WO2018124726A1 - Procédé de diagnostic d'une insuffisance rénale par analyse métagénomique bactérienne - Google Patents
Procédé de diagnostic d'une insuffisance rénale par analyse métagénomique bactérienne Download PDFInfo
- Publication number
- WO2018124726A1 WO2018124726A1 PCT/KR2017/015537 KR2017015537W WO2018124726A1 WO 2018124726 A1 WO2018124726 A1 WO 2018124726A1 KR 2017015537 W KR2017015537 W KR 2017015537W WO 2018124726 A1 WO2018124726 A1 WO 2018124726A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- derived
- extracellular vesicles
- renal failure
- bacteria
- content
- Prior art date
Links
- 208000001647 Renal Insufficiency Diseases 0.000 title claims abstract description 59
- 201000006370 kidney failure Diseases 0.000 title claims abstract description 59
- 238000000034 method Methods 0.000 title claims abstract description 40
- 230000001580 bacterial effect Effects 0.000 title claims abstract description 38
- 238000004458 analytical method Methods 0.000 title abstract description 28
- 241000894006 Bacteria Species 0.000 claims abstract description 63
- 230000007423 decrease Effects 0.000 claims abstract description 13
- 210000004369 blood Anatomy 0.000 claims description 39
- 239000008280 blood Substances 0.000 claims description 39
- 238000012163 sequencing technique Methods 0.000 claims description 11
- 241001260322 Elusimicrobia <phylum> Species 0.000 claims description 9
- 241001265526 Gemmatimonadetes <phylum> Species 0.000 claims description 9
- 241001657523 Coriobacteriaceae Species 0.000 claims description 8
- 229940039696 lactobacillus Drugs 0.000 claims description 8
- 241001662476 Acidimicrobiales Species 0.000 claims description 7
- 241000588921 Enterobacteriaceae Species 0.000 claims description 7
- 241000186394 Eubacterium Species 0.000 claims description 7
- 241000186660 Lactobacillus Species 0.000 claims description 7
- 241000605861 Prevotella Species 0.000 claims description 7
- 241000426682 Salinispora Species 0.000 claims description 7
- 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 claims description 6
- 241000580482 Acidobacteria Species 0.000 claims description 6
- 241000466670 Adlercreutzia Species 0.000 claims description 6
- 241000328900 Candidatus Solibacter Species 0.000 claims description 6
- 241000324980 Chthoniobacteraceae Species 0.000 claims description 6
- 241001337904 Gordonia <angiosperm> Species 0.000 claims description 6
- 241000770998 Methylacidiphilae Species 0.000 claims description 6
- 241000588771 Morganella <proteobacterium> Species 0.000 claims description 6
- 241000121237 Nitrospirae Species 0.000 claims description 6
- 241001248479 Pseudomonadales Species 0.000 claims description 6
- 241000930965 Spartobacteria Species 0.000 claims description 6
- 241000194017 Streptococcus Species 0.000 claims description 6
- 241000644105 Tissierellaceae Species 0.000 claims description 6
- 241000589218 Acetobacteraceae Species 0.000 claims description 5
- 241001185328 Acidobacteriaceae Species 0.000 claims description 5
- 241001185327 Acidobacteriales Species 0.000 claims description 5
- 241000589291 Acinetobacter Species 0.000 claims description 5
- 241001135756 Alphaproteobacteria Species 0.000 claims description 5
- 241000606126 Bacteroidaceae Species 0.000 claims description 5
- 241000606125 Bacteroides Species 0.000 claims description 5
- 241001568341 Bdellovibrionaceae Species 0.000 claims description 5
- 241000191912 Beijerinckiaceae Species 0.000 claims description 5
- 241001135755 Betaproteobacteria Species 0.000 claims description 5
- 241001430332 Bifidobacteriaceae Species 0.000 claims description 5
- 241001655328 Bifidobacteriales Species 0.000 claims description 5
- 241000186000 Bifidobacterium Species 0.000 claims description 5
- 241000131971 Bradyrhizobiaceae Species 0.000 claims description 5
- 241000253402 Burkholderiaceae Species 0.000 claims description 5
- 241000589876 Campylobacter Species 0.000 claims description 5
- 241001248433 Campylobacteraceae Species 0.000 claims description 5
- 241000263905 Candidatus Koribacter Species 0.000 claims description 5
- 241000930909 Candidatus Xiphinematobacter Species 0.000 claims description 5
- 241000852385 Chitinophagaceae Species 0.000 claims description 5
- 241001185363 Chlamydiae Species 0.000 claims description 5
- 241000498849 Chlamydiales Species 0.000 claims description 5
- 241001185364 Chlamydiia Species 0.000 claims description 5
- 241000324968 Chthoniobacterales Species 0.000 claims description 5
- 241000781381 Chthonomonadetes Species 0.000 claims description 5
- 241001112696 Clostridia Species 0.000 claims description 5
- 241001430149 Clostridiaceae Species 0.000 claims description 5
- 241001464956 Collinsella Species 0.000 claims description 5
- 241001600130 Comamonadaceae Species 0.000 claims description 5
- 241001662464 Coriobacteriales Species 0.000 claims description 5
- 241000186031 Corynebacteriaceae Species 0.000 claims description 5
- 241000186216 Corynebacterium Species 0.000 claims description 5
- 241000246077 Coxiellaceae Species 0.000 claims description 5
- 241001528480 Cupriavidus Species 0.000 claims description 5
- 241000031711 Cytophagaceae Species 0.000 claims description 5
- 241000343673 Cytophagia Species 0.000 claims description 5
- 241001143296 Deferribacteres <phylum> Species 0.000 claims description 5
- 241000305071 Enterobacterales Species 0.000 claims description 5
- 241000194033 Enterococcus Species 0.000 claims description 5
- 241001148568 Epsilonproteobacteria Species 0.000 claims description 5
- 241000609971 Erysipelotrichaceae Species 0.000 claims description 5
- 241001081259 Erysipelotrichia Species 0.000 claims description 5
- 241000588722 Escherichia Species 0.000 claims description 5
- 241000605909 Fusobacterium Species 0.000 claims description 5
- 241000192128 Gammaproteobacteria Species 0.000 claims description 5
- 241000589950 Gemmata Species 0.000 claims description 5
- 241000953972 Gemmataceae Species 0.000 claims description 5
- 241000191917 Hyphomicrobiaceae Species 0.000 claims description 5
- 241001655312 Intrasporangiaceae Species 0.000 claims description 5
- 241000005706 Isosphaeraceae Species 0.000 claims description 5
- 241000316163 Jeotgalicoccus Species 0.000 claims description 5
- 241000588748 Klebsiella Species 0.000 claims description 5
- 241000276942 Kofleriaceae Species 0.000 claims description 5
- 241000558696 Ktedonobacteraceae Species 0.000 claims description 5
- 241001112693 Lachnospiraceae Species 0.000 claims description 5
- 241001468155 Lactobacillaceae Species 0.000 claims description 5
- 241000246099 Legionellales Species 0.000 claims description 5
- 241001430266 Methylocystaceae Species 0.000 claims description 5
- 241001655310 Microbacteriaceae Species 0.000 claims description 5
- 241001134635 Micromonosporaceae Species 0.000 claims description 5
- 241000186360 Mycobacteriaceae Species 0.000 claims description 5
- 241000863421 Myxococcaceae Species 0.000 claims description 5
- 241000863434 Myxococcales Species 0.000 claims description 5
- 241000122116 Parvimonas Species 0.000 claims description 5
- 241000351207 Peptoniphilus Species 0.000 claims description 5
- 241000601428 Phycisphaerae Species 0.000 claims description 5
- 241000982667 Phyllobacteriaceae Species 0.000 claims description 5
- 241001180199 Planctomycetes Species 0.000 claims description 5
- 241000588769 Proteus <enterobacteria> Species 0.000 claims description 5
- 241000947836 Pseudomonadaceae Species 0.000 claims description 5
- 241000589516 Pseudomonas Species 0.000 claims description 5
- 241001212087 Rhodocyclales Species 0.000 claims description 5
- 241000131970 Rhodospirillaceae Species 0.000 claims description 5
- 241001453443 Rothia <bacteria> Species 0.000 claims description 5
- 241000095588 Ruminococcaceae Species 0.000 claims description 5
- 241000030357 Saprospirales Species 0.000 claims description 5
- 241000107801 Shewanellaceae Species 0.000 claims description 5
- 241000919492 Sinobacteraceae Species 0.000 claims description 5
- 241000328896 Solibacterales Species 0.000 claims description 5
- 241001662782 Solirubrobacterales Species 0.000 claims description 5
- 241001141544 Sphingobacteriales Species 0.000 claims description 5
- 241000194018 Streptococcaceae Species 0.000 claims description 5
- 241001568368 Syntrophobacteraceae Species 0.000 claims description 5
- 241001568376 Syntrophobacterales Species 0.000 claims description 5
- 241000343985 Thermogemmatisporaceae Species 0.000 claims description 5
- 241001425419 Turicibacter Species 0.000 claims description 5
- 241001453327 Xanthomonadaceae Species 0.000 claims description 5
- 241000947909 Xanthomonadales Species 0.000 claims description 5
- 210000002966 serum Anatomy 0.000 claims description 5
- 241000590020 Achromobacter Species 0.000 claims description 4
- 241001185330 Acidobacteriia Species 0.000 claims description 4
- 241001156739 Actinobacteria <phylum> Species 0.000 claims description 4
- 241000186033 Alloiococcus Species 0.000 claims description 4
- 241000379991 Anaerococcus Species 0.000 claims description 4
- 241001136700 Anaerolineae Species 0.000 claims description 4
- 241001291843 Caulobacteraceae Species 0.000 claims description 4
- 241000781407 Chthonomonadaceae Species 0.000 claims description 4
- 241000781405 Chthonomonadales Species 0.000 claims description 4
- 241001604712 Conexibacteraceae Species 0.000 claims description 4
- 241001464948 Coprococcus Species 0.000 claims description 4
- 241000343666 Cytophagales Species 0.000 claims description 4
- 241001552883 Enhydrobacter Species 0.000 claims description 4
- 241000606790 Haemophilus Species 0.000 claims description 4
- 241000558694 Ktedonobacterales Species 0.000 claims description 4
- 241000558695 Ktedonobacteria Species 0.000 claims description 4
- 241000589289 Moraxellaceae Species 0.000 claims description 4
- 241000186359 Mycobacterium Species 0.000 claims description 4
- 241000777895 Opitutus Species 0.000 claims description 4
- 241000266824 Oscillospira Species 0.000 claims description 4
- 241001277521 Oxalobacteraceae Species 0.000 claims description 4
- 241000179039 Paenibacillus Species 0.000 claims description 4
- 241000216465 Pedomicrobium Species 0.000 claims description 4
- 241000959234 Pedosphaera Species 0.000 claims description 4
- 241001180192 Planctomycetia Species 0.000 claims description 4
- 241000692844 Prevotellaceae Species 0.000 claims description 4
- 241000589157 Rhizobiales Species 0.000 claims description 4
- 241001148164 Rhodoplanes Species 0.000 claims description 4
- 241001185316 Rhodospirillales Species 0.000 claims description 4
- 241000863430 Shewanella Species 0.000 claims description 4
- 241000328898 Solibacteraceae Species 0.000 claims description 4
- 241000328868 Solibacteres Species 0.000 claims description 4
- 241000131972 Sphingomonadaceae Species 0.000 claims description 4
- 241000736131 Sphingomonas Species 0.000 claims description 4
- 241000122971 Stenotrophomonas Species 0.000 claims description 4
- 241000343983 Thermogemmatisporales Species 0.000 claims description 4
- 210000001616 monocyte Anatomy 0.000 claims description 4
- 210000002381 plasma Anatomy 0.000 claims description 4
- 241000604933 Bdellovibrio Species 0.000 claims description 3
- 241000605894 Porphyromonas Species 0.000 claims description 3
- 241000192031 Ruminococcus Species 0.000 claims description 3
- 238000002405 diagnostic procedure Methods 0.000 claims 6
- 238000013399 early diagnosis Methods 0.000 abstract description 7
- 238000011282 treatment Methods 0.000 abstract description 4
- 230000003907 kidney function Effects 0.000 abstract description 2
- 208000024891 symptom Diseases 0.000 abstract description 2
- 241000617156 archaeon Species 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
- 108020004414 DNA Proteins 0.000 description 15
- 108090000623 proteins and genes Proteins 0.000 description 11
- 241000203069 Archaea Species 0.000 description 8
- 241000894007 species Species 0.000 description 8
- 108020004465 16S ribosomal RNA Proteins 0.000 description 7
- 238000000692 Student's t-test Methods 0.000 description 6
- 238000003745 diagnosis Methods 0.000 description 6
- 230000035945 sensitivity Effects 0.000 description 6
- 238000012353 t test Methods 0.000 description 6
- 244000005700 microbiome Species 0.000 description 5
- 239000000090 biomarker Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000000968 intestinal effect Effects 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 241001662478 Acidimicrobiia Species 0.000 description 3
- 241000946390 Catenibacterium Species 0.000 description 3
- 241001609975 Enterococcaceae Species 0.000 description 3
- 241001655307 Gordoniaceae Species 0.000 description 3
- 241000230565 Sphingobacteriia Species 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 208000020470 nervous system symptom Diseases 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 208000009304 Acute Kidney Injury Diseases 0.000 description 2
- 241001453380 Burkholderia Species 0.000 description 2
- 241001142109 Chloroflexi Species 0.000 description 2
- 241001662466 Coriobacteriia Species 0.000 description 2
- 241001427825 Gaiellaceae Species 0.000 description 2
- 241000736262 Microbiota Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 241000319342 Parachlamydiaceae Species 0.000 description 2
- 241000606752 Pasteurellaceae Species 0.000 description 2
- 241000232299 Ralstonia Species 0.000 description 2
- 208000033626 Renal failure acute Diseases 0.000 description 2
- 241000392412 Thermoleophilia Species 0.000 description 2
- 201000011040 acute kidney failure Diseases 0.000 description 2
- 208000012998 acute renal failure Diseases 0.000 description 2
- 210000000577 adipose tissue Anatomy 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 208000020832 chronic kidney disease Diseases 0.000 description 2
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 238000007481 next generation sequencing Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 206010010071 Coma Diseases 0.000 description 1
- 208000022540 Consciousness disease Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 238000007400 DNA extraction Methods 0.000 description 1
- 206010014418 Electrolyte imbalance Diseases 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 241000589565 Flavobacterium Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000031361 Hiccup Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000192017 Micrococcaceae Species 0.000 description 1
- 208000001089 Multiple system atrophy Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 206010031127 Orthostatic hypotension Diseases 0.000 description 1
- 241001112734 Paenibacillaceae Species 0.000 description 1
- 241000191992 Peptostreptococcus Species 0.000 description 1
- 206010037596 Pyelonephritis Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 235000015107 ale Nutrition 0.000 description 1
- 210000003403 autonomic nervous system Anatomy 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000009982 effect on human Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000011331 genomic analysis Methods 0.000 description 1
- 244000005709 gut microbiome Species 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000010339 medical test Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 244000005706 microflora Species 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 208000035824 paresthesia Diseases 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000031068 symbiosis, encompassing mutualism through parasitism Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000028016 temperature homeostasis Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- the present invention relates to a method for diagnosing renal failure through bacterial metagenome analysis, and more specifically, to diagnose kidney failure by performing bacterial metagenomic analysis using a sample derived from a subject, analyzing the increase or decrease in the content of specific bacterial-derived extracellular vesicles. It is about how to.
- Renal failure refers to the loss of kidney (renal) function and is classified into acute and chronic renal failure according to the time of occurrence.
- Acute renal failure occurs due to bacterial infections such as pyelonephritis and nephritis, ingestion of external drugs, kidney damage caused by poisons, and insufficient blood volume.
- Chronic renal failure is often caused by complications of chronic diseases such as hypertension and diabetes. Kidney function is often lost and progresses slowly over a period of 3-12 months.
- the urinary tract does not produce systemic symptoms, including memory and concentration problems, sleep disorders, headaches, consciousness disorders, loss of coordination, confusion, convulsions, coma, central nervous system symptoms, anxiety-leg syndrome, hiccups, tingling, Peripheral nervous system symptoms such as autologous abnormalities, dizziness, orthostatic hypotension, decreases in tom and saliva, autonomic nervous system symptoms such as abnormal thermoregulation, swelling, cokalemia, metabolic fluids and electrolyte abnormalities.
- Diagnosis of renal failure is done through a medical test, such as a blood test.
- a medical test such as a blood test.
- most cases of renal failure are difficult to treat when the disease is already advanced. Therefore, it is effective to provide a method for preventing the occurrence of renal failure in the high-risk group by predicting the occurrence and causes of renal failure in advance.
- Microbiota refers to a microbial community including bacteria, archaea and eukarya that exist in a given settlement.Intestinal microbiota is an important role in human physiology. It is known to have a great effect on human health and disease through interaction with human cells.
- the symbiotic bacteria secrete nanometer-sized vesicles to exchange information about genes and proteins in other cells.
- the mucous membrane forms a physical protective film that particles larger than 200 nanometers (nm) in size can't pass through, so that the symbiotic bacteria cannot pass through the mucosa, but bacterial-derived vesicles are usually less than 100 nanometers in size. It freely speaks to the mucous membrane and is absorbed by our body.
- Metagenomics also called environmental genomics, can be said to be an analysis of metagenomic data obtained from samples taken from the environment (Korean Patent Publication No. 2011-0073049). Recently, it has become possible to list the bacterial composition of the human microflora by a method based on 16s ribosomal RNA (16s rRNA) sequencing. Next generation sequencing of 16s rDNA sequencing gene of 16s ribosomal RNA is performed. , NGS) platform to analyze.
- NGS 16s ribosomal RNA
- the present inventors extracted the genes from the extracellular vesicles derived from bacteria present in the blood, which is a sample derived from the sample, and performed a metagenome analysis on them in order to diagnose the cause factors and risk of renal failure in advance. To identify a bacterial-derived extracellular vesicle that can act as a bar, the present invention was completed based on this.
- an object of the present invention is to provide a method for providing information for diagnosing renal failure through metagenome analysis of bacterial extracellular vesicles.
- the present invention provides a method for providing information for diagnosing kidney failure, comprising the following steps:
- the present invention also provides a renal failure diagnosis method comprising the following steps:
- the present invention also provides a method for predicting the risk of developing renal failure, comprising the following steps:
- step (c) Nitrospirae, Nitrospirae, Chlooflexi, Planctomycetes, Gemmatimonadetes, Acidobacteria, Acidobacteria, WPS-2 Diagnosing renal failure by comparing the increase in the amount of one or more phylum bacterial-derived extracellular vesicles selected from the group consisting of, AD3, Chlamydiae, Elusimicrobia, OD1, and TM6 It may be.
- deferribacteres In another embodiment, deferribacteres, Coriobacacteriia, Erysipelotrichi, Gamma proteobacteria, Clostridia in step (c) , Actinbacteria, Alphaproteobacteria, Betaproteobacteria, Cytophagia, Thermomephilia, Chloracidobacteria, Methylacididibacteria Methylacidiphilae, Sphingobacteriia, Saprospirae, Anaerolineae, Elin 6529, Planctomycetia, Epsilonproteobacteria, Spaniproproteobacteria Spartobacteria, Acidimicrobiia, Chlamydiia, Acidobacteria-6, Phycisphaerae, TM1, Gemmamati Gemmatimonadetes, DA052, Ktedonobacteria, Pedosphaerae, Acidobacteriia, Soli
- step (c) Coriobacteriales, Bifidobacteriales, Enterobacteriales, Pseudomonadales, Pseudomonadales, Rizobiales , Acidimicrobiales, Acantimicrobiales, Xanthomonadales, Myxococcales, Rhodocyclales, Solirubrobacterales, Pirellulales, Sphingobacteriales, Rhodospirillales, Thermogemmatisporales, Gemmatales, Saprospirales, Chthoniobacterales, Scintropore Syntrophobacterales, Acidobacteriales, Solibacterales, Pedosphaerales, Cytophag extracellular vesicles derived from one or more order bacteria selected from the group consisting of ales, Chlamydiales, Legionellales, Ktedonobacterales, and Chthonomonadales. It may be to diagnose renal failure by comparing the increase and decrease of the content in the group consisting of ales, Chla
- Turicibacteraceae Enteriticoccaceae
- Enterococcaceae Enterobacteriaceae
- Coriobacteriaceae Coriobacteriaceae
- Ruminococcaceae Ruminococcaceae
- Erysipelotrichaceae Pseudomonadaceae
- Lachnospiraceae Bifidobacteriaceae, Enterobacteriaceae Enterobacteriaceae, Clostridiaceae, Bacteroidaceae, Oxalobacteraceae, Moraxellaceae, Prevotellaceae
- Sphingo Monadasi Sphingomonadaceae, Caulobacteraceae, Bradyrhizobiaceae, Corynebacteriaceae, Intrasporangiaceae, Streptococcaceae, Zeptococcaceae Tomona Xanthomonadaceae, Chitinophagaceae,
- step (c) Morganella (Morganella), Adlercreutzia (Adlercreutzia), Turicibacter, Eubacterium (Eubacterium), Cardenibacterium (Catenibacterium) ), Collinsella, Enterococcus, Cupriavidus, Proteus, Escherichia, Osscillospira, Pseudomonas, Yacht Gallicocus () Jeotgalicoccus, Lactobacillus, Enhydrobacter, Luminococcus, Coprococcus, Bifidobacterium, Bacteroides, Acinetobacter ), Prevotella, Fusobacterium, Corynebacterium, Rothia, Gemmata, Pedomicrobium, Mycobacterium , Streptococcus, Opitutus, Kaistobacter, Shewanella, Candidatus Xiphinematobacter, Flavoacterium, Porphyromonas, Peptopteptococcus
- the blood may be whole blood, serum, plasma, or blood monocytes.
- Extracellular vesicles secreted by microorganisms, such as bacteria, archaea, etc. present in the environment can be absorbed directly into the body and directly affect cancer development, kidney failure is difficult to diagnose early, so the efficient treatment is difficult, so the present invention
- Meta-genomic analysis of bacterial-derived extracellular parcel vesicles using human-derived samples according to the pre-diagnosis of the risk of renal failure in advance by early diagnosis and prediction of the risk group of renal failure can be delayed or prevented by proper management.
- early diagnosis is possible even after the onset of the disease, thereby reducing the incidence of renal failure and increasing the therapeutic effect.
- metagenome analysis avoids causative agents in patients diagnosed with renal failure, thereby improving cancer progression and preventing recurrence.
- Figure 1a is a photograph of the distribution of bacteria and vesicles by time after the oral administration of enteric bacteria and bacterial derived vesicles (EV) to the mouse
- Figure 1b is 12 hours after oral administration, blood And several organs were extracted to evaluate the distribution of bacteria and vesicles in the body.
- FIG. 2 shows the distribution of bacterial derived vesicles (EVs) with significant diagnostic performance at the phylum level by separating bacteria-derived vesicles from renal inverters and normal blood.
- EVs bacterial derived vesicles
- FIG. 3 is a result showing the distribution of bacteria-derived vesicles (EVs) with significant diagnostic performance at a class level by separating bacteria-derived vesicles from renal inverters and normal blood, and performing a metagenome analysis.
- EVs bacteria-derived vesicles
- FIG. 4 is a result showing the distribution of bacteria-derived vesicles (EVs) with significant diagnostic performance at the order level by separating the bacteria-derived vesicles from renal inverters and normal blood, and performing a metagenome analysis.
- EVs bacteria-derived vesicles
- FIG. 5 is a result showing the distribution of bacteria-derived vesicles (EVs) with significant diagnostic performance at the family level by separating bacteria-derived vesicles from the renal inverter and normal blood, and performing a metagenome analysis.
- EVs bacteria-derived vesicles
- FIG. 6 shows the distribution of bacteria-derived vesicles (EVs) with significant diagnostic performance at genus level after separation of bacterial-derived vesicles from renal inverters and normal blood.
- EVs bacteria-derived vesicles
- the present invention relates to a method for diagnosing renal failure through bacterial metagenome analysis.
- the present inventors extracted a gene from a bacterial-derived extracellular vesicle using a sample derived from a subject, and performed a metagenome analysis on it.
- Bacterial-derived extracellular vesicles that can act as
- the present invention comprises the steps of (a) extracting DNA from the extracellular vesicles isolated from the subject sample;
- (c) provides an information providing method for diagnosing renal failure, comprising comparing the increase and decrease of the content of bacteria and archaea-derived extracellular vesicles with normal-derived samples by sequencing the PCR product.
- the term "diagnosis of renal failure” refers to determining whether a kidney failure is likely to occur in a patient, whether the kidney failure is relatively high, or whether renal failure has already occurred.
- the method of the present invention can be used to prevent or delay the onset of the disease through special and appropriate management as a patient at high risk of developing renal failure for any particular patient.
- the methods of the present invention can be used clinically to determine treatment by early diagnosis of renal failure and by selecting the most appropriate treatment regimen.
- metagenome used in the present invention, also referred to as “metagenome”, refers to the total of the genome including all viruses, bacteria, fungi, etc. in an isolated area such as soil, animal intestine, It is mainly used as a concept of genome explaining the identification of many microorganisms at once using sequencer to analyze microorganisms which are not cultured.
- metagenome does not refer to one species of genome or genome, but refers to a kind of mixed dielectric as the genome of all species of one environmental unit. This is a term from the point of view of defining a species in the course of the evolution of biology in terms of functional species as well as various species that interact with each other to create a complete species.
- rapid sequencing is used to analyze all DNA and RNA, regardless of species, to identify all species in one environment, and to identify interactions and metabolism.
- metagenome analysis was preferably performed using bacterial-derived extracellular vesicles isolated from serum.
- the subject sample may be blood, and the blood may preferably be whole blood, serum, plasma, or blood monocytes, but is not limited thereto.
- the metagenome analysis of the extracellular vesicles derived from bacteria and archaea was performed, and at the level of phylum, class, order, family, and genus, Each analysis was performed to identify bacterial-derived vesicles that could actually cause kidney failure.
- Deferribacteres Coriobacteriia, Erysipelotrichi, Gammaproteobacteria, Clostridia, Actinobacteria, Alphaproteobacteria, Betaproteobacteria, Cytophagia Thermoleophilia, Chloracidobacteria, Methylacidiphilae, Sphingobacteriia, Saprospirae, Anaerolineae, Ellin6529, Planctomycetia, Epsilonproteobacteria, Spartobacteria, Acidimicrobiia, Chlamydiia, Acidobacteria-6, Phycisphaerae, TM1, Gemmatiactadetesono, DAbacteria Acid, Peaeroceobacerii, Peaerceoerta,
- bacterial metagenomes were analyzed at the neck level for vesicles present in a blood sample derived from a subject.
- Solirubrobacterales Pirellulales, Sphingobacteriales, Rhodospirillales, Thermogemmatisporales, Gemmatales, Saprospirales, Chthoniobacterales, Syntrophobacterales, Acidobacteriales, Solibacterales, Pedosphaerales, Cytophagales, Chlamydiales, Legionellales, and Ktedonobacomoales
- Example 4 There was a significant difference (see Example 4).
- Turicibacteraceae as a result of analyzing the bacterial metagenome at the excessive level for the vesicles present in the blood samples from the subject, Turicibacteraceae, Enterococcaceae, Coriobacteriaceae, Lactobacillaceae, Ruminococcaceae, Erysipelotrichaceae, Pseudomonadaceae, Lachnospiraceae, Bifidobacteriaceae, Enterobacteriaceae, Clostridiaceae, Bacteroidaceae, Oxalobacteraceae, Moraxellaceae, Prevotellaceae, Sphingomonadaceae, Caulobacteraceae, Bradyrhizobiaceae, Corynebacteriaceae, Intrasporangiaceae, Streptococcaceae, Xanthomonadaceae, Chitinophagaceae, Mycobacteriaceae, Microbacteriaceae
- the fluorescently labeled 50 ⁇ g of bacteria and bacteria-derived vesicles were administered in the same manner as above 12 hours.
- Blood, Heart, Lung, Liver, Kidney, Spleen, Adipose tissue, and Muscle were extracted from mice.
- the intestinal bacteria (Bacteria) were not absorbed into each organ, whereas the intestinal bacteria-derived extracellular vesicles (EV) were detected in the tissues, as shown in FIG. And distribution in liver, kidney, spleen, adipose tissue, and muscle.
- the blood was first placed in a 10 ml tube and centrifuged (3,500 ⁇ g, 10 min, 4 ° C.) to settle the suspended solids to recover only the supernatant and then transferred to a new 10 ml tube. After removing the bacteria and foreign substances from the recovered supernatant using a 0.22 ⁇ m filter, transfer to centripreigugal filters (50 kD) and centrifuged at 1500 xg, 4 °C for 15 minutes to discard the material smaller than 50 kD and 10 ml Concentrated until.
- centripreigugal filters 50 kD
- PCR was performed using the 16S rDNA primer shown in Table 1 to amplify the gene and perform sequencing (Illumina MiSeq sequencer). Output the result as a Standard Flowgram Format (SFF) file, convert the SFF file into a sequence file (.fasta) and a nucleotide quality score file using GS FLX software (v2.9), check the credit rating of the lead, and window (20 bps) The part with the average base call accuracy of less than 99% (Phred score ⁇ 20) was removed.
- SFF Standard Flowgram Format
- the Operational Taxonomy Unit performed UCLUST and USEARCH for clustering according to sequence similarity. Specifically, the clustering is based on 94% genus, 90% family, 85% order, 80% class, and 75% sequence similarity. OTU's door, river, neck, family and genus level classifications were performed, and bacteria with greater than 97% sequence similarity were analyzed using BLASTN and GreenGenes' 16S DNA sequence database (108,453 sequences) (QIIME).
- Example 3 the vesicles were isolated from the blood of 21 renal inverters and 19 healthy subjects matched with age and sex, and then metagenome sequencing was performed.
- the strains whose p-value between the two groups is 0.05 or less and more than two times different between the two groups are selected in the t-test. under curve), sensitivity, and specificity.
- Bacterial-derived vesicles in the blood were analyzed at the genus level, Morganella, Adlercreutzia, Turicibacter, Eubacterium, Catenibacterium, Collinsella, Enterococcus, Cupriavidus, Proteus, Escherichia, Oscillospira, Pseudomonas, Jeotgalicoccus, Lactobacillus, Cocusoccoco, Bifidobacterium, Bacteroides, Acinetobacter, Prevotella, Fusobacterium, Corynebacterium, Rothia, Gemmata, Pedomicrobium, Mycobacterium, Streptococcus, Opitutus, Kaistobacter, Shewanella, Candidatus Xiphinematobacter, Flavobacterium, Porphyr opococtuscoccus When diagnostic models were developed with bacterial biomarkers of the genus Peptoniphilus, Salinispora, Anaerococcus, Candidatus
- the present invention relates to a method for diagnosing renal failure through analysis of bacterial metagenome, wherein the risk group of renal failure is predicted by predicting the risk of renal failure in advance through metagenomic analysis of bacterial extracellular vesicles using a human-derived sample according to the present invention.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Immunology (AREA)
- Physics & Mathematics (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Biophysics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
La présente invention concerne un procédé de diagnostic d'une insuffisance rénale par analyse métagénomique bactérienne et, plus particulièrement, un procédé de diagnostic d'une insuffisance rénale par la réalisation d'une analyse métagénomique bactérienne à l'aide d'un échantillon dérivé d'un sujet et par l'analyse d'une augmentation ou d'une diminution de la teneur en une vésicule extracellulaire dérivée d'une bactérie spécifique. Une vésicule extracellulaire sécrétée par un microbe, tel qu'une bactérie et une archée, présente dans l'environnement peut être absorbée dans le corps et influencer directement la fonction rénale et le diagnostic précoce d'une insuffisance rénale est difficile avant l'apparition d'un quelconque symptôme, ce qui complique un traitement efficace. Ainsi, par l'intermédiaire de l'analyse métagénomique d'une vésicule extracellulaire dérivée d'une bactérie à l'aide d'un échantillon dérivé du corps humain selon la présente invention, le risque d'apparition d'une insuffisance rénale peut être prédit à l'avance, ce qui permet un diagnostic précoce et la prédiction d'un groupe à risque d'une insuffisance rénale et de retarder le moment d'apparition ou de prévenir l'apparition par des soins appropriés et un diagnostic précoce est encore possible même après l'apparition, ce qui peut abaisser le taux d'incidence de l'insuffisance rénale et améliorer l'effet de traitement.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR10-2016-0181572 | 2016-12-28 | ||
| KR20160181572 | 2016-12-28 | ||
| KR1020170180003A KR101940424B1 (ko) | 2016-12-28 | 2017-12-26 | 세균 메타게놈 분석을 통한 신부전 진단방법 |
| KR10-2017-0180003 | 2017-12-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2018124726A1 true WO2018124726A1 (fr) | 2018-07-05 |
Family
ID=62709663
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/KR2017/015537 WO2018124726A1 (fr) | 2016-12-28 | 2017-12-27 | Procédé de diagnostic d'une insuffisance rénale par analyse métagénomique bactérienne |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2018124726A1 (fr) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20060019700A (ko) * | 2004-08-28 | 2006-03-06 | 김철민 | 모든 세균의 감별을 위한 세균 특이적, 속 특이적 및 종특이적 올리고뉴클레오티드, 이를 포함하는 진단 키트, 및이를 이용한 검출 방법 |
| KR20110025603A (ko) * | 2009-09-04 | 2011-03-10 | 주식회사이언메딕스 | 그람 양성 세균유래 세포밖 소포체 및 이의 용도 |
| KR20160073157A (ko) * | 2014-12-16 | 2016-06-24 | 이화여자대학교 산학협력단 | 세균 유래의 나노소포체를 이용한 세균성 감염질환 원인균 동정방법 |
-
2017
- 2017-12-27 WO PCT/KR2017/015537 patent/WO2018124726A1/fr active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20060019700A (ko) * | 2004-08-28 | 2006-03-06 | 김철민 | 모든 세균의 감별을 위한 세균 특이적, 속 특이적 및 종특이적 올리고뉴클레오티드, 이를 포함하는 진단 키트, 및이를 이용한 검출 방법 |
| KR20110025603A (ko) * | 2009-09-04 | 2011-03-10 | 주식회사이언메딕스 | 그람 양성 세균유래 세포밖 소포체 및 이의 용도 |
| KR20160073157A (ko) * | 2014-12-16 | 2016-06-24 | 이화여자대학교 산학협력단 | 세균 유래의 나노소포체를 이용한 세균성 감염질환 원인균 동정방법 |
Non-Patent Citations (2)
| Title |
|---|
| ERDBRUGGER, UTA: "Extracellular vesicles in renal diseases: more than novel biomarkers?", JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, vol. 27, no. 1, 6 August 2015 (2015-08-06), pages 12 - 26, XP055607375 * |
| VAZIRI, NOSRATOLA D.: "Altered intestinal microbial flora and impaired epithelial barrier structure and function in CKD: the nature , mechanisms, consequences and potential treatment", NEPHROLOGY DIALYSIS TRANSPLANTATION, vol. 31, no. 5, 16 April 2015 (2015-04-16), pages 737 - 746, XP055607374 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101940445B1 (ko) | 세균 메타게놈 분석을 통한 당뇨병 진단 방법 | |
| WO2018155961A1 (fr) | Procédé de diagnostic de la maladie de parkinson par analyse bactériologique de métagénome | |
| WO2018124606A1 (fr) | Procédé de diagnostic du cancer du sein par analyse métagénomique microbienne | |
| WO2018124617A1 (fr) | Procédé de diagnostic du cancer du poumon par analyse métagénomique bactérienne | |
| WO2018111040A1 (fr) | Procédé de diagnostic du cancer de l'estomac par analyse du métagénome bactérien | |
| KR101940426B1 (ko) | 세균 메타게놈 분석을 통한 대장종양 진단 방법 | |
| KR101944665B1 (ko) | 세균 메타게놈 분석을 통한 만성폐쇄성기도질환 진단 방법 | |
| WO2018155950A1 (fr) | Procédé de diagnostic du diabète par analyse du métagénome microbien | |
| WO2019160284A1 (fr) | Procédé de diagnostic d'un accident vasculaire cérébral par l'intermédiaire de l'analyse du métagénome bactérien | |
| KR102019646B1 (ko) | 미생물 메타게놈 분석을 통한 아토피피부염 진단방법 | |
| WO2018155960A1 (fr) | Procédé de diagnostic du cancer de l'ovaire par analyse du métagénome microbien | |
| KR101940423B1 (ko) | 세균 메타게놈 분석을 통한 심장질환 진단방법 | |
| KR102130485B1 (ko) | 세균 메타게놈 분석을 통한 알츠하이머치매 진단방법 | |
| US12084721B2 (en) | Inflammatory bowel disease diagnostic method by means of bacterial metagenomic analysis | |
| KR102019648B1 (ko) | 천식환자에서 세균 메타게놈 분석을 통한 폐암 진단방법 | |
| KR101944660B1 (ko) | 세균 메타게놈 분석을 통한 우울증 진단방법 | |
| KR102008451B1 (ko) | 세균 메타게놈 분석을 통한 자폐증 진단방법 | |
| WO2019156325A1 (fr) | Procédé de diagnostic du syndrome du côlon irritable par l'intermédiaire de l'analyse métagénomique bactérienne | |
| KR101940424B1 (ko) | 세균 메타게놈 분석을 통한 신부전 진단방법 | |
| WO2018124619A1 (fr) | Procédé de diagnostic du cancer de la vessie par analyse métagénomique microbienne | |
| WO2019146966A1 (fr) | Méthode de diagnostic d'un cholangiocarcinome par l'intermédiaire d'une analyse métagénomique bactérienne | |
| WO2018225945A1 (fr) | Procédé de diagnostic de la dermatite atopique par analyse métagénomique microbienne | |
| KR101936006B1 (ko) | 미생물 메타게놈 분석을 통한 방광암 진단방법 | |
| WO2018124726A1 (fr) | Procédé de diagnostic d'une insuffisance rénale par analyse métagénomique bactérienne | |
| WO2018124618A1 (fr) | Procédé de diagnostic du cancer du pancréas par analyse métagénomique bactérienne |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 17887818 Country of ref document: EP Kind code of ref document: A1 |
|
| NENP | Non-entry into the national phase |
Ref country code: DE |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 17887818 Country of ref document: EP Kind code of ref document: A1 |