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Okukyebera juba okutetema kw‘omugasho (ET) nikubaasa kuba kugumire, namunonga waataanisa n‘abaine amagara marungi (HC) n‘endwara ya Parkinson (PD). Enyimaho, okweshwijuma kw‘eby‘okureeberaho by‘omubiri gw‘omunda ahabw‘ebintu ebikye ebiri omu nda n‘ebiriisa byabyo, kihaire emiringo mirungi y‘okuzoora ebishushani bisya by‘amagara eby‘endwara z‘omubiri. Ebishaju by‘omurunga mukye (SCFA), nk‘ekintu kikuru ekirikuhindura ebimera by‘omu mara, nibikyendeera omu nshaho omu PD. Kwonka, fecal SCFA tizikakyeberwaga omu ET. Twine ekigyendererwa ky‘okucondooza aha rurengo rw‘omubiri rwa SCFAs omu ET, kukyebera akakwate kaabo n‘obumanyiso bw‘oburwaire na gut microbiota, n‘okumanyisa obushoboorozi bwabo oburikubaasa kukyebera. SCFA y‘omu nkari na microbiota y‘omu nda bikapimwa omu ETs 37, PDs ensya 37, na HCs 35. Okuzimba omunda, okuremwa kukora gye, n‘okutetema kw‘amaani bikakyeberwa barikukoresa eminzaani. Omubaro gw‘omubiri gw‘omubiri ogwa propionate, butyrate, na isobutyrate gukaba guri ahansi omu ET kukira omu HC. Omugaati gw‘eby‘okurya ebirimu ebiriisa by‘omubiri, ebiriisa by‘omubiri n‘ebiriisa by‘omubiri bikataanisa ET na HC na AUC ya 0.751 (95% CI: 0.634–0.867). Omubaro gw‘okusheeshasheesha n‘okusheeshasheesha gukaba guri ahansi omu ET kukira omu PD. Asidi y‘omubiri n‘ebiriisa by‘omubiri nibitaanisa ahagati ya ET na PD na AUC ya 0.743 (95% CI: 0.629–0.857). Fecal propionate neekwatagana n‘okuzimba omunda n‘okuremwa kukora gye. Isobutyric acid na isovaleric asidi ziine akakwate katari kamwe n‘oburemeezi bw‘okutetema. Okukyendeera kwa SCFAs z‘omubiri kukaba nikukwatagana n‘okukyendeera kw‘obungi bwa Faecalibacterium na Streptobacterium omu ET. Nahabwekyo, ebiri omu SCFA omu nshaho nibikyendeera omu ET kandi nibikwatagana n‘oburemeezi bw‘ekishushani ky‘oburwaire n‘empindahinduka omu bihingwa by‘omu mara. Propionate y‘omubiri, butyrate, isobutyrate, na isovalerate nibibaasa kuba eby‘okureeberaho by‘okukyebera n‘okukyebera eby‘entaaniso ahabwa ET.
Essential tremor (ET) n‘oburwaire oburikukurakurana, obutarikuhwaho oburikumanyirwa munonga aha kutetema kw‘ebicweka by‘omubiri eby‘ahaiguru, oburikubaasa kukwata n‘ebindi bicweka by‘omubiri nk‘omutwe, emitsi y‘eiraka, n‘ebicweka by‘omubiri eby‘ahansi 1 . Ebintu by‘oburwaire bwa ET tibirimu obumanyiso bw‘okuvuga kwonka kureka n‘obumanyiso obumwe obutari bw‘okuvuga, obariiremu endwara y‘omu nda 2 . Okucondooza kwingi kukozirwe kukyebera emitwarize y‘endwara n‘omubiri y‘okutetema okukuru, kwonka enkora z‘endwara ezirikwetegyerezibwa gye tizikamanyirwe3,4; Okucondooza okukozirwe juba nikworeka ngu okuremwa kukora gye kwa microbiota-gut-brain axis nikubaasa kureetaho endwara z‘obutafaari bw‘omubiri, kandi hariho obuhame oburikweyongyera oburikworeka ngu hariho akakwate akari ahagati y‘obutafaari bw‘omubiri oburikwetwa gut microbiota n‘endwara z‘obutafaari bw‘omubiri5,6. Ekikuru, omu ripoota y‘enshonga emwe, okutaho obukooko obukye bw‘omubiri (fecal microbiota transplantation) kukatunguura okutetema kw‘omugasho n‘oburwaire bw‘okugira ekiniga omu murwaire, ekirikubaasa kworeka akakwate ka haihi ahagati y‘obukooko obukye bw‘omunda n‘okutetema kw‘omugasho. Okwongyera ahari ekyo, tukashanga n‘empindahinduka z‘omutaano omu gut microbiota omu barwaire abaine ET, ekirikuhagira munonga omurimo mukuru gw‘okubura obutafaari bw‘omubiri omu ET8.
Aha bikwatiraine n‘okuburabura kw‘omunda omu ndwara z‘obutafaari bw‘omubiri, PD niyo erikukirayo kwega5. Microbiota etarikushushana neebaasa kwongyera aha kubaasa kuraba omu mara n’okukora glia y’omu mara, ekirikureetaho oburwaire bwa alpha-synucleinopathies9,10,11. PD na ET nizigaaniira aha bintu ebimwe ebirikushushana, nk‘emirundi erikushushana y‘okutetema omu barwaire ba ET na PD, okutetema kw‘okuhuumura okurikurenga (okutetema kw‘omutaano omu PD), n‘okutetema kw‘okushutama (okurikukirayo kushangwa omu barwaire ba ET), ekirikureetera kigumire kutaanisa ahagati yaabyo. emitendekyere y‘okubanza 12. N‘ahabw‘ekyo, twine kwiguraho ahonaaho edirisa y‘omugasho kutaanisa ahagati ya ET na PD. Omu nkora egi, okwega aha dysbiosis y‘omu mara etari emwe n‘emwe n‘empindahinduka z‘omubiri ezirikukwatagana nazo omu ET n‘okumanya entaaniso zaabo na PD nibibaasa kuba eby‘okureeberaho by‘amagara ebirikubaasa kukyeberwa n‘okukyebera ET omu muringo gw‘entaaniso.
Short-chain fatty acids (SCFAs) nizo nshonga nkuru ezirikuruga omu kuhindura kw‘obukooko bw‘omu mara kandi niziteekateekwaho kukora omurimo muhango omu nkoragana y‘omu mara n‘obwongo13,14. SCFAs nizitwarwa obutafaari bw‘omunda kandi zitwarwa omu kihaha kurabira omu nkora y‘emitsi y‘omuryango, kandi SCFA ezimwe nizitaaha omu nkora y‘okutambura kw‘eshagama. SCFAs ziine ebirugiremu omu mwanya aha kuguma n‘oburingaaniza bw‘omukingo gw‘omu mara n‘okutunguura oburinzi bw‘omubiri obuzaarwa omu nkora y‘omu mara15. Kandi ziine n‘ebirikurugamu kumara obwire buraingwa aha nkora y‘okuzibira eshagama n‘obwongo (BBB) ​​ahabw‘okureetaho puroteyini ezirikuteerana gye n‘okukora obutafaari bw‘omubiri oburikureetaho puroteyini ya G (GPCRs) okuraba omu BBB16. Acetate, propionate, na butyrate nizo zirikukirayo kuba nyingi omu SCFA omu nkora y‘okusheeshasheesha. Okucondooza okukozirwe enyima kworekire okukyendeera omu nkora y‘okusheeshasheesha kw‘ekiriisa kya acetic, propionic na butyric acids omu barwaire abaine endwara ya Parkinson17. Kwonka, ebiri omu nshaho z‘omubiri (fecal levels) bya SCFAs tibikakyeberwaga omu barwaire abaine ET.
Nahabwekyo, okucondooza kwaitu kukaba kugyendereire kumanya empindahinduka z‘omutaano omu SCFA y‘omubiri omu barwaire abaine ET n‘entaaniso zaabo n‘abarwaire abaine PD, kukyebera akakwate ka SCFA y‘omubiri n‘obumanyiso bw‘oburwaire bwa ET na microbiota y‘omu mara, hamwe n‘okumanyisa obushoboorozi bw‘okukyebera oburikubaasa kubaho n‘okukyebera okurikutaana kw‘eky‘okureeberaho ky‘omubiri. KZhK. Kushoboorora enshonga ezirikuteganisa eziine akakwate n‘emibazi y‘okurwanisa PD, tukatoorana abarwaire abaine endwara ya Parkinson erikutandika busya nk‘abarikukyebera endwara.
Emitwarize y‘abantu n‘oburwaire bwa ETs 37, PDs 37, na HCs 35 neefunzibwa omu kipande 1. ETs, PDs, na HCs zikagyeragyeranisibwa n‘emyaka, obuhangwa, na BMI. Ebibiina bishatu nabyo bikaba biine emihendo erikushushana y‘okunywa etaabe, okunywa amaarwa n‘okunywa kaawa n‘eby‘okunywa bya chai. Obubonero bwa Wexner (P = 0.004) n‘obubonero bwa HAMD-17 (P = 0.001) obw‘ekibiina kya PD bukaba buri ahaiguru kukira obw‘ekibiina kya HC, kandi obubonero bwa HAMA (P = 0.011) n‘obubonero bwa HAMD-17 (P = 0.011) obw‘ekibiina kya ET bukaba buri ahaiguru kukira obw‘ekibiina kya HC. Enkora y‘endwara omu guruupu ya ET ekaba eri mpango munonga kukira omu guruupu ya PD (P<0.001).
Hakaba hariho entaaniso mpango omu nkora y‘okusheeshasheesha kw‘omubiri (P = 0.023), asidi y‘omubiri (P = 0.039), asidi y‘omubiri (P = 0.020), asidi y‘omubiri (P = 0.045), na asidi y‘omubiri (P = 0.015). . Omu kucondooza okundi okwakozirwe bwanyima y‘okukora, emihendo y‘okukyebera asidi y‘omubiri (P = 0.023), asidi y‘okukyebera (P = 0.007), na asidi y‘okukyebera (P = 0.040) omu guruupu ya ET ekaba eri ahansi munonga kukira ey‘omu guruupu ya HC. Abarwaire abaine ET bakaba baine omubaro gw‘ahansi gw‘okukyebera (P = 0.014) n‘okukyebera (P = 0.005) kukira abarwaire abaine PD. Okwongyera ahari ekyo, emihendo y‘okusheeshasheesha kw‘omubiri (P = 0.013), asidi y‘okusheeshasheesha (P = 0.016), na asidi y‘okusheeshasheesha (P = 0.041) ekaba eri ahansi omu barwaire abaine PD kukira omu barwaire abaine CC (ekishushani 1 n‘ekipande ky‘okwongyeraho 1) .
ag neejwekyera okugyeragyeranisa kwa guruupu kwa asidi ya puropiyoniki, asidi ya asetiki, asidi ya butiriki, asidi ya isovaleriki, asidi ya valeriki, asidi ya kaproiki na asidi ya isobutiriki, nk‘oku biri. Hakaba hariho entaaniso mpango omu rurengo rw‘okusheeshasheesha kw‘omubiri, asidi y‘omubiri, asidi y‘omubiri, asidi y‘omubiri n‘ebiriisa by‘omubiri ahagati y‘ebicweka bishatu. ET okutetema okukuru, endwara ya Parkinson, okutegyeka HC okurimu amagara marungi, SCFA. Entaaniso z‘amaani nizoorekwa *P < 0.05 na **P < 0.01.
Kuteekateeka aha ntaaniso eri omu nkora y‘endwara ahagati y‘ekibiina kya ET n‘ekibiina kya PD, tukacondooza aha barwaire 33 abaine PD eya kare n‘abarwaire 16 abaine ET (enkora y‘endwara Tukakuratiraho kukyebera yaaba emihendo ya SCFA omu nshaho neebaasa kutaanisa abarwaire abaine ET n‘abarwaire abaine CU nari PD. Okurugirira aha kucondooza kwa ROC, entaaniso omu AUC y‘embeera za propionate ekaba eri 0.668 (95% CI: 0.538-0.797), ekyabaasiise kutaanisa abarwaire abaine ET na HC. Abarwaire abaine ET na GC bakaba nibabaasa kutaanisibwa aha rurengo rwa butyrate n‘AUC ya 0.685 (95% CI: 0.556–0.814). Entaaniso omu rurengo rwa isobutyric acid nizibaasa kutaanisa abarwaire abaine ET na HC abaine AUC ya 0.655 (95% CI: 0.525–0.786). Ku baateeraniire hamwe emiringo ya puropiyoni, butiri n‘ebiriisa, AUC y‘ahaiguru ya 0.751 (95% CI: 0.634–0.867) ekatunga okuhurira kwa 74.3% n‘okumanyisa kwa 72.9% (ekishushani 2a). Okutaanisa aha barwaire ba ET na PD, AUC ahabw‘embeera z‘okusheeshasheesha ekaba eri 0.700 (95% CI: 0.579–0.822) kandi ahabw‘embeera z‘okusheeshasheesha ekaba eri 0.718 (95% CI: 0.599–0.836). Omugaati gw‘eby‘okurya ebirimu ebiriisa by‘omubiri n‘ebiriisa by‘omubiri gukaba gwine AUC y‘ahaiguru ya 0.743 (95% CI: 0.629–0.857), okuhurira kwa 74.3% n‘okumanyisa kw‘omutaano kwa 62.9% (ekishushani 2b). Okwongyera ahari ekyo, tukakyebera yaaba emihendo ya SCFA omu nshaho z‘abarwaire abaine endwara ya Parkinson neetaanira kimwe n‘ey‘abaine oburwaire obu. Okurugirira aha kucondooza kwa ROC, AUC y‘okumanyisa abarwaire abaine PD kurugiirira aha ntaaniso omu rurengo rwa propionic acid ekaba eri 0.687 (95% CI: 0.559-0.814), n‘okuhurira kwa 68.6% n‘okumanyisa kwa 68.7%. Entaaniso omu rurengo rwa aseti nizibaasa kutaanisa abarwaire ba PD na HCs abaine AUC ya 0.674 (95% CI: 0.542–0.805). Abarwaire abaine PD nibabaasa kutaanisibwa na CU ahabw‘embeera za butyrate zonka eziine AUC ya 0.651 (95% CI: 0.515–0.787). Ku baateeraniire hamwe ebiriisa by‘omubiri, ebiriisa by‘omubiri n‘ebiriisa by‘omubiri, AUC ya 0.682 (95% CI: 0.553–0.811) ekatunga (ekishushani 2c).
okushoroora okurikukorwa Ekanisa ya Orthodox eya Russia ahari ET na HC; b okushoroora kwa ROC ahari ET na PD; c okushoroora kwa ROC ahari PD na HC; ET okutetema okukuru, endwara ya Parkinson, okutegyeka HC okurimu amagara marungi, SCFA.
Omu barwaire abaine ET, omutindo gw‘okusheeshasheesha gukaba gurimu akakwate kabi n‘obubonero bwa FTM (r = -0.349, P = 0.034), kandi omutindo gw‘okusheeshasheesha gukaba gurimu akakwate kabi n‘obubonero bwa FTM (r = -0.421, P = 0.001) n‘obubonero bwa TETRAS. (r = -0,382, P = 0,020). Omu barwaire abaine ET na PD, emihendo y‘eby‘okurya by‘omubiri ekaba eine akakwate karungi n‘obubonero bwa SCOPA-AUT (r = −0.236, P = 0.043) (ekishushani 3 n‘ekipande ky‘okwongyeraho 3). Tihaine nkoragana mpango ahagati y‘enkora y‘endwara na SCFA omu guruupu ya ET (P ≥ 0.161) nari guruupu ya PD (P ≥ 0.246) (Ekipande ky‘okwongyeraho 4). Omu barwaire abaine PD, emihendo y‘eshagama y‘omubiri ekaba eine akakwate karungi n‘obubonero bwa MDS-UPDRS (r = 0.335, P = 0.042). Omu beejumbiremu boona, emihendo y‘okusheeshasheesha (r = −0.230, P = 0.016) n‘okusheeshasheesha (r = −0.210, P = 0.029) ekaba eine akakwate kabi n‘obubonero bwa Wexner (ekishushani 3 n‘ekipande ky‘okwongyeraho 3).
Emiringo ya isobutyric acid omu nkari ekaba eine akakwate karungi n‘obubonero bwa FTM, isovaleric acid ekaba eine akakwate kabi n‘obubonero bwa FTM na TETRAS, propionic acid ekaba eine akakwate karungi n‘obubonero bwa SCOPA-AUT, caproic acid ekaba eine akakwate karungi n‘obubonero bwa MDS-UPDRS, kandi propionic acid ekaba eine akakwate kabi n‘obubonero bwa FTMTRAS. TETRAS na acetic acid bikaba biine akakwate karungi n‘obubonero bwa Wexner. Ekibiina kya MDS-UPDRS kikashagika omuringo gw‘okupima endwara ya Parkinson, okukyebera kw‘embeera y‘omu mutwe MMSE, omubaro gw‘okupima okwerarikirira kwa Hamilton HAMD-17, ebintu 17, omubaro gw‘okupima okwerarikirira kwa Hamilton HAMA, emitendekyere ya HY Hoehn na Yahr Di – ParksonPA‘AMPASE, AutosonPA SCFAUT S. Ekipimo ky‘ebirugiremu, ekipimo ky‘okupima okutetema kw‘eby‘amagara ekya FTM Fana-Tolosa-Marin, Ekipimo ky‘okupima okutetema kw‘omugasho omu guruupu y‘okucondooza eya TETRAS (TRG). Entaaniso z‘amaani nizoorekwa *P < 0.05 na **P < 0.01.
Twongyeire twacondooza aha nkora y‘okushoroora ey‘ebihangirwe ebikye ebiri omu nda turikukoresa okucondooza kwa LEfSE kandi twatoorana omutindo gw‘ebihandiiko by‘obungi bw‘ebika by‘ebihangirwe ahabw‘okushwijuma okurikukiraho. Okugyeragyeranisa kukakorwa ahagati ya ET na HC n‘ahagati ya ET na PD. Okushwijuma kwa Spearman correlation bwanyima kukakorwa aha bwingi bw‘ebintu ebikye ebiri omu nda n‘embeera za SCFA z‘omunda omu guruupu ibiri z‘okugyeragyeranisa.
Faecalibacterium (eine akakwate na asidi y‘omubiri, r = 0.408, P < 0.001), Lactobacillus (eine akakwate na asidi y‘omubiri, r = 0.283, P = 0.016), Streptobacterium (eine akakwate na asidi y‘omubiri, r = 0.016 zikaba ziriho omu kucondooza kwa ET na 0.32) . , P = 0,005; ekirikukwatagana n‘ekiriisa ky‘omubiri, r = 0.374, P = 0.001; n‘enkoragana n‘ekiriisa ky‘omubiri, r = 0.329, P = 0.005), Howardella (ekiine akakwate n‘ekiriisa ky‘omubiri, r = 0.242, P = 0.041), Raoultella (ekirikukwatagana n‘ekiriisa ky‘omubiri, r = 0.249, P = 0.035), na r = 0.302, P = 0.010) nikikyendeera omu ET kandi kiine akakwate karungi n‘embeera za SCFA z‘omu nkari. Kwonka, obungi bwa Stenotropomonas bukayeyongyera omu ET kandi bukaba bwine akakwate kabi n‘embeera z‘okusheeshasheesha (r = -0.250, P = 0.034). Bwanyima y‘okuhindura FDR, enkoragana eri ahagati ya Faecalibacterium, Catenibacter, na SCFA yonka ekaguma eri ey‘omugasho (P ≤ 0.045) (ekishushani 4 n‘ekipande ky‘okwongyeraho 5).
Okushwijuma enkoragana ya ET na HC. Bwanyima y‘okuhindura FDR, obungi bwa Faecalibacterium (obuine akakwate karungi na butyrate) na Streptobacterium (obuine akakwate karungi na propionate, butyrate, na isobutyrate) bukashangwa ngu nibukyendeera omu ET kandi buine akakwate karungi n‘embeera za SCFA z‘omu nkari. b Okushwijuma enkoragana ya ET na PD. Bwanyima y‘okuhindura FDR, tihaine nkoragana z‘amaani ezashangirwe. ET okutetema okukuru, endwara ya Parkinson, okutegyeka HC okurimu amagara marungi, SCFA. Entaaniso z‘amaani nizoorekwa *P < 0.05 na **P < 0.01.
Ku baashwijumire ET na PD, Clostridium trichophyton ekashangwa ngu eyeyongyeire omu ET kandi eine akakwate n‘eby‘okurya ebirimu ebiriisa by‘omubiri (r = -0.238, P = 0.041) n‘ebiriisa by‘omubiri (r = -0.257, P = 0.027). ). Bwanyima y‘okuhindura FDR, kimwe aharibyo kikaguma kiri eky‘omugasho (P≥0.295) (ekishushani 4 n‘ekipande ky‘okwongyeraho 5).
Okucondooza oku n‘okucondooza okuhikire okurikushwijuma emihendo ya SCFA omu nshaho kandi kugikwatanisa n‘empindahinduka omu gut microbiota n‘oburemeezi bw‘obumanyiso omu barwaire abaine ET kugyeragyeranisa n‘abarwaire abaine CU na PD. Twashanga ngu emihendo ya SCFA omu nshaho ekakyendeera omu barwaire abaine ET kandi ekaba neekwatagana n‘oburemeezi bw‘oburwaire n‘empindahinduka z‘omutaano omu gut microbiota. Omubaro gw‘ebishaju by‘omubiri ogurikuteerana (SCFAs) nigutaanisa ET na GC na PD.
Waagyeragyeranisa n‘abarwaire ba GC, abarwaire ba ET baine ebiriisa by‘omubiri ebikye ebirimu ebiriisa bya propionic, butyric, na isobutyric acids. Okuteerana kwa asidi za propionic, butyric na isobutyric kukataanisa ET na HC na AUC ya 0.751 (95% CI: 0.634–0.867), okuhurira kwa 74.3% n‘okumanyisa kwa 72.9%, ekirikworeka okukoresa kwazo nk‘ebirikumanyisa eby‘amagara eby‘okukyebera obushoboorozi bwa ET. Okweshwijuma okundi kukooreka ngu emihendo ya fecal propionic acid ekaba eine akakwate karungi n‘obubonero bwa Wexner n‘obubonero bwa SCOPA-AUT. Emiringo ya isobutyric acid omu nkari ekaba neekwatagana n‘obubonero bwa FTM. Aha rubaju orundi, okukyendeera kw‘omubaro gwa butyrate omu ET kukaba nikukwatagana n‘okukyendeera kw‘obungi bw‘ebintu ebikye ebirikureeta SCFA, Faecalibacterium, na Categorybacter. Okwongyera ahari ekyo, okukyendeera omu bwingi bwa Catenibacter omu ET nakyo kikaba kiine akakwate n‘okukyendeera omu nkora ya propionic na isobutyric acid omu nshaho.
SCFAs ezirikukira obwingi ezirikukorwa omu nkora y‘okusheeshasheesha nizitwarwa obutafaari bw‘omubiri oburikwetwa colonocytes okukira munonga kurabira omu nkora y‘okutwara ebintu ebirikwegamira ahari H+ nari sodium. Ebishaju ebiri omu mubiri ebirikunywa nibikoresibwa nk’entandikwa y’amaani g’obutafaari bw’omubiri, obwo ebyo ebitarikuhindurwa omu butafaari bw’omubiri nibitwarwa omu nkora y’okutambura kw’omubiri 18 . SCFAs nizibaasa kuhindura okutambura kw‘amara, kwongyera aha mirimo y‘okuzibira amara, n‘okuhindura okuhindura kw‘omubiri n‘obutafaari bw‘omubiri19. Enyima kikashangwa ngu ebiriisa by‘omubiri ebirimu butyrate, acetate, na propionate bikakyendeera omu barwaire ba PD kugyeragyeranisa na HCs17, ekirikuhikaana n‘ebyarugamu byaitu. Okucondooza kwaitu kukashanga okukyendeera omu SCFAs omu barwaire abaine ET, kwonka bikye nibimanyirwa aha murimo gwa SCFAs omu ndwara ya ET. Butyrate na propionate nibibaasa kukwatiraine na GPCRs kandi bihindure okumanyisa okurikurugiirira ahari GPCR nka okumanyisa kwa MAPK na NF-κB20. Enteekateeka y‘omutaano ey‘omutindo gw‘omunda n‘obwongo n‘okugira ngu SCFAs ezirikuruga omu bukooko bw‘omunda nizibaasa kuhindura okumanyisa kw‘omugyenyi, obwo nizihindura aha mirimo y‘omunda n‘obwongo. Ahabw’okugira ngu butyrate na propionate biine amaani g’okuzibira emirimo ya histone deacetylase (HDAC)21 kandi butyrate nayo neebaasa kukora nk’ekikwato ky’okuhandiika, biine amaani maingi aha nkora y’okuhindura eby’okurya omu mubiri, okutaanisa n’okukanyira, okukira munonga ahabw’okugira ngu nibikwata aha nkora y’obuzaarwa22 . Okurugirira aha buhame kuruga omu SCFA n‘endwara z‘obutafaari bw‘omubiri, butyrate neetwarwa nk‘omubazi gw‘okujanjaba ahabw‘obushoboorozi bwayo bw‘okutereeza emirimo ya HDAC erikuremeera, erikubaasa kureetaho okufa kw‘obutafaari bw‘omubiri oburikwetwa dopaminergic neuron omu PD23,24,25. Okucondooza aha nyamaishwa nakwo kworekire obushoboorozi bwa butyric acid okuzibira okusheeshasheesha kw‘obutafaari bw‘omubiri oburikwetwa dopaminergic neuron n‘okutunguura oburemeezi bw‘okutambura omu miringo ya PD26,27. Propionic acid eshangirwe ngu neekyendeeza aha kugarukamu kw‘okuzimba n‘okurinda obuhikiriire bwa BBB28,29. Okucondooza kworekire ngu propionic acid neetunguura okugumaho kw‘obutafaari bw‘omubiri oburikukora aha mubiri omu kugarukamu obutwa bwa rotenone omu miringo ya PD 30 kandi ngu okunywa propionic acid omu kanwa nikucungura okufeerwa kw‘obutafaari bw‘omubiri oburikukora aha mubiri n‘okubura amaani omu mbeba eziine PD 31 . Tihariho bingi ebirikumanywa aha murimo gwa isobutyric acid. Kwonka okucondooza okukozirwe juba kukashanga ngu okutwarwa kw’embeba eziine B. ovale kukaba kwongyera aha SCFA y’omu mara (obariiremu acetate, propionate, isobutyrate, na isovalerate) n’okugira GABA omu mara, ekirikworeka ngu hariho akakwate akateirweho ahagati y’ebicweka by’omubiri ebirikwetwa gut microbiota na SCFA y’omu mara. okuta omutima aha bikwatiraine n‘obutafaari bw‘omubiri32. Omu ET, empindahinduka z‘oburwaire ezitari za buriijo omu bwongo bw‘omutwe nizitwariramu empindahinduka omu nkora ya Purkinje cell axons na dendrites, okufuruka n‘okufeerwa obutafaari bwa Purkinje, empindahinduka omu nkora ya basket cell axons, empindahinduka omu nkora y‘okutunguuka kw‘obutafaari bw‘omubiri n‘okujanjaara kw‘obutafaari bwa Purkinje, n‘empindahinduka omu nkora ya GABA omu magufa g‘ameino. nuclei, ekirikureetaho okukyendeera kw‘ebirikuruga omu GABAergic kuruga omu bwongo3,4,33. Tikirikumanywa yaaba SCFAs ziine akakwate n‘okusheeshasheesha kw‘obutafaari bwa Purkinje n‘okukyendeera omu kureetaho GABA omu bwongo. Ebirugire omu kucondooza kwaitu nibyoreka ngu hariho akakwate k‘amaani ahagati ya SCFA na ET, kwonka enkora y‘okwega ey‘okuraba omu bicweka by‘abantu terikwikiriza okuhendera kwona aha nkoragana y‘enshonga ahagati ya SCFA n‘omuringo gw‘endwara ya ET; Ebindi bihandiiko by‘okukuratirira eby‘obwire buraingwa nibyetengyesa, obariiremu okupima okurikukuratana kw‘ebicweka by‘omubiri ebirikwetwa SCFAs, hamwe n‘okucondooza aha nyamaishwa okurikukyebera enkora.
SCFAs niziteekateekwaho kureetaho okuteerana kw‘enyama z‘omunda34. Okubura SCFA nikiija kwongyera aha bumanyiso bw‘okuzimba omunda, kandi okugaita SCFA nikibaasa kutunguura obumanyiso bw‘okuzimba omunda PD35. Ebirugire omu kucondooza kwaitu nabyo nibyoreka akakwate kakuru ahagati y‘okukyendeera omu SCFA omu nshaho n‘okwongyera aha kusheeshasheesha n‘okuremwa kukora gye omu barwaire abaine ET. Ripoota emwe ey‘enshonga ekashangwa ngu okutaho microbiota kukatunguura okutetema okukuru n‘okugira ekiniga omu murwaire 7, ekirikwongyera kworeka ngu hariho akakwate ka haihi ahagati ya microbiota y‘omunda na ET. Nahabwekyo, nitwikiriza ngu fecal SCFA/microbiota neebaasa kuhindura aha nkora y‘omu mara g‘omugyenyi n‘okukora kw‘enkora y‘obutafaari bw‘omubiri oburikwekorera.
Okucondooza kukashanga ngu okukyendeera omu rurengo rwa SCFAs z‘omu nkari omu ET kukaba nikukwatagana n‘okukyendeera omu bwingi bwa Faecalibacterium (oburikukwatagana na butyrate) na Streptobacterium (oburikukwatagana na propionate, butyrate, na isobutyrate). Bwanyima y‘okutereeza FDR, enkoragana egi neeguma eri ey‘omugasho. Obukooko oburikwetwa Faecalibacterium na Streptobacterium ni obukooko obukye oburikureeta SCFA. Faecalibacterium neemanyirwa aha kureetaho obukooko obukye oburikwetwa butyrate36, kandi ebikuru ebirikuruga omu kuhindura Catenibacter ni aseteti, butyrate na lactic acid37. Faecalibacterium ekashangwa omu 100% omu guruupu zombi eza ET na HC; obungi bw‘abantu b‘ahagati bw‘ekibiina kya ET bukaba buri 2.06% kandi obw‘ekibiina kya HC bukaba buri 3.28% (LDA 3.870). Ekicweka kya bacteria kikashangwa omu 21.6% (8/37) omu guruupu ya HC kandi omu sampo 1 yonka ey‘ekibiina kya ET (1/35). Okukyendeera n‘okutabaasa kumanyirwaho obukooko bwa streptobacteria omu ET nakyo nikibaasa kworeka akakwate n‘oburwaire bw‘endwara. Omubaro gw‘ahagati gw‘ebika bya Catenibacter omu guruupu ya HC gukaba guri 0.07% (LDA 2.129). Okwongyera ahari ekyo, obukooko bwa lactic acid bukaba bwine akakwate n‘empindahinduka omu nkora y‘okusheeshasheesha (P=0.016, P=0.096 bwanyima y‘okuhindura FDR), kandi orikwenda kukwatwa endwara y‘ebihaha akaba aine akakwate n‘empindahinduka omu nkora y‘okusheeshasheesha (P=0.016, P=0.072 bwanyima y‘okuhindura FDR). Bwanyima y‘okutereeza FDR, omuze gw‘enkoragana gwonka nigwo gusigaireho, ogutari gw‘omugasho omu by‘embariirira. Lactobacilli nazo nizimanyirwa aha kureetaho SCFA (asidi y‘omubiri, asidi y‘omubiri, asidi y‘omubiri, asidi y‘omubiri) 38 kandi Candidatus Arthromitus n‘ekintu ky‘omutaano ekirikureetaho okutaanisa kw‘obutafaari bwa T obuhwezi 17 (Th17), na Th1/2 na Tregs eziine akakwate n‘okurinda obutafaari bw‘omubiri /Th173. . Okucondooza okukozirwe juba nikworeka ngu okutunguuka kw‘oburwaire bwa fecal pseudoarthritis nikubaasa kureetera okuzimba kw‘omunda, okuremwa kukora gye kw‘ebizibu by‘omu mara, n‘okuzimba kw‘omubiri 40 . Omubaro gwa Clostridium trichoides gukeeyongyera omu ET kugyeragyeranisa na PD. Obungi bwa Clostridium trichoides bukashangwa burimu akakwate karungi n’ekiriisa kya isovaleric asidi n’ekiriisa kya isovaleric asidi. Bwanyima y‘okuhindura FDR, byombi bikaguma biri eby‘omugasho (P≥0.295). Clostridium pilosum ni obukooko obumanyirwe ngu nibukwatagana n‘okuzimba kandi nibubaasa kureetaho okuremwa kukora gye kw‘ebizibu by‘omu mara41. Okucondooza kwaitu okwabandize kukagamba aha mpindahinduka omu gut microbiota y‘abarwaire abaine ET8. Aha nituha n‘empindahinduka omu SCFA omu ET kandi nitureeba akakwate akari ahagati y‘okubura obuhuta bw‘omunda n‘empindahinduka omu SCFA. Okukyendeera omu rurengo rwa SCFA nikukwatagana munonga n‘okubura amaani omu nda n‘okutetema kw‘amaani omu ET. Ebirugire omu kucondooza kwaitu nibyoreka ngu gut-brain axis neebaasa kukora omurimo muhango omu kureetaho endwara ya ET, kwonka okucondooza okurikukiraho omu bishushani by‘enyamaishwa nikwetengyesa.
Waagyeragyeranisa n‘abarwaire abaine PD, abarwaire abaine ET baine omubaro mukye gw‘ebiriisa bya isovaleric na isobutyric acids omu nshaho zaabo. Okuteerana kwa isovaleric acid na isobutyric acid kukamanyisa ET omu PD na AUC ya 0.743 (95% CI: 0.629–0.857), okuhurira kwa 74.3% n‘okumanyisa kwa 62.9%, ekirikumanyisa omurimo gwabo ogurikubaasa kubaho nk‘ebimanyiso by‘amagara omu kucondooza kwa ET okw‘entaaniso. . Emiringo ya isovaleric acid omu nkari ekaba eine akakwate katari kamwe n‘obubonero bwa FTM na TETRAS. Emiringo ya isobutyric acid omu nkari ekaba neekwatagana n‘obubonero bwa FTM. Okukyendeera kw’omubaro gwa isobutyric acid kukaba nikukwatagana n’okukyendeera kw’obungi bwa catobacteria. Tihariho bingi ebirikumanywa aha mirimo ya isovaleriki asidi n’ekiriisa kya isobutiriki. Okucondooza okwabandize kworekire ngu okutwarwa kw‘embeba eziine B. ovale kukaba kwongyera aha mubaro gwa SCFAs z‘omu mara (obariiremu acetate, propionate, isobutyrate, na isovalerate) n‘ebicweka bya GABA eby‘omu mara, ebirikworeka akakwate k‘omu mara ahagati ya microbiota n‘ebicweka bya SCFA/neurotransmitter eby‘omu mara32. Ekirikushemeza, emihendo ya isobutyric acid eyaareebekire ekaba neeshushana ahagati y‘ebicweka bya PD na HC, kwonka ekaba neetaanira kimwe ahagati y‘ebicweka bya ET na PD (nari HC). Isobutyric acid ekaba neebaasa kutaanisa ahagati ya ET na PD n‘AUC ya 0.718 (95% CI: 0.599–0.836) kandi emanyise ET na NC n‘AUC ya 0.655 (95% CI: 0.525–0.786). Okwongyera ahari ekyo, emihendo ya isobutyric acid neekwatagana n‘oburemeezi bw‘okutetema, ekirikwongyera kuhamya akakwate kaayo na ET. Ekibuuzo ky‘okureeba yaaba oral isobutyric acid neebaasa kukyendeeza oburemeezi bw‘okutetema omu barwaire abaine ET kishemerire kwongyerwa kwega.
Nahabwekyo, ebiri omu SCFA omu nshaho nibikyendeera omu barwaire abaine ET kandi nibikwatagana n‘oburemeezi bw‘oburwaire bwa ET n‘empindahinduka z‘omutaano omu bihingwa by‘omu mara. Propionate y‘omubiri, butyrate, na isobutyrate nibibaasa kuba eby‘okureeberaho by‘okukyebera ET, obwo isobutyrate na isovalerate birikubaasa kuba eby‘okureeberaho by‘okukyebera eby‘entaaniso ahabwa ET. Empindahinduka omu fecal isobutyrate nizibaasa kuba ziri ez‘omutaano ahari ET kukira empindahinduka omu SCFA ezindi.
Okwega kwaitu kwine obugarukiro bwingi. Eky‘okubanza, enkora y‘eby‘okurya n‘eby‘okurya ebi orikukunda nibibaasa kuhindura aha kumanyisa kwa microbiota, eby‘okureeberaho by‘okwega ebihango omu bantu batari bamwe na bamwe nibyetengyesa, kandi okwega kw‘omumaisho kushemerire kutaho okucondooza kw‘eby‘okurya okuhikire kandi okutebeekanisiibwe nk‘ebibuuzo by‘emirundi y‘okurya. Ekyakabiri, enkora y‘okwega ey‘ebicweka by‘abantu neezibira ebirugiremu byona ebirikukwata aha nkoragana y‘enshonga ahagati ya SCFA n‘enkora y‘endwara ya ET. Ebindi bihandiiko by‘okukuratirira eby‘obwire buraingwa n‘okupima kw‘omubaro gw‘ebicweka bya SCFA by‘omubiri nibyetengyesa. Ekyakashatu, obushoboorozi bw‘okukyebera n‘okukyebera okurikutaana kw‘embeera za SCFA z‘omu nkari bushemerire kuhamibwa barikukoresa eby‘okureeberaho by‘obwegyese kuruga omu ET, HC, na PD. Sampuli z‘omukyeka ezindi ezirikwetongora ziine kukyeberwa omu biro by‘omumaisho. Eky‘aha muheru, abarwaire abaine PD omu guruupu yaitu bakaba baine obwire bukye bw‘endwara kukira abarwaire abaine ET. Twakira kugyeragyeranisa ET, PD na HC kurugiirira aha myaka, obuhangwa na BMI. Aha ntaaniso eri omu nkora y‘endwara ahagati y‘ekibiina kya ET n‘ekibiina kya PD, tukacondooza n‘abarwaire 33 abaine PD eya kare n‘abarwaire 16 abaine ET (obwire bw‘endwara ≤emyaka 3) kwongyera kugyeragyeranisa. Entaaniso ahagati y‘ebicweka by‘abantu omu SCFA okutwarira hamwe zikaba nizihikaana n‘ebihandiiko byaitu eby‘okubanza. Okwongyera ahari ekyo, titukashangireho kakwate koona ahagati y‘obwire bw‘endwara n‘empindahinduka omu SCFA. Kwonka omu biro by‘omumaisho, nikiija kuba kirungi kuhandiika abarwaire abaine PD na ET omu bwire bukye n‘obwire bukye bw‘endwara kuheza okuhamya omu sampo mpango.
Enkora y‘okwega ekaikirizibwa akakiiko k‘emitwarize y‘irwariro rya Ruijin akaine akakwate n‘eishomero ry‘eby‘obushaho erya yunivasite ya Shanghai Jiao Tong (RHEC2018-243). Okwikiriza omu buhandiikye kukatunga kuruga omu beejumbiremu boona.
Hagati ya Jenwari 2019 na Desemba 2022, abantu 109 (37 ET, 37 PD, na 35 HC) kuruga omu irwariro rya Ruijin, eriine akakwate n’eishomero ry’eby’obushaho erya Shanghai Jiao Tong University, bakateebwa omu kucondooza oku. Enkora ekaba eri: (1) emyaka 25–85, (2) abarwaire abaine ET bakakyeberwa kurugiirira aha nkora ya MDS Working Group 42 kandi PD bakakyeberwa kurugiirira aha nkora ya MDS 43, (3) abarwaire boona bakaba batarikunywa emibazi y‘okurwanisa PD batakatandikire entebe. okuteerana eby’okureeberaho. (4) Ekibiina kya ET kikanywa β-blockers zonka nari emibazi etari emwe n‘emwe batakatungire sampo z‘omubiri. HCs ezirikuhikaana n‘emyaka, obuhangwa, n‘omubaro gw‘omubiri (BMI) nazo zikatooranwa. Enkora y‘okubingamu ekaba eri: (1) abatarikurya by‘okurya by‘ebihimba, (2) eby‘okurya bibi, (3) endwara ezitarikukira z‘omu nda (obariiremu endwara z‘okuzimba kw‘omu nda, amazimba g‘omu nda nari omu nkari), (4) endwara ezitarikukira z‘amaani (obariiremu ebizimba by‘amaani), okuremwa kukora gye kw‘omutima, okuremwa kukora gye kw‘ebihaha (hiological renal diseases),) okushemezibwa kw‘omu nda, (6) Okunywa yogurt kumara obwire buraingwa nari buriijo, (7) Okukoresa emibazi yoona ey‘okurwanisa endwara nari emibazi y‘okurwanisa endwara kumara okwezi 1, (8) Okukoresa emibazi y‘okurwanisa obukooko obutarikukira, emibazi y‘okuzibira purotoni, statins, metformin, emibazi y‘okukyendeeza amaani g‘omubiri nari emibazi y‘okurwanisa ekookoro n‘oku (9) emibazi y‘okurwanisa endwara y‘omubiri erikurwanisa oburwaire bw‘omutwe.
Abashomesa boona bakaha ebyafaayo by‘obushaho, oburemeezi n‘amakuru g‘oburaingwa kubara BMI, kandi bakakyeberwa omu by‘obuhangwa bw‘ebihaha n‘okukyeberwa kw‘obushaho nk‘obubonero bw‘okwerarikirira bwa Hamilton (HAMA) 44 obubonero bw‘okwerarikirira, obubonero bw‘okwehwa amatsiko bwa Hamilton-17 (HAMD-17 condition of Wetipxner the Wetipxing depression of Wetipxner). Ekipimo ky‘okuzimba omunda 46 n‘ekipimo kya Bristol Stool 47 n‘okukora kw‘okumanya orikukoresa ekigyezo ky‘embeera y‘ebiteekateeko (MMSE) 48 . Ekipimo ky‘okushwijuma obumanyiso bw‘okwebaasa bw‘endwara ya Parkinson (SCOPA-AUT) 49 kikakyebera oburemeezi bw‘okwebaasa omu barwaire abaine ET na PD. Ekipimo ky‘okupima okutetema kw‘omu irwariro ekya Fana-Tolos-Marin (FTM) n‘ekipimo ky‘okupima okutetema kw‘omugasho (TETRAS) 50 Ekibiina ky‘okwega okutetema (TRG) 50 bikakyeberwa omu barwaire abaine ET; ekipimo ky‘okupima endwara ya Kinson (MDS-), ekirikushagikwa ekibiina ky‘endwara ya Parkinson ekya United States; UPDRS omuringo 51 na Hoehn na Yahr (HY) omuringo 52 bikakyeberwa.
Buri omwe omu beejumbiremu akashabwa kutwara sampo y‘omubiri omu kasheeshe arikukoresa ekikopo ky‘okutwaramu omubiri. Hindurira ebikwato omu barafu kandi obibiike aha -80°C otakabikozireho. Okushwijuma kwa SCFA kukakorwa kurugiirira aha mirimo ya buriijo eya Tiangene Biotechnology (Shanghai) Co., Ltd. 400 mg y‘eby‘okureeberaho by‘omubiri ebisya bikatorotoorwaho kuruga omu buri muntu kandi byakyeberwa barikukoresa SCFAs bwanyima y‘okushenda n‘okukyebera. SCFAs ezatoorainwe omu nshaho zikakyeberwa barikukoresa omuyaga-okupima obuhango (GC-MS) n‘okupima amaizi-tandem MS (LC-MS/MS).
DNA ekaruga omu bishushani bya mg 200 barikukoresa ekikwato kya QIAamp® eky‘okurahuka DNA (QIAGEN, Hilden, Germany) kurugiirira aha biragiro by‘omukozi. Ebirimu obukooko obukye bikamanyirwa aha kukuratana kw’obuzaarwa bwa 16 S rRNA aha DNA eyataanisiibwe kuruga omu nshaho barikukanyisa ekicweka kya V3-V4. Geeza DNA orikugyendesa sampo aha 1.2% agarose gel. Okutunguuka kw’omubazi gwa 16S rRNA kukakorwa barikukoresa ebikwato by’okubanza eby’obukooko (357 F na 806 R) hamwe n’eibiikiro ry’ebitabo ry’eitembezo ribiri eryombekirwe aha nkora ya Novaseq.
Ebirikuhinduka ebitarikuhwaho nibyorekwa nk‘ebiri ahagati ± okutaana kw‘omutindo, kandi ebirikuhinduka omu kicweka nibyorekwa nk‘enamba n‘ebicweka 10 ahari 100. Tukakozesa ekigyezo kya Levene kugyezaho obutashushana bw’ebintu ebirikutaana. Okugyeragyeranisa kukakorwa barikukoresa ebigyezo bya t eby‘emikira ebiri nari okucondooza kw‘okuhinduka (ANOVA) baaba nibahinduka omu muringo oguhikire, n‘ebigyezo bya Mann-Whitney U ebitari bya parametric baaba baaba nibateekateeka aha buteeka nari homoscedasticity. Twakoresa omwanya oguri ahansi y‘omutindo gw‘okukora (ROC) curve (AUC) kugyeragyeranisa okukora kw‘okukyebera kw‘eky‘okureeberaho n‘okushwijuma obushoboorozi bwa SCFA kutaanisa abarwaire abaine ET n‘abaine HC nari PD. Kushwijuma akakwate akari ahagati ya SCFA n‘oburemeezi bw‘oburwaire, tukakoresa okucondooza kwa Spearman correlation. Okushwijuma kw‘embariirira kukakorwa barikukoresa puroguraamu ya SPSS (omuringo 22.0; SPSS Inc., Chicago, IL) n‘omutindo gw‘obukuru (obariiremu omuhendo gwa P na FDR-P) guteirwe ahari 0.05 (embaju ibiri).
Ebicweka 16 ebya S bikakyeberwa barikukoresa puroguraamu za Trimmomatic (omuringo 0.35), Flash (omuringo 1.2.11), UPARSE (omuringo 1.1.1756), mothur (omuringo 1.33.3) na R (omuringo 3.6.3). Ebihandiiko by‘obuzaarwa bwa 16S rRNA ebitari birungi bikakorwa barikukoresa UPARSE kureetaho ebicweka by‘okushoroora ebirikukora (OTUs) ebiine 97% y‘okumanya. Ebicweka by’ebika bikashoboororwa barikukoresa Silva 128 nk’ekihandiiko ky’okureeberaho. Omutindo gw‘omutaano gw‘ebihandiiko by‘obungi bw‘ebintu gukatooranwa kwongyera kweshwijuma. Okushwijuma okuri omu nkora (LDA) okushwijuma obuhango bw‘ebirikurugamu (LEfSE) kukakoresibwa omu kugyeragyeranisa ahagati y‘ebicweka (ET vs. HC, ET vs. PD) n‘ekipimo kya α kya 0.05 n‘ekipimo ky‘obuhango bw‘ebirikurugamu kya 2.0. Ebika by‘okushoroora ebyamanyirwe omu kucondooza kwa LEfSE bikagaruka byakoresibwa omu kucondooza kwa Spearman okwa SCFA.
Okumanya ebindi aha ntebeekanisa y‘okwega, reeba Ripoota y‘okucondooza aha by‘obuhangwa Abstract erikukwatagana n‘ekicweka eki.
Ebihandiiko by’okukuratana kwa 16S ebitari birungi nibibiikwa omu kitongore ky’eihanga eky’amakuru g’eby’amagara (NCBI) BioProject (SRP438900: PRJNA974928), URL: https://www. =okutunga_ebirikukwataho% 3Aa. Ebindi bihandiiko ebiine akakwate n‘eki nibibaasa kutunga omuhandiiki orikukora aha kushaba okuhikire, nk‘okukoragana kwa sayansi n‘okuhindura eby‘obwegyese n‘emirimo y‘okucondooza eijwiire. Tihariho okuhitsya amakuru aha bantu abandi tutaine kwikiriza kwaitu okurikwikirizibwa.
Koodi y’entandikwa erikwiguka yonka n’okuteerana kwa Trimmomatic (omuringo 0.35), Flash (omuringo 1.2.11), UPARSE (omuringo v8.1.1756), mothur (omuringo 1.33.3) na R (omuringo 3.6.3), orikukoresa entebeekanisa z’okubanza nari ekicweka “Omuringo”. Amakuru agandi agarikushoboorora gye nigabaasa kuheebwa omuhandiiki orikukora aha nshonga egyo waashaba omu muringo oguhikire.
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