Cov teebmeem ntawm Perfluorooctanoic Acid Rau plab Microbiota Thiab Microbial Metabolites Hauv C57BL / 6J MiceⅢ
Nov 28, 2023
3. Cov txiaj ntsig
3.1. PFOAHloov Cov Txheej Txheem ntawm Gut Microbiota
Tag nrho ntawm 78 kab mob genera tau kuaj pom hauv peb txoj kev tshawb fawb, raws li qhia los ntawm 16S rRNAsequencing. Cov genera tshaj plaws yog qhia hauv daim duab 1A. Kev tshuaj xyuas LEfSe tau pom tias tsib kab mob genera tau nplua nuj nyob rau hauv PFOA-kho nas, uas yog Alistipes, LachnospiraceaeUCG 004, Clostridiales, Clostridium ASF356, thiab Incertae sedis (Daim duab 1B). Lub caij no, cov kab mob rau cov kab mob tau txo qis hauv PFOA-kho pab pawg, xws li Tyzzerella, Eubacteriumcoprostanoligenes, Intestinimonas, Clostridium septum, Roseburia, thiab Turicibacter (Daim duab 1B).
3.2. Kev sib raug zoo ntawm Gut Microbiota thiab Fecal Metabolites
Peb tau ua ib qho kev ntsuam xyuas ntawm lub plab microbiota thiab fecal metabolitesusing MixOmics. Tag nrho kev sib raug zoo ntawm lub plab microbiota thiab fecal metaboliteswas 0.74 (Daim duab 2A). Rau ob qho tib si fecal metabolites thiab kab mob genera, PFOA-kho pab pawg tau raug cais tawm ntawm pawg tswj hwm (Daim duab 2B, Daim duab ntxiv S1). Kev pom zoo ntawm fecal metabolites thiab kab mob genera yog qhia hauv daim duab 2C. Peb cov kab mob genera pom muaj kev sib raug zoo nrog yim fecal metabolites (Daim duab 2D).
3.3. PFOA-Induced Hloov hauv Fecal Metabolites
Tom qab PFOA raug, tag nrho ntawm 120 metabolites pom p-tus nqi < 0.05, ntawm cov uas tsib metabolites pom qhov tsis tseeb nrhiav tus nqi (FDR) < 0.05 (Daim duab 3A). Lub hierarchical pawg ntawm cov metabolites tseem ceeb yog qhia hauv daim duab 3B. Kev txheeb xyuas txoj kev txhawb nqa tau qhia tias cysteine thiab methionine metabolism tau hloov pauv los ntawm PFOA raug (Daim duab 3C). Qhov tseem ceeb, peb cov fecal bile acids tau txo qis los ntawm PFOA raug, xws li glycodeoxycholic acid, beta-hyodeoxycholic acid, thiab gamma-muricholic acid (Daim duab 3D).
3.4. PFOA Induced Hloov hauv Serum Metabolites
Pawg PFOA-kho thiab pab pawg tswj tau zoo sib cais hauv PLS-DA zaj duab xis (Daim duab 4A). Tag nrho ntawm 59 cov tshuaj metabolites tau pom qhov p-value < 0.05, ntawm cov 10 metabolites pom FDR < 0.05 (Daim duab 4B). Txoj kev tsom xam pom tau tias nicotin thiab nicotinamide metabolism thiab histidine metabolism tau hloov pauv los ntawm PFOA raug (Daim duab 4C). Ob lub kua tsib acids, taurocholic acid, thiab deoxycholic acid, tau txo qis hauv PFOA-kho pab pawg, nyob rau hauv txoj kab nrog kev txo qis hauv TMAO thiab nce choline los ntawm PFOA raug (Daim duab 4D).
3.5. PFOA Induced Hloov hauv daim siab metabolites
PLS-DA tsom xam ntawm daim siab metabolites pom tias pawg PFOA kho tau raug cais tawm ntawm pawg tswj hwm (Daim duab 5A). Tag nrho ntawm 94 daim siab metabolites pom p-tus nqi < 0.05 tom qab PFOA raug (Daim duab 5B). Pathway enrichment tsom xam pom tias argininebiosynthesis tau hloov pauv loj heev (Daim duab 5C). Peb cov metabolites tau pom tias tseem ceeb hauv daim siab, ntshav, thiab quav, uas yog 1-(1Z-hexadecyl)-sn-glycero-3-phosphocholine,decanoyl-L-carnitine, thiab 1- hexadecyl-sn-glycero-3-phosphocholine (Daim duab 5D). Ob lub bileacids, tauroursodeoxycholic acid thiab taurochenodeoxycholic acid, raug txo los ntawm PFOAexposure, nrog rau kev txo qis hauv ob tryptophan metabolites, 3-indoleacrylic acid thiab 3-indoleacetic acid, thiab nce taurine (Daim duab 5E).
4. Kev sib tham
Cov pa roj carbon-fluorine daim ntawv cog lus ua rau PFOA tiv taus photolysis thiab hydrolysis, uas ua rau muaj kev pheej hmoo ntawm PFOA hauv ib puag ncig. Ib qho kev sib raug zoo tau pom nyob nruab nrab ntawm cov ntshav plasma PFAS ntau thiab kev noj zaub mov ntawm cov ntses dej qab zib, marinefish, crab, thiab cws hauv 933 cov poj niam cev xeeb tub hauv Shanghai, Suav [32]. Thaum ntxov-lifeexposure rau PFOA yog ib qho tseem ceeb ntawm cov ntshav concentration hauv cov me nyuam [33]. Nyob rau hauv ib txoj kev tshawb fawb uas tshuaj xyuas qhov kev sib raug zoo ntawm PFAS thiab mob o thiab oxidativestress markers nyob rau hauv National Health and Nutrition Examination Survey (NHANES) los ntawm 2005 txog 2012 (n=6652), ib feem pua ntawm cov kev hloov pauv hauv PFOA tau cuam tshuam nrog feem pua ntawm cov lymphocytes. suav, serum hlau, thiab serum tag nrho bilirubin [34].Lub raum thiab qog nqaij hlav cancer yuav nce ib 10 ng/mL nce hauv cov ntshav PFOAconcentration [35].
Tsis tas li ntawd, cov ntshav PFOA concentration tau zoo cuam tshuam nrog hepatocellular puas tsuaj cim alanine aminotransferase (ALT) hauv 47,092 tus neeg laus hauv C8 Health Project [36]. Serum PFOA kuj muaj txiaj ntsig zoo nrog immunoglobulinG, anti-cyclic citrullinated peptide antibodies, thiab rheumatoid yam [37].Rau qhov teeb meem loj thiab thoob plaws ib puag ncig, PFOA-induced metabolic alterations tau qhia nyob rau hauv cov lymphocytes nyob rau hauv tib neeg peripheral ntshav [38] thiab Cov menyuam yaus uas muaj tus kws kho mob kuaj pom tias tsis muaj tus kab mob rog rog (NAFLD) [39].
Txawm li cas los xij, kev sib koom ua ke ntawm kev cuam tshuam ntawm metabolome thiab plab microbiota los ntawm PFOA raug tsis tau ua. Hauv txoj kev tshawb no, peb tsis tsuas yog nthuav tawm cov kev hloov pauv hauv cov piam thaj hauv cov ntshav, tab sis kuj tseem cuam tshuam cov metabolic hauv cov quav thiab daim siab. Tsis tas li ntawd, peb tau ua ib qho kev soj ntsuam kev sib koom ua ke ntawm fecal metabolites thiab lub plab microbiota thiab qhia txog kev koom tes ntawm lawv nyob rau hauv kev cuam tshuam ntawm PFOA raug. Cov profiles ntawm ob qho tib si fecal metabolites thiab lub plab microbiota tau cuam tshuam los ntawm PFOA raug.
Cov txheeb ze ntawm Roseburia, Tyzzerella, Eubacterium coprostanoligenes, thiab Intestinimonas raug txo los ntawm PFOA raug. Roseburia yog suav hais tias yog cov kab mob uas muaj txiaj ntsig zoo nrog cov tshuaj tiv thaiv kab mob, uas tuaj yeem kho cov kab mob plab muaj txiaj ntsig [40].
Roseburia plab hnyuv muaj peev xwm tswj tau lub zog homeostasis thiab tiv thaiv plab o [41] .Tyzzerella qis dua tau pom nyob rau hauv cov neeg mob uas mob myocardial infarction thiab cov neeg mob uas muaj mob qog noj ntshav [42,43]. Mozzarella tau raug tshaj tawm tias muaj feem cuam tshuam nrog kev noj zaub mov kom tsawg ntawm fatty acids [44]. Kev loj hlob ntawm Tyzzerella yog inhibited los ntawm kev sib txuas ntxiv ntawm cov brownie thiab cov khoom noj qab zib siab [45]. E. coprostanoligeneswas correlated nrog qib ntawm diacylglycerols [46]. Kev txo qis hauv E. coprostanoligenes tau cuam tshuam nrog cov ntshav aspartate transferase (AST) thiab ALT qib hauv cov nas uas muaj rog ntau [47].
Intestinimonas spp. tau kuaj pom nyob rau hauv lysine-enriched quav dilutions, thiabIntestinimonas-zoo li kab mob hu ua butyrate producers, uas siv lysine thiab Nεfructosyllysine nyob rau hauv cov mis nyuj pub mis nyuj thiab cov neeg laus [48]. Kev txo qis ntawm cov kab mob no tuaj yeem cuam tshuam rau lub cev tiv thaiv kab mob thiab kev ua haujlwm metabolic ntawm tus tswv.Cov txheeb ze ntawm Alistipes, Clostridium ASF 356, Clostridiales, thiab LachnospiraceaeUCG 004 tau ua kom muaj txiaj ntsig zoo los ntawm PFOA raug. Alistipes yog cov kab mob pathogenic, thiab nws tau nce los ntawm kev noj zaub mov muaj roj ntau thiab cov khoom noj muaj sucrose [49].
Alistipes raug suav hais tias yog lub plab microbiota marker uas tau koom nrog cov neeg mob rog rog uas muaj ntau yam kev mob metabolic [50]. Ntau dua ntawm Alistipes tau pom nyob rau hauv cov neeg mob uas muaj cov kab mob sib txawv ntawm lub paj hlwb, suav nrog Alzheimer's kab mob, tsis hnov lus tsis zoo siab, schizophrenia, autism spectrum tsis meej, kev nyuaj siab loj, Parkinson's disease, thiab kev puas siab puas ntsws bipolar [51]. Tsis tas li ntawd, Alistipes raug cais tawm ntawm cov neeg mob nrog lub plab thiab qhov quav abscesses thiab cuam tshuam nrog kev nyuaj siab thiab mob qog noj ntshav [52]. Raws li cov kab mob uas ua rau cov kab mob uas tsis muaj kab mob, qhov ntau ntawm Alistipes tuaj yeem nce ntxiv los ntawm kev noj zaub mov zoo rau tsiaj [53].
Lub enrichment ntawm Alistipes kuj yog induced los ntawm kev noj haus supplementation ntawm castalagin, uas yog ib tug active compound nyob rau hauv lub polyphenol-richberry camu-camu [54]. Ib qho kev tshawb fawb hauv vitro tau qhia tias Clostridium ASF 356 consumedisoleucine, valine, alanine, threonine, lactate, thiab lwm yam metabolites, thiab nws kuj tau koom nrog hauv kev pub mis. Qee hom hauv Clostridium yog cov kab mob, xws li C. difficile.Bile acid metabolism tau cuam tshuam los ntawm PFOA raug rau hauv txoj kev tshawb no. Cov kua tsib acids tau tsim nyob rau hauv daim siab los ntawm cov roj (cholesterol) thiab khaws cia rau hauv lub gallbladder, thiab lawv raug tso tawm rau hauv cov hnyuv hauv cov lus teb rau kev noj mov thiab tom qab ntawd dhau los ntawm cov kab mob enterohepatic.
Ua ntej tso tawm, thawj cov kua tsib acids feem ntau yog conjugated rau taurine thiab glycine.Primary bile acids, cholic acid, thiab chenodeoxycholic acid tuaj yeem hloov mus rau hauv cov kua tsib acids los ntawm cov kua tsib acid deconjugation thiab 7-alpha hydroxylation. Lub plab microbiotacan tswj cov kua tsib kua qaub metabolism los ntawm kev txo cov tauro- -muricholic acid theem, uas yog ib tug nuclear receptor farnesoid X receptor (FXR) antagonist [55]. Lub synthesis ntawm bileacids yog nyob rau hauv kev tswj tsis zoo nyob rau hauv daim siab thiab ileum los ntawm FXR activation [55].Ib qho kev koom tes ntawm cov kua tsib kua qaub thiab ob leeg ntshav PFOA thiab fetal loj hlob endpointswas pom nyob rau hauv ib pawg ntawm 313 cev xeeb tub African-Asmeskas cov poj niam [56].
Cov kua qaub ntau ntxiv vim yog sib xyaw ntawm tsib PFAS, uas muaj PFOA, PFOS, PFNA, PFHxS, thiab GenX, tau pom hauv C57BL / 6J nas [57]. Lub hnub nyoog ntsig txog cov plab hnyuv plab tuaj yeem ua rau muaj kev cuam tshuam los ntawm probiotic cocktail supplementation los ntawm kev ua kom cov dej ntawm cov dej ntsev hydrolase, ua rau muaj kev nce hauv taurine uas txhawb nqa nruj junctions [58] .Qhov tsis txaus ntawm cov kua tsib acids uas cuam tshuam los ntawm dysbiosis tuaj yeem txhawb cov kab mob hauv plab, uas tuaj yeem ua tau. alleviated los ntawm supplementation ntawm theem nrab bileacids nyob rau hauv nas qauv [59].
Kev puas tsuaj ntawm cov noob qhia koom nrog hauv cov kua tsib acid metabolism los ntawm PFOA tau tshaj tawm hauv tib neeg HepaRG hepatoma hlwb. Hauv particular, CYP7A1, qhov tseem ceeb enzymecatalyzing tus nqi-txheej theem ntawm cov kua tsib acid synthesis, tau txo qis [60].
Ntxiv nrog rau cov enzymes koom nrog hauv bile acid biosynthesis, cov theem qhia ntawm cov noob muaj feem xyuam rau kev thauj mus los ntawm bileacid, Bsep, thiab Mrp2, kuj raug txo los ntawm PFOA hauv 3D thawj nas liverspheroid qauv [61]. Tsis tas li ntawd, PFOA tau raug tshaj tawm tias muaj kev cuam tshuam nrog tib neeg kev thauj khoom bileacid Na + / taurocholate co-transporting polypeptide [62]. PFOA txo lawvRNA thiab cov protein qhia ntawm cov organic anion thauj polypeptides1a1, 1a4, thiab1b2 hauv tus qauv nas los ntawm kev ua kom cov peroxisome proliferator-activated receptor (PPAR) alpha; Cov no yog cov thauj khoom loj uas muaj lub luag haujlwm rau kev tso cov kua tsib kua qaub rau hauv lub siab [63].
Kev hloov pauv ntawm tryptophan metabolism yog qhov tshaj tawm tshaj tawm PFAS-txuas metabolicsignature hauv tib neeg kev tshawb fawb [64]. Cov plab hnyuv microbes tuaj yeem hloov pauv tryptophan rau hauv indole thiab nws cov derivatives, xws li 3-indole acrylic acid thiab 3-indoleacetic acid, qib uas raug txo los ntawm PFOA raug rau hauv txoj kev tshawb no. Hauv particular, 3-indoleacetic acid tau tshaj tawm los txhawb txoj hnyuv epithelial barrier muaj nuj nqi thiab suppress inflammatory teb [65]. Lub peev xwm ntawm caj ces ntawm plab hnyuv microorganisms siv mucins thiab metabolizingtryptophan raug txo qis hauv cov neeg mob uas mob plab hnyuv [65].
Raws li cytoplastic receptor, AhR yog qhov tseem ceeb hauv cov ntaub so ntswg homeostasis thiab kev tiv thaiv kab mob, uas tso cai rau kev hloov pauv ntawm lub cev tiv thaiv kab mob rau ib puag ncig [66]. Ntxiv mus, 3-indoleaceticacid tau tshaj tawm tias yog ib qho ntawm cov tseem ceeb activators ntawm AhR nyob rau hauv cov ntsiab lus cecal ntawm nas thiab quav cov qauv los ntawm tib neeg cov neeg koom [67]. Tsis tas li ntawd, 3-indoleacetic acid tuaj yeem txhawb txoj kev ua haujlwm ntawm lub plab zom mov thiab txo qis cov lus teb los ntawm kev ua haujlwm ntawm AhR transcription factor, uas txhawb nqa AhR-dependent IL-22transcription [68]; 3-indoleacetic acid kuj yog tus activator ntawm pregnane X receptor (PXR), uas induces IL-35+ B cell tiam ua ke nrog lipopolysaccharide los ntawm PXRand Hu-zoo li receptor 4 [69]. Tsis tas li ntawd, 3-indoleacetic acid muaj txiaj ntsig zoo xws li alleviating ankylosing spondylitis [70]; 3-indoleacetic acid tau txo qis hauv cov nas noj cov zaub mov muaj roj ntau [71].
Ntxiv ntawm 3-indoleacetic acid tuaj yeem ua rau mob siab rau cov kab mob hauv lub siab los ntawm kev txo qis ntawm cov lus teb inflammatory, oxidative stress, thiab hepatic lipogenesis [72]. Ntxiv mus, 3-indoleacetic acid cuam tshuam rau kev kho mob zoo hauv cov neeg mob uas mob qog noj ntshav pancreatic hauv ob txoj kab mob pancreaticductal adenocarcinoma cohorts [73]. Nyob rau hauv tus qauv pancreatic ductal adenocarcinoma nas, fecal microbiota hloov pauv thiab ntxiv ntawm 3-indoleacetic acid kuj tuaj yeem txhim kho cov tshuaj khomob zoo hauv tib neeg gnotobiotic nas [73]. Nrog rautxo ntawm 3-indole acrylic acid thiab 3-indoleacetic acid los ntawm PFOA, cov txiaj ntsig zoo no yuav raug cuam tshuam.
Txoj kev tshawb no muaj ntau yam kev txwv. Ua ntej, txoj kev tshawb no tsuas yog suav nrog txiv neej nas, hos poj niam nas tsis suav nrog. Txoj kev tshawb fawb txog poj niam txiv neej sib npaug uas suav nrog cov txiv neej thiab poj niam nas tuaj yeem txhim kho qhov kev kawm no. Qhov thib ob, PFOA qib hauv cov dej haus uas cov nas tswj tau txais tsis pom. Xav txog qhov kev faib tawm dav dav ntawm PFOA, muaj qhov tshwm sim uas cov dej haus uas tswj cov micerceived muaj qis PFOA. PFOA qib hauv cov dej haus tau tshaj tawm tias nyob nruab nrab ntawm 20 thiab 70 ng / L hauv Georgia, US [74]. Txhawm rau kuaj cov nyhuv tshuaj lom ntawm PFOAon lub plab-microbiota-hais txog cov metabolites, qhov cuam tshuam ntawm qhov kev tshawb fawb no tau teeb tsa rau 1 ppm, uas yog siab dua li cov qib ib puag ncig. Cov koob tshuaj yuav tsum tau txo qis cov kev tshawb fawb yav tom ntej los tshawb txog kev noj qab haus huv ntawm PFOA ntawm ib puag ncig cuam tshuam.
5. Cov lus xaus
PFOA tau dhau los ua kev txhawj xeeb txog kev noj qab haus huv rau pej xeem tsis ntev los no. Nyob rau hauv txoj kev tshawb no, PFOAdisturbed ob lub plab microbiota muaj pes tsawg leeg thiab cov metabolic profiles ntawm cov quav, ntshav, thiab daim siab nyob rau hauv nas. Ib qho kev sib raug zoo tau pom ntawm lub plab microbiota thiab cov metabolites sib txawv. PFOA raug cuam tshuam ua rau muaj kev hloov pauv loj ntawm plab-microbiota-txog metabolites, suav nrog cov kua tsib acids thiab tryptophan metabolites, xws li 3-indoleacrylic acid thiab 3-indoleacetic acid. Peb qhov kev tshawb pom tuaj yeem txhim kho kev nkag siab txog kev noj qab haus huv ntawm PFOA kho los ntawm lub plab microbiota.
Ntuj Herbal Tshuaj Rau Relieving cem quav-Cistanche
Cistanche yog ib tug genus ntawm parasitic nroj tsuag uas belongs rau tsev neeg Orobanchaceae. Cov nroj tsuag no paub txog lawv cov khoom siv tshuaj thiab tau siv hauv Cov Tshuaj Suav Tshuaj (TCM) rau ntau pua xyoo. Cov hom Cistanche feem ntau pom muaj nyob hauv thaj av qhuav thiab suab puam ntawm Tuam Tshoj, Mongolia, thiab lwm qhov chaw ntawm Central Asia. Cistanche nroj tsuag yog tus cwj pwm los ntawm lawv cov nqaij tawv, yellowish stems thiab muaj nuj nqis heev rau lawv cov txiaj ntsig kev noj qab haus huv. Hauv TCM, Cistanche ntseeg tau tias muaj cov khoom siv tonic thiab feem ntau yog siv los kho lub raum, txhim kho qhov tseem ceeb, thiab txhawb kev ua haujlwm ntawm kev sib deev. Nws kuj yog siv los daws cov teeb meem ntsig txog kev laus, qaug zog, thiab kev noj qab haus huv tag nrho. Thaum Cistanche muaj keeb kwm ntev ntawm kev siv tshuaj ib txwm siv, kev tshawb fawb tshawb fawb txog nws txoj kev ua tau zoo thiab kev nyab xeeb yog tsis tu ncua thiab txwv. Txawm li cas los xij, nws paub tias muaj ntau yam bioactive tebchaw xws li phenylethanoid glycosides, iridoids, lignans, thiab polysaccharides, uas tuaj yeem ua rau nws cov teebmeem tshuaj.
Wecistanche covcistanche hmoov, cistanche ntsiav tshuaj, cistanche capsules, thiab lwm yam khoom tsim los sivsuab puamcistancheraws li cov khoom siv raw, txhua yam muaj txiaj ntsig zoo rau kev tshem tawm cem quav. Cov txheej txheem tshwj xeeb yog raws li hauv qab no: Cistanche ntseeg tau tias muaj cov txiaj ntsig zoo rau kev tshem tawm cem quav raws li nws cov kev siv ib txwm siv thiab qee cov tshuaj uas nws muaj. Txawm hais tias kev tshawb fawb tshawb fawb tshwj xeeb ntawm Cistanche qhov cuam tshuam rau cem quav yog txwv, nws tau xav tias muaj ntau lub tswv yim uas yuav ua rau nws muaj peev xwm txo tau cem quav. Laxative nyhuv:Cistanchetau ntev tau siv nyob rau hauv tsoos suav tshuaj raws li ib tug tshuaj rau cem quav. Nws ntseeg tau tias muaj cov nyhuv laxative me me, uas tuaj yeem pab txhawb kev zom zaub mov thiab ua rau cem quav. Cov nyhuv no tuaj yeem raug ntaus nqi rau ntau lub tebchaw hauv Cistanche, xws li phenylethanoid glycosides thiab polysaccharides. Moistening cov hnyuv: Raws li kev siv ib txwm siv, Cistanche suav hais tias muaj cov khoom siv moisturizing, tshwj xeeb yog tsom rau cov hnyuv. Txhawb nqa dej thiab lubrication ntawm cov hnyuv yuav pab tau cov cuab yeej soften thiab yooj yim dua, yog li no relieving cem quav. Anti-inflammatory Effect: cem quav tej zaum yuav txuam nrog o nyob rau hauv lub plab zom mov. Cistanche muaj qee qhov sib txuas, suav nrog phenylethanoid glycosides thiab lignans, uas ntseeg tau tias muaj cov tshuaj tiv thaiv kab mob. Los ntawm kev txo cov kab mob hauv cov hnyuv, nws tuaj yeem pab txhim kho kev zom zaub mov tsis tu ncua thiab txo qhov cem quav.
