Hu rau: jerry.he@wecistanche.com

Ana Merino-Ribas1,2,3,4 · Ricardo Araujo4 · Ioana Bancu1,2 · Fredzzia Graterol1,2 · Andrea Vergara5 · Marc Noguera-Julian5 · Roger Paredes5 · Jordi Bonal2 · Benedita Sampaio-Maia4,6

Tau Txais: 23 Lub Rau Hli 2021 / Txais: 8 Kaum Ob Hlis 2021

© Tus sau 2021

Cistanche tuaj yeem txhim kho lub raum ua haujlwm

Abstract

Lub Hom Phiaj Nws tau raug pov thawj tias lub plab microbiome hloov pauv hauv cov neeg mob uas mob ntevraumkab mob. Qhov no ua rau muaj kev mob ntev thiab ua rau muaj kev pheej hmoo plawv thiab kev tuag, tshwj xeeb tshaj yog nyob rau hauv cov neeg mob hemodialysis. Phosphate binders tuaj yeem ua rau muaj kev hloov pauv hauv lawv cov microbiome. Qhov kev sim no tsom los sib piv cov kev hloov hauv plab microbiome ntawm cov neeg mob hemodialysis kho nrog calcium acetate rau cov neeg kho nrog sucroferric oxyhydroxide.

Txoj kev Kaum ob tus neeg mob hemodialysis tau faib kom tau txais calcium acetate lossis sucroferric oxyhydroxide rau 5 lub hlis. Cov ntshav kuaj (rau kev tshuaj xyuas biochemical) thiab cov quav hauv plab (rau kev tshuaj xyuas microbiome) tau muab khaws cia ntawm lub hauv paus, 4, 12, thiab 20 lub lis piam tom qab pib kho. Fecal DNA tau muab rho tawm thiab lub tsev qiv ntawv 16S rRNA sequencing tau tsim lub hom phiaj rau thaj tsam V3 thiab V4 hypervariable.

Cov txiaj ntsig ntsig txog kev hloov pauv hauv chaw kho mob thiab cov ntsuas ntsuas, tsis muaj qhov sib txawv tseem ceeb ntawm cov calcium acetate lossis sucroferric oxyhydroxide pawg. Thaum soj ntsuam cov quav, peb pom tias txhua tus neeg mob muaj qhov sib txawv (p=0.001) ntawm lawv tus kheej thiab qhov sib txawv no tau khaws cia nyob rau 20 lub lis piam ntawm kev kho mob. Kev txheeb xyuas pawg hauv cov kab mob microbial tau muab faib ua cov qauv ntawm tib tus neeg mob ntawm nws tus kheej ntawm kev kho mob ua raws thiab theem ntawm kev kho mob.

kev kho mob.

Xaus Cov txiaj ntsig no qhia tau tias kev kho mob ib hlis 5- nrog calcium acetate lossis sucroferric oxyhydroxide tsis hloov pauv qhov sib txawv ntawm cov kab mob hauv cov neeg mob hemodialysis, kuj tseem hais txog qhov sib txawv ntawm cov plab hnyuv microbiome pom ntawm cov neeg mob no.

Cov ntsiab lus ntawm plab microbiome · Mob raum mob · Hemodialysis · Phosphate binders · Sucroferric oxyhydroxide ·

Calcium acetate

Taw qhia

NtevraumKab mob (CKD) yog ib qho teeb meem kev noj qab haus huv thoob ntiaj teb, nrog kev nce zuj zus, kev lag luam hnyav, thiab kev mob hnyav thiab kev tuag [1].

Hauv cov neeg mob CKD, cov hlab plawv pathology ua lub luag haujlwm tseem ceeb. Cov neeg mob no muaj kev pheej hmoo ntawm kev tsim kab mob plawv (CVD) thiab kev tuag ntawm cov hlab plawv 30 npaug ntau dua li cov pej xeem [2]. Dhau li ntawm cov kev pheej hmoo ntawm cov hlab plawv uas feem ntau tshwm sim hauv cov neeg mob cuam tshuam los ntawm CKD ntau dua li cov pej xeem, kev sib cuam tshuam ntawm CKD thiab CVD tuaj yeem piav qhia los ntawm qhov muaj cov pob txha thiab pob zeb tsis zoo, dej dej, thiab kev ua tsis zoo. uas peb cov neeg mob txhim kho.

Nyob rau hauv ib txwm muaj mob, infammation yog ib qho kev tiv thaiv thiab physiological teb rau ntau yam inimical stimuli. Txawm li cas los xij, nyob rau hauv ntau yam kev puas siab puas ntsws, xws li CKD, kev ua tsis zoo yuav ua rau muaj teeb meem thiab tsis tu ncua [3]. Nws yog qhov paub zoo tias CKD yog nrog los ntawm cov xwm txheej tsis txaus ntseeg tsis tu ncua [4, 5]. Infammation yuav yog qhov tshwm sim ntawm ntau yam etiology thiab cuam tshuam nrog ntau yam uas tshwm sim thaum uremic toxins sib sau ua ke thiab tau piav qhia raws li kev kwv yees ntawm cov hlab plawv thiab tag nrho cov neeg tuag [6]. Tsis tas li ntawd, muaj cov pov thawj ruaj khov uas txhawb nqa lub plab zom mov tsis ua haujlwm thiab kev hloov pauv hauv plab microbiota muaj pes tsawg leeg hauv CKD, feem ntau hu ua plab dysbiosis [7-9]. Lub xeev dysbiotic concomitantly tsim cov tshuaj lom los ntawm cov khoom lag luam thiab ua rau cov xwm txheej ntev ntawm oxidative kev nyuaj siab thiab infammation hauv cov neeg mob no [10-12].

Ntau yam ua rau lub plab microbial dysbiosis hauv cov neeg mob uas muaj CKD siab heev. Kev sib sau ntawm urea nyob rau hauv lub cev fuids thiab nws difusion mus rau txoj hnyuv ua rau lub expansion ntawm urease-muaj cov kab mob. Tsis tas li ntawd, hydrolysis ntawm urea tsim cov khoom uas degrade lub epithelial nruj hlws ris, yog li yooj yim translocation ntawm endotoxin thiab microbial fragments mus rau hauv lub systemic ncig [7, 8, 10, 13–15]. Cov lus pom zoo ntawm kev noj zaub mov hauv CKD suav nrog txwv tsis pub noj cov poov tshuaj, phosphate, sodium, thiab cov proteins ua rau cov khoom noj tsis txaus ntawm fermentable carbohydrate thiab qhov no yuav ua rau muaj kev nthuav dav ntawm cov kab mob proteolytic thiab tsim cov kab mob ntau ntxiv [12, 13, 16]. Tsis tas li ntawd, cov neeg mob CKD feem ntau cuam tshuam nrog lwm yam mob, xws li ntshav qab zib, kab mob autoimmune, thiab kub siab. Tag nrho cov comorbidities no tshwm sim hauv plab microbiota hloov pauv [17, 18].

Ib qho tseem ceeb heev uas nyiam dysbiosis yog tshuaj. Nws paub zoo tias cov neeg mob uas muaj CKD siab heev feem ntau yog siv tshuaj kho mob. Iron supplementation los yog tshuaj tua kab mob, feem ntau siv rau hauv peb cov neeg mob, tau raug pom los hloov lub plab microbiome [19–21]. Txawm li cas los xij, qhov cuam tshuam ntawm lub plab microbiome ntawm lwm cov tshuaj siv dav hauv cov neeg mob CKD tseem tsis paub.

Feem ntau cov neeg mob hemodialysis zoo li muaj hyperphosphatemia thiab lawv xav tau ntau hom phosphate binders los kho tus mob no. Phosphate binders tuaj yeem muab faib ua calcium thiab non-calcium-based phosphate binders. Nws tau raug piav qhia tias ob pawg ntawm phosphate-binding cov neeg ua haujlwm tuaj yeem tsim cov kev hloov pauv ntawm cov microbiome [22-25].

Tsis ntev los no, cov tshuaj tshiab uas tsis yog-calcium-based phosphate-binding agents tau pom zoo rau kev kho mob hyperphosphatemia hauv cov ntsiab lus hemodialysis. Qee tus neeg ua haujlwm tshiab no, xws li sucroferric oxyhydroxide (SFO) thiab ferric citrate, tuav hlau hauv lawv cov khoom xyaw. Nws ntseeg tau hais tias, muab lub luag haujlwm tseem ceeb ntawm cov hlau hauv kev loj hlob ntawm cov kab mob microbial thiab kab mob, cov hlau loj loj tau tswj hwm nrog cov tshuaj no, tuaj yeem hloov cov plab hnyuv microbiome [26, 27]. Txawm li cas los xij, tseem muaj pov thawj me me txog qhov tshwm sim ntawm cov phosphate tshiab khi rau ntawm lub plab microbiome [25].

Muab qhov tseem ceeb ntawm kev hloov plab hnyuv microbiome nyob rau hauv cov neeg mob CKD thiab nws txoj kev koom tes rau lawv lub xeev infammatory, thiab tsis muaj cov ntaub ntawv hais txog kev cuam tshuam ntawm plab microbiome ntawm cov tshuaj niaj hnub no, peb tau txiav txim siab los saib xyuas thiab sib piv cov kev hloov hauv plab microbiome. ntawm cov neeg mob uas tau txais hemodialysis noj SFO lossis calcium-based phosphate binder calcium acetate (CA).

Cov ntaub ntawv thiab cov txheej txheem

Kev nrhiav neeg ua haujlwm

Kaum ob tus neeg mob ntawm hemodialysis hauv Tsev Kho Mob Univer- sitari Germans Trias i Pujol tau raug caw tuaj koom nrog peb txoj kev tshawb fawb nrog 5-hloov tshuaj xyuas. Txhua yam kev kawm tau raug xaiv los ntawm Hemodialysis Department ntawm Tsev Kho Mob Universitari Germans Trias i Pujol, hauv Badalona, ​​Spain. Txhua tus neeg mob muaj hnub nyoog qis dua 18 xyoo thiab tau ua hemodialysis tsawg kawg yog 1 xyoo (4 h zaug, 3 zaug hauv ib lub lis piam). Txoj kev tshawb no tau pom zoo los ntawm Pawg Neeg Saib Xyuas Kev Tshawb Fawb Kev Ncaj Ncees ntawm Tsev Kho Mob Universi-tari Germans Trias i Pujol (PI-16-169, NCT5551048) thiab ua raws li cov hauv paus ntsiab lus tau teev tseg hauv Kev Tshaj Tawm ntawm Helsinki. Txhua tus neeg tuaj koom tau raug xaiv los ntawm kev yeem tom qab tau txais cov ntaub ntawv ntxaws ntxaws ntawm txoj kev kawm. Sau ntawv tso cai tau txais los ntawm txhua tus neeg mob.

Cov txheej txheem tsis suav nrog suav nrog kev tsis muaj peev xwm muab kev pom zoo, keeb kwm ntawm kab mob plab hnyuv, mus pw hauv tsev kho mob, thiab noj tshuaj tua kab mob hauv 3 lub hlis dhau los.

Cov ntaub ntawv kho mob ntsig txog thiab pej xeem raug sau tseg rau txhua tus neeg ntawm qhov pib. Cov kws kho mob tau sau tseg: poj niam txiv neej, hnub nyoog, CKD etiology, keeb kwm ntawm ntshav siab, ntshav qab zib mellitus, dyslipi-demia, kab mob plawv ( kab mob peripheral vascular, ischemic cardiomyopathy lossis stroke), thiab mob qog noj ntshav.

Peb kuj tau sau cov ntaub ntawv hais txog lawv cov hlab ntsha, thiab lawv cov kev kho mob phosphate-binder yav dhau los thaum pib ntawm txoj kev tshawb no (cuaj tau txais calcium acetate, ib qho tau txais calcium carbonate, thiab ob tug tsis tau kho rau hyperphosphatemia yav dhau los).

Peb faib cov neeg mob ua ob pawg, thiab peb tau hloov kho lawv cov kev kho mob hyperphosphatemia: 5 tus neeg mob tau muab tso rau hauv CA pawg (4 txuas ntxiv CA kho thiab 1 tus neeg mob hloov los ntawm kev kho calcium carbonate) thiab 7 tau hloov mus rau SFO (5 hloov los ntawm CA therapy thiab 2. pib kho phosphate-binding).

Qauv sau

Cov qauv Fecal tau sau los ntawm 12 tus neeg mob hemodialysis tau txais phosphate binders, 5 hauv pawg CA thiab 7 hauv pawg SFO. Peb kuj sau cov qauv ntshav los ntawm cov kev kuaj xyuas niaj hnub pom hauv peb chav hemodialysis. Cov qauv kuaj ntshav (cov ntshav thiab cov quav hauv plab) tau sau rau hauv 5- lub hlis tom qab: ntawm qhov pib, 4, 12, thiab 20 lub lis piam tom qab pib kho.

Hauv kev kuaj ntshav, peb tau txheeb xyuas cov kev ntsuas hauv qab no: hemoglobin, ferritin, transferrin saturation Performance index, calcium, phosphate, parathyroid hormone, C-reactive protein, sedimentation tshaj tawm, thiab albumin.

Kev rho tawm DNA, kev tsim kho tsev qiv ntawv, thiab ua raws

Fecal DNA tau muab rho tawm los ntawm Powersoil DNA Isolation Kit MoBio, thiab 16S rRNA sequencing tsev qiv ntawv tau tsim lub hom phiaj rau thaj tsam V3 thiab V4 hypervariable.

Sequence tau ua tiav ntawm MiSeq platform (2 × 300). OTU lub rooj tsim, kev ua haujlwm taxonomic, thiab kev piav qhia thiab kev txheeb cais tau ua tiav siv R version 3.4.2. thiab cov pob khoom sib txawv (DADA 2, vega, ggplot, phyloseq) thiab Greengenes rRNA database.

Cov ntaub ntawv thiab kev txheeb xyuas

Primer v7 (PRIMER-e, Auckland, New Zealand) tau siv rau kev suav ntawm ntau hom indices, qhov feem pua ​​​​ntawm qhov zoo sib xws (SIMPER) tsom xam, thiab kev txheeb xyuas ntau yam, feem ntau yog kev tshuaj xyuas qhov sib xws (ANOSIM) ib txoj kev tsom xam thiab permutational multivariate tsom xam ntawm qhov sib txawv ( PER- MANOVA; siv cov ntaub ntawv squared hloov pauv, Bray-Curtis zoo sib xws thiab 4999 permutations ntawm residuals raws li tus qauv txo) siv los ntsuas qhov tseem ceeb ntawm Beta-diversity. Qhov feem pua ​​​​ntawm OTU cov ntaub ntawv ib qho piv txwv tau siv rau cov kev tshuaj ntsuam no, ua raws li cov ntaub ntawv hloov pauv hloov pauv, zoo ib yam li cov ntaub ntawv zoo sib xws, siv Bray-Curtis zoo sib xws, ntxiv tus nqi dummy, thiab kuaj 4999 permutations. STAMP tau siv los txheeb xyuas cov ntaub ntawv sau se ntawm pawg ntawm cov qauv thiab suav cov lej sib txawv [28].

Rau kev kho mob ntawm cov ntaub ntawv kho mob, cov ntaub ntawv txheeb xyuas software Statistical Package for Social Sciences (SPSS) 26.0 tau siv rau MAC OS. Cov kev sib txawv ntawm pawg tau piav qhia los ntawm cov txheeb ze frequencies (feem pua) thaum qhov sib txawv tsis tu ncua tau piav qhia siv qhov txhais tau tias ± tus qauv sib txawv (SD). Peb tau thov thaum tsim nyog Chi-square kev ywj pheej xeem los soj ntsuam cov kev xav hais txog qhov sib txawv ntawm cov categorical thiab Student's t-test txog qhov sib txawv tsis tu ncua. Ib qib ntawm 0.05 tau suav tias yog qhov tseem ceeb.

Cov txiaj ntsig

Cov kev kho mob tseem ceeb tsis txawv ntawm cov neeg mob uas tau muab rau CA lossis SFO pawg ntawm lub hauv paus (Table 1). Peb tau pom tias nyob rau hauv pab pawg CA, muaj kev nce ntxiv, tab sis tsis yog qhov tseem ceeb, hauv keeb kwm ntawm arterial hypertension, dyslipidemia, peripheral vascular disease, stroke, ischemic cardiomyopathy dua li hauv pawg SFO. Cov neeg mob raug xa mus rau pawg SFO tau nthuav tawm qhov tshwm sim ntau dua ntawm lub catheter li vascular nkag, tab sis kuj tsis yog qhov tseem ceeb.

Ntawm qhov pib, tsis muaj tus neeg mob tau kho nrog SFO, qee qhov tau kho nrog CA hauv ob pawg kev kho mob, thiab 2 cov neeg mob hauv pawg SFO tsis muaj phosphate-binding kho. Nyob rau lub sijhawm no, peb pom tsis muaj qhov sib txawv ntawm qhov ntsuas qhov ntsuas, xws li hemoglobin, ferritin, transferrin saturation index, calcium, phosphate, parathyroid hormone, C-reactive protein, sedimentation tshaj tawm, thiab albumin (Table 2). Ua ke, peb tau pom nyob rau hauv pawg SFO ntawm lub hauv paus siab dua transferrin saturation indexes, thiab qis dua cov txiaj ntsig ntawm C-reactive protein ntau dua li pawg CA, tab sis cov kev sib txawv no tsis yog qhov tseem ceeb. Peb kuj tau sau tseg hauv cov neeg mob uas tau muab rau pawg CA, ib qho kev nce ntxiv rau hyperphosphatemia ntawm lub hauv paus, tab sis qhov no kuj tsis yog qhov tseem ceeb.

Hauv Table 2, peb nthuav qhia cov kev hloov pauv ntawm cov ntsuas ntsuas ntawm lub sijhawm sib txawv. Peb pom tias nyob rau hauv pab pawg CA, 20-lub lim tiam calcium tau siab dua hauv pawg SFO nrog qhov tseem ceeb (p=0.02). Sedi-mentation tshaj tawm tau nce hauv pawg CA ntawm lub lim tiam 12 ntawm kev kho mob thaum piv nrog pab pawg SFO, nrog rau

Table 1 Clinical characterization ntawm cov neeg mob uas tau txais calcium acetate (CA) los yog sucroferric oxyhydroxide (SFO) ua phosphate-binding agent

Tus nqi yog txhais tau tias ± SD lossis txheeb ze zaus (feem pua). Tsis pom qhov sib txawv ntawm CA vs SFO

Table 2 Laboratory soj ntsuam cov ntaub ntawv ntawm cov neeg mob uas tau txais calcium ace-tate (CA) los yog sucroferric oxyhydroxide (SFO) ua phosphate-binding tus neeg sawv cev

Tus nqi yog txhais tau tias ± SD. * Cov txiaj ntsig hauv SFO yog qhov txawv ntawm CA

statistical signifcance (p {{0}}.04). Tsis tas li ntawd, qhov tseem ceeb ntawm cov albumin qis dua tau pom nyob rau hauv pawg SFO ntawm 20-kev kho mob lub lis piam thaum peb piv nrog CA pawg (p <0.01). cov="" qib="" ferritin="" nyob="" rau="" hauv="" ob="" pawg="" ntawm="" lub="" hauv="" paus="" thiab="" tom="" qab="" 20="" lub="" lis="" piam="" ntawm="" kev="" kho="" mob="" yog="" siab="" nyob="" rau="" hauv="" ob="" pawg,="" thiab="" ob="" pab="" pawg="" tau="" txais="" ib="" txwm="" theem="" ntawm="" phosphate="" nyob="" rau="" hauv="" 20="" lub="" lis="" piam="" ntawm="" kev="" kho="" mob,="" tsis="" muaj="" statistical="" sib="" txawv.="" cov="" theem="" ntawm="" kev="" hloov="" pauv="" saturation="" indexes,="" parathormone,="" c-reactive="" protein,="" sedimentation="" tshaj="" tawm,="" thiab="" albumin,="" ntawm="" 20="" lub="" lis="" piam="" ntawm="" kev="" kho="" mob="" zoo="" sib="" xws="" hauv="" ob="">

Cov qauv ntawm txhua lub sijhawm cov ntsiab lus (lub hauv paus, lub lim tiam 4, lub lim tiam 12, thiab lub lim tiam 20) tau sau hauv yim ntawm kaum ob tus neeg, hauv tag nrho ntawm 38 cov quav thiab ntshav. Los ntawm cov txheej txheem pib ntawm 12 tus neeg mob, tus neeg mob 7 (SFO pawg) tau tawm mus vim nws tau mus rau lwm lub tsev kho mob vim yog qhov chaw kho mob thiab peb tsis tuaj yeem soj ntsuam tag nrho cov kev hloov pauv uas cuam tshuam rau txoj kev tshawb no, tus neeg mob 3 (SFO pawg) tau txais daim ntawv pov thawj.raumHloov pauv ua ntej sau cov qauv ntawm 20-lub lim tiam, tus neeg mob 9 (SFO pab pawg) tuag ua ntej sau cov qauv ntawm 12- lub lim tiam, thiab peb tsuas tuaj yeem tau txais cov qauv zoo rau lub plab microbiome los ntawm lub lim tiam 12 thiab lub lim tiam 20 ntawm tus neeg mob 8 (SFO pawg).

Cov txheej txheem ntawm 38 fecal kuaj tau pom ntau dua 2 lab nyeem, tom qab ntawd cais siv Greengenes database. Ib tus lej siab ntawm ASVs (33,734) tau pom nyob rau hauv cov qauv kuaj thiab cais raws li cov kab mob hauv lub nceeg vaj. Shannon-tsis muaj ntau haiv neeg tau ntsuas nyob rau hauv txhua tus qauv thiab pab pawg ntawm 38 cov qauv qhia qhov muaj nuj nqis rau Shannon ntau haiv neeg xws li 6.2 txog 7.7.

Qhov zoo siab, peb pom tias txhua tus neeg mob sib txawv heev ntawm lawv tus kheej (p=0.001) thaum muab piv rau ib tus neeg mob nrog lwm tus neeg mob ntawm qhov pib (Fig. 1A). Cov kev sib txawv ntawm cov neeg mob tau khaws cia raws li 20 lub lis piam ntawm kev kho mob; tsis muaj qhov sib txawv tseem ceeb (p> 0.05) thaum cov qauv tau muab faib ua pawg raws li lub lim tiam ntawm kev kho mob (piv txwv li, 4, 12, lossis 20 lub lis piam). Nws yog ib qho tseem ceeb uas yuav tsum nco ntsoov tias cov plab hnyuv microbiome tau pom muaj kev ruaj ntseg thoob plaws hauv 20 lub lis piam ntawm kev kawm hauv cov neeg mob uas nyob hauv CA ua ntej txoj kev tshawb fawb thiab tswj xyuas qhov kev kho mob hauv cov txheej txheem kev tshawb fawb, thiab tseem nyob rau hauv cov neeg mob uas hloov kho phosphate-binding therapeutics (los ntawm tsis muaj kev kho mob. , CA los yog calcium carbonate rau CA los yog SFO).

Thaum peb piv cov microbial profles ntawm cov neeg mob kho nrog CA piv rau SFO xav txog txhua lub sijhawm cov ntsiab lus, peb pom qhov sib txawv ntawm cov ntaub ntawv (Fig. 1B); thiab cov kev sib txawv no tau lees paub los ntawm ANOSIM (p=0.002) thiab PERMANOVA (p=0.001). Qhov kev txheeb xyuas txheeb cais no tau ua tiav ntawm nws tus kheej ntawm qhov sib txawv uas tau pom hauv lub hauv paus.

Cov kab mob hauv zej zog tau kawm thiab Bacteroi-detes thiab Firmicutes yog cov phyla feem ntau pom hauv cov qauv fecal, tom qab ntawd Proteobacteria, Actinobacte-ria, thiab Verrucomicrobia. Nrhiav kom paub ntau qhov sib txawv ntawm qhov sib txawv, peb piv ntau theem taxonomical ntawm cov qauv no. Thaum soj ntsuam cov kab mob

Fig. 1 Tus Thawj Saib Xyuas Kev Sib Koom Tes (PCO) ntawm microbiome profles rau ntau tus neeg mob. B Principal Co-ordinate Analysis (PCO) ntawm microbiome profles rau kev kho tshuaj (calcium acetate ver-sus sucroferric oxyhydroxide)

muaj pes tsawg leeg nyob rau theem genus, Bacteroides feem ntau tshwm sim hauv ob pawg neeg mob, ntawm nws tus kheej yog tias lawv tau kho nrog CA lossis SFO (Fig. 2). Cov kab mob microbial tau txawv heev ntawm cov neeg mob thiab, ib zaug ntxiv, kev txheeb xyuas pawg tau muab cov qauv ntawm tib tus neeg mob ntawm nws tus kheej ntawm kev kho mob raws li thiab theem ntawm kev kho mob (piv txwv li, 4, 12, lossis 20 lub lis piam).

Thaum peb xav txog txhua lub sijhawm cov ntsiab lus (txhua tus neeg mob thiab txhua lub lis piam), nws muaj peev xwm fnd qhov sib txawv ntawm cov ntaub ntawv (p < 0.05)="" rau="" cov="" zej="" zog="" microbial="" thaum="" piv="" cov="" qauv="" rau="" ntau="" qhov="" sib="" txawv,="" suav="" nrog="" poj="" niam="" txiv="" neej,="" ischemic="" cardiomyopathy,="" siv="" lub="" catheter="" li="" vascular="" nkag,="" lossis="" hnub="" nyoog="" (cov="" neeg="" mob="" tau="" teeb="" tsa="" hauv="" peb="" pawg:="" qis="" dua="" 45,="" thaj="" tsam="" 61-69,="" saum="" toj="" 71).="" cov="" kev="" sib="" txawv="" li="" no="" tsis="" tuaj="" yeem="" pom="" thaum="" txhua="" theem="" kev="" kho="" mob="" (lub="" hauv="" paus,="" 4,="" 12,="" lossis="" 20="" lub="" lis="" piam)="" raug="" txiav="" txim="" siab="" cais;="" yog="" li="" ntawd,="" tsis="" muaj="" qhov="" sib="" txawv="" ntawm="" qhov="" sib="" txawv="" ntawm="" poj="" niam="" txiv="" neej,="" hnub="" nyoog,="" ischemic="" cardiomyopathy,="" kev="" siv="" catheter,="" thiab="" kev="" kho="" tshuaj="" (ca="" piv="" rau="">

Kev sib tham

Qhov no yog qhov kev tshawb fawb frst piv cov kev hloov pauv hauv plab microbiome ntawm cov neeg mob hemodialysis noj CA piv rau SFO. Hauv peb txoj kev tshawb fawb, tsis muaj qhov sib txawv ntawm cov kab mob hauv plab microbiome ntawm cov phosphate-binding agents sib txawv. Txawm hais tias peb pom qhov sib txawv microbiome profles thaum ob pawg kev kho mob tau muab piv, qhov sib txawv no tau tshwm sim nyob rau hauv lub hauv paus, thiab kev kho mob mus sij hawm ntev tsis tau hloov qhov ntau haiv neeg ntawm ob pawg. Yog li, tsis muaj qhov hloov pauv tseem ceeb

Fig. 2 Clustering tsom xam thiab microbiome profles (ntawm genus theem) rau cov qauv txiav txim siab hauv txoj kev tshawb no

tau pom ntau lub sijhawm sib txawv (piv txwv li, lub lim tiam 4, lub lim tiam 12, lub lim tiam 20) hauv cov neeg mob hemodialysis plab hnyuv microbiome kho nrog CA piv rau cov kho nrog SFO.

Lub plab microbiome ntawm peb cov neeg mob yog raws li cov ntaub ntawv yav dhau los, dominated los ntawm Bacteroidetes thiab Firmicutes phyla, ua Actinobacteria, Proteobacteria, thiab Verrucomi-crobia nyob rau hauv kab thib ob ntawm colonization [29]. Raws li yav dhau los tau tham txog, CKD cov neeg mob muaj ntau yam hauv nruab nrog cev uas txhawb lub plab dysbiosis ntxiv rau cov kev kho mob tshuaj, xws li txo cov kab mob colonic, hloov lub plab zom mov, metabolic acidosis, plab hnyuv phab ntsa edema, thiab ib qho tseem ceeb tshaj plaws, txoj hnyuv siab. muaj uremic toxins. Hauv kev sib piv rau kev tswj hwm kev noj qab haus huv, cov neeg mob uas tau txais hemodialysis nthuav tawm qhov nce Bacteroidetes ntau ntxiv [30], kuj tseem cuam tshuam nrog cov txiaj ntsig ntawm peb txoj kev tshawb fawb.

Tsis muaj pov thawj me ntsis txog qhov tshwm sim ntawm phosphate binders ntawm lub plab microbiome [25]. Cov kev tshawb fawb soj ntsuam cov txiaj ntsig ntawm calcium-based phosphate binders, suav nrog CA, ntawm CKD cov neeg mob plab microbiome, tshuaj xyuas cov qauv fecal, tsis muaj [31]. Trautvetter et al. [32], pom qhov nce ntawm fecal tag nrho luv-chain fatty acids thiab ntau dua cov txheeb ze ntawm genus Clostridium XVIII hauv cov neeg noj qab haus huv noj calcium carbonate. Navarro-Gonzalez et al. [22], soj ntsuam hemodialysis cov neeg mob ntshav cov qauv coj los ntawm cov uas tsis yog-calcium-based phosphate binder sevelamer los yog calcium-based phosphate binder CA thiab xaus lus tias kev kho mob nrog sevelamer cuam tshuam nrog qhov txo qis hauv cov protein ntau C-reactive, IL. -6, serum endotoxin, thiab soluble CD14 concentrations ywj siab kwv yees ntawm kev tuag hauv cov neeg mob hemodialysis.

SFO yog ib qho hlau-phosphate binder, thiab cov ntaub ntawv qhia tias cov hlau uas muaj nyob rau hauv cov compound yuav hloov plab microbiota vim qee cov kab mob plab siv hlau los ua kom cov txheeb ze ntau ntxiv [26, 33, 34]. Tsis tas li ntawd, nws tau pom tias qhov nce ntawm cov hlau ncav cuag cov nyuv tuaj yeem txhawb nqa kev ua phem ntawm qee cov kab mob pathogenic thiab ib puag ncig tsis zoo [20, 35]. Tab sis txawm hais tias cov pov thawj no, peb txoj kev tshawb fawb qhia tau hais tias kev kho SFO hauv cov neeg mob hemodialysis tsis zoo li hloov lub plab microbiome, lossis kev kho CA.

Ling Lau et al. [27], piv rau fecal microbiome thiab uremic co toxins hauv cov qauv kuaj ntshav ntawm CKD nas (uas tau txais 5/6 nephrectomy) thiab cov nas ib txwm, random muab rau kev noj zaub mov tsis tu ncua lossis cov khoom noj uas muaj 4 feem pua ​​​​ferric cit-rate rau 6 lub lis piam. Lawv tau pom tias CKD nas muaj qis dua cov txheeb ze ntawm qee qhov Firmicutes thiab Lactobacillus thiab qis dua plab microbial ntau haiv neeg piv rau cov nas ib txwm, tab sis lawv kuj tau piav qhia tias kev kho ferric citrate hauv CKD nas nce cov kab mob sib txawv yuav luag mus rau theem pom hauv kev tswj nas thiab qhov kev kho mob no. tsis nce uremic toxins. Hauv kev tshawb fawb tsis ntev los no, Wu et al. [36], piv rau cov neeg mob hemodialysis plab microbiome kho nrog calcium carbonate lossis ferric citrate. Lawv tau pom qhov muaj txiaj ntsig zoo ntawm microbial ntau haiv neeg hauv cov pab pawg kho nrog ferric citrate, nrog kev nce ntxiv ntawm Bacteroidetes thiab txo qis ntawm Firmicutes.

Rau peb txoj kev paub, tsuas yog ib qho kev tshawb fawb ua rau tib neeg txog SFO cuam tshuam rau lub plab microbiome. Iguchi et al. [37], piv rau 3 lub hlis hloov pauv hauv plab microbiome thiab uremic co toxins ntawm hemodialysis cov neeg mob kho nrog SFO piv rau tsis muaj kev kho mob rau hyperphosphatemia. Lawv kuj pom tsis muaj kev hloov pauv hauv plab microbiome hauv cov neeg mob kho nrog SFO txhua lub sijhawm. Yog li, peb txoj kev tshawb fawb confrms qhov kev ruaj ntseg ntev ntawm lub plab microbiome hauv cov neeg mob hemodialysis kho nrog SFO rau 5 lub hlis.

Lwm lub ntsiab lus tseem ceeb los tham txog yog tias hauv peb txoj kev tshawb fawb, peb tau pom qhov sib txawv ntawm cov neeg mob hemodialysis plab hnyuv micro- biome piv los ntawm hnub nyoog lossis poj niam txiv neej, tab sis peb tsis pom qhov sib txawv thaum peb sib piv los ntawm pab pawg kho mob (CA piv rau SFO). Raws li txoj cai, qee qhov kev hloov pauv tau pom hauv lub plab microbiome los ntawm kev laus [38]. Cov neeg laus, tshwj xeeb tshaj yog cov neeg uas muaj cov qhab nias siab, tam sim no cov txheeb ze ntawm Bacteroidetes predominating, tsawg dua microbial ntau haiv neeg, thiab txo qis hauv Bifdobacteria, Bacteroides / Prevotella, Lactobacillus, thiab Clostridium pawg IV, thaum piv nrog cov tub ntxhais hluas, uas muaj ntau hom kab mob microbial. thiab ntau dua ntawm Firmicutes, ntawm lwm tus [39, 40]. Kuj tseem muaj cov ntaub ntawv pov thawj txhawb nqa tias muaj kev hloov pauv hauv plab microbiome yog tias muab piv rau poj niam thiab txiv neej [41, 42]. Hauv peb txoj kev tshawb fawb, qee qhov sib txawv tau pom hauv lub plab microbiome raws li poj niam txiv neej thiab hnub nyoog, tab sis qhov sib txawv ntawm txhua tus neeg mob tau hais ntau dua.

Hais txog kev kuaj pom, raws li qhov xav tau, cov neeg mob kho nrog calcium-based phosphate binder CA qhia cov calcium ntau dua li cov neeg kho nrog SFO. Peb tau pom, txawm hais tias tsis yog qhov tseem ceeb, nce qib ntawm cov kab mob inflammatory, xws li sedimentation tshaj tawm, C-reactive protein, thiab ferritin hauv CA pab pawg thaum piv nrog SFO pawg; xws li cov nyhuv pleiotropic ntawm qhov txo qis qhov mob tau piav qhia rau qee qhov phosphate binders uas tsis yog calcium-based binders [43].

Nws yog ib qho tseem ceeb kom xav txog tias peb txoj kev tshawb fawb nthuav tawm qee qhov kev txwv. Ntawm qhov tod tes, qhov loj ntawm tus neeg mob tus qauv yog me me, yog li nws yog ib qho nyuaj rau kos cov lus xaus, tshwj xeeb tshaj yog rau cov teebmeem ntawm kev soj ntsuam thiab biochemical variables soj ntsuam. Txhawm rau txheeb xyuas peb cov txiaj ntsig, kev tshawb fawb loj dua, nrog rau cov neeg mob ntau ntxiv yog xav tau. Ntawm qhov tod tes, peb cov neeg mob pom cov keeb kwm sib txawv, nrog cov kab mob sib txawv uas tuaj yeem cuam tshuam rau lub plab microbiome. Yog li, peb txoj kev tshawb fawb ceeb toom txog qhov hloov pauv siab ntawm cov ntaub ntawv pom ntawm lub plab microbiome ntawm cov neeg mob tau txais phosphate binders. Cov kev sib txawv no txwv ib qho kev txiav txim siab ntxiv thiab qhov sib txawv ntawm cov neeg mob tau txais cov phosphate binders sib txawv.

Raws li peb tau tshaj tawm, txhawm rau tshawb nrhiav seb qhov chaw kho mob tshwj xeeb tuaj yeem cuam tshuam qhov sib txawv ntawm microbiome profile, peb tau txheeb xyuas cov kev kho mob tseem ceeb ntawm peb cov neeg mob thiab peb pom tsis muaj qhov sib txawv tseem ceeb ntawm ob pawg kev kho mob. Cov neeg mob 5 thiab 6 tau raug txiav tawm me ntsis thiab nws tuaj yeem hais tau tias tus neeg mob 5 tau txais vancomycin thiab tobramycin rau 3 lub lis piam, thaum tus neeg mob 6 tau hais tias mob raws plab nrog ntau zaus tsis zoo kab lis kev cai thiab muaj feem cuam tshuam nrog kev mob plab.

Hauv peb txoj kev tshawb fawb, peb pom tsis muaj kev hloov pauv hauv plab micro-biome ntawm peb cov neeg mob hemodialysis tom qab 20 lub lis piam ntawm kev kho mob, ntawm nws tus kheej ntawm phosphate binder. Rau lub sijhawm no, thaum xaiv cov phosphate binder, peb yuav tsum tso siab rau lawv lub zog ntawm kev txo cov ntshav phosphate, lub nra hnyav, kev koom tes rau kev ua haujlwm ntawm vascular calcification, cov xwm txheej tsis zoo, lossis kev mob plab [44–47]; Txawm hais tias qhov kev cuam tshuam ntawm cov phosphate binders ntawm lub plab microbiome tau xav tau, thiab tseem tseem ua tau, rau tam sim no, tsis muaj pov thawj tias qhov no yuav cuam tshuam rau peb txoj hauv kev thaum kho hyperphosphatemia.

Hauv kev xaus, peb txoj kev tshawb fawb tau pom tias 5-kev kho mob ib hlis nrog CA lossis SFO tsis tau hloov pauv qhov sib txawv ntawm cov kab mob hauv cov neeg mob hemodialysis, tab sis ceeb toom txog qhov hloov pauv siab ntawm cov ntaub ntawv pom ntawm lub plab microbiome ntawm CKD cov neeg mob.

Kev lees paub Tsis siv tau.

Tus sau kev koom tes IB, FG, thiab JB tau xeeb thiab pab txhawb rau kev tsim qauv; AMR, IB, thiab FG pab txhawb rau cov neeg mob suav nrog thiab kev tswj xyuas kev kho mob; AMR, IB, FG. pab txhawb rau sampling thiab cov ntaub ntawv sau, AV, MNJ., RP pab txhawb rau cov extraction ntawm fecal DNA thiab sequencing ntawm 16S rRNA; RA, AV, MNJ, RP, thiab BSM tau pab txhawb rau kev tsim kho ntawm OTU lub rooj, kev ua haujlwm taxonomic thiab cov ntaub ntawv thiab kev txheeb xyuas kev txheeb xyuas; AMR, RA, IB, FG, BSM tau pab tsim cov ntawv sau thiab muab cov kev hloov kho tseem ceeb ntawm cov ntawv sau. Cov kws sau ntawv tau nkag mus rau tag nrho cov ntaub ntawv, thiab tus neeg sau ntawv muaj lub luag haujlwm fnal rau xa cov ntawv sau rau kev tshaj tawm.

Kev Tshawb Fawb Kev Tshawb Fawb no tau txais nyiaj los ntawm FEDER-Fundo Europeu de Desenvolvimento Cov nyiaj hauv cheeb tsam los ntawm COMPETE 2020- Kev Ua Haujlwm rau Kev Sib Tw thiab Kev Sib Tw Thoob Ntiaj Teb (POCI), Portugal 2020, thiab los ntawm Portuguese cov nyiaj los ntawm FCT / MCTES hauv lub moj khaum ntawm txoj haujlwm MicroMOB "POCI{ {2}} FEDER-029777 / PTDC/MEC-MCI/29777/2017".

Cov ntaub ntawv muaj Cov ntaub ntawv siv thiab/lossis tshuaj xyuas thaum lub sijhawm kawm tam sim no muaj los ntawm tus kws sau ntawv raws li kev thov tsim nyog.

Code muaj Tsis siv tau.

Cov lus tshaj tawm

Kev tsis sib haum xeeb ntawm kev txaus siab AMR, RA, IB, FG, AV, MNJ, RP, JB, BSM tsis muaj qhov tsis sib haum xeeb los tshaj tawm.

Kev pom zoo Ethics Txoj kev tshawb no tau pom zoo los ntawm Pawg Saib Xyuas Kev Tshawb Fawb Kev Ncaj Ncees ntawm Tsev Kho Mob Universitari Germans Trias i Pujol (PI-16–169, NCT5551048) thiab ua raws li cov hauv paus ntsiab lus tau teev tseg hauv Kev Tshaj Tawm ntawm Helsinki.

Kev tso cai los koom Txhua tus neeg tuaj koom tau raug xaiv los ntawm kev yeem tom qab tau txais cov ntaub ntawv ntxaws ntxaws ntawm txoj kev kawm. Sau ntawv tso cai tau txais los ntawm txhua tus neeg mob.

Kev tso cai rau kev tshaj tawm Tsis siv tau.

Qhib Kev Nkag Mus Kab lus no tau tso cai raws li Creative Commons Attribution 4.0 Daim ntawv tso cai thoob ntiaj teb, uas tso cai siv, sib koom, hloov kho, faib thiab luam tawm hauv ib qho nruab nrab lossis hom ntawv, tsuav yog koj muab credit tsim nyog rau tus sau thawj ( s) thiab qhov chaw, muab qhov txuas mus rau Creative Commons daim ntawv tso cai, thiab qhia seb puas tau hloov pauv. Cov duab lossis lwm yam khoom siv thib peb hauv tsab xov xwm no suav nrog hauv tsab xov xwm Creative Commons daim ntawv tso cai, tshwj tsis yog qhia lwm yam hauv kab qiv nyiaj rau cov khoom siv. Yog tias cov ntaub ntawv tsis suav nrog hauv tsab xov xwm Creative Commons daim ntawv tso cai thiab koj qhov kev npaj siv tsis raug tso cai los ntawm txoj cai lij choj lossis tshaj qhov kev tso cai siv, koj yuav tsum tau txais kev tso cai ncaj qha los ntawm tus tuav ntaub ntawv. Txhawm rau saib daim ntawv tso cai no, mus saib http://creativecommons.org/licenses/by/4.0/.