JP6329553B2 - Ibsの診断マーカーとしての微生物バイオームに対する抗体、ストレス因子及びマスト細胞マーカー - Google Patents
Ibsの診断マーカーとしての微生物バイオームに対する抗体、ストレス因子及びマスト細胞マーカー Download PDFInfo
- Publication number
- JP6329553B2 JP6329553B2 JP2015535149A JP2015535149A JP6329553B2 JP 6329553 B2 JP6329553 B2 JP 6329553B2 JP 2015535149 A JP2015535149 A JP 2015535149A JP 2015535149 A JP2015535149 A JP 2015535149A JP 6329553 B2 JP6329553 B2 JP 6329553B2
- Authority
- JP
- Japan
- Prior art keywords
- ibs
- bacterial antigen
- antibody
- level
- markers
- 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.)
- Expired - Fee Related
Links
- 210000003630 histaminocyte Anatomy 0.000 title claims description 147
- 230000000813 microbial effect Effects 0.000 title description 8
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 348
- 239000000427 antigen Substances 0.000 claims description 341
- 108091007433 antigens Proteins 0.000 claims description 341
- 102000036639 antigens Human genes 0.000 claims description 341
- 230000001580 bacterial effect Effects 0.000 claims description 333
- 239000000523 sample Substances 0.000 claims description 221
- 239000003550 marker Substances 0.000 claims description 165
- 241000588724 Escherichia coli Species 0.000 claims description 149
- 238000000034 method Methods 0.000 claims description 143
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 claims description 109
- 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 claims description 102
- 239000012634 fragment Substances 0.000 claims description 86
- 239000002771 cell marker Substances 0.000 claims description 78
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 claims description 58
- 229960001340 histamine Drugs 0.000 claims description 55
- 229960000890 hydrocortisone Drugs 0.000 claims description 51
- 229960002986 dinoprostone Drugs 0.000 claims description 48
- 238000003745 diagnosis Methods 0.000 claims description 47
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 claims description 46
- 230000000890 antigenic effect Effects 0.000 claims description 43
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 38
- 238000007619 statistical method Methods 0.000 claims description 30
- 238000007477 logistic regression Methods 0.000 claims description 28
- 239000012472 biological sample Substances 0.000 claims description 27
- 238000001514 detection method Methods 0.000 claims description 25
- 241000607768 Shigella Species 0.000 claims description 24
- 208000015181 infectious disease Diseases 0.000 claims description 20
- 101100173787 Campylobacter jejuni flaB gene Proteins 0.000 claims description 18
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 claims description 17
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 claims description 17
- 101100227198 Campylobacter jejuni flaA gene Proteins 0.000 claims description 17
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 claims description 17
- 241001333951 Escherichia coli O157 Species 0.000 claims description 16
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)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)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 claims description 16
- 229960000258 corticotropin Drugs 0.000 claims description 16
- 229940076279 serotonin Drugs 0.000 claims description 16
- 206010010774 Constipation Diseases 0.000 claims description 13
- 206010012735 Diarrhoea Diseases 0.000 claims description 13
- 108090000765 processed proteins & peptides Proteins 0.000 description 134
- 102000004196 processed proteins & peptides Human genes 0.000 description 106
- 229920001184 polypeptide Polymers 0.000 description 94
- 150000001413 amino acids Chemical group 0.000 description 91
- 102000001400 Tryptase Human genes 0.000 description 84
- 108060005989 Tryptase Proteins 0.000 description 84
- 108090000623 proteins and genes Proteins 0.000 description 79
- 102000004169 proteins and genes Human genes 0.000 description 79
- 235000018102 proteins Nutrition 0.000 description 78
- 238000003556 assay Methods 0.000 description 52
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 44
- 108010040721 Flagellin Proteins 0.000 description 43
- 210000002966 serum Anatomy 0.000 description 42
- 241000589875 Campylobacter jejuni Species 0.000 description 41
- 201000010099 disease Diseases 0.000 description 32
- 241000894006 Bacteria Species 0.000 description 31
- 108010079246 OMPA outer membrane proteins Proteins 0.000 description 29
- 239000007790 solid phase Substances 0.000 description 27
- 239000000243 solution Substances 0.000 description 27
- 240000001046 Lactobacillus acidophilus Species 0.000 description 26
- 235000013956 Lactobacillus acidophilus Nutrition 0.000 description 25
- 229940039695 lactobacillus acidophilus Drugs 0.000 description 25
- 238000010647 peptide synthesis reaction Methods 0.000 description 25
- 108020004707 nucleic acids Proteins 0.000 description 24
- 102000039446 nucleic acids Human genes 0.000 description 24
- 150000007523 nucleic acids Chemical class 0.000 description 24
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 23
- 238000003259 recombinant expression Methods 0.000 description 23
- 239000002438 stress hormone Substances 0.000 description 23
- 241000193468 Clostridium perfringens Species 0.000 description 22
- 238000000746 purification Methods 0.000 description 22
- 208000024891 symptom Diseases 0.000 description 22
- 238000004422 calculation algorithm Methods 0.000 description 19
- 241000305071 Enterobacterales Species 0.000 description 18
- 102000004190 Enzymes Human genes 0.000 description 18
- 108090000790 Enzymes Proteins 0.000 description 18
- 235000001014 amino acid Nutrition 0.000 description 18
- 238000004458 analytical method Methods 0.000 description 18
- 229940088598 enzyme Drugs 0.000 description 18
- 239000000090 biomarker Substances 0.000 description 16
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 16
- 102000012289 Corticotropin-Releasing Hormone Human genes 0.000 description 15
- 108010022152 Corticotropin-Releasing Hormone Proteins 0.000 description 15
- 241000736262 Microbiota Species 0.000 description 15
- 210000004369 blood Anatomy 0.000 description 15
- 239000008280 blood Substances 0.000 description 15
- 238000002560 therapeutic procedure Methods 0.000 description 15
- 101800000414 Corticotropin Proteins 0.000 description 14
- 101000851240 Homo sapiens Elongation factor Tu, mitochondrial Proteins 0.000 description 14
- 230000002496 gastric effect Effects 0.000 description 14
- 102100033238 Elongation factor Tu, mitochondrial Human genes 0.000 description 13
- 241001468157 Lactobacillus johnsonii Species 0.000 description 13
- 238000012896 Statistical algorithm Methods 0.000 description 13
- 241000606124 Bacteroides fragilis Species 0.000 description 12
- 241000186779 Listeria monocytogenes Species 0.000 description 12
- 238000012544 monitoring process Methods 0.000 description 12
- 239000000758 substrate Substances 0.000 description 12
- 208000035475 disorder Diseases 0.000 description 11
- 102000004127 Cytokines Human genes 0.000 description 10
- 108090000695 Cytokines Proteins 0.000 description 10
- 241000194033 Enterococcus Species 0.000 description 10
- 241001646716 Escherichia coli K-12 Species 0.000 description 10
- 230000000968 intestinal effect Effects 0.000 description 10
- 238000007637 random forest analysis Methods 0.000 description 10
- 238000002965 ELISA Methods 0.000 description 9
- 238000013528 artificial neural network Methods 0.000 description 9
- 241000194032 Enterococcus faecalis Species 0.000 description 8
- 241000208202 Linaceae Species 0.000 description 8
- 235000004431 Linum usitatissimum Nutrition 0.000 description 8
- 241000605861 Prevotella Species 0.000 description 8
- 230000000844 anti-bacterial effect Effects 0.000 description 8
- 244000005706 microflora Species 0.000 description 8
- 210000002381 plasma Anatomy 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 210000002700 urine Anatomy 0.000 description 8
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 7
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 7
- 241000589876 Campylobacter Species 0.000 description 7
- 208000011231 Crohn disease Diseases 0.000 description 7
- 108090001005 Interleukin-6 Proteins 0.000 description 7
- 238000001574 biopsy Methods 0.000 description 7
- 230000000903 blocking effect Effects 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 239000013024 dilution buffer Substances 0.000 description 7
- 210000001035 gastrointestinal tract Anatomy 0.000 description 7
- 238000003018 immunoassay Methods 0.000 description 7
- 238000004020 luminiscence type Methods 0.000 description 7
- 238000010801 machine learning Methods 0.000 description 7
- 238000012545 processing Methods 0.000 description 7
- 241000894007 species Species 0.000 description 7
- 206010009900 Colitis ulcerative Diseases 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 201000006704 Ulcerative Colitis Diseases 0.000 description 6
- 238000013019 agitation Methods 0.000 description 6
- 244000005709 gut microbiome Species 0.000 description 6
- 229940088597 hormone Drugs 0.000 description 6
- 239000005556 hormone Substances 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 230000000670 limiting effect Effects 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 210000003296 saliva Anatomy 0.000 description 6
- 230000000405 serological effect Effects 0.000 description 6
- 108010074051 C-Reactive Protein Proteins 0.000 description 5
- 102100032752 C-reactive protein Human genes 0.000 description 5
- 208000015943 Coeliac disease Diseases 0.000 description 5
- 241001354013 Salmonella enterica subsp. enterica serovar Enteritidis Species 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000002163 immunogen Effects 0.000 description 5
- 210000000936 intestine Anatomy 0.000 description 5
- 244000005700 microbiome Species 0.000 description 5
- 239000006041 probiotic Substances 0.000 description 5
- 235000018291 probiotics Nutrition 0.000 description 5
- 238000002864 sequence alignment Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 241000606125 Bacteroides Species 0.000 description 4
- 241001646719 Escherichia coli O157:H7 Species 0.000 description 4
- 102000004890 Interleukin-8 Human genes 0.000 description 4
- 108090001007 Interleukin-8 Proteins 0.000 description 4
- 241000607762 Shigella flexneri Species 0.000 description 4
- 206010071061 Small intestinal bacterial overgrowth Diseases 0.000 description 4
- 102100040247 Tumor necrosis factor Human genes 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 238000011088 calibration curve Methods 0.000 description 4
- 230000002055 immunohistochemical effect Effects 0.000 description 4
- 238000012417 linear regression Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 210000004877 mucosa Anatomy 0.000 description 4
- 235000013406 prebiotics Nutrition 0.000 description 4
- NZCRJKRKKOLAOJ-XRCRFVBUSA-N rifaximin Chemical compound OC1=C(C(O)=C2C)C3=C4N=C5C=C(C)C=CN5C4=C1NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@H](C)[C@@H](OC)\C=C\O[C@@]1(C)OC2=C3C1=O NZCRJKRKKOLAOJ-XRCRFVBUSA-N 0.000 description 4
- 229960003040 rifaximin Drugs 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 230000007142 small intestinal bacterial overgrowth Effects 0.000 description 4
- 210000000813 small intestine Anatomy 0.000 description 4
- 238000010200 validation analysis Methods 0.000 description 4
- 102100035923 4-aminobutyrate aminotransferase, mitochondrial Human genes 0.000 description 3
- 108010078791 Carrier Proteins Proteins 0.000 description 3
- 241000193403 Clostridium Species 0.000 description 3
- 101000821449 Homo sapiens Secreted and transmembrane protein 1 Proteins 0.000 description 3
- 241000186781 Listeria Species 0.000 description 3
- 102000018697 Membrane Proteins Human genes 0.000 description 3
- 108010052285 Membrane Proteins Proteins 0.000 description 3
- 241000192142 Proteobacteria Species 0.000 description 3
- 102100021853 Secreted and transmembrane protein 1 Human genes 0.000 description 3
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 230000001387 anti-histamine Effects 0.000 description 3
- 239000000739 antihistaminic agent Substances 0.000 description 3
- 238000003491 array Methods 0.000 description 3
- 239000012131 assay buffer Substances 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 210000001124 body fluid Anatomy 0.000 description 3
- 239000010839 body fluid Substances 0.000 description 3
- 210000001072 colon Anatomy 0.000 description 3
- 239000013068 control sample Substances 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 210000003608 fece Anatomy 0.000 description 3
- 210000003495 flagella Anatomy 0.000 description 3
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 230000007149 gut brain axis pathway Effects 0.000 description 3
- 230000004179 hypothalamic–pituitary–adrenal axis Effects 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 238000010166 immunofluorescence Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000013610 patient sample Substances 0.000 description 3
- 238000002823 phage display Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000013179 statistical model Methods 0.000 description 3
- 239000012089 stop solution Substances 0.000 description 3
- 238000012706 support-vector machine Methods 0.000 description 3
- 238000012549 training Methods 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- 108020004465 16S ribosomal RNA Proteins 0.000 description 2
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
- 208000004998 Abdominal Pain Diseases 0.000 description 2
- 241001156739 Actinobacteria <phylum> Species 0.000 description 2
- 239000000275 Adrenocorticotropic Hormone Substances 0.000 description 2
- 108091005471 CRHR1 Proteins 0.000 description 2
- 108091005470 CRHR2 Proteins 0.000 description 2
- 102000004414 Calcitonin Gene-Related Peptide Human genes 0.000 description 2
- 108090000932 Calcitonin Gene-Related Peptide Proteins 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 102100038018 Corticotropin-releasing factor receptor 1 Human genes 0.000 description 2
- 102100038019 Corticotropin-releasing factor receptor 2 Human genes 0.000 description 2
- 241000588921 Enterobacteriaceae Species 0.000 description 2
- 102000013446 GTP Phosphohydrolases Human genes 0.000 description 2
- 108091006109 GTPases Proteins 0.000 description 2
- 241000186660 Lactobacillus Species 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- 101710164702 Major outer membrane protein Proteins 0.000 description 2
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 2
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 102100029441 Nucleotide-binding oligomerization domain-containing protein 2 Human genes 0.000 description 2
- STJFYCWYHROASW-UHFFFAOYSA-N O-methyl-glaucamine Natural products CN1CCC2=CC(OC)=C(OC)C=C2C2OC(OC)C3=C4OCOC4=CC=C3C12 STJFYCWYHROASW-UHFFFAOYSA-N 0.000 description 2
- 108010022181 Phosphopyruvate Hydratase Proteins 0.000 description 2
- 241000611831 Prevotella sp. Species 0.000 description 2
- 241000192031 Ruminococcus Species 0.000 description 2
- 102000012479 Serine Proteases Human genes 0.000 description 2
- 108010022999 Serine Proteases Proteins 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 108090000340 Transaminases Proteins 0.000 description 2
- 206010000059 abdominal discomfort Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000003044 adaptive effect Effects 0.000 description 2
- 210000005006 adaptive immune system Anatomy 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003593 chromogenic compound Substances 0.000 description 2
- 238000003759 clinical diagnosis Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 229940041967 corticotropin-releasing hormone Drugs 0.000 description 2
- KLVRDXBAMSPYKH-RKYZNNDCSA-N corticotropin-releasing hormone (human) Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(N)=O)[C@@H](C)CC)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1N(CCC1)C(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CO)[C@@H](C)CC)C(C)C)C(C)C)C1=CNC=N1 KLVRDXBAMSPYKH-RKYZNNDCSA-N 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 238000009795 derivation Methods 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 230000008482 dysregulation Effects 0.000 description 2
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 2
- 230000005934 immune activation Effects 0.000 description 2
- 229940127121 immunoconjugate Drugs 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 229940039696 lactobacillus Drugs 0.000 description 2
- 208000008585 mastocytosis Diseases 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
- 238000007392 microtiter assay Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000035764 nutrition Effects 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000007310 pathophysiology Effects 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 230000008092 positive effect Effects 0.000 description 2
- 150000003180 prostaglandins Chemical class 0.000 description 2
- 238000000611 regression analysis Methods 0.000 description 2
- 230000003938 response to stress Effects 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 102000014898 transaminase activity proteins Human genes 0.000 description 2
- 210000004760 visceral afferent Anatomy 0.000 description 2
- 239000011534 wash buffer Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 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 1
- 108010022379 (N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase Proteins 0.000 description 1
- QCHPKSFMDHPSNR-VKHMYHEASA-N (S)-3-aminoisobutyric acid Chemical compound [NH3+]C[C@H](C)C([O-])=O QCHPKSFMDHPSNR-VKHMYHEASA-N 0.000 description 1
- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 1
- 108010060511 4-Aminobutyrate Transaminase Proteins 0.000 description 1
- 101710094518 4-aminobutyrate aminotransferase Proteins 0.000 description 1
- 101710115046 4-aminobutyrate aminotransferase, mitochondrial Proteins 0.000 description 1
- MVEOHWRUBFWKJY-UHFFFAOYSA-N 7-hydroxynaphthalene-2-sulfonic acid Chemical compound C1=CC(S(O)(=O)=O)=CC2=CC(O)=CC=C21 MVEOHWRUBFWKJY-UHFFFAOYSA-N 0.000 description 1
- 102000012440 Acetylcholinesterase Human genes 0.000 description 1
- 108010022752 Acetylcholinesterase Proteins 0.000 description 1
- 241000589291 Acinetobacter Species 0.000 description 1
- 102000002572 Alpha-Globulins Human genes 0.000 description 1
- 108010068307 Alpha-Globulins Proteins 0.000 description 1
- 102100038910 Alpha-enolase Human genes 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241000605059 Bacteroidetes Species 0.000 description 1
- 241000186000 Bifidobacterium Species 0.000 description 1
- 241000186560 Blautia coccoides Species 0.000 description 1
- 101001031467 Campylobacter jejuni Flagellin B Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 102100032219 Cathepsin D Human genes 0.000 description 1
- 108010059892 Cellulase Proteins 0.000 description 1
- 241001112696 Clostridia Species 0.000 description 1
- 241001443882 Coprobacillus Species 0.000 description 1
- 241001464948 Coprococcus Species 0.000 description 1
- 102400000739 Corticotropin Human genes 0.000 description 1
- 150000008574 D-amino acids Chemical class 0.000 description 1
- 241001135761 Deltaproteobacteria Species 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- 241001143779 Dorea Species 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 102100030801 Elongation factor 1-alpha 1 Human genes 0.000 description 1
- 241001148568 Epsilonproteobacteria Species 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000186394 Eubacterium Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 206010017367 Frequent bowel movements Diseases 0.000 description 1
- 241001453172 Fusobacteria Species 0.000 description 1
- 241000192128 Gammaproteobacteria Species 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- 101800001586 Ghrelin Proteins 0.000 description 1
- 102400000442 Ghrelin-28 Human genes 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 102100034221 Growth-regulated alpha protein Human genes 0.000 description 1
- 102100025255 Haptoglobin Human genes 0.000 description 1
- 241000589989 Helicobacter Species 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101100449532 Homo sapiens CXCL1 gene Proteins 0.000 description 1
- 101000869010 Homo sapiens Cathepsin D Proteins 0.000 description 1
- 101001125026 Homo sapiens Nucleotide-binding oligomerization domain-containing protein 2 Proteins 0.000 description 1
- 101000830742 Homo sapiens Tryptophan 5-hydroxylase 1 Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000005712 Keratin-8 Human genes 0.000 description 1
- 108010070511 Keratin-8 Proteins 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 125000002066 L-histidyl group Chemical group [H]N1C([H])=NC(C([H])([H])[C@](C(=O)[*])([H])N([H])[H])=C1[H] 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 241001112693 Lachnospiraceae Species 0.000 description 1
- 102000010445 Lactoferrin Human genes 0.000 description 1
- 108010063045 Lactoferrin Proteins 0.000 description 1
- 102000016267 Leptin Human genes 0.000 description 1
- 108010092277 Leptin Proteins 0.000 description 1
- 102000001109 Leukocyte L1 Antigen Complex Human genes 0.000 description 1
- 108010069316 Leukocyte L1 Antigen Complex Proteins 0.000 description 1
- 238000012897 Levenberg–Marquardt algorithm Methods 0.000 description 1
- 108050006654 Lipocalin Proteins 0.000 description 1
- 102000019298 Lipocalin Human genes 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010028116 Mucosal inflammation Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101001034845 Mus musculus Interferon-induced transmembrane protein 3 Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 108091007491 NSP3 Papain-like protease domains Proteins 0.000 description 1
- 241000588652 Neisseria gonorrhoeae Species 0.000 description 1
- 102400001103 Neurotensin Human genes 0.000 description 1
- 101800001814 Neurotensin Proteins 0.000 description 1
- 108700002045 Nod2 Signaling Adaptor Proteins 0.000 description 1
- 101150083031 Nod2 gene Proteins 0.000 description 1
- 108700028353 OmpC Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000012868 Overgrowth Diseases 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108010049977 Peptide Elongation Factor Tu Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 241000191992 Peptostreptococcus Species 0.000 description 1
- 102000012288 Phosphopyruvate Hydratase Human genes 0.000 description 1
- 101000992168 Porphyromonas gingivalis (strain ATCC BAA-308 / W83) Outer membrane protein 40 Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 101710194807 Protective antigen Proteins 0.000 description 1
- 241000691806 Rhinobatos productus Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 102000013674 S-100 Human genes 0.000 description 1
- 108700021018 S100 Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 1
- 241001138501 Salmonella enterica Species 0.000 description 1
- 101100173866 Shigella flexneri fliC gene Proteins 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 102000003141 Tachykinin Human genes 0.000 description 1
- 102000011923 Thyrotropin Human genes 0.000 description 1
- 108010061174 Thyrotropin Proteins 0.000 description 1
- 102000008234 Toll-like receptor 5 Human genes 0.000 description 1
- 108010060812 Toll-like receptor 5 Proteins 0.000 description 1
- 108060008539 Transglutaminase Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 102100024971 Tryptophan 5-hydroxylase 1 Human genes 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102100024584 Tumor necrosis factor ligand superfamily member 12 Human genes 0.000 description 1
- 101710097155 Tumor necrosis factor ligand superfamily member 12 Proteins 0.000 description 1
- QWXOJIDBSHLIFI-UHFFFAOYSA-N [3-(1-chloro-3'-methoxyspiro[adamantane-4,4'-dioxetane]-3'-yl)phenyl] dihydrogen phosphate Chemical compound O1OC2(C3CC4CC2CC(Cl)(C4)C3)C1(OC)C1=CC=CC(OP(O)(O)=O)=C1 QWXOJIDBSHLIFI-UHFFFAOYSA-N 0.000 description 1
- 241000985257 [Clostridium] cocleatum Species 0.000 description 1
- 241001531188 [Eubacterium] rectale Species 0.000 description 1
- 229940022698 acetylcholinesterase Drugs 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000006229 amino acid addition Effects 0.000 description 1
- 230000002391 anti-complement effect Effects 0.000 description 1
- 230000000356 anti-lactoferrin effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000003431 anti-prostaglandin Effects 0.000 description 1
- 108010008730 anticomplement Proteins 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 150000003943 catecholamines Chemical class 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 238000009388 chemical precipitation Methods 0.000 description 1
- 230000027288 circadian rhythm Effects 0.000 description 1
- 102000003899 claudin 8 Human genes 0.000 description 1
- 108090000239 claudin 8 Proteins 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 238000002052 colonoscopy Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- 230000009266 disease activity Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 210000002049 efferent pathway Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229940032049 enterococcus faecalis Drugs 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002550 fecal effect Effects 0.000 description 1
- 239000002350 fibrinopeptide Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 108010028610 formyl-coenzyme A transferase Proteins 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- 210000005095 gastrointestinal system Anatomy 0.000 description 1
- GNKDKYIHGQKHHM-RJKLHVOGSA-N ghrelin Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)CN)COC(=O)CCCCCCC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C1=CC=CC=C1 GNKDKYIHGQKHHM-RJKLHVOGSA-N 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 230000036433 growing body Effects 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000008975 immunomodulatory function Effects 0.000 description 1
- 238000000126 in silico method Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 230000007413 intestinal health Effects 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 description 1
- 229940078795 lactoferrin Drugs 0.000 description 1
- 235000021242 lactoferrin Nutrition 0.000 description 1
- JCQLYHFGKNRPGE-FCVZTGTOSA-N lactulose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 JCQLYHFGKNRPGE-FCVZTGTOSA-N 0.000 description 1
- 229960000511 lactulose Drugs 0.000 description 1
- PFCRQPBOOFTZGQ-UHFFFAOYSA-N lactulose keto form Natural products OCC(=O)C(O)C(C(O)CO)OC1OC(CO)C(O)C(O)C1O PFCRQPBOOFTZGQ-UHFFFAOYSA-N 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 229940039781 leptin Drugs 0.000 description 1
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 125000003588 lysine group Chemical class [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 108010026228 mRNA guanylyltransferase Proteins 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000003475 metalloproteinase inhibitor Substances 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 230000004682 mucosal barrier function Effects 0.000 description 1
- 238000002887 multiple sequence alignment Methods 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 1
- PCJGZPGTCUMMOT-ISULXFBGSA-N neurotensin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 PCJGZPGTCUMMOT-ISULXFBGSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000007918 pathogenicity Effects 0.000 description 1
- CMPQUABWPXYYSH-UHFFFAOYSA-N phenyl phosphate Chemical compound OP(O)(=O)OC1=CC=CC=C1 CMPQUABWPXYYSH-UHFFFAOYSA-N 0.000 description 1
- 238000013081 phylogenetic analysis Methods 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000000529 probiotic effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000092 prognostic biomarker Substances 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- NGVDGCNFYWLIFO-UHFFFAOYSA-N pyridoxal 5'-phosphate Chemical compound CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O NGVDGCNFYWLIFO-UHFFFAOYSA-N 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000003488 releasing hormone Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 230000000697 serotonin reuptake Effects 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 201000000498 stomach carcinoma Diseases 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 210000002820 sympathetic nervous system Anatomy 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 108060008037 tachykinin Proteins 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229960000874 thyrotropin Drugs 0.000 description 1
- 230000001748 thyrotropin Effects 0.000 description 1
- 102000003601 transglutaminase Human genes 0.000 description 1
- 241001478234 unclassified Cyanobacteria Species 0.000 description 1
- 230000007923 virulence factor Effects 0.000 description 1
- 239000000304 virulence factor Substances 0.000 description 1
- 108010027843 zonulin Proteins 0.000 description 1
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56911—Bacteria
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/564—Immunoassay; Biospecific binding assay; Materials therefor for pre-existing immune complex or autoimmune disease, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/06—Gastro-intestinal diseases
- G01N2800/065—Bowel diseases, e.g. Crohn, ulcerative colitis, IBS
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/60—Complex ways of combining multiple protein biomarkers for diagnosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- Pathology (AREA)
- Biotechnology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Microbiology (AREA)
- General Health & Medical Sciences (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Rheumatology (AREA)
- Rehabilitation Therapy (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Peptides Or Proteins (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261710574P | 2012-10-05 | 2012-10-05 | |
| US61/710,574 | 2012-10-05 | ||
| US201361871853P | 2013-08-29 | 2013-08-29 | |
| US61/871,853 | 2013-08-29 | ||
| PCT/IB2013/059045 WO2014053996A2 (en) | 2012-10-05 | 2013-10-01 | Antibodies to microbiome, stress factors and mast cell markers as diagnostic markers for ibs |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2015533213A JP2015533213A (ja) | 2015-11-19 |
| JP2015533213A5 JP2015533213A5 (enExample) | 2016-11-24 |
| JP6329553B2 true JP6329553B2 (ja) | 2018-05-23 |
Family
ID=49447585
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015535149A Expired - Fee Related JP6329553B2 (ja) | 2012-10-05 | 2013-10-01 | Ibsの診断マーカーとしての微生物バイオームに対する抗体、ストレス因子及びマスト細胞マーカー |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US10184940B2 (enExample) |
| EP (1) | EP2904395B1 (enExample) |
| JP (1) | JP6329553B2 (enExample) |
| CN (1) | CN104884959B (enExample) |
| AU (1) | AU2013326133B2 (enExample) |
| CA (1) | CA2886991A1 (enExample) |
| MX (1) | MX360479B (enExample) |
| SG (2) | SG11201502641YA (enExample) |
| WO (1) | WO2014053996A2 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0720250D0 (en) * | 2007-10-17 | 2007-11-28 | Univ Edinburgh | Immunogenic compositions containing escherichia coli h7 flagella and methods of use thereof |
| US20160096819A1 (en) * | 2013-05-17 | 2016-04-07 | Basf Se | Process for preparing n-substituted 1h-pyrazole-5-carboxylic acid compounds and derivatives thereof |
| RU2015155552A (ru) | 2013-05-24 | 2017-06-27 | Нестек С.А. | Путеспецифические способы прогнозирования диагноза синдрома раздраженного кишечника |
| WO2017079653A2 (en) | 2015-11-06 | 2017-05-11 | Vetica Labs, Inc. | Methods of detecting inflammatory markers and treating inflammatory conditions in companion animals |
| EP3421616A1 (en) * | 2017-06-29 | 2019-01-02 | Tata Consultancy Services Limited | Method and system for monitoring the gut health of an individual |
| CN111432825A (zh) * | 2017-10-03 | 2020-07-17 | 赛里斯治疗公司 | 色胺代谢的操纵 |
| JP6533930B1 (ja) * | 2018-08-23 | 2019-06-26 | 一般社団法人日本農業フロンティア開発機構 | 疾病評価指標算出方法、装置、システム、及び、プログラム、並びに、疾病評価指標を算出するためのモデル作成方法。 |
| US11884958B2 (en) | 2019-04-30 | 2024-01-30 | Mayo Foundation For Medical Education And Research | Assessing and treating functional gastrointestinal disorders |
| WO2025071560A1 (en) * | 2023-09-28 | 2025-04-03 | Rutgers, The State University Of New Jersey | Methods of diagnosing b cell malignancies, detecting b cell malignancy relapse, and treating thereof |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2003298703A1 (en) * | 2002-11-22 | 2004-06-18 | Emory University | Diagnostic tests and methods for diagnosing inflammatory bowel disease |
| US20060154276A1 (en) * | 2004-05-13 | 2006-07-13 | Prometheus Laboratories Inc. | Methods of diagnosing inflammatory bowel disease |
| US7943328B1 (en) * | 2006-03-03 | 2011-05-17 | Prometheus Laboratories Inc. | Method and system for assisting in diagnosing irritable bowel syndrome |
| US20080085524A1 (en) | 2006-08-15 | 2008-04-10 | Prometheus Laboratories Inc. | Methods for diagnosing irritable bowel syndrome |
| US20100094560A1 (en) * | 2006-08-15 | 2010-04-15 | Prometheus Laboratories Inc. | Methods for diagnosing irritable bowel syndrome |
| WO2011027971A2 (ko) * | 2009-09-01 | 2011-03-10 | 주식회사이언메딕스 | 장내 공생 세균유래 세포밖 소포체, 및 이를 이용한 질병모델, 백신, 후보 약물 탐색 방법, 및 진단 방법 |
| EP2494074A4 (en) * | 2009-10-30 | 2013-06-12 | Nestec Sa | METHOD FOR DIAGNOSING IRRITATION SYNDROME |
-
2013
- 2013-10-01 JP JP2015535149A patent/JP6329553B2/ja not_active Expired - Fee Related
- 2013-10-01 CN CN201380063446.2A patent/CN104884959B/zh not_active Expired - Fee Related
- 2013-10-01 AU AU2013326133A patent/AU2013326133B2/en not_active Expired - Fee Related
- 2013-10-01 MX MX2015004271A patent/MX360479B/es active IP Right Grant
- 2013-10-01 WO PCT/IB2013/059045 patent/WO2014053996A2/en not_active Ceased
- 2013-10-01 EP EP13779635.5A patent/EP2904395B1/en not_active Not-in-force
- 2013-10-01 SG SG11201502641YA patent/SG11201502641YA/en unknown
- 2013-10-01 CA CA2886991A patent/CA2886991A1/en not_active Abandoned
- 2013-10-01 SG SG10201702773QA patent/SG10201702773QA/en unknown
-
2015
- 2015-03-30 US US14/673,660 patent/US10184940B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| MX360479B (es) | 2018-11-05 |
| EP2904395A2 (en) | 2015-08-12 |
| SG10201702773QA (en) | 2017-06-29 |
| US10184940B2 (en) | 2019-01-22 |
| EP2904395B1 (en) | 2018-09-05 |
| WO2014053996A3 (en) | 2014-05-30 |
| CA2886991A1 (en) | 2014-04-10 |
| SG11201502641YA (en) | 2015-05-28 |
| CN104884959A (zh) | 2015-09-02 |
| AU2013326133B2 (en) | 2019-07-04 |
| JP2015533213A (ja) | 2015-11-19 |
| CN104884959B (zh) | 2017-12-01 |
| US20150346200A1 (en) | 2015-12-03 |
| MX2015004271A (es) | 2015-08-14 |
| HK1213050A1 (en) | 2016-06-24 |
| WO2014053996A2 (en) | 2014-04-10 |
| AU2013326133A1 (en) | 2015-04-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6329553B2 (ja) | Ibsの診断マーカーとしての微生物バイオームに対する抗体、ストレス因子及びマスト細胞マーカー | |
| US10338083B2 (en) | Pathway specific markers for diagnosing irritable bowel syndrome | |
| ES3028294T3 (en) | Methods and systems for distinguishing irritable bowel syndrome from inflammatory bowel disease and celiac disease | |
| JP2022528466A (ja) | 疾患を診断する方法 | |
| JP6193976B2 (ja) | バイオマーカーとしてのクロストリジウム・ディフィシル(Clostridiumdifficile)・デヒドロゲナーゼおよび毒素 | |
| Juzlova et al. | Gastrointestinal comorbidities in patients with psoriasis in the Czech Republic: The results of 189 patients with psoriasis and 378 controls | |
| CN105242045A (zh) | 胃泌素-17作为具有增加的数种相关后发病风险的萎缩性胃炎的生物标志物的用途 | |
| HK1213050B (en) | Antibodies to microbiome as diagnostic markers for ibs | |
| Balaji et al. | Infection in Systemic Sclerosis and its Association with Upper Gastrointestinal Dysfunction | |
| Ajamian | Investigating Markers of Intestinal Barrier Dysfunction in Gastrointestinal Diseases | |
| JP2024522606A (ja) | 機能性消化管障害のための診断マーカー | |
| Breckan | Helicobacter pylori infection in the 21st century: Epidemiology, transmission and clinical aspects | |
| WO2018130855A1 (en) | Typhoid biomarkers | |
| Casellas et al. | Effects of Adherence to Gluten-Free Diet on Quality of Life in Adult Celiac Disease Patients | |
| HK1223416B (en) | Method for diagnosing irritable bowel syndrome |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20161003 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20161003 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20170713 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20170725 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20171024 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180122 |
|
| 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: 20180327 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20180420 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6329553 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: R313111 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| LAPS | Cancellation because of no payment of annual fees |