Gut Microbiome Thiab Organ Fibrosis Ⅱ

4. Lub raum Fibrosis

Mob raum mob (CKD)yog ib qho teeb meem kev noj qab haus huv thoob ntiaj teb loj zuj zus, cuam tshuam tsawg kawg 10 feem pua ​​​​ntawm cov neeg hauv ntiaj teb, thiab feem pua ​​​​ntawm cov neeg no nce zuj zus nrog kev laus [56]. Fibrosis yog qhov kawg pathological feature ntawm CKD thiab tau lees paub zoo los pab txhawb kev loj hlob ntawm yuav luag txhua homkab mob raum, coj tus cwj pwm ywj pheej ntawmdeterioration ntawm lub raum ua haujlwm[57]. Hauv CKD, fibrosis feem ntau tshwm sim los ntawmmob moblub raum parenchyma [58] Txawm hais tias TGF- 1 tau raug suav hais tias yog qhov tseem ceeb rau cov txheej txheem pathological fibrotic hauv CKD, cov lus teb metabolic thiab hauv lub cev tsis muaj zog tam sim no tau lees paub tias yog cov neeg txhawb nqa tseem ceeb rau lub hom phiaj hauv txoj haujlwm no. Tsis tas li ntawd, cov pov thawj tam sim no qhia tau hais tias lub tshuab ua haujlwm pathological fibroblast yog lub hauv paus tseem ceeb hauv kev tsim cov cytokines thiab chemokines hauv CKD [59].

NEW HERBAL FORMULATION RAUCHRONIC KIDNEY DISEASE (CKD)

Hauv kaum xyoo dhau los, cov ntaub ntawv ntau ntxiv tau hais txog lub plab microbiota ua tus neeg ua haujlwm tseem ceeb hauv lub raum fibrosis, uas yog, los ntawm kev ua lub luag haujlwm tseem ceeb hauv ob qho tib si hauv zos thiab kab mob [60]. Ntau qhov kev tshawb fawb tau tsim tias cov neeg mob plab hnyuv microbiome hauv cov neeg mob CKD yog qhov txawv ntawm qhov pom hauv cov kev noj qab haus huv. Feem ntau cov ntawv ceeb toom yog tsom rau cov neeg mob kawg-theem raum kab mob (ESRD) thiab ob peb hais txog lub plab microbiota nyob rau theem CKD thaum ntxov, tab sis tag nrho, cov neeg mob raum muaj qhov txo qis hauv plab microbiome ntau haiv neeg nrog kev nce ntxiv ntawm cov kab mob pathogenic ntawm En Enterobacteriaceae. tsev neeg thiab txo qis hauv cov txiaj ntsig microbes ntawm Bifidobacteriaceae thiab Lactobacillaceae tsev neeg [61,62]. Xws li kev hloov hauv plab microbiota hauv CKD cov neeg mob los ntawm symbiotic mus rau ntau cov kab mob pathogenic microbiota muaj kev sib raug zoo nrog lub xeev uremic thiab lub raum fibrosis, txhawb lub hav zoov ntawm bidirectional thiab synergistic interchange ntawm uremic xeev ntawm tus tswv tsev, o, thiab plab dysbiosis. [63].

Kev loj hlob ntawm lub raum tsis ua haujlwm, ua ke nrog cov kev hloov pauv hauv kev ua neej, kev noj haus, thiab tshuaj, hloov cov microbiota muaj pes tsawg leeg thiab cov metabolism ua rau dysbiosis - thiab tsim cov tshuaj uremic toxins los ntawm dysbiotic microbiota ntxiv ua rau lub xeev uremic, ua rau cov kab mob epithelial teeb meem, nce ntxiv. txoj hnyuv permeability thiab txhawb o thiab oxidative kev nyuaj siab [64]. Ntau qhov kev tshawb fawb hauv vivo thiab hauv vitro tau pom tias ib puag ncig uremic plab hnyuv ib puag ncig hloov qhov nruj hlws ris protein qhia qauv rau ib qho phenotype ntawm cov plab hnyuv permeability ntxiv [65-68], uas pab txhawb kev hloov pauv ntawm cov kab mob co toxins (xws li endotoxins), microbial metabolites thiab txawm kab mob mus rau hauv kev [69]. DNA los ntawm cov kab mob hauv plab hnyuv tau kuaj pom hauv cov ntshav ntawmpre-dialysis CKDthiab cov neeg mob hemodialysis thiab cuam tshuam nrog nce ntshav plasma c-reactive protein (CRP) thiab IL-6 qib [70–72]; Cov kab mob hauv plab tau pom nyob rau hauv mesenteric lymph nodes ntawm uremic nas [73], thiab endotoxemia tau pom hauv cov neeg mob CKD thiab cuam tshuam nrog cov kab mob hauv lub cev thiab kab mob plawv hauv cov neeg no [74-76]. Bacterial translocation ua rau kev ua kom lub cev tiv thaiv kab mob los ntawm kev ua kom muaj zog ntawm TLR4 / NF-κB / mitogen-activated protein kinase txoj hauv kev, tsim kom muaj lub xeev mob ntev uas txhawb kev mob sclerosis [76,77]. Kev nce qib ntawm cov kab mob endotoxins thoob plaws txhua theem CKD, nce mus txog qhov siab tshaj plaws hauv cov neeg mob lim ntshav, tau pom tias muaj feem cuam tshuam nrog cov kab mob hauv lub cev, atherosclerosis, thiab kev tuag hauv cov neeg mob CKD [75,76]. Siv tus qauv LPS-kho murine (cov nas tau txhaj tshuaj intraperitoneally nrog 10 mg / kg / lub lis piam ntawm LPS rau 4 lub lis piam), Fereshteh Asgharzadeh thiab cov npoj yaig [78] tau pom tias nyob rau hauv kev kho mob uas muaj LPS mob ntev, ob qho tib si plawv thiab lub raum fibrosis tuaj yeem tshwm sim. txawm tias tsis muaj cov ntaub so ntswg ua ntej raug mob vim qhov tsis txaus ntawm oxidative kev nyuaj siab,qhia tias plab dysbiosis tuaj yeem muaj lub luag haujlwm hauv kev tsim cov kab mob hauv nruab nrog cev los ntawm nws tus kheej.

Qhov cuam tshuam ntawm plab-derived circulating metabolites nyob rau hauv lub systemic immuno-inflammatory teb nyob rau hauv cov kab mob ntawm lub raum thiab cov txiaj ntsig, uas yog, nyob rau hauv cov kab mob plawv, tam sim no tau lees paub zoo [79]. Ntawm cov plab hnyuv metabolites pom tau hais tias sib txawv hauv cov neeg mob CKD, tshwj xeeb yog tau txais kev saib xyuas rau cov nyhuv ntawm uremic toxins thiab SCFAs [79]. Cov ntsiab lus siab dua ntawm uremic co toxins trimethylamine N-oxide (TMAO) [80], p-cresyl sulfate (PCS), thiab indoxyl sulfate (IS) [81], thiab qis dua ntawm SCFAs [82] tau raug soj ntsuam tas li hauv CKD thiab Cov neeg mob ESRD [83,84]. Cov txiaj ntsig zoo li no tau pom zoo nrog daim ntawv tshaj tawm qhia tias muaj cov kab mob loj hlob ntxiv uas muaj urease-, urease-, indole-, thiab para-cresol-forming enzymes thiab txo qis hauv cov kab mob nrog butyrate-forming enzymes hauv ESRD cov neeg mob [85-87] , ntxiv kev txhawb nqa muaj feem cuam tshuam ntawm plab microbiota rau lub raum fibrosis.

TMAO yog lub plab-derived toxic metabolite uas tshwm sim los ntawm cov kab mob metabolism ntawm quaternary amines los ntawm cov khoom noj (xws li choline, phosphatidylcholine, thiab L-carnitine) rau hauv trimethylamine, uas tom qab ntawd hloov mus rau hauv TMAO los ntawm hepatic flavin monooxygenases (FMO1 thiab FMO3) [88]. Hauv CKD, TMAO qib siab tau cuam tshuam nrog rau lub raum tsis ua haujlwm, mob ntev (siab IL-6 thiab CRP), thiab kev tuag ntau ntxiv (a 2.8-fold nce hauv kev pheej hmoo tuag) [89]. Tom qab hloov lub raum, TMAO plasma concentration txo qis mus rau qib ib txwm [90] tab sis hauv cov neeg mob hemodialysis, txawm hais tias nws muaj txiaj ntsig zoo tshem tawm los ntawm hemodialysis, TMAO plasma qib tseem muaj txiaj ntsig zoo tom qab kev lim ntshav, qhia txog kev cuam tshuam ntawm dysbiotic plab microbiota kom nce ntxiv. production of TMAO in ESRD [80,91]. Kev nce qib TMAO yog txuam nrog raum tubulointerstitial fibrosis thiab collagen deposition los ntawm kev ua kom TGF- 1/p-Smad3 thiab renin-angiotensin-aldosterone txoj kev [89,92]. Inhibition ntawm TMAO ntau lawm nyob rau hauv murine qauv ntawm CKD ho retarded qhov poob ntawm lub raum kev ua haujlwm thiab txo qis tubulointerstitial fibrosis [93,94], qhia txog TMAO ntau lawm mechanisms raws li lub hom phiaj rau kev kho mob raum fibrosis.

Cov theem ntawm IS thiab pCS tau pom tias muaj feem cuam tshuam nrog kev nce mus rau ESRD thiab txhim kho kev tuag hauv cov neeg mob CKD los ntawm mob me mus rau lub raum tsis zoo los ntawm kev txhim kho oxidative kev nyuaj siab thiab mob [81,83,95–97]. IS kuj tsis ntev los no cuam tshuam nrog CKD kev loj hlob hauv cov menyuam yaus [98]. Kev nce qib ntawm IS tau pom tias txhawb nqa tubulointerstitial fibrosis los ntawm kev ua kom muaj kev qhia ntawm NF-κB, plasminogen activator inhibitor hom 1, cov ntaub so ntswg inhibitor ntawm metalloproteinases, thiab TGF- 1 txoj hauv kev [99]. Augmented pCS qib tau cuam tshuam nrog kev puas tsuaj loj ntawm tubular los ntawm kev txhim kho oxidative kev nyuaj siab thiab inflammatory cytokine qib [100] thiab tau cuam tshuam nrog kev pheej hmoo ntawm kev tuag tag nrho thiab kab mob plawv hauv cov neeg mob uas mob raum tsis ua haujlwm thiab mob me-rau-mob CKD [83 Ib., 84]. Cov kev tshawb fawb tsiaj sib txawv tau pom tias IS thiab pCS plasma concentration cuam tshuam nrog tubular fibrosis los ntawm kev ua kom lub raum renin-angiotensin system thiab TGF- 1/p-Smad3 txoj hauv kev [100,101]. Tsis tas li ntawd, kev tshawb fawb ntau ntxiv kuj tau tsim lub luag haujlwm tseem ceeb ntawm plab-derived tryptophan metabolites (xws li IS, 3-IS, thiab indole-3 acetic acid (IAA)), hauv lub raum fibrosis los ntawm kev ua kom muaj zog. ntawm aryl hydrocarbon receptor signaling txoj hauv kev, tshwj xeeb, los ntawm kev ua kom muaj zog ntawm aryl hydrocarbon receptor / p38 mitogen-activated protein kinase / NF-κB txoj hauv kev uas tswj cov cell proliferation, sib txawv, thiab lub cev tsis muaj zog thiab ua rau cov kab mob plawv hauv cov neeg mob ESRD [102]. IAA qib tau cuam tshuam nrog glomerular sclerosis thiab interstitial fibrosis los ntawm inducing pro-inflammatory enzyme cyclooxygenase -2 thiab oxidative kev nyuaj siab thiab nws cov concentration tau pom tias yuav kwv yees txog kev tuag thiab mob plawv hauv cov neeg mob CKD [103].

Los ntawm qhov sib txawv ntawm qhov pom, SCFAs yog cov khoom lag luam loj ntawm fermentation ntawm cov hmoov txhuv nplej siab los ntawm cov kab mob aerobic hauv txoj hnyuv [104]. Lawv qhov kev xav tau nce ntxiv tau pom tias muaj txiaj ntsig zoo hauv kev saib xyuas ntawm epithelial barrier thiab kev tswj hwm lub cev tiv thaiv kab mob los ntawm kev ua kom muaj zog tiv thaiv kab mob, txo qis kev cuam tshuam ntawm autoimmunity, thiab txhim kho kev tswj T (Treg) hlwb ntawm G- protein-coupled receptors (GPCRs) (piv txwv li, GPR41, GPR43, thiab GPR109A) [105–108]. SCFAs yog cov tshuaj histone deacetylase inhibitors uas tuaj yeem cuam tshuam TGF{10}} kev taw qhia, tiv thaiv pericyte sib txawv rau hauv myofibroblasts [109,110]. Acetate, propionate, thiab butyrate yog peb qhov SCFAs ntau tshaj plaws thiab yog lub hauv paus ntawm lub zog rau cov hlwb epithelial, muab kwv yees li 10% ntawm qhov xav tau caloric txhua hnub hauv tib neeg [104]. Hauv cov kab mob hauv lub raum, qhov sib xyaw ua ke ntawm kev txwv kev noj zaub mov (xws li, kev pom zoo kom tsawg ntawm cov khoom noj uas muaj cov poov tshuaj xws li txiv hmab txiv ntoo, zaub, thiab cov zaub mov muaj fiber ntau) thiab plab microbiome dysbiosis ua rau txo qis ntawm SCFA-ua cov kab mob thiab hauv qhov txo qis ntawm SCFA concentration [111]. Qhov kev txo qis SCFA concentration no ua rau muaj kev cuam tshuam ntawm cov txheej txheem inflammatory thiab raum fibrosis [112]. Ib qho ntxiv ntawm cov pov thawj tau tsim SCFA supplementation raws li ib txoj hauv kev rau kev kho mob raum thiab mob plawv los ntawm kev txhim kho lub raum tsis ua haujlwm thiab txo qis hauv zos thiab kab mob, oxidative kev nyuaj siab, thiab cell apoptosis [82,113].

Nws yog tam sim no tau tsim kom meej meej tias plab microbiome dysbiosis muaj lub luag haujlwm tseem ceeb hauv lub raum fibrosis thiab cov kab mob raum tshwm sim, nrog ntau tus neeg ua si thiab cov txheej txheem metabolic cuam tshuam rau hauv cov txheej txheem [114,115]. Txawm li cas los xij, qhov tseeb ntawm kev poob ntawm lub raum ua haujlwm thiab kev txwv kev noj haus rau qhov dysbiosis no tseem yog qhov tsis sib haum xeeb. Qee cov kev tshawb fawb qhia tias kev noj zaub mov muaj lub luag haujlwm tseem ceeb hauv kev hloov cov hnyuv microbial metabolism hauv CKD [85], thaum lwm tus qhia tias qhov tseem ceeb ntawm plab dysbiosis pom hauv cov neeg mob CKD yog txuam nrog kev nce biosynthesis ntawm uremic toxins nrog rau qhov cuam tshuam ntawm kev poob. kev ua haujlwm ntawm lub raum [116]

Ntau cov kev tshawb fawb suav nrog prebiotics, probiotics, thiab symbiotics (sib tham ntxiv hauv Tshooj 8) tau ua, aiming kom rov qab noj qab haus huv plab microbiota thiab, los ntawm qhov no, los ntawm qhov no, los tswj uremia thiab txwv tsis pub cov kab mob hauv lub raum (tus cwj pwm los ntawm kev nce fibrosis ntawm lub plab. cov ntaub so ntswg, tsis hais txog ntawm etiology ntawm tus kab mob) [117]. Txawm hais tias qee qhov txiaj ntsig tau zoo, cov lus teb ntawm tus kheej heev ntawm ib lub plab microbiome rau ntau qhov stimuli thiab cov qib siab ntawm kev sib txawv ntawm cov kev tshawb fawb tau ua kom deb li deb tau cuam tshuam qhov kev ua tiav ntawm ib qho loj-haum-tag nrho cov qauv. Cov tshuaj kho tus kheej, uas yog, cov txheej txheem tsim kho uas hais txog tus neeg xav tau kev pab, tuav lub peev xwm zoo rau kev tswj lub raum fibrosis, uas tseem tsis tau tshawb nrhiav ntau.

5. Pulmonary Fibrosis

Pulmonary fibrosis yog txheej txheem pathologic uas underlies ib pab pawg neeg heterogeneous ntawm cov kab mob ntsws nrog ntau yam ua rau, kev kho mob tshwm sim, thiab cov yam ntxwv pathological [118]. Nws yog tshwj xeeb tshaj yog tshwm sim los ntawm o thiab los ntawm ntau ntau deposition ntawm ECM nyob rau hauv lub ntsws, uas ua rau architectural hloov nyob rau hauv lub ntsws parenchyma, xws li thickening thiab stiffening ntawm lub ntsws phab ntsa uas tej zaum yuav ua rau mob ua pa poob thiab lub cev tsis ua hauj lwm [119,120]. Raws li feem ntau cov kev hloov pauv pathological muaj nyob rau hauv lub ntsws interstitium, cov kab mob feem ntau yog hu ua kab mob ntsws interstitial (ILDs). Kev puas tsuaj rau lub ntsws los ntawm ILDs feem ntau yog nce thiab hloov tsis tau thiab sawv cev rau qhov tseem ceeb ntawm kev mob nkeeg thiab kev tuag [121].

Muaj ntau tshaj 200 qhov ua rau ILDs. Lub ntsiab paub ua rau tus kab mob muaj xws li hnub nyoog thiab tus kheej genetic susceptibility (xws li, genetic tej yam kev mob xws li neurofibromatosis thiab Gaucher kab mob), ib puag ncig raug rau tej yam phom sij (xws li, asbestos, silica, thee plua plav, beryllium, ib co nyuaj hlau, kev kho hluav taws xob, tshuaj kho mob, tshuaj tua kab mob, tshuaj tiv thaiv kab mob thiab mob plawv, tsiaj proteins, pwm lossis microbes) thiab muaj cov kab mob hauv qab xws li kab mob plab hnyuv thiab kab mob autoimmune (xws li lupus, rheumatoid mob caj dab, sarcoidosis, thiab scleroderma) [122 — 125]. Rau kev tswj hwm lub hom phiaj, ILDs tuaj yeem raug cais raws li lawv cov kab mob hauv qab no (xws li, pulmonary fibrosis txuam nrog rheumatoid mob caj dab), raws li lawv cov kab mob tshwm sim (xws li pneumoconiosis), lossis lawv tuaj yeem raug xa mus rau idiopathic pulmonary fibrosis [126,127]. ILDs muaj feem ntau ntawm ~ 70–80 tus neeg rau 100,{10}} cov neeg nyob hauv Europe thiab hauv Tebchaws Meskas. Sarcoidosis, connective-tissue disease-associated ILDs and idiopathic pulmonary fibrosis is the most common fibrotic ILDs, with an estimated prevalence of 30, 12, and 8 case per 100, 000 neeg, feem [128].

Nyob rau hauv xyoo tas los no, ntau qhov kev tshawb fawb txog kev kis kab mob thiab kev sim tau qhia txog qhov muaj nyob ntawm bidirectional gut-lung axis nrog rau cov kev cuam tshuam hauv pathophysiology ntawm ntau cov kab mob ntsws, xws li mob hawb pob, mob ntsws ntsws, mob cystic fibrosis, kab mob ua pa, mob ntsws cancer thiab ILDs [129,130]. Ntau qhov kev tshawb fawb tau tsim kom muaj kev sib koom ua ke ntawm cov kab mob ua pa thiab kab mob hauv plab [131-141]. Vim hais tias txoj kev ua pa thiab plab hnyuv sib koom tib lub hauv paus chiv keeb thiab zoo sib xws hauv cov qauv [142], qhov sib tshooj ntawm lub ntsws thiab cov kab mob plab tsis yog qhov xav tsis thoob. Cov ntaub so ntswg muaj xws li ep epithelial nto npog nrog submucosa ntawm cov ntaub so ntswg xoob thiab cov ntaub so ntswg mucosal-koom nrog lymphoid cov ntaub so ntswg uas muab kev tiv thaiv lub cev tiv thaiv kab mob sab nraud, tswj cov qauv antigen, lymphocyte thauj, thiab mucosal tiv thaiv, yog li ua haujlwm ua thawj innate thiab adaptive tiv thaiv kab mob. kab mob [142]. Ntxiv mus, ob qho tib si cov ntaub so ntswg yog vascularized heev thiab colonized los ntawm microbiota uas txhim kho nrog lawv thaum ntxov lub neej [143].

Txawm hais tias feem ntau cov pov thawj hais txog lub luag haujlwm ntawm microbiome hauv lub ntsws-lub plab axis tseem yog koom nrog, qee qhov kev pom zoo txhawb nqa kev sib tham ntawm lub plab thiab lub ntsws, ua rau muaj kev sib hloov ntawm cov kab mob [144–147], kev tiv thaiv kab mob [17,1414,146. -151] thiab metabolites [129,151] los ntawm cov hlab ntsha thiab lymphatic system.

Hais txog qhov cuam tshuam ntawm plab metabolites hauv lub ntsws homeostasis, feem ntau cov kev tshawb fawb qhia txog lub luag haujlwm tseem ceeb ntawm SCFAs hauv cov kab mob ntsws los ntawm inhibition ntawm histone deacetylase thiab GPCRs, uas koom nrog hauv cov kab mob ntsws [152]. Butyrate, propionate, thiab acetate tau qhiaanti-inflammatorythiabimmunomodulatory muaj nuj nqintawm lub ntsws homeostasis thiab tiv thaiv kab mob [104,153].

Ua ke, cov pov thawj muaj zog txhawb nqa qhov tseem ceeb ntawm lub plab microbiome thiab nws cov metabolites hauv ntsws homeostasis. Ua tib zoo xav txog qhov tseeb tias ILDs yog tus cwj pwm los ntawm kev txhim kho inflammatory xeev uas zoo sib xws hauv nws cov players rau feem ntau cov kab mob ntsws, cov ntaub ntawv qhia txog lub luag haujlwm ntawm lub plab microbiome hauv pulmonary fibrosis uas tseem tsis tau tshawb nrhiav. Qee qhov kev tshawb fawb qhia txog kev sib txuas ncaj qha ntawm lub plab microbiome thiab lub ntsws fibrosis. Ib txoj kev tshawb nrhiav kev tshawb fawb txog qhov tshwm sim ntawm plab hnyuv dysbiosis hauv cov kab mob sclerosis (ib kab mob sib txuas ntawm cov ntaub so ntswg uas tshwm sim los ntawm cov kab mob fibrosis thiab vascular txawv txav hauv daim tawv nqaij, pob qij txha, thiab cov kab mob hauv nruab nrog cev) cov neeg mob tau pom tias 76% ntawm cov neeg mob no pom cov plab dysbiosis thiab qhov ntawd. dysbiosis qhov qhab nia hnyav tau hnyav dua rau cov neeg mob uas muaj lwm yam kab mob sib kis, xws li ILD, sib cuam tshuam nrog cov kab mob ntshav siab inflammatory (xws li, CRP thiab erythrocyte sedimentation rate) [154].

Hauv kev tshawb fawb los ntawm Zhou et al. [155], qhov kev sib piv ntawm cov plab hnyuv microbial composi tion ntawm cov qauv fecal los ntawm 18 cov neeg mob uas muaj silica-induced pulmonary fibrosis thiab 21 cov neeg noj qab haus huv, siv 16S rRNA gene sequencing thev naus laus zis, qhia tias cov neeg mob silicosis muaj cov kab mob plab microbiota sib txawv, pom cov kab mob qis dua los ntawm phyla Firmicutes thiab Actinobacteria, genus Devosia, qhov kev txiav txim Clostridiales, genus Alloprevotella, thiab Rikenellaceae RC9 pawg neeg plab thiab nce se ntawm tsev neeg Lachnospiraceae thiab Lachnoclostridium genus, uas tau cuam tshuam nrog cov kab mob. kev vam meej.

Siv cov qauv tsiaj, Gong et al. [124] txheeb xyuas lub plab microbiome thiab cov metabolites hauv silica thiab bleomycin pulmonary fibrotic qauv, thiab cov txiaj ntsig ntawm 16S rDNA sequencing thiab metabolomics txhawb kev sib raug zoo ntawm plab microbiota thiab pulmonary fibrosis. Cov txiaj ntsig tau rov qab pom tau pom tus qauv-kev ywj pheej tshwj xeeb hloov pauv hauv 412 genera ntawm plab microbiota thiab 28 hom metabolites hauv ob qho tib si qauv. Xya tus neeg sawv cev sib txawv ntawm plab hnyuv kab mob (los ntawm cov genera Allopre Botella, Dubosiella, Helicobacter, OIsenella, Parasutterella, Rikenella, thiab Rikenllaceae RC9 pawg) thiab cuaj metabolites (trigonelline, betaine, cytosine, thymidine, glycerophocytine, chocolate, adenine) tau correlated nrog fibrotic ntsuas. Ntxiv mus, tus txais kev khiav hauj lwm tus yam ntxwv nkhaus (siv los ntsuam xyuas tus sawv cev tiv thaiv kab mob sib txawv plab microbiota thiab metabolites rau kev kuaj mob fibrotic xeev nyob rau hauv ob txoj kev sim) qhia tias nws muaj peev xwm paub qhov txawv pulmonary fibrotic raws li txoj cai los ntawm ib txwm tswj los ntawm kev soj ntsuam ntawm plab microbiota thiab muaj feem cuam tshuam metabolites hauv nas qauv [124].

Tsis ntev los no, tus qauv nas tshiab ntawm scleroderma cuam tshuam nrog kev tiv thaiv topoisomerase-I kev tiv thaiv tau qhia tias kev hloov pauv hauv lub neej thaum ntxov hauv lub plab microbial zej zog tuaj yeem tsim cov neeg mob cov lus teb fibrotic thoob plaws hauv lawv lub neej [156]. Los ntawm ib qho kev xav txawv, Wand thiab cov npoj yaig [157] tau nthuav tawm tias cov qauv ntawm lub plab dysbiosis-vim cov tsiaj ua rau cov tsiaj muaj ntshav qab zib mellitus thiab pulmonary fibrosis cuam tshuam nrog NF-kB txoj kev taw qhia. Cov teebmeem ntawm phycocyanin (lub teeb-txiav protein los ntawm algal photosynthesis uas tuaj yeem fermented los ntawm plab hnyuv microbiota) ntawm bleomycin-induced thiab hluav taws xob-induced pulmonary fibrosis nas qauv qhia tau hais tias phycocyanin cuam tshuam attenuated pulmonary fibrosis thiab cuam tshuam cov khoom tsim tawm. thaum ua kom cov kab mob plab muaj ntau haiv neeg thiab kev nplua nuj [158,159]. Hauv bleomycin-induced fibrotic qauv, phycocyanin inhibited cov synthesis ntawm IL-1, qog necrosis factor- (TNF- ), thiab LPSs, thaum txo qis cov kab mob cuam tshuam nrog o thiab nce SCFA-ua cov kab mob thiab probiotics [159 ]. Nyob rau hauv hluav taws xob-induced pulmonary fibrosis, ob qho tib si ua ntej kev tswj hwm thiab kev kho mob ntawm phycocyanin txo qis kev puas tsuaj thiab collagen fiber ntau thiab txo cov qib ntawm TNF-, LPS, thiab IL -6 hauv ntsws, hnyuv, thiab ntshav [ 158] ib.

Hauv vitro, kev tshuaj xyuas ntawm cov txiaj ntsig ntawm SCFAs ntawm TGF- 1-induced sib txawv ntawm MRC5 tib neeg fetal ntsws fibroblasts cell kab tau pom tias butyrate (C4), SCFA uas tshwm sim los ntawm cov metabolism hauv plab microbiome, inhibits qhov kev qhia. ntawm cov cim fibrosis thiab txhim kho mitochondrial muaj nuj nqi, yog li tiv thaiv TGF- 1-induced alveolar myofibroblast sib txawv, qhov tseem ceeb ntawm pulmonary fibrosis [160]. Ua ke, ob qho tib si ncaj qha thiab tsis ncaj qha pov thawj cuam tshuam rau lub plab microbiome hauv kev tswj hwm lub cev tiv thaiv kab mob thiab lub xeev ntawm cov khoom, nrog rau cov txiaj ntsig cuam tshuam rau kev tswj cov kab mob pulmonary fibrosis.