Gut Microbiome Thiab Organ Fibrosis
Jul 15, 2024
Abstract:Fibrosis yog cov txheej txheem pathological cuam tshuam nrog feem ntaumob inflammatory kab mob. Nws yog txhais raws li ib tug ntau deposition ntawmextracellular matrix proteinsthiab tuaj yeem cuam tshuam yuav luag txhua cov ntaub so ntswg thiab lub cev hauv lub cev. Fibroproliferative kab mob, xws liplab hnyuv fibrosis, daim siab cirrhosis, mob raum mob, thiabkab mob plawv, feem ntau ua rau lub cev puas tsuaj loj thiab yog qhov ua rau muaj mob thiab tuag thoob ntiaj teb, uas tam sim no tsis muaj kev kho mob zoo. Nyob rau hauv lub xyoo caum dhau los, lub cev loj hlob ntawm cov pov thawj tau hais txog lub plab microbiome ua ib qho tseem ceeb hauv kev tswj hwm ntawm lub cev thiab lub cev tiv thaiv kab mob, nrog rau kev cuam tshuam loj heev hauv cov kab mob ntawm ntau yam kev tiv thaiv kab mob. Lub plab microbiota dysbiosis tau cuam tshuam nrog kev loj hlob thiab kev loj hlob ntawm cov txheej txheem fibrotic nyob rau hauv ntau yam kabmob thiab tau kwv yees ua lub hom phiaj kho mob rau kev tswj fibrosis. Hauv qhov kev tshuaj xyuas no peb piav qhia txog lub xeev ntawm kev kos duab hais txog kev sib tham ntawm txoj hnyuv microbiota thiab lub cev fibrosis, hais txog qhov cuam tshuam ntawm kev noj zaub mov hauv cov kab mob sib txawv, thiab sib tham txog kev kho mob plab microbiome-tshuaj uas tam sim no tau tshawb nrhiav.
Ntsiab lus:plab microbiome; plab hnyuv fibrosis; daim siab fibrosis; raum fibrosis; mob ntsws fibrosis; plawv fibrosis; kev noj haus; cov tswv yim kho mob
NEW HERBAL FORMULATION RAUKIDNEY FIBROSIS
1. Taw qhia
Fibrosis yog ib qho txheej txheem pathological uas tshwm sim los ntawm kev tso tawm ntau dhau ntawm extracellular matrix (ECM) cov lus teb rau cov ntaub so ntswg raug mob [1]. Nws yog qhov kawg pathological tshwm sim ntawm feem ntau mob inflammatory kab mob thiab ib tug loj contributor rau lub cev malfunction thiab tsis ua hauj lwm [2]. Fibrotic cov ntaub so ntswg teb tuaj yeem cuam tshuam ze li txhua cov ntaub so ntswg thiab lub cev thiab lub luag haujlwm txog li 45% ntawm tag nrho cov neeg tuag hauv cov tebchaws tsim [3]. Txawm hais tias tau lees paub tias yog ib qho teeb meem kev noj qab haus huv thoob ntiaj teb, kev kho mob tsawg heev tam sim no muaj rau kev kho mob ntawm cov kab mob fibrotic thiab lawv muaj kev ua tau zoo [3]. Raws li cov ntaub so ntswg raug mob, ib qho nyuaj cascade ntawm cov xwm txheej aiming ntawm kev kho cov ntaub so ntswg architecture thiab kev ua haujlwm yuav tshwm sim. Kev puas tsuaj ntawm tes ua rau kev tso tawm tam sim ntawm ntau yam ntawm cov kab mob inflammatory xws li kev loj hlob, cytokines, thiab chemokines, uas txhawb cov leukocyte infiltration, ua kom cov fibroblasts rau hauv myofibroblasts (collagen secreting, -smooth leeg actin (SMA) - nthuav qhia fibroblasts) thiab synthesis ntawm ECM Cheebtsam. Hauv cov neeg mob me thiab tsis yog-tsis rov ua dua, qhov nce ntxiv ntawm ECM Cheebtsam yog ib ntus thiab thaum lub qhov txhab raug kho, myofibroblasts tau txais apoptosis thiab cov lus teb rov qab tso tseg. Thaum qhov kev raug mob hnyav los yog ua kom ntev, txawm li cas los xij, fibroblast activation txuas ntxiv mus ua haujlwm ntev, tsis muaj kev tswj hwm thiab ECM cov khoom yuav sib sau ua ntu zus, ua rau tsim cov caws pliav fibrotic, lub cev tsis ua haujlwm, thiab thaum kawg ntawm lub cev tsis ua haujlwm [1]. Myofibroblasts yog qhov tseem ceeb ntawm cov cellular mediators ntawm cov txheej txheem kho thiab lub luag haujlwm tseem ceeb rau kev tso tawm ntawm ECM cov protein ntau. Cov hlwb no tuaj yeem tshwm sim los ntawm kev ua kom cov neeg nyob hauv fibroblasts thiab mesenchymal hlwb tab sis kuj tuaj yeem tshwm sim los ntawm ntau hom cell sib txawv xws li cov hlwb ntawm cov phab ntsa vascular, endothelial hlwb, cov hlwb epithelial, fibrocytes (ntshav fibroblast zoo li cov hlwb tau los ntawm cov pob txha pob txha. stem cells) thiab cov pob txha-marrow-derived progenitors xws li adipogenic progenitors [4]. Myofibroblasts tuaj yeem qhib tau los ntawm ntau qhov sib txawv stimuli, xws li paracrine signals los ntawm lub cev tiv thaiv kab mob, autocrine yam secreted los ntawm myofibroblasts, thiab pathogen-associated molecular patterns (PAMPS) uas tsim los ntawm cov kab mob kab mob uas cuam tshuam nrog cov qauv lees paub receptors (PPRs, xws li tus xov tooj hu. receptors (TLRs)) ntawm fibroblasts [5].
Lub ntsiab lus tawg ntawm cov txheej txheem rov qab tsis tuaj yeem tiv thaiv kev thuam thiab ua rau tsis zoo, yog li nkag mus rau txoj hauv kev fibrotic, tsis paub. Txawm li cas los xij, nws tau lees paub tias ib zaug txoj hauv kev fibrinogenic tau qhib, cov txheej txheem nkag mus rau lub voj voog tsis zoo uas txawm tias cov txheej txheem hloov pauv ntawm cov ntaub so ntswg lawv tus kheej yog cov khoom noj ntawm cov lus teb fibrotic ntxiv los ntawm kev tswj hwm qhov sib txawv, kev nrhiav neeg ua haujlwm, kev loj hlob, thiab ua kom ECM-tsim. myofibroblasts [6].
Lub ntsiab lus tawg ntawm cov txheej txheem rov qab tsis tuaj yeem tiv thaiv kev thuam thiab ua rau tsis zoo, yog li nkag mus rau txoj hauv kev fibrotic, tsis paub. Txawm li cas los xij, nws tau lees paub tias ib zaug txoj hauv kev fibrinogenic tau qhib, cov txheej txheem nkag mus rau lub voj voog tsis zoo uas txawm tias cov txheej txheem hloov pauv ntawm cov ntaub so ntswg lawv tus kheej yog cov khoom noj ntawm cov lus teb fibrotic ntxiv los ntawm kev tswj hwm qhov sib txawv, kev nrhiav neeg ua haujlwm, kev loj hlob, thiab ua kom ECM-tsim. myofibroblasts [6].
Txawm hais tias qhov pib tshwm sim, lub hauv paus thiab hloov caj npab ntawm lub cev tiv thaiv kab mob muaj lub luag haujlwm tseem ceeb hauv qhov pib thiab kev loj hlob ntawm cov lus teb fibrotic thiab ntau txoj hauv kev tiv thaiv kab mob sib txawv tau raug pinpointed [7]. Txawm li cas los xij, ntau daim ntawv pov thawj taw qhia rau lwm yam kev tiv thaiv kab mob tsis muaj zog ua rau cov txheej txheem fibrotic thiab qhov o tuaj yeem tsim nyog rau kev thim rov qab ntawm kev mob fibrosis [8,9]. Cov pov thawj zoo li no ua rau qee qhov teeb meem ntawm qhov tsis muaj kev vam meej ntawm kev kho mob los tiv thaiv fibrotic tsom rau cov txheej txheem inflammatory thiab qhia tias txoj kev sib txawv yuav tsum tau tshawb xyuas.
Nyob rau hauv xyoo tas los no, lub luag haujlwm ntawm lub plab microbiota hauv cov txheej txheem fibrotic tau txais kev txaus siab ntxiv. Lub plab hnyuv microbiota yog tsim los ntawm ib ncig ntawm 100 trillion kab mob ntawm txog 1000 hom sib txawv uas, nyob rau hauv kev noj qab haus huv, muaj kev sib raug zoo nrog tus tswv tsev, ua haujlwm tseem ceeb thiab nyuaj hauv cov metabolism thiab kev tiv thaiv kab mob [10].
Kev hloov pauv ntawm cov kab mob hauv plab mus rau cov kab mob phenotype-dysbiosis- tuaj yeem ua rau muaj cov tshuaj lom ntau ntxiv, uas yog, uremic toxins, thiab cov khoom siv tsis txaus (xws li cov saw hlau luv fatty acids (SCFAs)) [11,12 ]. Lub xeev dysbiotic feem ntau cuam tshuam nrog kev cuam tshuam ntawm plab hnyuv teeb meem kev ncaj ncees, ua kom yooj yim rau kev hloov pauv ntawm cov kab mob thiab cov khoom siv kab mob mus rau hauv kev, thiab ua rau lub cev ua kom lub cev tiv thaiv kab mob thiab cov kab mob inflammatory uas tuaj yeem ncaj qha lossis tsis ncaj qha rau cov ntaub so ntswg puas tsuaj [13]. Hauv cov neeg muaj kab mob genetic susceptible hosts, ib qho dysregulation ntawm microbiota-kev tiv thaiv kev sib cuam tshuam yog ntseeg tau los pab rau qhov pib thiab kev loj hlob ntawm ntau yam kab mob tiv thaiv kab mob [13]. Ib qho kev nce ntxiv ntawm cov ntaub ntawv tau hais txog lub plab dysbiosis ua ib qho kev txhawb nqa loj ntawm cov kab mob pathogenesis, sawv cev rau qhov sib txuas nrog kev loj hlob ntawm fibrosis hauv ntau lub cev (Daim duab 1).
Qhov kev tshuaj xyuas no yog txhawm rau txheeb xyuas lub luag haujlwm ntawm plab hnyuv microbiota hauv kev txhim kho thiab kev loj hlob ntawm fibrosis hauv cov kabmob sib txawv, xws li cov hnyuv, lub siab, lub raum, lub ntsws, thiab lub plawv, thiab muab cov kev hloov tshiab ntawm cov tswv yim tam sim no tsom rau lub plab. microbiome hauv kev kho cov kab mob fibrotic.
Daim duab 1. Gut dysbiosis thiab organ fibrosis. TMAO, trimethylamine N-oxide; pCS, p-cresyl sulfate; IS, indoxyl sulfate; SCFAs, luv-chain fatty acids; KEGG, Kyoto Encyclopedia of Genes thiab Genomes. ↑ nce; ↓ txo;=hloov.
2. plab hnyuv Fibrosis
Mob mobzoo nkaus li yog qhov kev tshwm sim loj ua rau lub plab fibrogenesis, los ntawm mesenchymal cell recruitment thiab ua kom [14]. Cov kab mob hauv plab hnyuv uas cuam tshuam nrog kev mob tshwm sim tuaj yeem tshwm sim ntau dua hauv daim siab, lub raum, lossis lub ntsws fibrosis [15,16], xws li tshwm sim hauv kab mob plab hnyuv (IBD). Txawm hais tias txoj hnyuv qhia tau hais tias muaj peev xwm ua kom rov ua tau zoo dua tom qab kev thuam ntawm lub sijhawm luv luv (kab mob, mob plab ulcer, thiab lwm yam), nyob rau hauv lub xub ntiag ntawm qhov mob hnyav, cov hlwb mesenchymal (hauv daim ntawv ntawm fibroblasts, myofibroblasts, lossis cov leeg nqaij mos. ) ua haujlwm tsis tu ncua, ua rau ECM ntau dhau, thiab ua rau fistulae lossis nruj tsim nrog cov hnyuv txhaws [15]. Txog rau tam sim no, tsis muaj kev kho tshuaj pharmacological uas muaj txiaj ntsig zoo hauv kev rov qab plab hnyuv fibrosis; Yog li ntawd, kev nkag siab tob dua ntawm txoj hnyuv fibrosis mechanisms yog qhov ceev hauv kev tshawb nrhiav cov tswv yim tshiab.
Kev nkag siab ntawm lub luag haujlwm ntawm lub plab microbiome nyob rau hauv pathogenesis ntawm plab hnyuv fibrosis pib unraveled nyob rau hauv IBD, uas yog feem ntau kawm txog kab mob uas muaj feem xyuam rau txoj hnyuv fibrosis. IBD suav nrog ulcerative colitis thiab Crohn tus kab mob. Nyob rau hauv Crohn tus kab mob, plab hnyuv fibrosis yog ib qho teeb meem uas yuav ua rau lub plab phab ntsa thickening, strictures, thiab stenosis vim o, ua rau lub remodeling ntawm tag nrho cov hnyuv phab ntsa, txuam nrog txhim kho deposition ntawm ECM Cheebtsam [17,18]. Hauv cov kab mob ulcerative colitis, qhov tshwm sim ntawm fibrosis tsis ntev los no tau lees paub thiab cuam tshuam nrog txoj hnyuv loj thiab txhav vim qhov sib txuam ntawm ECM hauv cov mucosal thiab submucosal txheej, nrog rau kev mob thiab cuam tshuam ntawm cov txheej txheem epithelial vim yog kev sib tshuam ntawm cov kab mob sib kis. 19, 20] ib.
Qhov kev sib txuas ntawm lub plab microbiome thiab plab hnyuv fibrosis tau nthuav tawm hauv IBD, ntawm ib sab, vim tias cov neeg mob no tau pom muaj dysbiotic thiab pro-inflammatory plab microbiota [21] thiab, ntawm qhov tod tes, hauv cov tsiaj tsis muaj kab mob ntawm cov kab mob colitis lossis hauv Crohn tus kab mob cov neeg mob tau txais kev kho mob tshuaj tua kab mob, qhov uas lub plab o tau pom tias tsis tuaj lossis txhim kho [22]. Ntxiv mus, adherent-invasive Escherichia coli (AIEC), ib hom kab mob ntawm E. coli, thiab Salmonella enterica serovar Typhimurium (S. Typhimurium) tau pom tias yuav ua rau mob (los ntawm kev txhawb nqa T pab (TH) 1 thiab TH17 tiv thaiv kab mob) hauv IBD. tsiaj qauv, ua rau kev txhim kho fibrosis tom qab [23–26]. Tsis tas li ntawd, thiab zoo ib yam li qhov pom nyob rau hauv cov neeg mob Crohn tus kab mob, ntau ECM deposition tau pom nyob rau hauv AIEC-mob nas, nrog rau cov kev qhia ntau dua ntawm collagen hom I / III, thiab cov kev qhia ntawm profibrotic mediators xws li kev hloov pauv loj hlob. {10}} (TGF{11}}), connective-tissue growth factor, and insulin-like growth factor I (IGF-I) [26]. Raws li kev pom zoo nrog qhov no, hauv cov neeg mob Crohn tus kab mob, AIEC hom kab mob tau cuam tshuam tshwj xeeb nrog ileal mucosa thiab tau hais kom nyob hauv zos ua rau kev pib lossis txuas ntxiv ntawm cov kab mob inflammatory [27].
Tam sim no, qee cov txheej txheem thiab cov molecules cuam tshuam nrog lub plab microbiome twb tau lees paub tias muaj kev koom tes hauv cov kab mob hauv plab hnyuv fibrosis. Cov kab mob lipopolysaccharides (LPSs), tseem hu ua endotoxins, tam sim no nyob rau hauv cov qauv sab nraud ntawm cov kab mob gram-tsis zoo kab mob cell phab ntsa, paub los txhawb cov profibrotic activation ntawm plab hnyuv fibroblasts, nrog nce nuclear factor-κB (NF-κB)-lub teeb. -chain-enhancer ntawm activated B cell txhawb kev ua si thiab collagen contraction [28]. Flagellin, cov txheej txheem protein los ntawm cov kab mob flagellum, induced qhia ntawm interleukin (IL) -33 receptor ST2 nyob rau hauv plab hnyuv epithelium ntawm nas co-colonized nrog AIEC thiab ib tug attenuated hom ntawm S. Typhimurium, uas nyob rau hauv lem augmented IL-33 taw qhia thiab txhawb txoj kev loj hlob ntawm plab hnyuv fibrosis [24,29].
Tsis ntev los no, cov khoom siv hluav taws xob nuclear erythroid 2- cuam tshuam txog 2 (Nrf2) / Kelch-zoo li ECH cuam tshuam cov protein 1 (Keap1) axis tau pom zoo los ntawm Piotrowska thiab cov npoj yaig [19] ua tus neeg sib tw muaj txiaj ntsig rau kev tiv thaiv IBD thiab nws Cov teeb meem loj, xws li plab hnyuv fibrosis, muab qhov Nrf2/Keap1 axis tau pom tias cuam tshuam rau kev tsim ECM cov khoom xws li collagen thiab TGF- 1 hauv plab. Qhov tseem ceeb, cov kab mob hauv plab, lawv cov khoom (xws li LPS), lossis lawv cov metabolites (xws li urolithin A) tau pom los ua kom Nrf2 txoj hauv kev [19,30–33].
Lwm qhov kev nthuav dav uas cuam tshuam nrog plab hnyuv fibrosis thiab lub plab microbiome tau piav qhia los ntawm Jacob thiab cov npoj yaig [34], uas pom tias txoj hnyuv fibrosis thiab fibroblast ua kom sib haum xeeb los ntawm cov qog necrosis zoo li cytokine 1A (TNF-L1A) thiab cov qog necrosis factor ligand. Tus tswv cuab superfamily 15 (TNF-SF15) yog nyob ntawm cov kab mob tshwj xeeb thiab muaj kev ywj pheej ntawm kev mob. Ua ntej, lawv tau pom tias profibrotic thiab inflammatory phenotype tshwm sim los ntawm TNF-L1A-overexpression raug tshem tawm thaum tsis muaj cov neeg nyob hauv microbiota. Tom qab ntawd, hom kab mob tsis muaj kab mob thiab TNF L1A-transgenic nas fecal hloov pauv (los ntawm gavage) nrog cov quav los ntawm cov nas tsis muaj kab mob tshwj xeeb thiab cov neeg noj qab haus huv pub dawb tau pom tias rov kho dua nrog cov nas tsis muaj kab mob, tab sis tsis noj qab haus huv tib neeg pub microbiota, ua rau muaj zog plab hnyuv collagen deposition thiab fibroblast activation nyob rau hauv TNF-L1A-transgenic nas. Fibrosis-triggering microbial pejxeem tau txheeb xyuas nyob rau hauv cecum raws li cov kab mob mucolytic xws li hom Mucispirillum schaedleri, genus Ruminococcus, thiab genus Anaeroplasma, thiab hauv ileum, xws li genera Streptococcus thiab Lactobacillus. Nyob rau hauv sib piv, cov tswv cuab ntawm lub gen era Oscillospira thiab Coprococcus nyob rau hauv lub cecum, raws li zoo raws li Faecalibacterium prausnitzii thiab cov tswv cuab ntawm genus Bacteroides nyob rau hauv lub ileum, twb tsis zoo correlated nrog fibrosis. Ntxiv mus, nyob rau hauv vitro, qee cov kab mob uas muaj kev cuam tshuam zoo nrog rau qib ntawm fibrosis txhawb fibroblast migration thiab collagen qhia, hos lwm hom kab mob uas cuam tshuam tsis zoo nrog fibrosis pib tsis tau. Interestingly, tsis muaj histologically tseem ceeb cecal o nrog rau nce cecal collagen deposition nyob rau hauv tej yam pathogen-dawb microbial tej yam kev mob, qhia txog qhov tseem ceeb ntawm TNF-L1A raws li ib tug pro-fibrotic mediator uas yuav ua tau ntawm nws tus kheej ntawm nws pro-inflammatory teebmeem. Nyob rau hauv tas li ntawd, qhov kev tshawb fawb txog qhov no taw qhia rau lub hav zoov ntawm tshwj xeeb profibrotic mediators, uas yog cytokine- los yog microbiome-driven (los yog ob qho tib si).
Kev txheeb xyuas cov txiaj ntsig ntawm Yakhauj thiab cov npoj yaig [34], ib pawg ntawm cov menyuam yaus uas muaj tus kab mob Crohn los ntawm RISK pawg (Risk Stratification thiab Kev Qhia Txog Immunogenetic thiab Microbial Markers of Rapid Disease Progression in Children with Crohn's disease) qhia tias cov kab mob los ntawm cov genus Ruminococcus. muaj feem cuam tshuam rau kev teeb tsa. Tsis tas li ntawd, cov se uas muaj nyob rau hauv Veillonella genus kuj tau pom tias muaj kev nce ntxiv hauv kev nkag mus rau cov teeb meem, qhia txog kev sib txawv ntawm cov kab mob sib txawv hauv cov kab mob sib txawv [35].
Tshaj li IBD, muaj pov thawj hais txog lub luag haujlwm ntawm lub plab microbiota hauv fibrosis pib hauv hluav taws xob vim mob plab hnyuv [36]. Zhao thiab cov npoj yaig [36] tau pom tias cov tshuaj tua kab mob ua ntej kev kho mob tau txhim kho lub peev xwm ntawm lub plab microbiota hauv cov nas tom qab hluav taws xob. Cov tshuaj tua kab mob ua ntej no hauv cov nas tau txo qis cov ntsiab lus ntawm LPS, inhibited TLR4 / MyD88 / NF-κB txoj hauv kev thiab tswj cov macrophage cell polarization hauv ileum, downregulated TGF- 1 phosphorylated Smad-3 thiab SMA qib protein ntau thiab upregulated E-cadherin protein qhia. Nyob rau hauv tas li ntawd, Zhao thiab cov npoj yaig [36] hais tias cov tshuaj tua kab mob ua ntej kev kho mob tuaj yeem txhim kho txoj kev ciaj sia thiab txo cov hnyuv raug mob tom qab hluav taws xob los ntawm kev txo qhov mob thiab tiv thaiv plab hnyuv fibrosis. Hauv luv luv, muaj ntau qhov kev sib cav hais txog lub luag haujlwm ntawm lub plab microbiome nyob rau hauv pathogenesis ntawm plab hnyuv fibrosis, ncaj qha lossis los ntawm o. Vim li ntawd, kev hloov pauv ntawm lub plab microbiome (raws li tau tham hauv Tshooj 8) yuav yog ib qho cuab yeej kho mob tseem ceeb hauv kev tswj cov plab hnyuv fibrosis.
Lub plab-siab axis suav nrog ob txoj kev sib cuam tshuam / kev sib txuas lus ntawm txoj hnyuv thiab lub siab, los ntawm cov kab mob biliary, cov hlab ntsha portal, thiab cov kab mob hauv lub cev, ua rau kev thauj khoom ntawm cov hnyuv ncaj qha mus rau daim siab, uas lawv cuam tshuam ntau lub siab. kev ua haujlwm, thiab lub siab tawm tswv yim txoj hauv kev mus rau txoj hnyuv, qhov twg nws tswj kev ua haujlwm metabolic thiab cuam tshuam lub plab barrier kev ncaj ncees thiab microbiota muaj pes tsawg leeg [38]. Qhov kev sib koom ua ke no piav qhia txog kev cuam tshuam ntawm lub plab hnyuv microbiome (lub plab dysbiosis) thiab kev cuam tshuam hauv plab hnyuv hauv qhov nce ntawm cov kab mob hauv cov kab mob, cov kab mob tawg, thiab lawv cov khoom rau lub siab [39]. Lub translocated microbes thiab molecules ces qhib PPRs ntawm daim siab hlwb, stimulating zus tau tej cov inflammatory cytokines thiab cov synthesis ntawm ECM los ntawm hepatic stellate hlwb, uas ua rau mob o thiab mob fibrosis [40].
Cov pov thawj tsis ntev los no tau pom tias muaj kev sib koom ua ke ntawm plab hnyuv dysbiosis thiab cov kab mob uas tsis yog-alcoholic fatty siab (NAFLD), txawm hais tias causality tseem tsis tau tsim [41]. Kev hloov pauv hauv plab microbiota muaj pes tsawg leeg raws li theem fibrosis tau pom hauv cov neeg mob NAFLD. Siv 16S rRNA sequencing, Boursier li al. [42] pom muaj ntau dua ntawm cov chav kawm Bacteroidetes thiab qis dua ntawm cov genus Prevotella hauv cov neeg mob nrog NASH, daim ntawv hnyav ntawm NAFLD uas suav nrog o, hepatocellular puas, steatosis, thiab fibrosis. Ntawm cov neeg mob no (piv txwv li, NASH) cov neeg uas muaj fibrosis ntau dua (theem 2 lossis siab dua) kuj pom muaj ntau dua ntawm cov genus Ruminococcus [42]. Loomba et al. [43], siv tag nrho-genome metagenomics, txheeb xyuas qhov muaj ntau ntxiv ntawm hom Escherichia coli thiab Bacteroides vulgatus hauv cov neeg mob nrog NAFLD nrog cov fibrosis siab heev. Ib yam li ntawd, muaj ntau dua ntawm cov genus Escherichia tau pom nyob rau hauv cov menyuam rog rog nrog NASH, piv nrog cov menyuam rog rog tsis muaj NASH [44]. Txawm li cas los xij, tsis ntev los no, Schwimmer et al. [45] pom tias muaj ntau ntawm Prevotella copri yog txuam nrog fibrosis hnyav dua hauv cov menyuam yaus nrog NAFLD. Muaj qhov tsis muaj kev ua raws li cov kev tshawb fawb, uas tuaj yeem piav qhia los ntawm qhov sib txawv loj hauv kev kawm tsim thiab xaiv cov pej xeem, nrog rau cov chaw sib txawv thiab cov qauv kev noj haus [41]. Ntxiv mus, qhov sib txawv NAFLD phenotypes yuav tshwm sim los ntawm kev sib txawv microbiome kos npe ntawm tus tswv tsev raws li nws cov caj ces predisposition los yog ib puag ncig yam [39].
Tseem, ntxiv rau kev hloov pauv hauv microbiome muaj pes tsawg leeg, kev hloov pauv hauv kev ua haujlwm ntawm lub plab microbiome tau pom hauv NAFLD. Thaum qhov kev ua haujlwm ntawm lub plab microbiota tau kwv yees los ntawm bioinformatics, kev hloov pauv tseem ceeb hauv kev ua haujlwm ntawm plab hnyuv microbiota tau tshwm sim hauv NAFLD le sions (NASH thiab tseem ceeb fibrosis), feem ntau cuam tshuam rau Kyoto Encyclopedia of Genes thiab Genomes (KEGG) txoj hauv kev. muaj feem xyuam rau carbohydrate, lipid, thiab amino acid metabolism [42]. Tsis tas li ntawd, hauv cov neeg mob NASH cov neeg mob, nce cov ntshav ethanol ntau ntxiv tau pom, feem ntau yuav yog los ntawm lub plab-microbiota qhov chaw uas muaj cov kab mob uas ua rau cawv (xws li E. coli) [44]. Qhov no tej zaum yuav yog qhov ua rau muaj kev pheej hmoo ua rau muaj kab mob, txij li lub luag haujlwm ntawm cawv metabolism hauv kev tsim cov pa oxygen reactive tau tsim zoo, uas tom qab ntawd cuam tshuam rau daim siab mob [44].
Raws li hauv NAFLD, plab hnyuv dysbiosis tau pom tias yog ib qho tseem ceeb ntawm cov kab mob cawv cawv (ALD). Thaum lub sij hawm kev loj hlob thiab kev loj hlob ntawm ALD, muaj kev hloov hauv cov qauv, muaj pes tsawg leeg, thiab kev ua haujlwm ntawm cov hnyuv microbiome [40]. Kev haus cawv ntev ntev ua rau muaj kev hloov pauv hauv cov kab mob hauv plab hnyuv microbiome thiab nce qib ntawm LPS, yuav yog vim qhov nce hauv plab permeability, uas tom qab ntawd accumulates hauv daim siab thiab ua kom PPRs, uas ua rau, raws li twb tau hais tseg, hauv kev tsim cov inflammatory cytokines thiab ua kom cov kab mob siab hepatic stellate, uas yuav ua rau kom cov kev qhia ntawm ECM [40,46]. Ntxiv mus, qhov hnyav ntawm ALD tau pom tias muaj feem cuam tshuam nrog rau qib ntawm plab hnyuv dysbiosis [47]. Cov neeg mob uas muaj kab mob siab dej cawv hnyav harbored ntau ntawm Bifidobacteria, Strepto cocci, thiab Enterobacteria thiab tsawg dua ntawm cov genus Atopobium piv nrog cov neeg mob uas haus cawv ntau tab sis tsis muaj kab mob siab [47]. Tsis tas li ntawd, qhov phenotype hnyav tau hloov pauv los ntawm cov neeg mob mus rau nas los ntawm kev hloov pauv fecal microbiota [47]. Cov tsiaj no tau pom tias muaj kev nce hauv plab hnyuv permeability, uas ua rau muaj kab mob ntau ntxiv, nrog rau kev txo qis hauv cov kua tsib acid derivatives, uas nyob rau hauv lem tuaj yeem cuam tshuam rau kev ua haujlwm ntawm cawv metabolism [47].
Cirrhosis, lig-theem fibrosis thiab ib tug heev tshwm sim ntawm lub siab mob ntev yog txuam nrog lub plab barrier impairment txuam nrog cov kab mob uas tshwm sim nrog microbial translocation. Cov kab mob translocated, dominated los ntawm phylum Proteobacteria, muaj ntau nyob rau hauv cov hlab ntsha portal thiab lub siab thiab peripheral ntshav ntawm decompensated cirrhotic cov neeg mob thiab muaj feem xyuam rau cov kab mob inflammatory [48]. Cov txheej txheem physiopathological koom nrog cov teeb meem xws li hepatic encephalopathy thiab spontaneous bacterial peritonitis yog nruj me ntsis cuam tshuam nrog kev hloov pauv ntawm cov kab mob enteric lossis lawv cov khoom rau hauv lub cev [49]. Hais txog microbiome muaj pes tsawg leeg, tsis ntev los no, cov txheej txheem metagenomic tau siv los ua tus yam ntxwv ntawm fecal microbiome hauv cirrhosis, qhia txog kev txo ntau haiv neeg thiab kev loj hlob ntawm cov kab mob uas muaj feem cuam tshuam rau cov tsev neeg Enterococcaceae, Staphylococcaceae, thiab Enterobacteriaceae tsev neeg, thiab txo qis ntau ntawm cov txiaj ntsig tau txais txiaj ntsig au autoch. uas yog, cov uas nyob rau Lachnospiraceae thiab Ruminococcaceae tsev neeg [50,51]. Qhov txo qis ntawm cov kua tsib kua qaub qhia hauv cirrhosis tuaj yeem ua rau muaj kev loj hlob ntawm cov kab mob pathogenic no [52]. Ib qho tshwj xeeb ntawm cirrhosis yog kev cuam tshuam ntawm cov hnyuv hauv plab los ntawm cov kab mob ntawm qhov ncauj, xws li cov kab mob los ntawm cov kab mob Veillonella thiab Streptococcus [50].
Raws li cov pov thawj tsis ntev los no qhia tau hais tias, ntawm nws tus kheej ntawm lub hauv paus etiology, daim siab fibrosis nws tus kheej yog feem ntau nrog plab dysbiosis [53]. Ua ke nrog cov kab mob hnyav hnyav, plab dysbiosis, nrog rau kev loj hlob ntawm cov kab mob uas muaj peev xwm ua tau, ua rau cov kab mob siab tiv thaiv kab mob los ntawm kev xa khoom ntawm PAMPs. Cov PAMPs no tau lees paub los ntawm PPRs, xws li TLRs thiab nucleotide-binding oligomerization domain-zoo li receptors (NOD-NLRs), nyob rau saum npoo ntawm hepatic stellate cells, hepatocytes, lossis lub cev tiv thaiv kab mob [54]. Yog li ntawd, hepatic stellate cell fibrogenesis tuaj yeem tshwm sim ncaj qha lossis tsis ncaj los ntawm cov kab mob inflammatory uas tsim los ntawm cov hlwb nyob sib ze [54]. Tsis tas li ntawd, qhov hloov pauv microbiome kuj ua rau lub plab hnyuv deconjugation ntawm cov kua tsib acids thiab tsim cov kua tsib theem ob uas ua rau cov kab mob farnesoid-X receptor signaling [39]. Farnesoid-X receptor signaling exerts tiv thaiv cov teebmeem ntawm plab hnyuv epithelial barrier zog, thiab yog li ntawd nws surges txhawb kev cuam tshuam ntawm txoj hnyuv barrier [55], uas muaj peev xwm ua rau lub perpetuation ntawm kev thuam ntawm daim siab thiab tsis tu ncua ua kom cov stellate hlwb, uas. Tom qab ntawd yuav ua rau muaj kev cuam tshuam ntawm qhov sib npaug ntawm ECM deposition thiab dissolution, ua rau lub siab mob fibrosis.
Hauv kev xaus, txawm hais tias tam sim no tau lees paub tias daim siab puas thiab fibrosis tuaj yeem tshwm sim los ntawm kev sib cuam tshuam ntawm lub plab microbiota thiab lub siab lub cev thiab lub cev tiv thaiv kab mob, cov kev tshawb fawb ntxiv yuav tsum tau ua kom nkag siab zoo dua qhov kev cuam tshuam no rau yav tom ntej microbiome cov tswv yim.
