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Tlhahlobo ea pele ea essential tremor (ET) e ka ba phephetso, haholo-holo ha e khetholloa ho taolo e phetseng hantle (HC) le lefu la Parkinson (PD). Haufinyane tjena, tlhahlobo ea lisampole tsa mantle bakeng sa microbiota ea mala le metabolites ea eona e fane ka mekhoa e mecha ea ho sibolla li-biomarker tse ncha tsa mafu a methapo. Li-fatty acid tse khutšoane (SCFA), e le metabolite e ka sehloohong ea limela tsa mala, li fokotseha mantle ho PD. Leha ho le joalo, SCFA ea mantle ha e so ka e ithutoa ho ET. Re ne re ikemiselitse ho batlisisa maemo a mantle a SCFA ho ET, ho hlahloba kamano ea tsona le matšoao a kliniki le microbiota ea mala, le ho fumana bokhoni ba tsona ba ho hlahloba. SCFA ea mantle le microbiota ea mala li lekantsoe ho ET tse 37, PD tse ncha tse 37, le HC tse 35. Ho pipitleloa, ho se sebetse hantle ha autonomic, le ho thothomela ho matla li ile tsa hlahlojoa ho sebelisoa likala. Maemo a mantle a propionate, butyrate, le isobutyrate a ne a le tlase ho ET ho feta ho HC. Motsoako oa li-acid tsa propionic, butyric le isobutyric o ile oa khetholla ET ho HC ka AUC ea 0.751 (95% CI: 0.634–0.867). Maemo a asiti ea isovaleric ea fecal le isobutyric acid a ne a le tlase ho ET ho feta ho PD. Asiti ea Isovaleric le isobutyric acid li khetholla pakeng tsa ET le PD ka AUC ea 0.743 (95% CI: 0.629–0.857). Fecal propionate e amahanngoa ka tsela e fapaneng le ho pipitleloa le ho se sebetse hantle ha autonomic. Asiti ea Isobutyric le isovaleric acid li amana ka tsela e fapaneng le ho thothomela ho matla. Ho fokotseha ha litaba tsa SCFA ea fecal ho ne ho amahanngoa le ho fokotseha ha bongata ba Faecalibacterium le Streptobacterium ho ET. Kahoo, litaba tsa SCFA mantle lia fokotseha ho ET 'me li amahanngoa le ho teba ha setšoantšo sa kliniki le liphetoho ho microbiota ea mala. Asiti ea Propionic, asiti ea butyric, asiti ea isobutyric, le asiti ea isovaleric ka har'a mantle e ka ba li-biomarker tse ka bang teng tsa tlhahlobo le tse fapaneng bakeng sa ET.
Ho thothomela ho matla (ET) ke lefu le tsoelang pele, le sa foleng la methapo ea kutlo le khetholloang haholo-holo ke ho thothomela ha litho tse ka holimo, tse ka boela tsa ama likarolo tse ling tsa 'mele tse kang hlooho, lithapo tsa lentsoe le litho tse ka tlase 1. Litšobotsi tsa kliniki tsa ET ha li kenyelle matšoao a ho sisinyeha feela empa hape le matšoao a mang a seng a mesifa, ho kenyeletsoa le lefu la mala 2. Lithuto tse ngata li entsoe ho hlahloba litšobotsi tsa pathological le tsa 'mele tsa ho thothomela ho matla, empa mekhoa e hlakileng ea pathophysiological ha e so fumanoe3,4. Lithuto tsa morao tjena li bontša hore ho se sebetse hantle ha motsoako oa microbiota-gut-brain ho ka kenya letsoho mafung a methapo ea kutlo, 'me ho na le bopaki bo ntseng bo hola ba khokahano e ka bang teng lipakeng tsa microbiota ea mala le mafu a methapo ea kutlo5,6. Haholo-holo, tlalehong e 'ngoe ea nyeoe, ho kenngoa ha microbiota ea mantle ho ntlafalitse essential tremor le irritable bowel syndrome ho mokuli, e leng se ka bontšang kamano e haufi pakeng tsa microbiota ea mala le essential tremor. Ho phaella moo, re boetse re fumane liphetoho tse itseng ho microbiota ea mala ho bakuli ba nang le ET, e tšehetsang ka matla karolo ea bohlokoa ea dysbiosis ea mala ho ET8.
Mabapi le dysbiosis ea mala mafung a methapo ea kutlo, PD ke eona e ithutoang haholo5. Microbiota e sa leka-lekanang e ka eketsa ho kenella ha mala le ho kenya tšebetsong glia ea mala, e leng se lebisang ho alpha-synucleinopathies9,10,11. PD le ET li na le litšobotsi tse itseng tse tšoanang, joalo ka makhetlo a tšoanang a ho thothomela ho bakuli ba ET le PD, ho thothomela ho phomotseng ho phomola (ho thothomela ho tloaelehileng ho PD), le ho thothomela ha boemo ba 'mele (bo fumanehang haholo ho bakuli ba ET), ho etsang hore ho be thata ho khetholla pakeng tsa bona. mekhahlelo ea pele ea 12. Ka hona, re hloka ka potlako ho bula fensetere e thusang ho khetholla pakeng tsa ET le PD. Moelelong ona, ho ithuta dysbiosis e itseng ea mala le liphetoho tse amanang le metabolite ho ET le ho khetholla liphapang tsa tsona ho PD e ka ba li-biomarker tse ka bang teng bakeng sa tlhahlobo le tlhahlobo e fapaneng ea ET.
Li-acid tse nang le mafura a makhutšoane (SCFAs) ke li-metabolite tse kholo tse hlahisoang ke ho belisoa ha baktheria ea mala ea faeba ea lijo 'me ho nahanoa hore li bapala karolo ea bohlokoa likamanong tsa mala le boko13,14. Li-SCFA li nkuoa ke lisele tsa colon 'me li isoa sebeteng ka sistimi ea methapo ea portal, 'me li-SCFA tse ling li kena potolohong ea mali ea 'mele. Li-SCFA li na le litlamorao tsa lehae ho bolokeng botšepehi ba mokoallo oa mala le ho khothaletsa sesole sa 'mele sa tlhaho ka har'a mucosa ea mala15. Li boetse li na le litlamorao tsa nako e telele mokoallong oa mali le boko (BBB) ​​​​ka ho hlohlelletsa liprotheine tse kopaneng tse tiileng le ho kenya tšebetsong li-neurone ka ho hlohlelletsa li-receptor tsa protheine tse kopantsoeng le G (GPCRs) ho tšela BBB16. Acetate, propionate, le butyrate ke li-SCFA tse ngata ka ho fetisisa ka har'a colon. Lithuto tsa pejana li bontšitse maemo a fokotsehileng a acetic, propionic le butyric acid ho bakuli ba nang le lefu la Parkinson17. Leha ho le joalo, maemo a SCFA ea fecal ha a e-so ka a ithutoa ho bakuli ba nang le ET.
Ka hona, phuputso ea rona e ne e reretsoe ho khetholla liphetoho tse itseng ho SCFA ea mantle ho bakuli ba nang le ET le liphapang tsa tsona ho bakuli ba nang le PD, ho hlahloba kamano ea SCFA ea mantle le matšoao a kliniki a SCFA le microbiota ea mala, hammoho le ho khetholla bokhoni ba ho hlahloba le ho khetholla ba lisampole tsa mantle. KZHK. Ho sebetsana le lintlha tse ferekanyang tse amanang le meriana e loantšang PD, re khethile bakuli ba nang le lefu la Parkinson le lecha e le taolo ea mafu.
Litšobotsi tsa batho le tsa bongaka tsa ET tse 37, PD tse 37, le HC tse 35 li akaretsoa ho Tafole ea 1. ET, PD, le HC li ne li bapisoa ka lilemo, bong le BMI. Lihlopha tsena tse tharo le tsona li ne li e-na le litekanyo tse tšoanang tsa ho tsuba, ho noa joala le ho noa kofi le tee. Lintlha tsa Wexner (P = 0.004) le HAMD-17 (P = 0.001) tsa sehlopha sa PD li ne li le holimo ho feta tsa sehlopha sa HC, 'me lintlha tsa HAMA (P = 0.011) le lintlha tsa HAMD-17 (P = 0.011) tsa sehlopha sa ET li ne li le holimo ho feta tsa sehlopha sa HC. Tsela eo lefu lena le ileng la hlaha ka eona sehlopheng sa ET e ne e le telele haholo ho feta sehlopheng sa PD (P<0.001).
Ho bile le dipharologanyo tse kgolo maemong a mantle a asiti ya propionic ya mantle (P = 0.023), asiti ya acetic (P = 0.039), asiti ya butyric (P = 0.020), asiti ya isovaleric (P = 0.045), le asiti ya isobutyric (P = 0.015). . Tlhahlobong e nngwe ya kamora hoc, maemo a asiti ya propionic (P = 0.023), asiti ya butyric (P = 0.007), le asiti ya isobutyric (P = 0.040) sehlopheng sa ET a ne a le tlase haholo ho feta a sehlopheng sa HC. Bakuli ba nang le ET ba ne ba na le maemo a tlase a isovalerate (P = 0.014) le isobutyrate (P = 0.005) ho feta bakudi ba nang le PD. Ho phaella moo, maemo a fecal propionic acid (P = 0.013), acetic acid (P = 0.016), le butyric acid (P = 0.041) a ne a le tlase ho bakuli ba nang le PD ho feta ho bakuli ba nang le CC (Setšoantšo sa 1 le Tafole e Tlatsetsang ea 1).
ag e emela papiso ea sehlopha sa propionic acid, acetic acid, butyric acid, isovaleric acid, valeric acid, caproic acid le isobutyric acid, ka ho latellana. Ho bile le liphapang tse kholo maemong a fecal propionic acid, acetic acid, butyric acid, isovaleric acid le isobutyric acid lipakeng tsa lihlopha tse tharo. ET essential tremor, lefu la Parkinson, taolo e phetseng hantle ea HC, SCFA. Liphapang tse kholo li bontšoa ke *P < 0.05 le **P < 0.01.
Ha re nahana ka phapang ea tsela ea lefu pakeng tsa sehlopha sa ET le sehlopha sa PD, re ile ra leka bakuli ba 33 ba nang le PD ea pele le bakuli ba 16 ba nang le ET (lefu la ≤ lilemo tse 3) bakeng sa papiso e 'ngoe (Tafole e Tlatsetsang ea 2). Liphetho li bontšitse hore tekanyo ea asiti ea propionic ea mantle ea ET e ne e le tlase haholo ho feta ea HA (P=0.015). Phapang pakeng tsa ET le HC bakeng sa asiti ea butyric le asiti ea isobutyric e ne e se ea bohlokoa, empa mokhoa o ntse o bonoa (P= 0.082). Maemo a isobutyrate ea mantle a ne a le tlase haholo ho bakuli ba nang le ET ha a bapisoa le bakuli ba nang le PD (P= 0.030). Phapang pakeng tsa ET le PD ea asiti ea isovaleric e ne e se ea bohlokoa, empa ho ne ho ntse ho e-na le mokhoa (P= 0.084). Asiti ea Propionic (P = 0.023), asiti ea acetic (P = 0.020), le asiti ea butyric (P = 0.044) li ne li le tlase haholo ho bakuli ba PD ho feta ho bakuli ba HC. Liphetho tsena (Setšoantšo se Tlatsetsang sa 1) hangata li lumellana le liphetho tse kholo. Phapang lipakeng tsa sampole ka kakaretso le sehlopha se senyenyane sa bakuli ba pele e ka bakoa ke boholo bo bonyenyane ba sampole sehlopheng se senyenyane, e leng se fellang ka matla a tlase a lipalo-palo a data.
Ka mor'a moo re ile ra hlahloba hore na maemo a SCFA a mantle a ka khetholla bakuli ba nang le ET ho bakuli ba nang le CU kapa PD. Ho ea ka tlhahlobo ea ROC, phapang ho AUC ea maemo a propionate e ne e le 0.668 (95% CI: 0.538-0.797), e leng se ileng sa etsa hore ho khonehe ho khetholla bakuli ba nang le ET ho tsoa ho HC. Bakuli ba nang le ET le GC ba ka khetholloa ka maemo a butyrate ka AUC ea 0.685 (95% CI: 0.556–0.814). Phapang maemong a isobutyric acid e ka khetholla bakuli ba nang le ET ho tsoa ho HC ka AUC ea 0.655 (95% CI: 0.525–0.786). Ha ho kopanngoa maemo a propionate, butyrate le isobutyrate, AUC e phahameng ea 0.751 (95% CI: 0.634–0.867) e fumanoe ka kutloisiso ea 74.3% le ho totobala ha 72.9% (Setšoantšo sa 2a). Ho khetholla pakeng tsa bakuli ba ET le PD, AUC bakeng sa maemo a isovaleric acid e ne e le 0.700 (95% CI: 0.579–0.822) 'me bakeng sa maemo a isobutyric acid e ne e le 0.718 (95% CI: 0.599–0.836). Motsoako oa maemo a isovaleric acid le isobutyric acid o ne o e-na le AUC e phahameng ea 0.743 (95% CI: 0.629–0.857), kutloisiso ea 74.3% le ho totobala ha 62.9% (Setšoantšo sa 2b). Ho phaella moo, re hlahlobile hore na maemo a SCFA mantle a bakuli ba nang le lefu la Parkinson a fapane le a taolo. Ho ya ka tlhahlobo ya ROC, AUC bakeng sa ho hlwaya bakudi ba nang le PD ho latela dipharologanyo maemong a propionic acid e ne e le 0.687 (95% CI: 0.559-0.814), ka kutlwisiso ya 68.6% le ho ikgetha ha 68.7%. Dipharologanyo maemong a acetate di ka kgetholla bakudi ba PD ho HCs tse nang le AUC ya 0.674 (95% CI: 0.542–0.805). Bakudi ba nang le PD ba ka kgethollwa ho tloha ho CU feela ka maemo a butyrate ka AUC ya 0.651 (95% CI: 0.515–0.787). Ha ho kopanngwa maemo a propionate, acetate le butyrate, AUC ya 0.682 (95% CI: 0.553–0.811) e fumanwe (Setshwantsho sa 2c).
Khethollo ea Kereke ea Orthodox ea Russia khahlanong le ET le HC; khethollo ea Kereke ea Orthodox ea Russia khahlanong le ET le PD; khethollo ea ROC khahlanong le PD le HC. ET essential tremor, lefu la Parkinson, taolo e phetseng hantle ea HC, SCFA.
Ho bakuli ba nang le ET, maemo a asiti ea isobutyric ea mantle a ne a amana hampe le lintlha tsa FTM (r = -0.349, P = 0.034), 'me maemo a asiti ea isovaleric ea mantle a ne a amana hampe le lintlha tsa FTM (r = -0.421, P = 0.001) le lintlha tsa TETRAS. (r = -0.382, P = 0.020). Ho bakuli ba nang le ET le PD, maemo a propionate ea mantle a ne a amana hampe le lintlha tsa SCOPA-AUT (r = -0.236, P = 0.043) (Setšoantšo sa 3 le Tafole e Tlatsetsang ea 3). Ho ne ho se na kamano e kholo pakeng tsa tsela ea lefu le SCFA sehlopheng sa ET (P ≥ 0.161) kapa sehlopheng sa PD (P ≥ 0.246) (Tafole e Tlatsetsang ea 4). Ho bakuli ba nang le PD, maemo a caproic acid ea fecal a ne a amana hantle le lintlha tsa MDS-UPDRS (r = 0.335, P = 0.042). Ho barupeluoa bohle, maemo a fecal propionate (r = −0.230, P = 0.016) le acetate (r = −0.210, P = 0.029) a ne a amana hampe le lintlha tsa Wexner (Setšoantšo sa 3 le Tafole e Tlatsetsang ea 3).
Maemo a asiti ya isobutyric ya fecal a ne a amana hampe le dintlha tsa FTM, asiti ya isovaleric e ne e amana hampe le dintlha tsa FTM le TETRAS, asiti ya propionic e ne e amana hampe le dintlha tsa SCOPA-AUT, asiti ya caproic e ne e amana hantle le dintlha tsa MDS-UPDRS, mme asiti ya propionic e ne e amana hampe le dintlha tsa FTM le TETRAS. TETRAS le asiti ya acetic di ne di amana hampe le lintlha tsa Wexner. Mokhatlo wa MDS-UPDRS o tsheheditse mofuta wa Sekala sa Tekanyetso ya Mafu a Unified Parkinson, Mini-Mental State Examination MMSE, Sekala sa Tekanyetso ya Kgatelelo ...
Re ile ra boela ra hlahloba tlhaho e khethollang ea microbiota ea mala re sebelisa tlhahlobo ea LEfSE 'me ra khetha boemo ba data ea bongata bo amanang le mofuta bakeng sa tlhahlobo e eketsehileng. Ho ile ha etsoa lipapiso pakeng tsa ET le HC le pakeng tsa ET le PD. Tlhahlobo ea kamano ea Spearman e ile ea etsoa holim'a bongata bo amanang le microbiota ea mala le maemo a SCFA ea mantle lihlopheng tse peli tsa papiso.
Faecalibacterium (e amanang le asiti ea butyric, r = 0.408, P < 0.001), Lactobacillus (e amanang le asiti ea butyric, r = 0.283, P = 0.016), Streptobacterium (e amanang le asiti ea propionic, r = 0.327) e ne e le teng tlhahlobong ea ET le CA. , P = 0.005; e amanang le asiti ea butyric, r = 0.374, P = 0.001; e amana le asiti ea isobutyric, r = 0.329, P = 0.005), Howardella (e amana le asiti ea propionic, r = 0.242, P = 0.041), Raoultella (e amana le propionate, r = 0.249, P = 0.035), 'me Candidatus Arthromitus (e amana le asiti ea isobutyric, r = 0.302, P = 0.010) e fumanoe e fokotsehile ho ET 'me e amana hantle le maemo a SCFA a mantle. Leha ho le joalo, bongata ba Stenotropomonas bo ile ba eketseha ho ET 'me bo ne bo amana hampe le maemo a isobutyrate a mantle (r = -0.250, P = 0.034). Kamora phetoho ea FDR, ke likamano feela lipakeng tsa Faecalibacterium, Catenibacter, le SCFA tse ileng tsa sala li le bohlokoa (P ≤ 0.045) (Setšoantšo sa 4 le Tafole e Tlatsetsang ea 5).
Tlhahlobo ea kamano ea ET le HC. Kamora tokiso ea FDR, bongata ba Faecalibacterium (e amanang hantle le butyrate) le Streptobacterium (e amanang hantle le propionate, butyrate, le isobutyrate) bo fumanoe bo fokotsehile ho ET 'me bo amahanngoa hantle le maemo a SCFA a mantle. b Tlhahlobo ea kamano ea ET le PD. Kamora tokiso ea FDR, ha ho na likamano tsa bohlokoa tse fumanoeng. ET essential tremor, lefu la Parkinson, taolo e phetseng hantle ea HC, SCFA. Liphapang tse kholo li bontšoa ke *P < 0.05 le **P < 0.01.
Ha ho sekasekwa ET khahlanong le PD, ho fumanoe hore Clostridium trichophyton e eketsehile ho ET mme e amana le fecal isovaleric acid (r = -0.238, P = 0.041) le isobutyric acid (r = -0.257, P = 0.027). ). Kamora phetoho ea FDR, e 'ngoe ea tsona e ile ea lula e le ea bohlokoa (P≥0.295) (Setšoantšo sa 4 le Tafole e Tlatsetsang ea 5).
Phuputso ena ke phuputso e felletseng e hlahlobang maemo a SCFA a mantle mme e a amahanya le diphetoho tsa microbiota ya mala le boima ba matshwao ho bakudi ba nang le ET ha ba bapiswa le bakudi ba nang le CU le PD. Re fumane hore maemo a SCFA a mantle a fokotsehile ho bakudi ba nang le ET mme a ne a amana le boima ba kliniki le diphetoho tse itseng ho microbiota ya mala. Maemo a bokellanang a di-fatty acid tse kgutshwane (di-SCFA) mantleng a kgetholla ET ho GC le PD.
Ha ho bapisoa le bakuli ba GC, bakuli ba ET ba na le maemo a tlase a mantle a li-acid tsa propionic, butyric, le isobutyric. Motsoako oa li-acid tsa propionic, butyric le isobutyric o ka khetholla pakeng tsa ET le HC ka AUC ea 0.751 (95% CI: 0.634–0.867), kutloisiso ea 74.3% le ho hlaka ha 72.9%, ho bontšang tšebeliso ea tsona e le karolo e ka bang teng e le li-biomarker tsa tlhahlobo bakeng sa ET. Tlhahlobo e 'ngoe e bontšitse hore maemo a acid ea propionic ea mantle a ne a amana hampe le lintlha tsa Wexner le lintlha tsa SCOPA-AUT. Maemo a acid ea isobutyric ea mantle a ne a amana ka tsela e fapaneng le lintlha tsa FTM. Ka lehlakoreng le leng, ho fokotseha ha maemo a butyrate ho ET ho ne ho amahanngoa le ho fokotseha ha bongata ba microbiota e hlahisang SCFA, Faecalibacterium, le Categorybacter. Ho phaella moo, ho fokotseha ha bongata ba Catenibacter ho ET ho ne ho boetse ho amahanngoa le ho fokotseha ha maemo a acid ea propionic le isobutyric ea mantle.
Bongata ba li-SCFA tse hlahisoang ka har'a mala li nkuoa ke li-colonocyte haholo-holo ka li-transporter tsa monocarboxylate tse itšetlehileng ka H+ kapa tse itšetlehileng ka sodium. Li-acid tse nang le ketane e khuts'oane tse monngoang li sebelisoa e le mohloli oa matla bakeng sa li-colonocyte, athe tse sa sebelisoang ka har'a li-colonocyte li isoa ka har'a potoloho ea portal 18. Li-SCFA li ka susumetsa motility oa mala, tsa ntlafatsa ts'ebetso ea thibelo ea mala, 'me tsa susumetsa metabolism ea moamoheli le sesole sa 'mele19. Pele ho fumanoe hore mahloriso a mantle a butyrate, acetate, le propionate a fokotsehile ho bakuli ba PD ha a bapisoa le HCs17, e leng se lumellanang le liphetho tsa rona. Phuputso ea rona e fumane hore SCFA e fokotsehile ho bakuli ba nang le ET, empa ho tsejoa hanyane ka karolo ea SCFA ho pathology ea ET. Butyrate le propionate li ka tlama ho GPCRs 'me tsa susumetsa matšoao a itšetlehileng ka GPCR joalo ka MAPK le NF-κB20 signaling. Khopolo ea motheo ea motsoako oa mala le boko ke hore li-SCFA tse nkiloeng ke likokoana-hloko tsa mala li ka susumetsa matšoao a moamoheli, ka hona tsa susumetsa ts'ebetso ea mala le boko. Hobane butyrate le propionate li na le litlamorao tse matla tsa thibelo mosebetsing oa histone deacetylase (HDAC)21 mme butyrate le eona e ka sebetsa e le ligand bakeng sa lintlha tsa transcription, li na le litlamorao tse pharaletseng metabolism ea moamoheli, phapang le ho ata, haholo-holo ka lebaka la tšusumetso ea tsona taolong ea liphatsa tsa lefutso22. Ho ipapisitsoe le bopaki bo tsoang ho SCFA le mafu a neurodegenerative, butyrate e nkoa e le mokhethoa oa phekolo ka lebaka la bokhoni ba eona ba ho lokisa ts'ebetso e sa sebetseng hantle ea HDAC, e ka bakang lefu la dopaminergic neuron ho PD23,24,25. Lithuto tsa liphoofolo li boetse li bontšitse bokhoni ba butyric acid ho thibela ho senyeha ha dopaminergic neuron le ho ntlafatsa mathata a motsamao ho mehlala ea PD26,27. Propionic acid e fumanoe e fokotsa likarabo tsa ho ruruha le ho sireletsa botšepehi ba BBB28,29. Lithuto li bontšitse hore propionic acid e khothalletsa ho phela ha li-neuron tsa dopaminergic ho arabela chefo ea rotenone ho mehlala ea PD 30 le hore tsamaiso ea propionic acid ka molomo e pholosa tahlehelo ea dopaminergic neuron le khaello ea motlakase ho litoeba tse nang le PD 31. Ho tsejoa hanyane ka mosebetsi oa isobutyric acid. Leha ho le jwalo, phuputso ya moraorao e fumane hore ho kenngwa ha ditoeba tse nang le B. ovale ho ekeditse dikahare tsa SCFA ya mala (ho kenyeletswa acetate, propionate, isobutyrate, le isovalerate) le mahloriso a GABA ya mala, ho totobatsa hore ho se ho thehilwe kamano pakeng tsa makgopo a mala le mahloriso a SCFA ya mala a di-neurotransmitters32. Bakeng sa ET, diphetoho tse sa tlwaelehang tsa pathological ho cerebellum di kenyeletsa diphetoho ho axon le di-dendrite tsa sele ya Purkinje, ho falla le ho lahlehelwa ke disele tsa Purkinje, diphetoho ho axon tsa sele ya baskete, le ho se tloaelehe dikgokelong tsa faeba tse nyolohang ho di-nuclei tsa sele ya Purkinje, e leng se lebisang phokotsong ya tlhahiso ya GABAergic ho tswa ho cerebellum3,4,33. Ha ho so hlaka hore na di-SCFA di amana le ho senyeha ha methapo ya kutlo ya sele ya Purkinje le ho fokotseha ha tlhahiso ya GABA ya cerebellar. Diphetho tsa rona di bontsha kamano e haufi pakeng tsa SCFA le ET; leha ho le jwalo, moralo wa thuto ya dikarolo tse fapaneng ha o dumelle diqeto dife kapa dife mabapi le kamano ya sesosa pakeng tsa SCFA le tshebetso ya lefu la ET. Dithuto tse ding tsa ho latela nako e telele di a hlokahala, ho kenyeletswa le ditekanyo tse latellanang tsa di-SCFA tsa mantle, hammoho le dithuto tsa diphoofolo tse hlahlobang mekgwa.
Ho nahanoa hore li-SCFA li khothalletsa ho honyela ha mesifa e boreleli ea colonic34. Ho hloka SCFA ho tla mpefatsa matšoao a ho pipitleloa, 'me ho tlatsetsoa ka SCFA ho ka ntlafatsa matšoao a ho pipitleloa PD35. Liphetho tsa rona li boetse li bontša kamano e kholo pakeng tsa ho fokotseha ha litaba tsa SCFA tsa mantle le ho eketseha ha ho pipitleloa le ho se sebetse hantle ha autonomic ho bakuli ba nang le ET. Tlaleho e 'ngoe ea nyeoe e fumane hore ho kenngoa ha microbiota ho ntlafalitse essential tremor le irritable bowel syndrome ho mokuli oa 7, e leng se bontšang kamano e haufi pakeng tsa gut microbiota le ET. Ka hona, re lumela hore fecal SCFA/microbiota e ka ama motility oa mala le ts'ebetso ea tsamaiso ea methapo ea autonomic.
Phuputso e fumane hore maemo a fokotsehileng a li-SCFA tsa mantle ho ET a ne a amahanngoa le bongata bo fokotsehileng ba Faecalibacterium (e amanang le butyrate) le Streptobacterium (e amanang le propionate, butyrate, le isobutyrate). Kamora tokiso ea FDR, kamano ena e ntse e le ea bohlokoa. Faecalibacterium le Streptobacterium ke likokoana-hloko tse hlahisang SCFA. Faecalibacterium e tsejoa e le microorganism e hlahisang butyrate36, ha lihlahisoa tse ka sehloohong tsa ho belisoa ha Catenibacter e le acetate, butyrate le lactic acid37. Faecalibacterium e fumanoe ho 100% ea lihlopha tsa ET le HC; Bongata bo mahareng ba sehlopha sa ET e ne e le 2.06% mme ba sehlopha sa HC e ne e le 3.28% (LDA 3.870). Baktheria ea sehlopha e fumanoe ho 21.6% (8/37) ea sehlopha sa HC mme ke sampole e le 'ngoe feela ea sehlopha sa ET (1/35). Ho fokotseha le ho se fumanehe ha streptobacteria ho ET ho ka boela ha bontša kamano le ho ata ha lefu lena. Palo e mahareng ea mefuta ea Catenibacter sehlopheng sa HC e ne e le 0.07% (LDA 2.129). Ho phaella moo, libaktheria tsa lactic acid li ne li amahanngoa le liphetoho ho butyrate ea mantle (P=0.016, P=0.096 kamora phetoho ea FDR), 'me mokhethoa oa ramatiki o ne a amahanngoa le liphetoho ho isobutyrate (P=0.016, P=0.072 kamora phetoho ea FDR). Kamora tokiso ea FDR, ke mokhoa oa kamano feela o setseng, oo e seng oa bohlokoa ka lipalo-palo. Lactobacilli le tsona li tsejoa e le bahlahisi ba SCFA (acetic acid, propionic acid, isobutyric acid, butyric acid) 38 'me Candidatus Arthromitus ke ntho e ikgethang e bakang phapang ea lisele tsa T helper 17 (Th17), ka Th1/2 le Tregs tse amanang le botsitso ba' mele /Th1739. . Phuputso ea morao tjena e bontša hore maemo a phahameng a pseudoarthritis ea mantle a ka tlatsetsa ho ruruha ha mala a maholo, ho se sebetse hantle ha thibelo ea mala, le ho ruruha ha tsamaiso ea 'mele 40. Clostridium trichophyton e eketsehile ho ET ha e bapisoa le PD. Bongata ba Clostridium trichoides bo fumanoe bo amana hampe le isovaleric acid le isobutyric acid. Kamora ho lokisoa ha FDR, ka bobeli li ile tsa lula li le bohlokoa (P≥0.295). Clostridium pilosum ke baktheria e tsejoang e amahanngoa le ho ruruha 'me e ka tlatsetsa ho se sebetse hantle ha thibelo ea mala a maholo41. Phuputso ea rona ea pele e tlalehile liphetoho ho microbiota ea mala a bakuli ba nang le ET8. Mona re boetse re tlaleha liphetoho ho SCFAs ho ET 'me re khetholla kamano pakeng tsa dysbiosis ea mala le liphetoho ho SCFAs. Maemo a fokotsehileng a SCFA a amana haufi-ufi le dysbiosis ea mala le ho thothomela ho matla ho ET. Liphetho tsa rona li bontša hore motsoako oa mala le boko o ka bapala karolo ea bohlokoa ho pathogenesis ea ET, empa lithuto tse ling mehlaleng ea liphoofolo lia hlokahala.
Ha ho bapisoa le bakuli ba nang le PD, bakuli ba nang le ET ba na le maemo a tlase a isovaleric le isobutyric acid mantle a bona. Motsoako oa isovaleric acid le isobutyric acid o hlwaile ET ho PD ka AUC ea 0.743 (95% CI: 0.629–0.857), kutloisiso ea 74.3% le ho hlaka ha 62.9%, e leng se bontšang karolo ea bona e ka bang teng e le li-biomarker tlhahlobong e fapaneng ea ET. Maemo a fecal isovaleric acid a ne a amana ka tsela e fapaneng le lintlha tsa FTM le TETRAS. Maemo a fecal isobutyric acid a ne a amana ka tsela e fapaneng le lintlha tsa FTM. Ho fokotseha ha maemo a isobutyric acid ho ne ho amahanngoa le ho fokotseha ha bongata ba catobacteria. Ha ho tsejoe hakaalo ka mesebetsi ea isovaleric acid le isobutyric acid. Phuputso e fetileng e bontšitse hore ho kolonea ha litoeba ka Bacteroides ovale ho ekelitse litaba tsa SCFA mala (ho kenyeletsoa acetate, propionate, isobutyrate, le isovalerate) le mahloriso a GABA mala, e leng se totobatsang kamano ea mala pakeng tsa microbiota le mahloriso a SCFA/neurotransmitter mala32. Hoa thahasellisa hore maemo a asiti ea isobutyric a hlokometsoeng a ne a tšoana pakeng tsa lihlopha tsa PD le HC, empa a fapane pakeng tsa lihlopha tsa ET le PD (kapa HC). Asiti ea Isobutyric e ka khetholla pakeng tsa ET le PD ka AUC ea 0.718 (95% CI: 0.599–0.836) le ho khetholla ET le NC ka AUC ea 0.655 (95% CI: 0.525–0.786). Ho phaella moo, maemo a asiti ea isobutyric a amana le matla a ho thothomela, e leng se matlafatsang kamano ea eona le ET. Potso ea hore na asiti ea isobutyric ea molomo e ka fokotsa matla a ho thothomela ho bakuli ba nang le ET e hloka ho ithutoa haholoanyane.
Ka hona, palo ea SCFA ea mantle e fokotsehile ho bakuli ba nang le ET 'me e amahanngoa le boima ba kliniki ba ET le liphetoho tse itseng ho microbiota ea mala. Fecal propionate, butyrate, le isobutyrate e ka ba li-biomarker tsa tlhahlobo bakeng sa ET, athe isobutyrate le isovalerate e ka ba li-biomarker tse fapaneng tsa tlhahlobo bakeng sa ET. Liphetoho ho isobutyrate ea mantle e ka ba tse tobileng haholoanyane bakeng sa ET ho feta liphetoho ho li-SCFA tse ling.
Thuto ea rona e na le mefokolo e 'maloa. Ea pele, mekhoa ea lijo le likhetho tsa lijo li ka susumetsa tlhahiso ea microbiota, lisampole tse kholo tsa thuto ho baahi ba fapaneng lia hlokahala, 'me lithuto tsa nakong e tlang li lokela ho hlahisa liphuputso tse felletseng le tse hlophisitsoeng tsa lijo tse kang lipotso tsa khafetsa ea lijo. Ea bobeli, moralo oa thuto ea likarolo tse fapaneng o thibela liqeto life kapa life mabapi le kamano ea sesosa pakeng tsa li-SCFA le nts'etsopele ea ET. Lithuto tse ling tsa ho latela tsa nako e telele tse nang le litekanyo tse latellanang tsa li-SCFA tsa mantle lia hlokahala. Ea boraro, bokhoni ba ho hlahloba le ho khetholla maemo a SCFA ea mantle bo lokela ho netefatsoa ho sebelisoa lisampole tse ikemetseng ho tsoa ho ET, HC, le PD. Lisampole tse ling tse ikemetseng tsa mantle li lokela ho lekoa nakong e tlang. Qetellong, bakuli ba nang le PD sehlopheng sa rona ba bile le nako e khuts'oane haholo ea lefu ho feta bakuli ba nang le ET. Re ile ra bapisa haholo-holo ET, PD le HC ka lilemo, bong le BMI. Ka lebaka la phapang ea tsela ea lefu pakeng tsa sehlopha sa ET le sehlopha sa PD, re boetse ra ithuta bakuli ba 33 ba nang le PD ea pele le bakuli ba 16 ba nang le ET (nako ea lefu ≤ lilemo tse 3) bakeng sa papiso e eketsehileng. Liphapang pakeng tsa lihlopha ho SCFA ka kakaretso li ne li lumellana le lintlha tsa rona tsa mantlha. Ho phaella moo, ha re a fumana kamano pakeng tsa nako ya lefu le diphetoho ho SCFA. Leha ho le jwalo, nakong e tlang, ho ka ba molemo ho hira bakudi ba nang le PD le ET ba sa le banyenyane ba nang le nako e kgutshwane ya lefu ho phethela netefatso ka sampole e kgolo.
Mokhoa oa thuto o amohetsoe ke komiti ea boitšoaro ea Sepetlele sa Ruijin, e amanang le Sekolo sa Bongaka sa Univesithi ea Shanghai Jiao Tong (RHEC2018-243). Tumello e ngotsoeng e nang le tsebo e fumanoe ho tsoa ho barupeluoa bohle.
Pakeng tsa Pherekhong 2019 le Tshitwe 2022, batho ba 109 (37 ET, 37 PD, le 35 HC) ba tsoang ho Movement Disorder Center Clinic ea Sepetlele sa Ruijin, e amanang le Sekolo sa Bongaka sa Univesithi ea Shanghai Jiao Tong, ba kenyelelitsoe thutong ena. Mekhoa e ne e le: (1) lilemo tse 25-85, (2) bakuli ba nang le ET ba fumanoe ho latela mekhoa ea Sehlopha sa Ts'ebetso sa MDS 42 le PD ba fumanoe ho latela mekhoa ea MDS 43, (3) bakuli bohle ba ne ba sa nke meriana ea anti-PD pele ho pokello ea lisampole. (4) Sehlopha sa ET se nkile β-blockers feela kapa ho se sebelise meriana e amanang le eona pele se bokella lisampole tsa mantle. Li-HC tse tsamaellanang le lilemo, bong, le index ea boima ba 'mele (BMI) le tsona li khethiloe. Mekhoa ea ho se kenyeletsoe e ne e le: (1) batho ba jang meroho feela, (2) phepo e mpe, (3) mafu a sa foleng a tšilo ea lijo (ho kenyeletsoa le lefu la ho ruruha ha mala, liso tsa ka mpeng kapa tsa duodenal), (4) mafu a sa foleng a tebileng (ho kenyeletsoa le lihlahala tse mpe), ho hloleha ha pelo, ho hloleha ha liphio, mafu a mali) (5) Nalane ea opereishene e kholo ea mala, (6) Ho noa yogurt ka nako e telele kapa kamehla, (7) Tšebeliso ea li-probiotic kapa lithibela-mafu khoeli e le 'ngoe, (8) Tšebeliso e sa feleng ea li-corticosteroids, li-proton pump inhibitors, li-statins, metformin, li-immunosuppressants kapa meriana e loantšang kankere le (9) ho senyeha ho tebileng ha kelello ho sitisang liteko tsa kliniki.
Batho bohle ba fane ka nalane ea bongaka, boima le tlhahisoleseling ea bolelele ho bala BMI, 'me ba ile ba hlahlojoa methapo ea kutlo le tlhahlobo ea bongaka joalo ka lintlha tsa matšoenyeho tsa Hamilton Anxiety Rating Scale (HAMA) 44, lintlha tsa Hamilton Depression Rating Scale-17 (HAMD-17) 45. khatello ea maikutlo, ho teba ha pipitlelano ho sebelisoa Wexner Constipation Scale 46 le Bristol Stool Scale 47 le ts'ebetso ea kelello ho sebelisoa Mini-Mental State Examination (MMSE) 48. Sekala sa Tlhahlobo ea Matšoao a Ikemetseng a Lefu la Parkinson (SCOPA-AUT) 49 se hlahlobile ho se sebetse hantle ha autonomic ho bakuli ba nang le ET le PD. Sekala sa Tekanyo ea Tekanyo ea Tekanyo ea Tekanyo ea Fan-Tolos-Marin Clinical Tremor (FTM) le Sekala sa Tekanyo ea Tekanyo ea Bohlokoa ea Tekanyo ...
Motho e mong le e mong ea nkileng karolo o ile a kopuoa ho bokella sampole ea mantle hoseng a sebelisa setshelo sa pokello ea mantle. Fetisetsa lijana leqhoang 'me u li boloke ho -80°C pele li sebetsoa. ​​Tlhahlobo ea SCFA e entsoe ho latela ts'ebetso ea kamehla ea Tiangene Biotechnology (Shanghai) Co., Ltd. 400 mg ea lisampole tse foreshe tsa mantle li ile tsa bokelloa ho tsoa ho motho ka mong 'me tsa hlahlojoa ho sebelisoa li-SCFA kamora ho sila le ho etsa sonication pele. Li-SCFA tse khethiloeng mantle li ile tsa hlahlojoa ho sebelisoa gas chromatography-mass spectrometry (GC-MS) le liquid chromatography-tandem MS (LC-MS/MS).
DNA e ntšitsoe disampoleng tsa 200 mg ho sebelisoa QIAamp® Fast DNA Stool Mini Kit (QIAGEN, Hilden, Jeremane) ho latela litaelo tsa moetsi. Sebopeho sa dikokwana-hloko se ile sa fumanoa ka ho hlophisa jini ea 16 S rRNA ho DNA e arohantsoeng le mantle ka ho eketsa sebaka sa V3-V4. Leka DNA ka ho tsamaisa sampole holim'a gel ea agarose ea 1.2%. Ho atolosoa ha jini ea 16S rRNA ka polymerase chain reaction (PCR) ho entsoe ka ho sebelisa li-primer tsa baktheria tsa bokahohleng (357 F le 806 R) le laeborari ea amplicon ea mehato e 'meli e hahiloeng sethaleng sa Novaseq.
Diphetoho tse tswelang pele di hlahiswa e le karolelano ya ± ho kheloha ho tloaelehileng, mme diphetoho tsa sehlopha di hlahiswa e le dipalo le diperesente. Re sebedisitse teko ya Levene ho leka ho tshwana ha diphetoho. Dipapiso di entswe ho sebediswa diteko tsa t tse nang le mehatla e mmedi kapa tlhahlobo ya diphetoho (ANOVA) haeba diphetoho di ne di ajwa ka tlwaelo le diteko tse seng tsa parametric tsa Mann-Whitney U haeba dikakanyo tsa ho tlola maemo a tlwaelehileng kapa a homoscedasticity di ne di tlotswe. Re sebedisitse sebaka se ka tlasa sekgahla sa tshebetso ya receiver operating characteristic (ROC) (AUC) ho lekanya tshebetso ya tlhahlobo ya mohlala le ho hlahloba bokgoni ba SCFA ba ho kgetholla bakudi ba nang le ET ho ba nang le HC kapa PD. Ho hlahloba kamano pakeng tsa SCFA le boima ba kliniki, re sebedisitse tlhahlobo ya kamano ya Spearman. Tlhahlobo ya dipalopalo e entswe ho sebediswa software ya SPSS (mofuta wa 22.0; SPSS Inc., Chicago, IL) ka boemo ba bohlokwa (ho kenyeletswa boleng ba P le FDR-P) bo behilweng ho 0.05 (mahlakore a mabedi).
Ditatelano tsa 16 S di hlahlobilwe ho sebediswa motswako wa software ya Trimmomatic (mofuta wa 0.35), Flash (mofuta wa 1.2.11), UPARSE (mofuta wa v8.1.1756), mothur (mofuta wa 1.33.3) le R (mofuta wa 3.6.3). Lintlha tsa gene ya rRNA ya Raw 16S di sebedisitswe ho sebediswa UPARSE ho hlahisa diyuniti tsa taxonomic tsa tshebetso (OTUs) tse nang le boitsebiso ba 97%. Ditaxonomies di hlalositswe ho sebediswa Silva 128 e le database ya referense. Boemo ba kakaretso ba data ya bongata bo amanang bo kgethilwe bakeng sa tlhahlobo e eketsehileng. Tlhahlobo ya boholo ba phello ya linear discriminant analysis (LDA) (LEfSE) e sebediseditswe papiso pakeng tsa dihlopha (ET vs. HC, ET vs. PD) ka moedi wa α wa 0.05 le moedi wa boholo ba phello wa 2.0. Genera ya dispriminant e hlwailweng ke tlhahlobo ya LEfSE e ile ya sebediswa hape bakeng sa tlhahlobo ya kamano ya Spearman ya SCFA.
Bakeng sa tlhahisoleseding e batsi mabapi le moralo oa thuto, bona Kakaretso ea Tlaleho ea Lipatlisiso tsa Tlhaho e amanang le sengoloa sena.
Lintlha tse tala tsa tatellano ea 16S li bolokiloe polokelongtshedimosetsong ea BioProject ea Setsi sa Naha sa Tlhahisoleseling ea Biotechnology (NCBI) (SRP438900: PRJNA974928), URL: https://www.ncbi.nlm.nih.gov/Traces/study/?acc= SRP438900&o. =acc_s% 3Aa. Lintlha tse ling tse amehang li fumaneha ho mongoli ea tsamaellanang ha ho kopuoa ka nepo, joalo ka tšebelisano-'moho ea saense le phapanyetsano ea thuto le merero e felletseng ea lipatlisiso. Ha ho lumelloe phetisetso ea data ho batho ba boraro ntle le tumello ea rona.
Khoutu e bulehileng ea mohloli feela ka motsoako oa Trimmomatic (mofuta oa 0.35), Flash (mofuta oa 1.2.11), UPARSE (mofuta oa v8.1.1756), mothur (mofuta oa 1.33.3) le R (mofuta oa 3.6.3), ho sebelisoa litlhophiso tsa kamehla kapa karolo ea "Mokhoa". Tlhahisoleseling e eketsehileng e hlalosang e ka fanoa ho mongoli ea tsamaellanang ha ho kopuoa ho utloahalang.
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