ZHIBQGJKHVBLJJ-UHFFFAOYSA-N histamine phosphate Chemical compound OP(O)(O)=O.OP(O)(O)=O.NCCC1=CNC=N1 ZHIBQGJKHVBLJJ-UHFFFAOYSA-N 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000007366 host health Effects 0.000 description 1
- 230000007236 host immunity Effects 0.000 description 1
- 102000052624 human CXCL8 Human genes 0.000 description 1
- 102000052620 human IL10 Human genes 0.000 description 1
- 102000057041 human TNF Human genes 0.000 description 1
- 229940116886 human interleukin-6 Drugs 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 230000004179 hypothalamic–pituitary–adrenal axis Effects 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 230000005965 immune activity Effects 0.000 description 1
- 230000008076 immune mechanism Effects 0.000 description 1
- 230000008629 immune suppression Effects 0.000 description 1
- 201000007294 immune system cancer Diseases 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 210000002602 induced regulatory T cell Anatomy 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000031261 interleukin-10 production Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 210000005024 intraepithelial lymphocyte Anatomy 0.000 description 1
- JDNTWHVOXJZDSN-UHFFFAOYSA-N iodoacetic acid Chemical compound OC(=O)CI JDNTWHVOXJZDSN-UHFFFAOYSA-N 0.000 description 1
- 230000000622 irritating effect Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 230000037231 joint health Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 229940017800 lactobacillus casei Drugs 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000002794 lymphocyte assay Methods 0.000 description 1
- 231100001023 lymphopenia Toxicity 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 235000013622 meat product Nutrition 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 239000011325 microbead Substances 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 230000001483 mobilizing effect Effects 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 229940031348 multivalent vaccine Drugs 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- 229920001206 natural gum Polymers 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 208000030212 nutrition disease Diseases 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229940035567 orencia Drugs 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 235000020232 peanut Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229960000292 pectin Drugs 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000008855 peristalsis Effects 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 210000001986 peyer's patch Anatomy 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 235000015277 pork Nutrition 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000009696 proliferative response Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000007363 regulatory process Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 150000004666 short chain fatty acids Chemical class 0.000 description 1
- 235000021391 short chain fatty acids Nutrition 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 230000004215 skin function Effects 0.000 description 1
- RPACBEVZENYWOL-XFULWGLBSA-M sodium;(2r)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate Chemical compound [Na+].C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)[O-])CO1 RPACBEVZENYWOL-XFULWGLBSA-M 0.000 description 1
- YEENEYXBHNNNGV-XEHWZWQGSA-M sodium;3-acetamido-5-[acetyl(methyl)amino]-2,4,6-triiodobenzoate;(2r,3r,4s,5s,6r)-2-[(2r,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound [Na+].CC(=O)N(C)C1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I.O[C@H]1[C@H](O)[C@@H](CO)O[C@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 YEENEYXBHNNNGV-XEHWZWQGSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 239000002438 stress hormone Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 230000031068 symbiosis, encompassing mutualism through parasitism Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 230000003868 tissue accumulation Effects 0.000 description 1
- 230000003614 tolerogenic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 230000005951 type IV hypersensitivity Effects 0.000 description 1
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229960001763 zinc sulfate Drugs 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
- A23C9/00—Milk preparations; Milk powder or milk powder preparations
- A23C9/12—Fermented milk preparations; Treatment using microorganisms or enzymes
- A23C9/123—Fermented milk preparations; Treatment using microorganisms or enzymes using only microorganisms of the genus lactobacteriaceae; Yoghurt
- A23C9/1234—Fermented milk preparations; Treatment using microorganisms or enzymes using only microorganisms of the genus lactobacteriaceae; Yoghurt characterised by using a Lactobacillus sp. other than Lactobacillus Bulgaricus, including Bificlobacterium sp.
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K10/00—Animal feeding-stuffs
- A23K10/10—Animal feeding-stuffs obtained by microbiological or biochemical processes
- A23K10/16—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions
- A23K10/18—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions of live microorganisms
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/40—Feeding-stuffs specially adapted for particular animals for carnivorous animals, e.g. cats or dogs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
- A23K50/40—Feeding-stuffs specially adapted for particular animals for carnivorous animals, e.g. cats or dogs
- A23K50/48—Moist feed
-
- 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
- A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/745—Bifidobacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
- 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
- A61P37/04—Immunostimulants
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
- C12N1/205—Bacterial isolates
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2400/00—Lactic or propionic acid bacteria
- A23V2400/51—Bifidobacterium
- A23V2400/533—Longum
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Microbiology (AREA)
- Polymers & Plastics (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Zoology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Food Science & Technology (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Animal Husbandry (AREA)
- Mycology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Virology (AREA)
- Birds (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
Description
本発明の第一の態様は、動物内でプロバイオティク活性を有する切除及び洗浄されたネコ科動物の胃腸管から単離することにより得られる、ビフィズス菌属の乳酸菌株を含む。プロバイオティクは、生存微生物又は死滅微生物、微生物の加工組成物、タンパク質又は炭水化物のようなそれらの構成成分、あるいは宿主に有益な作用を及ぼす細菌発酵の精製画分である。プロバイオティク菌は、生存細胞形態で一般に使用される。しかし、プロバイオティク菌により発現される有益な因子を含有する、死滅した培養物又は組成物のような非生存細胞にも及ぶことができる。これには、熱で死滅した微生物、あるいは、pH変化に曝されることにより又は圧力を受けることにより死滅した微生物が含まれ得る。本発明の目的では、「プロバイオティク」は、特に指定がない限り、本発明の微生物によって発酵中に産生される代謝産物を更に含むことが意図される。これらの代謝産物は、発酵の媒質に放出されてもよいし、微生物内に蓄えられてもよい。本明細書で使用する時、「プロバイオティク」は、また、治療的用量で与えられた場合に宿主動物に有益な機能を果たす、細菌、細菌性ホモジネート、細菌性タンパク質、細菌抽出物、細菌発酵上清、及びこれらの混合物も含む。
ビフィズス菌ロンガム菌株AH121aは、ネコ科動物の腸組織から単離した。
16s遺伝子間スペーサ(IGS)シークエンシングを行って、単離されたビフィズス菌の種を同定した。簡潔に、100μLの抽出液及び25μLの組織調製液(Sigma、XNAT2 Kit)を用いて、DNAをAH121Aから単離した。試料を室温で5分間インキュベートした後、95℃で2時間インキュベートし、次いで、100μLの中和溶液(XNAT2キット)を添加した。ナノドロップ分光分析装置を使用してゲノムDNA溶液を定量化し、4℃で保存した。PCRは、IGSプライマー、IGS L:5’−GCTGGATCACCTCCTTTCT−3’(SEQ ID NO.3)を用いて行った結果、SEQ ID NO.1が同定され、IGS R:5’−CTGGTGCCAAGGCATCCA−3’(SEQ ID NO.4)ではSEQ ID NO.2が同定された。サイクル条件は、94℃で3分間(1サイクル)、94℃で30秒間、53℃で30秒間、72℃で30秒間(28サイクル)であった。PCR反応は、4μL(50ng)のDNA、PCRミックス(XNAT2キット)、0.4μMのIGS L及びRプライマー(MWG Biotech、ドイツ)を含有していた。PCR反応は、エッペンドルフ熱サイクラー(Eppendorf thermocycler)にて行われた。PCR産物(10μL)を、TAE中2%アガロースEtBr染色ゲル上で分子量マーカー(100bp Ladder、Roche)と並べて分析して、IGSプロファイルを決定した。ビフィズス菌のPCR製品(単一バンド)を、Promega Wizard PCR精製キットを使用して精製した。遺伝子間スペーサ−領域に関して、精製されたPCR製品をプライマー配列(上記)を使用して、配列した。次いで、ヌクレオチド相同性により、菌株の同一性を決定するために、配列データを、NCBIヌクレオチドデータベースに対して検索した。得られたDNA配列データを、NCBI標準ヌクレオチド−ヌクレオチド相同性BLAST検索エンジン(http://www.ncbi.nlm.nih.gov/BLAST/)にかけた。この配列に最も近い配列を同定し、次いでDNASTAR MegAlignソフトウェアを用いてそれらの配列を整列させて比較した。得られた配列(SEQ ID NO.1[IGS正順]及びSEQ ID NO.2[IGS逆順])は配列一覧で見ることができる。NCIMBデータベースの検索は、AH121Aがビフィズス菌ロンガムに最も近い配列相同性を伴う特有のIGS(SEQ ID NO.1[正順]及びSEQ ID NO.2[逆順])配列を有することを明らかにした。
コンゴレッド寒天スクリーンを使用して、EPS発現菌株を表現型的にスクリーニングした。つまり、10mLの変性Rogosaブロス培養基(+0.05%システイン)を、新しく増殖させた菌株のコロニーとともに無菌で植菌し、濁るまで37℃で嫌気的にインキュベートした(約16〜約24時間)。ブロス培養物をコンゴレッド寒天平板上に無菌でストリーキングし、37℃で48時間、嫌気的にインキュベートした。増殖の副生成物として生成されたEPS及び/又は特定の株の代謝が、コンゴレッド染料の摂取を防いだ結果としてクリーム/白色コロニー形態をもたらすと考えられる。より少ないEPSを生成する株(Stains)は容易にコンゴレッド染料を摂取し、ピンク/赤色コロニー形態をもたらす。赤色EPSを生成しない株は赤色に染色し、赤色寒天を背景にほとんど透明に見える。
様々な濃度のブタ胆汁に対するネコ科動物細菌の単離物AHF121Aの耐性を判定し、pH 2.5でのネコ科動物細菌の単離物AHF121Aの生存を6時間及び様々な濃度の胆汁を用いたそれに続く胆汁耐性を評価する。
試験株はAHF121Aビフィズス菌ロンガムである。胆汁耐性は、ブタの胆汁を補ったMRS/RCA寒天平板(0.3、0.5、1.0、2.0、5.0、7.5、及び10%)を用いて検査する。pH 2.5での株の生存を、平板計数法を用いて−5、5、30、60、120、180、及び360分間隔で監視する。pH 2.5で6時間、株に課された後、胆汁耐性を検査する。
ネコ科胆汁耐性の判定手順の概略を以下に記す。
1%(3.33mL胆汁原液+146.67mLの寒天)、
0.5%(1.67mL胆汁原液+148.33mLの寒天)の様々な胆汁濃度を使用した。
○ 表1は、ネコ科動物の胆汁が菌株の増殖に与える影響を示す。ネコ科動物の菌株は≦2%の濃度のネコ科動物胆汁に耐性があった。
○ 図3は、pH 2.5での酸への耐性を示す。
BDバキュテイナーCPT管(BDカタログ番号362761)を製造業者の指示にしたがって用い、健康なヒト末梢血から末梢血単核細胞(PBMC)を単離した。PBMCを洗浄し、DulbeccoのModified Eagle Medium−Glutamax(商標)(Glutamax(グルタミン代用品)+ピルビン酸+ブドウ糖4.5g/L(Gibcoカタログ番号10569−010)、10%のウシ胎児血清(Sigmaカタログ番号F4135)、及び1%のペニシリン/ストレプトマイシン(Sigmaカタログ番号P0781)に再懸濁した。PBMCを平底96ウェルプレートでインキュベートし(各ウェルに2×105細胞)、20μLの細菌懸濁液(1×107CFU/mLの濃度)を添加した。PBMCをインキュベータ内で37℃/5% CO2にて細菌と48時間共インキュベートした。2日のインキュベーション期間の後、300×gでプレートを遠心分離し、上清を取り除き、−80℃で冷凍保存してから分析した。Meso Scale Discovery(メリーランド州Gaithersburg(カタログ番号K15008B−1))の96ウェルアッセイキットを用いて、培養上清におけるインターロイキン−10(IL−10)及びインターロイキン−12p70(IL−12p70)の濃度を定量化した。
宿主の総合的な健康の重要な決定因子における、微生物に対する適切な免疫応答。過剰な応答は炎症性疾患(例えば大腸炎)につながる可能性があり、一方、不十分な応答は病原体の持続及び播種につながる。本明細書に記載の免疫アッセイは、特定の微生物に対する応答としての宿主の免疫活性の決定のための有用な方法として本文献に十分に説明されている。
PBMCサイトカイン誘導アッセイにより、ビフィズス菌ロンガムインファンティス菌株UCC35624(B624)及びビフィズス菌ロンガム菌株121aのアッセイを行った。細菌は、以下の形式で共培養実験用に調製した。Difco MRS培養基にて37℃で嫌気性条件下で細菌を増殖し、固定相に入った直後に採集する。これらの細菌のそれぞれの凍結乾燥粉末を生成し、予めアリコートした100mgバイアル瓶にて−80℃で保存する。使用の直前に各菌株のアリコートを冷凍庫から1つ取り出し、室温に戻す。各菌株を10mLのリンガーで3回洗浄し、遠心分離する。その都度、新しいバイアル瓶を使用する。
BDバキュテイナーCPT管(BDカタログ番号362761)を製造業者の指示に従って用い、健康なヒト末梢血から末梢血単核細胞(PBMC)を単離する。PBMCを洗浄し、DulbeccoのModified Eagle Medium−Glutamax(商標)(Glutamax(グルタミン代用品)+ピルビン酸+ブドウ糖4.5g/L(Gibcoカタログ番号10569−010)、10%のウシ胎児血清(Sigmaカタログ番号F4135)、及び1%のペニシリン/ストレプトマイシン(Sigmaカタログ番号P0781)に再懸濁する。PBMCを平底96ウェルプレートでインキュベートし(各ウェルに2×105細胞)、20μLの細菌懸濁液(1×106〜8CFU/mLの濃度範囲)を添加する。最高6つの異なる量の細菌(2.5E+08、1.0E+08、5.0E+07、2.5E+07、1.0E+07、及び1.0E+06)を検査する。無細菌の対照も検査する。全てのアッセイを3回行う。2日のインキュベーション期間の後、300×gでプレートを回転させ、上清を取り除き、−80℃で冷凍保存してから分析する。PBMCをインキュベータ内で37℃/5% CO2にて細菌と48時間共インキュベートする。Meso Scale Discovery(メリーランド州Gaithersburg、カタログ番号K15008B−1)の96ウェルアッセイキットを用いて、培養上清のサイトカインのアッセイを行う。ヒトインターロイキン1β(Il−1β)、ヒトインターロイキン6(Il−β)、ヒトインターロイキン8(Il−8)、ヒトインターロイキン10(Il−10)、ヒトインターロイキン12p70(Il12p70)、ヒトインターロイキンガンマ(IFN−γ)、ヒト腫瘍壊死因子α(TNFα)、及びヒトG−CSFを定量化し、ミリリットル当たりのピコグラム(pg/mL)として報告する。各試料のアッセイを3回〜5回行う(A to E)。
ビフィズス菌ロンガムインファンティス菌株UCC35624(B624)及びビフィズス菌ロンガム菌株121aは、免疫調節のためにPBMCサイトカイン誘導アッセイを用いてアッセイされて、検査された最高6つの異なる量の細菌(2.5E+08、1.0E+08、5.0E+07、2.5E+0、1.0E+07、1.0E+06)での拡張用量応答曲線を生成する。IL−1β、IL−6、IL−8、IL−10、IL−12、TNF−α、IFN−γ、及びG−CSFを含むサイトカインの範囲に関して、上清をアッセイする。最高5人のドナー(A〜E)からのサイトカインの測定値を平均(+/−SEM)として表す。
概要
免疫応答は非常によく調節されたプロセスであり、通常、感染からの保護及び無害な環境抗原の寛容をもたらす。しかし、炎症性疾患では、活性化された免疫応答は、元来の免疫応答の活性化及び有極T細胞サブセットの拡張を特徴とする慢性的炎症性状態をもたらす。炎症性疾患の現在の治療は、主要な炎症メディエータ又は炎症細胞集団の抑制に焦点を当てている。しかし、これらのアプローチは疾患症状の一時的な抑制しか与えない。長期的治療又は予防の成功は、害を与える炎症性応答から守る細胞調節プロセスの強化によってのみ可能である。ビフィズス菌AHF121Aは、元来の免疫系(すなわち樹枝状細胞)からのIL−10の分泌を選択的に刺激するプロバイオティク微生物であり、インビトロでFoxp−3陽性調節性T細胞の極性化を誘導する。生体内では、IL−10分泌及び調節性T細胞は異常な炎症性応答の強力な抑制剤である。
免疫寛容の維持における調節性T(Treg)細胞の基本的役割は広範な動物モデルで実証されており、アレルゲン、自己抗原、又は同種抗原に対する免疫寛容を回復することによって、アレルギー、喘息性肺炎、自己免疫疾患、及び同種移植片拒絶を含む、T細胞メディエーションによるいくつかの疾患を予防又は治癒するTreg細胞の養子免疫伝達又は意図的な拡張が示された[8]。Tregメディエーションによる免疫抑制のための複数の分子機構では、IL−10の分泌が特に重要であると説明されてきた[9]。Treg細胞の欠如又は機能不良は、ヒトにおけるIgE過多症候群、過好酸球増加症、及び自己免疫とも相関されており、一方、それらの存在は免疫寛容と関連づけられている[10]。非病原性の環境抗原に対する免疫応答がアレルギー又は非有害性免疫のいずれかにつながる機構に関する研究は、アレルゲン特有のIL−10生成Tregs(TR1細胞)が健康な個体における支配的なT細胞サブセットであることを実証している[11,12]。アレルギー性でない健康な養蜂家を養蜂シーズン中に蜂毒抗原に繰り返し曝露させることは、毒抗原に対する免疫寛容の機構を確認するために有用な代表的なインビボモデルである[13]。蜂に複数回刺された後、毒抗原特有のTH1及びTH2細胞はIL−10−分泌性TR1細胞に切り替わる。これと並行して、アレルゲンに対する皮膚の後期応答の抑制並びにアレルゲン特有のTH1及びTH2細胞の阻害が生じる。この応答は、毒への曝露が続く限り観察され、養蜂シーズンの終わりから2〜3ヶ月内に初期レベルに戻る。
異常な炎症活性の治療のための、微生物及び微生物代謝物の意図的な投与への関心が高まっている。現在検討されている典型的な微生物としては、ビフィズス菌、乳酸菌、非病原性大腸菌、及びバクテロイデス菌株が挙げられる[26〜31]。これらの微生物に伴う保護効果は、おそらく、上皮細胞、樹枝状細胞、及びT細胞が関わる複数の機構を媒介としてもたらされるものである。しかし、これらの微生物に共通の特徴であるTreg細胞誘導能力がますます報告されている。例えば、ネズミ科動物の胃腸内の片利共生微生物の混合物(VSL#3プロバイオティクカクテル)との遭遇は、ネズミ科動物モデルの大腸炎における炎症の減衰と関連づけられる粘膜Treg細胞の発育を推進することが示されている[32]。加えて、ビフィズス菌インファンティス菌株の摂取は、Treg細胞の転換を促進し、生体内におけるLPS誘導型NF−κB活性から保護し、一方、ラクトバシラスロイテリは、マウスにおけるアレルギー性気道応答から保護するTreg細胞を誘導する[33、34]。Treg細胞は胸腺由来であるが、周辺器官(胃腸粘膜を含む)においても誘導され得る[35、36]。TGF−β及びレチノイン酸依存性プロセスを介するTreg細胞の転換は、主にこの粘膜内のCD103+樹枝状細胞による[37、38]。この転換は、多数の片利共生微生物の存在と関連づけられる胃腸管特有の環境因子によって推進される可能性が高い。しかし、生体内のTreg細胞の誘導において全ての片利共生微生物が同等に効果的である可能性は低い。最近の研究は、複数の片利共生微生物(ビフィズス菌ロンガムAH1206、ビフィズス菌ブレーAH1205、及びラクトバチラスサリバリウスAH102)を比較すると、ネズミ科動物モデルにおいてビフィズス菌ロンガムAH1206がTreg細胞を誘導したこと、及び肺への好酸球補充から保護し、血清IgEの誘導を遮断することが可能であったことを示した[39]。その他の菌株はTreg細胞を効果的に誘導せず、同じモデルにおいてアレルギー性炎症から保護することができなかった。したがって、Treg細胞の誘導は、潜在アレルゲンに対する異常な免疫応答性の発症に対する保護という、健康な微生物相の重要な特性であり得る。アレルギーの治療のための生きた微生物の使用に加えて、期待される別の方法は、その有益な効果に関与する微生物因子を特定し、それらの単離された因子を単独で使用することである。例えば、バクテロイデスフラジリス由来の多糖類Aは、粘膜樹枝状細胞による提示の後に無菌マウスにおける適切なTH1/TH2バランスを促進し、IL−10分泌性CD4+ T細胞を介して動物モデルにおいて大腸炎から保護する[29,40]。寛容原生樹枝状細胞及びTreg活性を誘導する新しい微生物化合物の継続的な同定は、臨床試験における評価のための新規な治療用分子を疑いなくもたらすであろう。
Ficoll密度遠心分離及び細胞分離の組み合わせを用い、CD14−特有抗体でコーティングした磁性マイクロビード(MiltentyiBiotec)を使用して、ヒト単球を血液から単離した。単離されたCD14+細胞分画の純度は、全ての実験で90%を超えていた。未熟のDC(iDC)を生成するために、精製したCD14+細胞を5日間、IL−4(R&D systems)及びGM−CFS(R&D systems)の存在下で培養して、骨髄樹枝状細胞に差別化した。6日目に、細胞を刺激しないまま残す(iDC)か、LPS(1mg/mL)5×105で細胞を刺激した。MDDCは細菌細胞で24時間刺激した。ビフィズス菌ロンガムAHF121A菌株(10:1の細菌対DC比(5×106)、1:1の細菌対DC比(5×105)で24時間。予測したとおり、抗生物質の適用の結果として、この期間中に細菌増殖は観察されなかった。この時点で上清を単離し、Luminexマルチプレックスプラットホームを用いてIL−10及びIL−12p70のレベルを分析した。
Lymphoprepグラジエントでバフィーコートの遠心分離によりPBMCを単離した。CD4+ T細胞は陰性選択アフィニティカラム(R&D Systems)を製造業者の指示どおりに用いて分離した。分離後、T細胞を洗浄し、加熱不活性化したウシ胎児血清10%、100IU/mLのペニシリン、100μg/mLのストレプトマイシン、及び2mmol/LのLグルタミンを補ったRPMI1640培養基に再懸濁した。精製したCD4+ T細胞(1×106/mL)を、固定化した抗CD3(1μg/mL)と可溶性抗CD28(5μg/mL)mAbs(Pharmingen)との組み合わせで刺激した。次いで、精製したCD4+ T細胞をDCでインキュベートした。48時間後、CD4+ T細胞は透過性になり、CD25及びFoxp−3に対して染色された。フローサイトメトリを使用して細胞を評価した。
1.McCracken V.J.and Gaskins H.R.Probiotics and the immune system.In:Probiotics a critical review,Tannock,GW(ed),Horizon Scientific Press,UK.1999,p.85〜113。
2.Savage D.C.Interaction between the host and its microbes.In:Microbial Ecology of the Gut,Clark and Bauchop(eds),Academic Press,London.1977,p.277〜310。
3.Kagnoff M.F.Immunology of the intestinal tract.Gastroenterol.1993;105(5):1275〜80。
4.Lamm M.E.Interaction of antigens and antibodies at mucosal surfaces.Ann.Rev.Microbiol.1997;51:311〜40。
5.Raychaudhuri S.,Rock KL.Fully mobilizing host defense:building better vaccines.Nat biotechnol.,1998;16:1025〜31。
6.Tomomatsu,H.Health effects of oligosaccharides(1994)Food Technol.48:61〜65。
7.Vickers et al.,Comparison of fermentation of selected fructooligosaccharides and other fibre substrates by feline colonic microflora(2001)Am.J.Vet.Res.61(4):609〜615。
8.Sakaguchi S,Yamaguchi T,Nomura T,Ono M.Regulatory T cells and immune tolerance.Cell 2008;133:775〜87。
9.Taylor A,Akdis M,Joss A,Akkoc T,Wenig R,Colonna M,Daigle I,Flory E,Blaser K,Akdis CA.IL−10 inhibits CD28 and ICOS costimulations of T cells via src homology 2 domain−containing protein tyrosine phosphatase 1.J Allergy Clin Immunol 2007;120:76〜83。
10.Chatila TA.Role of regulatory T cells in human diseases.J Allergy Clin Immunol 2005;116:949〜59。
11.Akdis M.Healthy immune response to allergens:T regulatory cells and more.Curr Opin Immunol 2006;18:738〜44。
12.Akdis M,Verhagen J,Taylor A,Karamloo F,Karagiannidis C,Crameri R,Thunberg S,Deniz G,Valenta R,Fiebig H,Kegel C,Disch R,Schmidt−Weber CB,Blaser K,Akdis CA.Immune responses in healthy and allergic Individuals are characterized by a fine balance between allergen−specific T regulatory 1 and T helper 2 cells.J Exp Med 2004;199:1567〜75。
13.Meiler F,Zumkehr J,Klunker S,Ruckert B,Akdis CA,Akdis M.In vivo switch to IL−10−secreting T regulatory cells in high dose allergen exposure.J Exp Med 2008;205;2887〜98。
14.Hendrikx TK,Velthuis JH,Klepper M,van Gurp E,Geel A,Schoordijk W,Baan CC,Weimar W.Monotherapy rapamycin allows an increase of CD4(+)CD25(bright+)FoxP3(+)T cells in renal recipients.Transpl Int 2009;22:884〜91。
15.Kremer JM,Dougados M,Emery P,Durez P,Sibilia J,Shergy W,Steinfeld S,Tindall E,Becker JC,Li T,Nuamah IF,Aranda R,Moreland LW.Treatment of rheumatoid arthritis with the selective costimulation modulator abatacept:twelve month results of a phase iib,double−blind,randomized,placebo−controlled trial.Arthritis Rheum 2005;52:2263〜71。
16.Utset TO,Auger JA,Peace D,Zivin RA,Xu D,Jolliffe L,Alegre ML,Bluestone JA,Clark MR.Modified anti−CD3 therapy in psoriatic arthritis:a phase I/II clinical trial.J Rheumatol 2002;29:1907〜13。
17.Isaacs JD,Greer S,Sharma S,Symmons D,Smith M,Johnston J,Waldmann H,Hale G,Hazleman BL.Morbidity and mortality in rheumatoid arthritis patients with prolonged and profound therapy−induced lymphopenia.Arthritis Rheum 2001;44:1998〜2008。
18.Ehrenstein MR,Evans JG,Singh A,Moore S,Warnes G,Isenberg DA,Mauri C.Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti−TNF−α therapy.J Exp Med 2004;200:277〜85。
19.O’Connor RA,Anderton SM.Multi−faceted control of autoaggression:Foxp3+ regulatory T cells in murine models of organ−specific autoimmune disease.Cell Immunol 2008;251:8〜18。
20.Roncarolo MG,Battaglia M.Regulatory T−cell immunotherapy for tolerance to selfantigens and alloantigens in humans.Nature Rev Immunol 2007;7:585〜98。
21.Peek EJ,Richards DF,Faith A,Lavender P,Lee TH,Corrigan CJ,Hawrylowicz CM.Interleukin−10−secreting「regulatory」T cells induced by glucocorticoids and beta2 Dagonists.Am J Respir Cell Mol Biol 2005;33:105〜11。
22.Karagiannidis C,Akdis M,Holopainen P,Woolley NJ,Hense G,Ruckert B,Mantel PY,Menz G,Akdis CA,Blaser K,Schmidt−Weber CB.Glucocorticoids upregulate FOXP3 expression and regulatory T cells in asthma.J Allergy Clin Immunol 2004;114:1425〜33。
23.Akdis M,Akdis CA.Mechanisms of allergenspecific immunotherapy.J Allergy Clin Immunol 2007;119:780〜91。
24.Klunker S,Chong MM,Mantel PY,Palomares O,Bassin C,Ziegler M,Ruckert B,Meiler F,Akdis M,Littman DR,Akdis CA.Transcription factors RUNX1 and RUNX3 in the induction and suppressive function of Foxp3+ inducible regulatory T cells.J Exp Med 2009;206:2701〜15。
25.Mantel PY,Kuipers H,Boyman O,Rhyner C,Ouaked N,Ruckert B,Karagiannidis C,Lambrecht BN,Hendriks RW,Crameri R,Akdis CA,Blaser K,Schmidt−Weber CB.GATA3−driven Th2 responses inhibit TGF−β 1−induced FOXP3 expression and the formation of regulatory T cells.PLoS Biol 2007;5:e329。
26.van der Kleij H,O’Mahony C,Shanahan F,O’Mahony L,Bienenstock J.Protective effects of Lactobacillus reuteri and Bifidobacterium infantis in murine models for colitis do notinvolve the vagus nerve.Am J Physiol Regul Integr Comp Physiol 2008;295:1131〜7。
27.Sheil B,McCarthy J,O’Mahony L,Bennett MW,Ryan P,Fitzgibbon JJ,Kiely B,Collins JK,Shanahan F.Is the mucosal route of administration essential for probiotic function? Subcutaneous administration is associated with attenuation of murine colitis and arthritis.Gut 2004;53:694〜700。
28.McCarthy J,O’Mahony L,O’Callaghan L,Sheil B,Vaughan EE,Fitzsimons N,Fitzgibbon J,O’Sullivan GC,Kiely B,Collins JK,Shanahan F.Double blind,placebo controlled trial of two probiotic strains in interleukin 10 knockout mice and mechanistic link with cytokine balance.Gut 2003;52:975〜80。
29.O’Mahony L,Feeney M,O’Halloran S,Murphy L,Kiely B,Fitzgibbon J,Lee G,O’Sullivan G,Shanahan F,Collins JK.Probiotic impact on microbial flora,inflammation and tumour development in IL−10 knockout mice.Aliment Pharmacol Ther 2001;15:1219〜25。
30.Mazmanian SK,Round JL,Kasper DL.A microbial symbiosis factor prevents intestinal inflammatory disease.Nature 2008;453:620〜5。
31.Grabig A,Paclik D,Guzy C,Dankof A,Baumgart DC,Erckenbrecht J,Raupach B,Sonnenborn U,Eckert J,Schumann RR,Wiedenmann B,Dignass AU,Sturm A.Escherichia coli strain Nissle 1917 ameliorates experimental colitis via toll−like receptor 2−and toll−like receptor 4−dependent pathways.Infect Immun 2006;74:4075〜82。
32.Di Giacinto C,Marinaro M,Sanchez M,Strober W,Boirivant M.Probiotics Ameliorate Recurrent Th1−Mediated Murine Colitis by Inducing IL−10 and IL−10−Dependent TGF−β.Bearing Regulatory Cells.J Immunol 2005;174:3237〜46。
33.O’Mahony C,Scully P,O’Mahony D,Murphy S,O’Brien F,Lyons A,Sherlock G,MacSharry J,Kiely B,Shanahan F,O’Mahony L.Commensal−Induced Regulatory T Cells Mediate Protection against Pathogen−Stimulated NF−kB Activation.PLOS Pathogens 2008;4:e1000112。
34.Karimi K,Inman MD,Bienenstock J,Forsythe P.Lactobacillus reuteri−induced regulatory T cells protect against an allergic airway response in mice.Am J Respir Crit Care Med 2009;179:186〜93。
35.Karim M,Kingsley CI,Bushell AR,Sawitzki BS,Wood KJ.Alloantigen−induced CD25+CD4+ regulatory T cells can develop in vivo from CD25−CD4+ precursors in a thymus−independent process.J Immunol 2004;172:923〜8。
36.Chen W,Jin W,Hardegen N,Lei KJ,Li L,Marinos N,McGrady G,Wahl SM.Conversion of peripheral CD4+CD25− naive T cells to CD4+CD25+ regulatory T cells by TGF−β induction of transcription factor Foxp3.J Exp Med 2003;198:1875〜86。
37.Coombes JL,Siddiqui KR,Arancibia−Carcamo CV,Hall J,Sun CM,Belkaid Y,Powrie F.A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF−β and retinoic acid−dependent mechanism.J Exp Med 2007;204:1757〜64。
38.Sun CM,Hall JA,Blank RB,Bouladoux N,Oukka M,Mora JR,Belkaid Y.Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid.J Exp Med 2007;204:1775〜85。
39.Lyons A,O’Mahony D,O’Brien F,MacSharry J,Sheil B,Ceddia M,Russell WM,Forsythe P,Bienenstock J,Kiely B,Shanahan F,O’Mahony L.Bacterial strain−specific induction of Foxp3+ T regulatory cells is protective in murine allergy models.Clin Exp Allergy 2009;in press。
40.Mazmanian SK,Liu CH,Tzianabos AO,Kasper DL.An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system.Cell 2005;122:107〜18。
41.Foligne B,Zoumpopoulou G,Dewulf J,Ben Younes A,Chareyre F,et al.(2007)A key role of dendritic cells in probiotic functionality.PLoS ONE 2:e313。
42.Smits HH,Engering A,van der Kleij D,de Jong EC,Schipper K,et al.(2005)Selective probiotic bacteria induce IL−10−producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell−specific intercellular adhesion molecule 3−grabbing nonintegrin.JAllergy Clin Immunol 115:1260〜1267。
43.Zuany−Amorim C,Sawicka E,Manlius C et al.Suppression of airway eosinophilia by killed mycobacterium vaccae induced allergen−specific regulatory T−cells.Nat Med 2002;8:625〜9。
44.Leech MD,Benson RA,De Vries A,Fitch PM,Howie SE.Resolution of Der p1−induced allergic airway inflammation is dependent on CD4+ CD25+ Foxp3+ regulatory cells.J Immunol 2007;179:7050〜8。
45.McGlade JP,Gorman S,Zosky GR et al.Suppression of the asthmatic phenotype by ultraviolet b−induced,antigen−specific regulatory cells.Clin Exp Allergy 2007;37:1267〜76。
46.Strickland DH,Stumbles PA,Zosky GR et al.Reversal of airway hyperresponsiveness by induction of airway mucosal CD4+CD25+ regulatory Tcells.J Exp Med 2006;203:2649〜60。
47.Wu K,Bi Y,Sun K,Xia J,Wang Y,Wang C.Suppression of allergic inflammation by allergen−DNA−modified dendritic cells depends on the induction of Foxp3+ regulatory T cells.Scand J Immunol 2008;67:140〜51。
48.Boudousquie C,Pellaton C,Barbier N,Spertini F.CD4+ CD25+ T cell depletion impairs tolerance induction in a murine model of asthma.Clin Exp Allergy 2009;39:1415〜26。
49.Round JL,Mazmanian SK.Inducible Foxp3+ regulatory T−cell development by a commensal bacterium of the intestinal microbiota.Proc Natl Acad Sci U S A.2010 Jul 6;107(27):12204〜9。
50.Rubtsov YP,et al.Regulatory T cell−derived interleukin−10 limits inflammation at environmental interfaces.Immunity.2008;28:546〜558。
Claims (25)
- ビフィズス菌NCIMB 41675の単離株。
- 生存細胞形態である、請求項1に記載のビフィズス菌株。
- 非生存細胞形態である、請求項1に記載のビフィズス菌株。
- 前記ビフィズス菌が、ネコ科動物被験体からの大腸生検組織から単離される、請求項1〜3のいずれか一項に記載のビフィズス菌株。
- 前記菌株が、経口摂取後に著しく免疫調節性である、請求項1〜4のいずれか一項に記載のビフィズス菌株。
- 請求項1〜5のいずれか一項に記載のビフィズス菌株を含む、製剤。
- プロバイオティク材料を更に含む、請求項6に記載の製剤。
- プレバイオティク材料を更に含む、請求項6又は7のいずれか一項に記載の製剤。
- 摂取可能な担体を更に含む、請求項6〜8のいずれか一項に記載の製剤。
- 前記摂取可能な担体が、カプセル、錠剤、又は粉末のような薬学的に許容可能な担体である、請求項9に記載の製剤。
- 前記摂取可能な担体が、油懸濁液、乳ベース懸濁液、チーズ、カカオバターベース組成物、グレービー及び/又はヨーグルトベース組成物のような食料製品である、請求項9に記載の製剤。
- 請求項1〜5のいずれか一項に記載のビフィズス菌株又は請求項6〜11のいずれか一項に記載の製剤を含む、食品。
- 前記食品が乾燥食品である、請求項12に記載の食品。
- 前記食品が湿潤食品である、請求項12に記載の食品。
- プロバイオティク材料を更に含む、請求項12〜14のいずれか一項に記載の食品。
- プレバイオティク材料を更に含む、請求項12〜15のいずれか一項に記載の食品。
- 前記食品がコンパニオンアニマル食品である、請求項12〜16のいずれか一項に記載の食品。
- 薬剤として使用するための、請求項1〜5のいずれか一項に記載のビフィズス菌株、又は請求項6〜11のいずれか一項に記載の製剤、又は請求項12〜17のいずれか一項に記載の食品。
- 望ましくない炎症活性の予防及び/又は治療に使用するための、請求項1〜5のいずれか一項に記載のビフィズス菌株、又は請求項6〜11のいずれか一項に記載の製剤、又は請求項12〜17のいずれか一項に記載の食品。
- 望ましくない胃腸管炎症活性の予防及び/又は治療に使用するための、請求項1〜5のいずれか一項に記載のビフィズス菌株、又は請求項6〜11のいずれか一項に記載の製剤、又は請求項12〜17のいずれか一項に記載の食品。
- 望ましくない炎症活性による自己免疫不全の予防及び/又は治療に使用するための、請求項1〜5のいずれか一項に記載のビフィズス菌株、又は請求項6〜11のいずれか一項に記載の製剤、又は請求項12〜17のいずれか一項に記載の食品。
- 望ましくない炎症活性による下痢疾患の予防及び/又は治療に使用するための、請求項1〜5のいずれか一項に記載のビフィズス菌株、又は請求項6〜11のいずれか一項に記載の製剤、又は請求項12〜17のいずれか一項に記載の食品。
- コンパニオンアニマルの免疫系の調節又は改善に使用するための、請求項1〜5のいずれか一項に記載のビフィズス菌株、又は請求項6〜11のいずれか一項に記載の製剤、又は請求項12〜17のいずれか一項に記載の食品。
- コンパニオンアニマルの自己免疫疾患の予防及び/又は治療に使用するための、請求項1〜5のいずれか一項に記載のビフィズス菌株、又は請求項6〜11のいずれか一項に記載の製剤、又は請求項12〜17のいずれか一項に記載の食品。
- コンパニオンアニマルの炎症の予防及び/又は治療に使用するための、請求項1〜5のいずれか一項に記載のビフィズス菌株、又は請求項6〜11のいずれか一項に記載の製剤、又は請求項12〜17のいずれか一項に記載の食品。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12/616,752 US9771624B2 (en) | 2008-11-11 | 2009-11-11 | Bifidobacterium longum |
US12/616,752 | 2009-11-11 | ||
IE2010/0290 | 2010-05-11 | ||
IE20100290 | 2010-05-11 | ||
PCT/IE2010/000067 WO2011058536A1 (en) | 2009-11-11 | 2010-11-11 | A bifidobacterium strain |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2013509204A true JP2013509204A (ja) | 2013-03-14 |
JP5600179B2 JP5600179B2 (ja) | 2014-10-01 |
Family
ID=43478228
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012537479A Expired - Fee Related JP5600179B2 (ja) | 2009-11-11 | 2010-11-11 | ビフィズス菌株 |
Country Status (11)
Country | Link |
---|---|
EP (2) | EP2823822B1 (ja) |
JP (1) | JP5600179B2 (ja) |
CN (1) | CN103037875B (ja) |
AU (1) | AU2010317423C1 (ja) |
BR (1) | BR112012010923B1 (ja) |
CA (1) | CA2779597C (ja) |
ES (1) | ES2610829T3 (ja) |
MX (1) | MX2012005449A (ja) |
PL (1) | PL2823822T3 (ja) |
RU (1) | RU2557310C2 (ja) |
WO (1) | WO2011058536A1 (ja) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2016003187A (ja) * | 2014-06-13 | 2016-01-12 | 森永乳業株式会社 | 統合失調症治療剤 |
WO2021024915A1 (ja) * | 2019-08-07 | 2021-02-11 | 日清食品ホールディングス株式会社 | 炎症性サイトカインの産生誘導活性は低いが抗炎症性サイトカインの産生誘導活性が高いビフィズス菌 |
JP2021512156A (ja) * | 2018-01-29 | 2021-05-13 | プリシジョンバイオティクス・グループ・リミテッド | 過敏性腸症候群の予防および処置のための組合せ製品 |
Families Citing this family (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AUPQ899700A0 (en) | 2000-07-25 | 2000-08-17 | Borody, Thomas Julius | Probiotic recolonisation therapy |
WO2011151941A1 (ja) | 2010-06-04 | 2011-12-08 | 国立大学法人東京大学 | 制御性t細胞の増殖または集積を誘導する作用を有する組成物 |
EP3311825A1 (en) | 2010-08-04 | 2018-04-25 | Thomas Julius Borody | Compositions for fecal floral transplantation and methods for making and using them |
JP6306507B2 (ja) | 2011-12-01 | 2018-04-18 | 国立大学法人 東京大学 | 制御性t細胞の増殖または集積を誘導するヒト由来細菌 |
WO2016191356A1 (en) | 2015-05-22 | 2016-12-01 | Arizona Board Of Regents On Behalf Of Arizona State University | Methods for treating autism spectrum disorder and associated symptoms |
US20170360848A1 (en) | 2016-06-15 | 2017-12-21 | Arizona Board Of Regents On Behalf Of Arizona State University | Methods for treating autism spectrum disorder and associated symptoms |
US11213549B2 (en) | 2016-10-11 | 2022-01-04 | Finch Therapeutics Holdings Llc | Compositions and method for treating primary sclerosing cholangitis and related disorders |
WO2018071537A1 (en) | 2016-10-11 | 2018-04-19 | Crestovo Holdings Llc | Compositions and methods for treating multiple sclerosis and related disorders |
CN107334786B (zh) * | 2016-12-29 | 2018-08-28 | 哈尔滨学院 | 双歧杆菌活菌胶囊及其在制备预防卵巢早衰药物中的应用 |
MX2019010143A (es) * | 2017-02-28 | 2019-10-02 | Alimentary Health Ltd | Bifidobacterium longum capaz de modular beneficiosamente la respuesta inmune contra una infeccion respiratoria por virus. |
CN110392734A (zh) | 2017-02-28 | 2019-10-29 | 营养健康有限公司 | 可以有益地调节针对呼吸道病毒感染的免疫应答的长双歧杆菌 |
US11433102B2 (en) | 2017-04-05 | 2022-09-06 | Finch Therapeutics Holdings Llc | Compositions and methods for treating Parkinson's disease (PD) and related disorders |
US11040073B2 (en) | 2017-04-05 | 2021-06-22 | Finch Therapeutics Holdings Llc | Compositions and methods for treating diverticulitis and related disorders |
JP2020521760A (ja) | 2017-05-26 | 2020-07-27 | クレストヴォ・ホールディングス・エルエルシー | 糞便微生物ベースの治療剤を含む凍結乾燥組成物ならびにそれを製造および使用する方法 |
WO2019032573A1 (en) | 2017-08-07 | 2019-02-14 | Finch Therapeutics, Inc. | COMPOSITIONS AND METHODS FOR MAINTAINING AND RESTORING A HEALTHY INTESTINAL BARRIER |
US11166990B2 (en) | 2018-07-13 | 2021-11-09 | Finch Therapeutics Holdings Llc | Methods and compositions for treating ulcerative colitis |
EP3849574A1 (en) | 2018-09-10 | 2021-07-21 | Lactobio A/S | Method for reducing the transfer of pathogenic microorganisms |
WO2020069280A1 (en) | 2018-09-27 | 2020-04-02 | Crestovo Holdings Llc | Compositions and methods for treating epilepsy and related disorders |
US20220015998A1 (en) | 2018-12-21 | 2022-01-20 | Lactobio A/S | Topical composition comprising viable microorganisms |
US20220110986A1 (en) | 2019-01-04 | 2022-04-14 | Lactobio A/S | Strains, composition and method of use |
CA3140493A1 (en) | 2019-05-20 | 2020-11-26 | Lactobio A/S | Composition for treatment, alleviation or prophylaxis of acne |
CA3142389A1 (en) | 2019-06-13 | 2020-12-17 | Lactobio A/S | A gel composition comprising viable microorganisms |
CN113209139B (zh) * | 2020-08-31 | 2022-09-23 | 内蒙古蒙牛乳业(集团)股份有限公司 | 乳双歧杆菌MN-Gup改善肥胖及其特征肠道菌群用途 |
CN112111424B (zh) * | 2020-09-03 | 2022-07-22 | 江南大学 | 一株可缓解类风湿性关节炎的短双歧杆菌及其应用 |
AU2021416723A1 (en) | 2021-01-05 | 2023-07-27 | Lactobio A/S | Strains, compositions and methods of use |
CA3204068A1 (en) | 2021-01-05 | 2022-07-14 | Charlotte VEDEL | Strains, compositions and methods of use |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006525313A (ja) * | 2003-05-08 | 2006-11-09 | アリメンタリー・ヘルス・リミテッド | 視床下部−脳下垂体−副腎軸過敏性により特徴付けられる非定型うつ病及び他の疾患の治療のプロバイオティック |
JP2007518712A (ja) * | 2003-12-19 | 2007-07-12 | ザ・アイムス・カンパニー | コンパニオンアニマルのためのプロバイオティクビフィズス菌の使用方法 |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS55113718A (en) | 1979-02-27 | 1980-09-02 | Yakult Honsha Co Ltd | Antitumor agent |
US4781939A (en) | 1986-10-28 | 1988-11-01 | Nestec, S.A. | Layered meat emulsion product and method of producing same |
DE3933528C1 (ja) | 1989-10-04 | 1990-12-06 | Effem Gmbh, 2810 Verden, De | |
US5952033A (en) | 1996-12-24 | 1999-09-14 | Nestec S.A. | Gelatinized cereal product containing oligosaccharide and processes of preparing and using same |
PT862863E (pt) | 1997-01-09 | 2002-04-29 | Nestle Sa | Produto cerealifero contendo probioticos |
US6133323A (en) | 1997-04-09 | 2000-10-17 | The Iams Company | Process for enhancing immune response in animals using β-carotene as a dietary supplement |
US5932258A (en) | 1998-04-06 | 1999-08-03 | The Iams Company | Composition and process for improving glucose metabolism in companion animals |
ID29150A (id) * | 1999-01-15 | 2001-08-02 | Entpr Ireland Cs | Penggunaan lactobacillus salivarius |
NZ514727A (en) | 1999-05-27 | 2003-10-31 | Iams Company | Enhancing immune response in pets using vitamin E, lutein and beta-carotene in a pet food product |
CN100396769C (zh) | 2000-05-25 | 2008-06-25 | 雀巢制品公司 | 宠物食物使用的新益生菌 |
EP1227152A1 (en) * | 2001-01-30 | 2002-07-31 | Société des Produits Nestlé S.A. | Bacterial strain and genome of bifidobacterium |
PT1986669E (pt) * | 2006-02-15 | 2012-05-15 | Nestec Sa | Utilização de bifidobacterium longum para a prevenção e tratamento de inflamação |
KR20100016012A (ko) * | 2007-03-28 | 2010-02-12 | 앨러멘터리 헬스 리미티드 | 프로바이오틱 비피도박테리움 스트레인 |
GB2460781B (en) * | 2007-03-28 | 2012-01-25 | Alimentary Health Ltd | Probiotic bifidobacterium strains |
RU2570557C2 (ru) * | 2008-11-11 | 2015-12-10 | Алиментари Хелс Лимитед | ПРОБИОТИЧЕСКАЯ БИФИДОБАКТЕРИЯ Bifidobacterium Longum |
-
2010
- 2010-11-11 MX MX2012005449A patent/MX2012005449A/es active IP Right Grant
- 2010-11-11 CA CA2779597A patent/CA2779597C/en active Active
- 2010-11-11 CN CN201080051602.XA patent/CN103037875B/zh active Active
- 2010-11-11 PL PL14180970T patent/PL2823822T3/pl unknown
- 2010-11-11 EP EP14180970.7A patent/EP2823822B1/en not_active Not-in-force
- 2010-11-11 RU RU2012116029/10A patent/RU2557310C2/ru active
- 2010-11-11 WO PCT/IE2010/000067 patent/WO2011058536A1/en active Application Filing
- 2010-11-11 ES ES14180970.7T patent/ES2610829T3/es active Active
- 2010-11-11 AU AU2010317423A patent/AU2010317423C1/en active Active
- 2010-11-11 JP JP2012537479A patent/JP5600179B2/ja not_active Expired - Fee Related
- 2010-11-11 EP EP10779341A patent/EP2498790A1/en not_active Withdrawn
- 2010-11-11 BR BR112012010923-5A patent/BR112012010923B1/pt active IP Right Grant
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006525313A (ja) * | 2003-05-08 | 2006-11-09 | アリメンタリー・ヘルス・リミテッド | 視床下部−脳下垂体−副腎軸過敏性により特徴付けられる非定型うつ病及び他の疾患の治療のプロバイオティック |
JP2007518712A (ja) * | 2003-12-19 | 2007-07-12 | ザ・アイムス・カンパニー | コンパニオンアニマルのためのプロバイオティクビフィズス菌の使用方法 |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2016003187A (ja) * | 2014-06-13 | 2016-01-12 | 森永乳業株式会社 | 統合失調症治療剤 |
JP2021512156A (ja) * | 2018-01-29 | 2021-05-13 | プリシジョンバイオティクス・グループ・リミテッド | 過敏性腸症候群の予防および処置のための組合せ製品 |
JP7460546B2 (ja) | 2018-01-29 | 2024-04-02 | プリシジョンバイオティクス・グループ・リミテッド | 過敏性腸症候群の予防および処置のための組合せ製品 |
WO2021024915A1 (ja) * | 2019-08-07 | 2021-02-11 | 日清食品ホールディングス株式会社 | 炎症性サイトカインの産生誘導活性は低いが抗炎症性サイトカインの産生誘導活性が高いビフィズス菌 |
JP2021023231A (ja) * | 2019-08-07 | 2021-02-22 | 日清食品ホールディングス株式会社 | 炎症性サイトカインの産生誘導活性は低いが抗炎症性サイトカインの産生誘導活性が高いビフィズス菌 |
JP7013419B2 (ja) | 2019-08-07 | 2022-02-15 | 日清食品ホールディングス株式会社 | 炎症性サイトカインの産生誘導活性は低いが抗炎症性サイトカインの産生誘導活性が高いビフィズス菌 |
Also Published As
Publication number | Publication date |
---|---|
EP2823822A1 (en) | 2015-01-14 |
CN103037875B (zh) | 2014-11-05 |
BR112012010923A2 (pt) | 2018-03-06 |
CA2779597C (en) | 2018-03-27 |
RU2557310C2 (ru) | 2015-07-20 |
MX2012005449A (es) | 2012-09-07 |
EP2498790A1 (en) | 2012-09-19 |
WO2011058536A1 (en) | 2011-05-19 |
PL2823822T3 (pl) | 2017-09-29 |
AU2010317423B2 (en) | 2014-07-10 |
BR112012010923B1 (pt) | 2021-03-23 |
RU2012116029A (ru) | 2013-12-20 |
AU2010317423A1 (en) | 2012-05-31 |
AU2010317423C1 (en) | 2015-01-22 |
CN103037875A (zh) | 2013-04-10 |
CA2779597A1 (en) | 2011-05-19 |
EP2823822B1 (en) | 2016-10-12 |
ES2610829T3 (es) | 2017-05-03 |
JP5600179B2 (ja) | 2014-10-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5600179B2 (ja) | ビフィズス菌株 | |
JP4938005B2 (ja) | ネコ科動物プロバイオティックであるラクトバシラス | |
JP4938006B2 (ja) | ネコ科動物プロバイオティク・ビフィドバクテリア | |
JP4503614B2 (ja) | イヌ科動物のプロバイオティク乳酸桿菌 | |
JP4607124B2 (ja) | イヌ科動物のプロバイオティク・ビフィドバクテリア・グロボーサム | |
Kneifel et al. | Probiotics and health claims | |
US9259019B2 (en) | Bifidobacteriumstrain | |
AU2011202947B2 (en) | Feline probiotic lactobacilli | |
GUIDESI | INTEGRATED APPROACH TO THE SELECTION OF NEW PROBIOTICS FOR HUMAN APPLICATION |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20131203 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20140303 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20140310 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140603 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20140603 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20140715 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20140814 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5600179 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313117 |
|
S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
LAPS | Cancellation because of no payment of annual fees |