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Gusuzuma kare indwara ya essential tremble (ET) bishobora kugorana, cyane cyane iyo bitandukanye n’indwara zisanzwe (HC) n’indwara ya Parkinson (PD). Vuba aha, isesengura ry’ingero z’umwanda ku mikorobe yo mu nda n’ibiyigize byatanze uburyo bushya bwo kuvumbura ibimenyetso bishya by’indwara zo mu mara. Aside fatty acids (SCFA), nk’ikintu nyamukuru kigize imiterere y’ibimera byo mu mara, igabanuka mu mwanda muri PD. Ariko, SCFA yo mu mwanda ntibyigeze byigwa muri ET. Twari tugamije gusuzuma urugero rw’imibiri ya SCFA mu mwanda muri ET, gusuzuma isano iri hagati yayo n’ibimenyetso by’uburwayi na mikorobe yo mu nda, no kumenya ubushobozi bwayo bwo gusuzuma. SCFA yo mu mwanda na mikorobe yo mu nda byapimwe muri ET 37, PD nshya 37, na HC 35. Kwituma, kudakora neza kw’umubiri, n’ubukana bw’imibiri byapimwe hakoreshejwe ibipimo. Urugero rw’imibiri ya propionate, butyrate, na isobutyrate rwari hasi muri ET ugereranyije na HC. Uruvange rwa aside propionic, butyric na isobutyric rwatandukanije ET na HC hamwe na AUC ya 0.751 (95% CI: 0.634–0.867). Urugero rwa aside isovaleric ya fecal na aside isobutyric rwari hasi muri ET ugereranyije na PD. aside isovaleric na aside isobutyric bitandukanya ET na PD hamwe na AUC ya 0.743 (95% CI: 0.629–0.857). Fecal propionate ifitanye isano ritandukanye no kutagira impatwe no kudakora neza kw'umubiri. aside isobutyric na aside isovaleric bifitanye isano ritandukanye n'ubukana bw'umutingito. Kugabanuka kwa SCFA z'imyanda byafitanye isano no kugabanuka k'ubwinshi bwa Faecalibacterium na Streptobacterium muri ET. Bityo, ingano ya SCFA mu myanda igabanuka muri ET kandi bifitanye isano n'ubukana bw'ishusho y'ubuvuzi n'impinduka mu mikorobe y'amara. Inkoko zikora nk'ibinyabutabire, butyrate, isobutyrate, na isovalerate bishobora kuba ibimenyetso by'isuzuma n'itandukaniro ry'ibipimo bya ET.
Guhindagura kw'ingingo (ET) ni indwara idakira kandi idakira irangwa ahanini no guhindagura kw'ingingo zo hejuru, bishobora no kugira ingaruka ku bindi bice by'umubiri nk'umutwe, imitsi y'ijwi, n'imyanya yo hasi 1. Ibiranga indwara ya ET ntibikubiyemo ibimenyetso by'imitsi gusa ahubwo harimo n'ibimenyetso bimwe na bimwe bitari ibyo mu mitsi, harimo n'indwara y'igifu 2. Ubushakashatsi bwinshi bwakozwe kugira ngo busuzume imiterere y'indwara n'imiterere y'umubiri y'uguhindagura kw'ingingo, ariko uburyo bwumvikana bwo kuvura ntabwo bwagaragajwe3,4; Ubushakashatsi buherutse gukorwa bwerekana ko kudakora neza k'umurongo wa microbiota-gut-brain bishobora gutera indwara zo kwangirika kw'ingingo, kandi hari ibimenyetso byinshi bigaragaza isano ishobora kuba hagati ya microbiota yo mu nda n'indwara zo kwangirika kw'ingingo5,6. Ikigaragara ni uko muri raporo imwe, gutera microbiota mu mwenge byazamuye ingenzi ya shitter na irritable bowel syndrome ku murwayi, bishobora kugaragaza isano ya hafi hagati ya microbiota yo mu nda n'ingenzi ya shitter. Byongeye kandi, twabonye impinduka zihariye muri microbiota yo mu nda ku barwayi ba ET, ibi bikaba bishyigikira cyane uruhare runini rwa dysbiosis y'igifu muri ET8.
Ku bijyanye na dysbiosis y'amara mu ndwara zitera indwara z'imitsi, PD ni yo yigwaho cyane5. Microbiota idahuje neza ishobora kongera ubushobozi bwo kwinjira mu mara no gukora glia y'amara, biganisha kuri alpha-synucleinopathies9,10,11. PD na ET bisangiye ibintu bimwe na bimwe, nko gutitira inshuro zimwe ku barwayi ba ET na PD, gutitira kuruhuka (gutitira gusanzwe kuri PD), no gutitira kw'inyuma (bikunze kuboneka ku barwayi ba ET), bigatuma bigorana kubitandukanya. mu ntambwe za mbere za 12. Kubwibyo, dukeneye byihutirwa gufungura idirishya ry'ingirakamaro ryo gutandukanya ET na PD. Muri urwo rwego, kwiga dysbiosis y'amara yihariye n'impinduka zijyanye na metabolite muri ET no kumenya itandukaniro ryabyo na PD bishobora kuba ibimenyetso bishobora kuba ibimenyetso byo gusuzuma no gutandukanya ET.
Aside fatty acids (SCFAs) ni zo zikora cyane mu mikorere y’uturemangingo tw’umubiri duto (short-chain fatty acids) zikorwa no guhinga fibre mu mara, kandi zikekwaho kugira uruhare runini mu mikoranire y’amara n’ubwonko13,14. SCFAs zifatwa n’uturemangingo tw’amara hanyuma zigajyanwa mu mwijima binyuze mu mitsi yo mu muyoboro w’amaraso, kandi zimwe muri SCFAs zinjira mu mikorere y’umubiri. SCFAs zigira ingaruka zo kubungabunga ubusugire bw’amara no guteza imbere ubudahangarwa bw’umubiri mu mara15. Zigira kandi ingaruka z’igihe kirekire ku mugozi w’amaraso n’ubwonko (BBB) ​​​​mu gukangura poroteyine zifatanye neza no gukora neurons mu gukangura receptors za poroteyine za G (GPCRs) kugira ngo zinyure muri BBB16. Acetate, propionate, na butyrate ni zo SCFAs nyinshi mu mara. Ubushakashatsi bwabanje bwagaragaje ko urugero rw’aside acetic, propionic na butyric mu mara rugabanuka ku barwayi ba Parkinson's disease17. Ariko, urugero rw’aside acetic, propionic na butyric mu mara ntirwigeze rwigwa ku barwayi ba ET.
Bityo, ubushakashatsi bwacu bwari bugamije kumenya impinduka zihariye mu maraso ya SCFA ku barwayi bafite ET n'itandukaniro ryabo n'abarwayi ba PD, gusuzuma isano iri hagati ya SCFA n'ibimenyetso bya ET n'udukoko two mu mara, ndetse no kumenya ubushobozi bwo gusuzuma no gutandukanya amasashe y'amasashe. KZhK. Kugira ngo dukemure ibintu bitera urujijo bifitanye isano n'imiti irwanya PD, twatoranyije abarwayi barwaye indwara ya Parkinson nshya nk'abashinzwe kurwanya indwara.
Imiterere y’abaturage n’imibanire y’abantu ku bantu 37 barwaye indwara zo mu mutwe (ETs), 37 barwaye indwara zo mu mutwe (PDs), na 35 barwaye indwara zo mu mutwe (HCs) ikubiye mu mbonerahamwe ya 1. ETs, PDs, na HCs byahujwe n’imyaka, igitsina, na BMI. Ayo matsinda atatu yari afite kandi ibipimo bimwe byo kunywa itabi, kunywa inzoga no kunywa ikawa n’icyayi. Amanota ya Wexner (P = 0.004) na HAMD-17 (P = 0.001) by’itsinda rya PD yari hejuru y’ay’itsinda rya HC, naho amanota ya HAMA (P = 0.011) na HAMD-17 (P = 0.011) by’itsinda rya ET yari hejuru y’ay’itsinda rya HC. Indwara mu itsinda rya ET yari miremire cyane kurusha mu itsinda rya PD (P <0.001).
Hari itandukaniro rinini mu rugero rw'aside propionic mu mayange (P = 0.023), aside asetiki (P = 0.039), aside butirike (P = 0.020), aside isovalerike (P = 0.045), na aside isobutirike (P = 0.015). . Mu isesengura ryakurikiyeho, urugero rwa aside propionic (P = 0.023), aside butirike (P = 0.007), na aside isobutirike (P = 0.040) mu itsinda rya ET rwari hasi cyane ugereranyije n'abari mu itsinda rya HC. Abarwayi ba ET bari bafite urugero rwo hasi rwa isovalerate (P = 0.014) na isobutirike (P = 0.005) ugereranyije n'abarwayi ba PD. Byongeye kandi, urugero rwa aside propionic yo mu matungo (P = 0.013), aside asetiki (P = 0.016), na aside butyric (P = 0.041) rwari hasi mu barwayi ba PD ugereranyije n'abarwayi ba CC (Ishusho ya 1 n'Imbonerahamwe y'inyongera ya 1).
ag igaragaza igereranya ry'itsinda rya aside propionic, aside asetiki, aside butyric, aside isovaleric, aside valeric, aside caproic na aside isobutyric. Hari itandukaniro rikomeye mu rugero rwa aside propionic yo mu matungo, aside asetiki, aside butyric, aside isovaleric na aside isobutyric hagati y'ayo matsinda atatu. ET essential tremble, Parkinson's disease, healthy HC control, SCFA. Itandukaniro rikomeye rigaragazwa na *P < 0.05 na **P < 0.01.
Dukurikije itandukaniro ry’uko indwara zigenda hagati y’itsinda rya ET n’itsinda rya PD, twize ku barwayi 33 bafite PD ya mbere n’abarwayi 16 bafite ET (indwara igenda munsi y’imyaka 3) kugira ngo tugere ku rugero rurambuye (Imbonerahamwe y’inyongera ya 2). Ibisubizo byagaragaje ko ingano ya aside propionic yo mu matungo ya ET yari hasi cyane ugereranyije n’iya HA (P=0.015). Itandukaniro riri hagati ya ET na HC kuri aside butyric na aside isobutyric ntiryari rinini, ariko hari icyerekezo cyagaragaye (P=0.082). Igipimo cya isobutyrate yo mu matungo cyari hasi cyane ku barwayi bafite ET ugereranije n’abarwayi bafite PD (P=0.030). Itandukaniro riri hagati ya ET na PD ya aside isovaleric ntabwo ryari rinini, ariko hari hakiri icyerekezo (P=0.084). Aside ya Propiyonike (P = 0.023), aside asetiki (P = 0.020), na aside butirike (P = 0.044) byari bike cyane ku barwayi ba PD ugereranyije n'abarwayi ba HC. Ibi bisubizo (Ishusho y'inyongera ya 1) muri rusange bihuye n'ibisubizo by'ingenzi. Itandukaniro ry'ibisubizo hagati y'icyitegererezo rusange n'itsinda ry'abarwayi ba mbere rishobora guterwa n'ingano nto y'icyitegererezo mu itsinda rito, bigatuma imbaraga z'imibare z'amakuru ziba nke.
Hanyuma twasuzumye niba urugero rwa SCFA mu matungo rushobora gutandukanya abarwayi bafite ET n'abarwayi bafite CU cyangwa PD. Dukurikije isesengura rya ROC, itandukaniro rya AUC ry'urugero rwa propionate ryari 0.668 (95% CI: 0.538-0.797), byatumye bishoboka gutandukanya abarwayi bafite ET na HC. Abarwayi bafite ET na GC bashobora gutandukana hakoreshejwe urugero rwa butyrate rufite AUC ya 0.685 (95% CI: 0.556–0.814). Itandukaniro riri hagati y'urugero rwa aside isobutyric rishobora gutandukanya abarwayi bafite ET na HC bafite AUC ya 0.655 (95% CI: 0.525–0.786). Mu guhuza urugero rwa propionate, butyrate na isobutyrate, habonetse AUC iri hejuru ya 0.751 (95% CI: 0.634–0.867) ifite ubushobozi bwo kumva 74.3% n'uburyo bwihariye bwa 72.9% (Ishusho ya 2a). Kugira ngo hamenyekane hagati y'abarwayi ba ET na PD, AUC ku rugero rwa aside isovaleric yari 0.700 (95% CI: 0.579–0.822) naho ku rugero rwa aside isobutyric yari 0.718 (95% CI: 0.599–0.836). Uruvange rwa aside isovaleric na aside isobutyric rwari rufite AUC iri hejuru ya 0.743 (95% CI: 0.629–0.857), ubushobozi bwo kumva 74.3% n'uburyo bwihariye bwa 62.9% (Ishusho ya 2b). Byongeye kandi, twasuzumye niba urugero rwa SCFA mu mwanda w’abarwayi ba Parkinson rwari rutandukanye n’urw’abagenzura. Dukurikije isesengura rya ROC, AUC yo kumenya abarwayi ba PD hashingiwe ku itandukaniro ry’urugero rwa aside propionic yari 0.687 (95% CI: 0.559-0.814), ifite ubushobozi bwo kwiyumvisha ibintu bwa 68.6% n’uburyo bwihariye bwa 68.7%. Itandukaniro mu rugero rwa acetate rishobora gutandukanya abarwayi ba PD na HC bafite AUC ya 0.674 (95% CI: 0.542–0.805). Abarwayi bafite PD bashobora gutandukana na CU gusa hakoreshejwe urugero rwa butyrate rufite AUC ya 0.651 (95% CI: 0.515–0.787). Mu guhuza urugero rwa propionate, acetate na butyrate, habonetse AUC ya 0.682 (95% CI: 0.553–0.811) (Ishusho ya 2c).
ivangura ryakozwe na Kiliziya y'Abaorthodokisi yo mu Burusiya kuri ET na HC; b ivangura ryakozwe na ROC kuri ET na PD; c ivangura ryakozwe na ROC kuri PD na HC; ET essential tremble, indwara ya Parkinson, uburyo bwo kurwanya HC mu buzima, SCFA.
Ku barwayi ba ET, urugero rwa aside isobutyric mu matungo rwari rufite isano mbi n'amanota ya FTM (r = -0.349, P = 0.034), naho urugero rwa aside isovaleric mu matungo rwari rufite isano mbi n'amanota ya FTM (r = -0.421, P = 0.001) n'amanota ya TETRAS. (r = -0.382, P = 0.020). Ku barwayi ba ET na PD, urugero rwa propionate mu matungo rwari rufite isano mbi n'amanota ya SCOPA-AUT (r = -0.236, P = 0.043) (Ishusho ya 3 n'Imbonerahamwe y'Inyongera ya 3). Nta sano rigaragara hagati y'uburyo indwara igenda n'amanota ya SCFA mu itsinda rya ET (P ≥ 0.161) cyangwa itsinda rya PD (P ≥ 0.246) (Imbonerahamwe y'Inyongera ya 4). Ku barwayi ba PD, urugero rwa aside caproic mu matungo rwahuye neza n'amanota ya MDS-UPDRS (r = 0.335, P = 0.042). Mu bitabiriye bose, urugero rwa propionate mu matungo (r = −0.230, P = 0.016) na acetate (r = −0.210, P = 0.029) rwahuye nabi n'amanota ya Wexner (Ishusho ya 3 n'Imbonerahamwe y'Inyongera ya 3).
Igipimo cya aside isobutyric mu matungo cyari gifitanye isano ribi n'amanota ya FTM, aside isovalerike yari ifitanye isano ribi n'amanota ya FTM na TETRAS, aside propionic yari ifitanye isano ribi n'amanota ya SCOPA-AUT, aside caproic yari ifitanye isano ribi n'amanota ya MDS-UPDRS, naho aside propionic yari ifitanye isano ribi n'amanota ya FTM na TETRAS. TETRAS na aside asetiki byari bifitanye isano ribi n'amanota ya Wexner. Ishyirahamwe rya MDS-UPDRS ryateye inkunga verisiyo ya Unified Parkinson's Disease Rating Scale, Mini-Mental State Examination MMSE, Hamilton Depression Rating Scale HAMD-17, ibintu 17, Hamilton Anxiety Rating Scale HAMA, HY Hoehn na Yahr stages, SCFA, SCOPA - AUT Parkinson's Disease Autonomic Symptom Outcome Scale, FTM Fana-Tolosa-Marin Clinical Tremor Rating Scale, TETRAS Research Group (TRG) Essential Tremor Rating Scale. Itandukaniro rikomeye rigaragazwa na *P < 0.05 na **P < 0.01.
Twakomeje gusuzuma ivangura rya mikorobe zo mu nda dukoresheje isesengura rya LEfSE, maze duhitamo urwego rw'amakuru yerekeye ubwinshi bw'uturemangingo kugira ngo dusesengure byinshi. Hakozwe igereranya hagati ya ET na HC na ET na PD. Isesengura rya Spearman ryakozwe ku bwinshi bwa mikorobe zo mu nda n'urugero rwa SCFA mu matsinda abiri yo kugereranya.
Faecalibacterium (ifitanye isano na aside butyric, r = 0.408, P < 0.001), Lactobacillus (ifitanye isano na aside butyric, r = 0.283, P = 0.016), Streptobacterium (ifitanye isano na aside propionic, r = 0.327) yagaragaye mu isesengura rya ET na CA. , P = 0.005; ifitanye isano na aside butyric, r = 0.374, P = 0.001; bifitanye isano na aside isobutyric, r = 0.329, P = 0.005), Howardella (ifitanye isano na aside propionic, r = 0.242, P = 0.041), Raoultella (ifitanye isano na propionate, r = 0.249, P = 0.035), na Candidatus Arthromitus (ifitanye isano na aside isobutyric, r = 0.302, P = 0.010) igabanuka muri ET kandi ifitanye isano ryiza n'urugero rwa SCFA mu matungo. Ariko, ubwinshi bwa Stenotropomonas bwiyongereye muri ET kandi bwari bufite isano mbi n'urugero rwa isobutyrate mu matungo (r = -0.250, P = 0.034). Nyuma yo guhindurwa kwa FDR, isano iri hagati ya Faecalibacterium, Catenibacter, na SCFA ni yo yonyine yagumyeho (P ≤ 0.045) (Ishusho ya 4 n'Imbonerahamwe y'Inyongera ya 5).
Isesengura ry’isano riri hagati ya ET na HC. Nyuma yo guhindurwa kwa FDR, ubwinshi bwa Faecalibacterium (ifitanye isano na butyrate) na Streptobacterium (ifitanye isano na propionate, butyrate, na isobutyrate) byagaragaye ko byagabanutse muri ET kandi ko bifitanye isano n’urugero rwa SCFA mu matungo. b Isesengura ry’isano riri hagati ya ET na PD. Nyuma yo guhindurwa kwa FDR, nta sano rikomeye ryabonetse. ET essential tremble, Parkinson's disease, healthful HC control, SCFA. Itandukaniro rikomeye rigaragazwa na *P < 0.05 na **P < 0.01.
Ubwo basesenguraga ET ugereranyije na PD, Clostridium trichophyton yagaragaye ko yiyongereye muri ET kandi ifitanye isano na aside isovaleric y'amase (r = -0.238, P = 0.041) na aside isobutyric (r = -0.257, P = 0.027). ). Nyuma yo guhindurwa kwa FDR, byombi byakomeje kuba ingenzi (P≥0.295) (Ishusho ya 4 n'Imbonerahamwe y'Inyongera ya 5).
Ubu bushakashatsi ni ubushakashatsi bwuzuye busuzuma urugero rwa SCFA mu matungo y’umura kandi bugahuza n’impinduka mu mikorobe zo mu mara n’ubukana bw’ibimenyetso ku barwayi ba ET ugereranije n’abarwayi ba CU na PD. Twasanze urugero rwa SCFA mu matungo y’umura rwaragabanutse ku barwayi ba ET kandi bifitanye isano n’ubukana bw’indwara ndetse n’impinduka zihariye mu matungo y’umura. Urugero rw’amatungo y’umura rugizwe n’aside fatty y’uruhererekane rugufi (SCFAs) rutandukanya ET na GC na PD.
Ugereranyije n'abarwayi ba GC, abarwayi ba ET bafite urugero rwo hasi rwa aside propionic, butyric, na isobutyric mu mayange. Uruvange rwa aside propionic, butyric na isobutyric rwagaragaje ET na HC hamwe na AUC ya 0.751 (95% CI: 0.634–0.867), ubushobozi bwo kumva 74.3% n'uburyo bwihariye bwa 72.9%, bigaragaza ko ikoreshwa ryabyo nk'ibipimo by'isuzuma ku ruhare rushoboka rwa ET. Isesengura ryinyongera ryagaragaje ko urugero rwa aside propionic mu mayange rwari rufitanye isano mbi n'amanota ya Wexner n'amanota ya SCOPA-AUT. Urugero rwa aside isobutyric mu mayange rwari rufitanye isano itandukanye n'amanota ya FTM. Ku rundi ruhande, kugabanuka k'urugero rwa butyrate muri ET byafitanye isano no kugabanuka k'ubwinshi bwa microbiota zikora SCFA, Faecalibacterium, na Categorybacter. Byongeye kandi, kugabanuka k'ubwinshi bwa Catenibacter muri ET byanafitanye isano no kugabanuka k'urugero rwa aside propionic na isobutyric mu mayange.
Inyinshi muri SCFA zikorerwa mu mara zifatwa na colonocytes cyane cyane binyuze mu byuma bitwara monocarboxylate ishingiye kuri H+ cyangwa sodium. Aside fatty iri mu miyoboro migufi ikoreshwa nk'isoko y'ingufu kuri colonocytes, mu gihe izidakoreshejwe muri colonocytes zijyanwa mu nzira y'amaraso 18. SCFA zishobora kugira ingaruka ku mikorere y'amara, kongera imikorere y'imyobo y'amara, no kugira ingaruka ku mikorere y'umubiri n'ubudahangarwa bw'umubiri19. Byagaragaye mbere ko ingano y'imyanda ya butyrate, acetate, na propionate yagabanutse ku barwayi ba PD ugereranije na HCs17, ibi bikaba bihuye n'ibyavuye mu bushakashatsi bwacu. Ubushakashatsi bwacu bwagaragaje ko SCFAs zagabanutse ku barwayi ba ET, ariko nta byinshi bizwi ku ruhare rwa SCFAs mu ndwara ya ET. Butyrate na propionate bishobora gufatana na GPCRs no kugira ingaruka ku byuma bishingira kuri GPCR nka MAPK na NF-κB20. Igitekerezo cy'ibanze cy'umurongo w'igifu n'ubwonko ni uko SCFAs zikurwa na mikorobe zo mu gifu zishobora kugira ingaruka ku byuma bitanga amakuru, bityo zigira ingaruka ku mikorere y'igifu n'ubwonko. Kubera ko butyrate na propionate bigira ingaruka zikomeye ku bikorwa bya histone deacetylase (HDAC)21 kandi butyrate nayo ishobora gukora nk'ikimenyetso cy'ibintu bihindura imikorere y'uturemangingo, bigira ingaruka nini ku mikorere y'umubiri, itandukaniro n'ubwiyongere bw'uturemangingo, ahanini bitewe n'ingaruka bigira ku mikorere ya gene22. Hashingiwe ku bimenyetso bya SCFA n'indwara zitera indwara z'ubwonko, butyrate ifatwa nk'umuti uvura bitewe n'ubushobozi bwayo bwo gukosora ibikorwa bya HDAC byangiritse, bishobora gutera urupfu rwa dopaminergic neuron muri PD23,24,25. Ubushakashatsi ku nyamaswa bwagaragaje kandi ubushobozi bwa aside butyric bwo gukumira kwangirika kwa dopaminergic neuron no kunoza ibibazo byo kugenda mu buryo bwa PD26,27. Aside propionic byagaragaye ko igabanya ingaruka zo kubyimba no kurinda ubusugire bwa BBB28,29. Ubushakashatsi bwagaragaje ko aside propionic itera imbere ku kubaho kwa dopaminergic neuron mu gusubiza uburozi bwa rotenone muri PD models 30 kandi ko gutanga aside propionic mu kanwa bikiza ibura rya dopaminergic neuron no kubura ubushobozi bwo gukora mu mbeba zifite PD 31. Nta byinshi bizwi ku mikorere ya aside isobutyric. Ariko, ubushakashatsi buherutse gukorwa bwagaragaje ko kwishyira mu myanya y’imbeba zifite B. ovale byongera ubwinshi bwa SCFA mu mara (harimo acetate, propionate, isobutyrate, na isovalerate) hamwe n’ubwinshi bwa GABA mu mara, bigaragaza ko hari isano yashyizweho hagati ya mikorobiota yo mu nda n’ubwinshi bwa SCFA mu mara. Muri ET, impinduka zidasanzwe mu mikorere ya cerebellum zirimo impinduka mu mikorere ya axon na dendrites mu turemangingo twa Purkinje, kwimuka no gutakaza uturemangingo twa Purkinje, impinduka mu mikorere ya axon mu turemangingo, ibitagenda neza mu mikorere ya fibre izamuka hamwe n’ikwirakwizwa ry’uturemangingo twa Purkinje, hamwe n’impinduka mu mikorere ya GABA mu igufwa rya dentate, bigatuma umusaruro wa GABAergic uva muri cerebellum3,4,33 ugabanuka. Ntibirasobanuka neza niba SCFA zifitanye isano no kwangirika kw’imitsi mu turemangingo twa Purkinje no kugabanuka k’umusaruro wa GABA mu turemangingo. Ibisubizo byacu bigaragaza isano ikomeye hagati ya SCFA na ET, ariko imiterere y’ubushakashatsi bw’ibice bitandukanye ntiyemera umwanzuro uwo ari wo wose ku isano iri hagati ya SCFA n’indwara ya ET; Hakenewe ubundi bushakashatsi bwo gukurikirana igihe kirekire, harimo gupima amacandwe y’ubwandu mu buryo bukurikiranye, ndetse no gusuzuma uburyo inyamaswa zikora.
Bitekerezwa ko SCFA zitera imbaraga zo gufunga imitsi yo mu mara 34. Kubura SCFA bizatuma ibimenyetso byo kunyara birushaho kwiyongera, kandi kongeramo SCFA bishobora kongera ibimenyetso byo kunyara PD35. Ibisubizo byacu bigaragaza kandi isano ikomeye hagati yo kugabanuka k'umusemburo wa SCFA mu mayange no kwiyongera k'impatwe no kudakora neza kw'umubiri ku barwayi ba ET. Raporo imwe y'ingero yagaragaje ko gutera microbiota byazamuye éssentials tremble na irritable bowel syndrome ku murwayi wa 7, bikongeraho isano ya hafi hagati ya microbiota mu mara na ET. Kubwibyo, twizera ko SCFA/microbiota mu mayange ishobora kugira ingaruka ku mikorere y'amara n'imikorere y'imitsi ikora.
Ubushakashatsi bwagaragaje ko kugabanuka k'urugero rwa SCFA z'amase muri ET bifitanye isano no kugabanuka k'ubwinshi bwa Faecalibacterium (ifitanye isano na butyrate) na Streptobacterium (ifitanye isano na propionate, butyrate, na isobutyrate). Nyuma yo gukosora FDR, iyi sano iracyari ingenzi. Faecalibacterium na Streptobacterium ni udukoko duto dutanga SCFA. Faecalibacterium izwiho kuba mikorobe ikora butyrate36, mu gihe umusaruro w'ingenzi wa Catenibacter fermentation ari acetate, butyrate na aside lactic37. Faecalibacterium yabonetse muri 100% by'amatsinda yombi ya ET na HC; ubwinshi bw'itsinda rya ET bwari 2.06% naho ubw'itsinda rya HC bwari 3.28% (LDA 3.870). Bagiteri yo mu cyiciro yabonetse muri 21.6% (8/37) by'itsinda rya HC kandi mu rugero 1 gusa rw'itsinda rya ET (1/35). Kugabanuka no kutagaragara kwa bagiteri za streptobacteri muri ET bishobora kandi kugaragaza isano iri hagati y’indwara. Ubwinshi bw’ubwoko bwa Catenibacter mu itsinda rya HC bwari 0.07% (LDA 2.129). Byongeye kandi, bagiteri za aside lactic zahujwe n’impinduka mu ifu y’umusemburo (P = 0.016, P = 0.096 nyuma yo guhindurwa kwa FDR), kandi rubagimpande rwahujwe n’impinduka muri isobutyrate (P = 0.016, P = 0.072 nyuma yo guhindurwa kwa FDR). Nyuma yo guhindurwa kwa FDR, niho gusa hasigaye isano, ariko ntabwo ari ingenzi cyane mu mibare. Lactobacilli izwiho kandi kuba SCFA (aside acetic, aside propionic, aside isobutyric, aside butyric) 38 naho Candidatus Arthromitus ni ikintu cyihariye gitera itandukanyirizo ry’uturemangingo twa T helper 17 (Th17), hamwe na Th1/2 na Tregs bifitanye isano no kuringaniza ubudahangarwa bw’umubiri /Th1739. . Ubushakashatsi buherutse gukorwa bwerekana ko urugero rwo hejuru rw’indwara ya pseudoarthritis mu matungo rushobora kugira uruhare mu kubyimba kw’amara, kudakora neza kw’imizigo y’amara, no kubyimba kw’umubiri 40. Urugero rwa Clostridium trichoides rwiyongereye muri ET ugereranije na PD. Ubunini bwa Clostridium trichoides bwagaragaye ko bufitanye isano ribi na aside isovaleric na aside isobutyric. Nyuma yo guhindurwa kwa FDR, byombi byakomeje kuba binini (P≥0.295). Clostridium pilosum ni bagiteri izwiho kuba ifitanye isano no kubyimba kandi ishobora kugira uruhare mu kubyimba kw’imizigo y’amara 41. Ubushakashatsi bwacu bwa mbere bwagaragaje impinduka mu mikorobe y’amara ku barwayi ba ET8. Aha tunagaragaza impinduka muri SCFA muri ET kandi tugaragaza isano iri hagati ya dysbiosis mu mara n’impinduka muri SCFA. Kugabanuka kw’urugero rwa SCFA bifitanye isano rya hafi na dysbiosis mu mara n’ubukana bw’umutingito muri ET. Ibisubizo byacu bigaragaza ko umurongo w’amara n’ubwonko ushobora kugira uruhare runini mu gutera ET, ariko hakenewe ubundi bushakashatsi mu nyamaswa.
Ugereranyije n'abarwayi ba PD, abarwayi ba ET bafite urugero rwo hasi rwa aside isovaleric na isobutyric mu mwanda wabo. Uruvange rwa aside isovaleric na aside isobutyric rwagaragaje ET muri PD hamwe na AUC ya 0.743 (95% CI: 0.629–0.857), ubushobozi bwo kumva 74.3% n'uburyo bwihariye bwa 62.9%, bigaragaza uruhare rwabo nk'ibipimo mu gusuzuma ET. Urugero rwa aside isovaleric mu matungo rwahuye n'ibipimo bya FTM na TETRAS. Urugero rwa aside isobutyric mu matungo rwahuye n'ibipimo bya FTM. Kugabanuka kw'urugero rwa aside isobutyric byajyanye no kugabanuka k'ubwinshi bwa catobacteria. Nta byinshi bizwi ku mikorere ya aside isovaleric na aside isobutyric. Ubushakashatsi bwakozwe mbere bwagaragaje ko kwibasira imbeba zifite B. ovale byongera ingano ya SCFA zo mu mara (harimo acetate, propionate, isobutyrate, na isovalerate) hamwe n’ubwinshi bwa GABA mu mara, bigaragaza isano iri hagati ya mikorobiota n’ubwinshi bwa SCFA/neurotransmitter mu mara32. Igishimishije ni uko urugero rwa aside isobutyric rwagaragaye rwari rusa hagati y’amatsinda ya PD na HC, ariko rwari rutandukanye hagati y’amatsinda ya ET na PD (cyangwa HC). Aside isobutyric yashoboraga gutandukanya ET na PD hamwe na AUC ya 0.718 (95% CI: 0.599–0.836) no kumenya ET na NC hamwe na AUC ya 0.655 (95% CI: 0.525–0.786). Byongeye kandi, urugero rwa aside isobutyric rufitanye isano n’ubukana bwa territure, bikomeza kurushaho isano yayo na ET. Ikibazo cyo kumenya niba aside isobutyric yo mu kanwa ishobora kugabanya ubukana bwa territure ku barwayi ba ET gikwiye kwigwaho byinshi.
Bityo, ingano ya SCFA mu matungo iragabanuka ku barwayi ba ET kandi bifitanye isano n'ubukana bwa ET n'impinduka zihariye mu mikorobe zo mu mara. Fecal propionate, butyrate, na isobutyrate bishobora kuba ibimenyetso by'isuzuma kuri ET, mu gihe isobutyrate na isovalerate bishobora kuba ibimenyetso by'isuzuma bitandukanye kuri ET. Impinduka muri isobutyrate mu matungo zishobora kuba zihariye kuri ET kurusha izindi mpinduka mu zindi SCFA.
Ubushakashatsi bwacu bufite imbogamizi nyinshi. Ubwa mbere, imiterere y'imirire n'ibyo dukunda bishobora kugira ingaruka ku mikorobe, ingero nini z'ubushakashatsi mu baturage batandukanye zirakenewe, kandi ubushakashatsi bw'ejo hazaza bugomba gutangiza ubushakashatsi bwuzuye kandi bunoze ku mirire nk'ibibazo by'ibiribwa. Icya kabiri, igishushanyo mbonera cy'ubushakashatsi kibuza imyanzuro iyo ari yo yose yerekeye isano iri hagati ya SCFA n'inzira y'indwara ya ET. Hakenewe ubundi bushakashatsi bw'igihe kirekire bupima SCFA z'umwanda. Icya gatatu, ubushobozi bwo gusuzuma no gutandukanya urugero rwa SCFA rw'umwanda bugomba kwemezwa hakoreshejwe ingero zigenga za ET, HC, na PD. Ingero nyinshi z'umwanda zigenga zigomba gupimwa mu gihe kizaza. Amaherezo, abarwayi ba PD mu itsinda ryacu bari bafite igihe gito cyane cy'uburwayi ugereranyije n'abarwayi ba ET. Twahuje cyane cyane ET, PD na HC dukurikije imyaka, igitsina na BMI. Bitewe n'itandukaniro ry'uburyo indwara igenda hagati y'itsinda rya ET n'itsinda rya PD, twanasuzumye abarwayi 33 bafite PD yo hambere n'abarwayi 16 bafite ET (igihe indwara imara ≤imyaka 3) kugira ngo tugere ku rugero rurambuye. Itandukaniro hagati y'amatsinda muri SCFA muri rusange ryari rihuye n'amakuru yacu y'ibanze. Byongeye kandi, nta sano twabonye hagati y’igihe indwara imara n’impinduka muri SCFA. Ariko, mu gihe kizaza, byaba byiza dushatse abarwayi bafite PD na ET hakiri kare bafite igihe gito cy’indwara kugira ngo harebwe neza mu cyiciro kinini.
Iyi gahunda y’ubushakashatsi yemejwe na Komite Ishinzwe Imyitwarire y’Ibitaro bya Ruijin ikorana n’Ishuri ry’Ubuganga rya Kaminuza ya Shanghai Jiao Tong (RHEC2018-243). Abitabiriye bose bahawe uburenganzira bwanditse.
Hagati ya Mutarama 2019 na Ukuboza 2022, abantu 109 (37 ET, 37 PD, na 35 HC) bo mu bitaro bya Ruijin, ishamikiye ku ishuri ry’ubuvuzi rya kaminuza ya Shanghai Jiao Tong, bashyizwe muri ubu bushakashatsi. Ibipimo byari: (1) imyaka 25-85, (2) abarwayi bafite ET basuzumwe hakurikijwe ibipimo bya MDS Working Group 42 na PD basuzumwe hakurikijwe ibipimo bya MDS 43, (3) abarwayi bose ntibafataga imiti igabanya ubukana bwa PD mbere yo gukusanya ingero. (4) Itsinda rya ET ryafashe imiti igabanya ubukana bwa β gusa cyangwa nta miti ifitanye isano na yo mbere yo gukusanya ingero z’imyanya. Imiti igabanya ubukana bwa HC ijyanye n’imyaka, igitsina, n’ibipimo by’uburemere bw’umubiri (BMI) nayo yatoranijwe. Ibipimo byo kwirukana ni ibi bikurikira: (1) abarya imboga gusa, (2) imirire mibi, (3) indwara zidakira zo mu nzira y'igifu (harimo indwara y'ububyimbirwe bw'amara, ibisebe byo mu gifu cyangwa mu duodenum), (4) indwara zidakira cyane (harimo ibibyimba bibi), umutima unanirwa gukora neza, impyiko zinanirwa gukora neza, indwara z'amaraso) (5) Amateka yo kubagwa igifu cyane, (6) Kurya yawurute idakira cyangwa isanzwe, (7) Gukoresha imiti ya probiotics cyangwa antibiyotike mu gihe cy'ukwezi 1, (8) Gukoresha imiti ya corticosteroids idakira, imiti igabanya ubukana bwa proton pump, statins, metformin, imiti igabanya ubukana bw'umubiri cyangwa imiti irwanya kanseri na (9) ubumuga bukomeye bwo mu mutwe bubangamira igeragezwa ry'ubuvuzi.
Abantu bose batanze amakuru y’amateka y’ubuzima, ibiro n’uburebure kugira ngo babare BMI, kandi bakorewe isuzuma ry’imitsi n’isuzuma ry’ubuvuzi nka Hamilton Anxiety Rating Scale (HAMA) 44 anxiety score, Hamilton Depression Rating Scale-17 (HAMD-17) 45. kwiheba, ubukana bw’impatwe hakoreshejwe Wexner Constipation Scale 46 na Bristol Stool Scale 47 hamwe n’imikorere y’ubwenge hakoreshejwe Mini-Mental State Examination (MMSE) 48. Igipimo cyo gusuzuma ibimenyetso by’indwara ya Parkinson (SCOPA-AUT) 49 cyasuzumye ikibazo cy’imikorere y’umubiri ku barwayi ba ET na PD. Igipimo cya Fana-Tolos-Marin Clinical Tremor Rating Scale (FTM) na Essential Tremor Rating Scale (TETRAS) 50 Itsinda ry’ubushakashatsi rya Tremor (TRG) 50 ryasuzumwe ku barwayi ba ET; Igipimo cya Kinson's Disease Rating Scale (MDS-), cyatewe inkunga n’ishyirahamwe ry’indwara ya Parkinson; UPDRS verisiyo ya 51 na Hoehn na Yahr (HY) verisiyo ya 52 byarasuzumwe.
Buri wese mu bitabiriye yasabwe gukusanya icyitegererezo cy'umwanda mu gitondo akoresheje agakoresho ko gukusanya umwanda. Shyira ibikoresho mu rubura ubibike kuri -80°C mbere yo kubitunganya. Isesengura rya SCFA ryakozwe hakurikijwe ibikorwa bisanzwe bya Tiangene Biotechnology (Shanghai) Co., Ltd. Hakusanyijwe mg 400 z'ingero z'umwanda mushya muri buri muntu hanyuma bigasesengurwa hakoreshejwe SCFA nyuma yo gusya no gusya. SCFA zatoranijwe mu mwanda zasesenguwe hakoreshejwe gaz chromatography-mass spectrometry (GC-MS) na liquid chromatography-tandem MS (LC-MS/MS).
ADN yakuwe mu bipimo bya 200 mg hakoreshejwe QIAamp® Fast DNA Stool Mini Kit (QIAGEN, Hilden, Ubudage) hakurikijwe amabwiriza y'uruganda. Imiterere ya mikorobe yagenwe hakoreshejwe uburyo bwo gukurikirana gene ya 16 S rRNA kuri ADN yakuwe mu mwanda binyuze mu kongera akarere ka V3-V4. Gerageza ADN ukoresheje icyitegererezo kuri gel ya agarose ya 1.2%. Polymerase chain reaction (PCR) amplification ya gene ya 16S rRNA yakozwe hakoreshejwe primers za bagiteri zisanzwe (357 F na 806 R) hamwe n'isomero rya amplicon ry'intambwe ebyiri ryubatswe kuri platform ya Novaseq.
Ibihinduka bihoraho bigaragazwa nk'ikigereranyo ± ihinduka risanzwe, naho ibihinduka mu byiciro bigaragazwa nk'imibare n'ijanisha. Twakoresheje ikizamini cya Levene kugira ngo tugerageze uburyo ibihinduka bingana. Kugereranya byakozwe hakoreshejwe ibizamini bya t bifite imirizo ibiri cyangwa isesengura ry'ubusumbane (ANOVA) niba ibihinduka bisanzwe byarakwirakwijwe, n'ibizamini bya Mann-Whitney U bitari ibya parametric niba ibitekerezo bisanzwe cyangwa homoscedasticity byararengagijwe. Twakoresheje agace kari munsi y'icyerekezo cy'imikorere ya receiver (ROC) (AUC) kugira ngo dupime imikorere y'icyitegererezo no gusuzuma ubushobozi bwa SCFA bwo gutandukanya abarwayi ba ET n'abafite HC cyangwa PD. Kugira ngo dusuzume isano iri hagati ya SCFA n'ubukana bw'indwara, twakoresheje isesengura rya Spearman. Isesengura ry'imibare ryakozwe hakoreshejwe porogaramu ya SPSS (version 22.0; SPSS Inc., Chicago, IL) hamwe n'urwego rw'uburemere (harimo agaciro ka P na FDR-P) rwashyizwe kuri 0.05 (ku mpande ebyiri).
Isesengura rya 16 S ryasesenguwe hakoreshejwe porogaramu ya Trimmomatic (version 0.35), Flash (version 1.2.11), UPARSE (version v8.1.1756), mothur (version 1.33.3) na R (version 3.6.3). Amakuru ya gene ya 16S rRNA yakozwe hakoreshejwe UPARSE kugira ngo hakorwe units operational taxonomic (OTUs) zifite 97% by'indangamuntu. Taxonomies zagenwe hakoreshejwe Silva 128 nk'ububiko bw'amakuru. Urwego rusange rw'amakuru y'ubwinshi bw'ikigereranyo rwatoranyijwe kugira ngo hakorwe isesengura ryinshi. Isesengura ry'ingano y'ingaruka rya Linear discriminant analysis (LDA) (LEfSE) ryakoreshejwe mu kugereranya amatsinda (ET vs. HC, ET vs. PD) hamwe n'umubare wa α wa 0.05 n'umubare wa ingano y'ingaruka wa 2.0. Imiterere ya Discriminant yagaragajwe na LEfSE analysis yongeye gukoreshwa mu isesengura rya Spearman correlation rya SCFA.
Kugira ngo umenye byinshi ku bijyanye n'igishushanyo mbonera cy'ubushakashatsi, reba Incamake ya Raporo y'Ubushakashatsi bw'Inyamaswa ijyanye n'iyi nkuru.
Amakuru y’uburyo bwo gukurikirana amakuru ya 16S abikwa muri database ya BioProject y’Ikigo cy’Igihugu cy’Amakuru ya Biotechnology (NCBI) (SRP438900: PRJNA974928), Aderesi: https://www.ncbi.nlm.nih.gov/Traces/study/?acc= SRP438900&o. =acc_s% 3Aa. Andi makuru ajyanye n’ibyo ashobora kuboneka ku mwanditsi ubishinzwe iyo abisabye, nko gukorana mu bya siyansi no guhanahana amakuru mu bushakashatsi n’imishinga y’ubushakashatsi yuzuye. Nta kohereza amakuru ku bandi bantu tutabiherewe uburenganzira.
Kode y'isoko ifunguye gusa hamwe n'uruvange rwa Trimmomatic (version 0.35), Flash (version 1.2.11), UPARSE (version v8.1.1756), mothur (version 1.33.3) na R (version 3.6.3), hakoreshejwe igenamiterere risanzwe cyangwa igice "Uburyo". Amakuru y'inyongera asobanura neza ashobora gutangwa ku mwanditsi ujyanye nayo mu gihe abisabye mu buryo bwumvikana.
Pradeep S na Mehanna R. Indwara zo mu gifu mu ndwara zo mu mikorere y’umubiri ziterwa no kubura umwuka no kudakora neza. Bifitanye isano n’indwara ya Parkinson. urujijo. 90, 125–133 (2021).
Louis, ED na Faust, PL Indwara y'umutingito w'ingenzi: kwangirika kw'imitsi no kongera gutunganya imikoranire y'imitsi. Nat. Pastor Nirol. 16, 69–83 (2020).
Gironell, A. Ese gutitira kw'ingenzi ni indwara y'ibanze iterwa no kudakora neza kwa Gaba? Yego. mpuzamahanga. Rev. Neuroscience. 163, 259–284 (2022).
Dogra N., Mani RJ na Katara DP Umutima n'ubwonko: uburyo bubiri bwo gutanga ibimenyetso ku ndwara ya Parkinson. Molekile z'uturemangingo. Neurobiology. 42, 315–332 (2022).
Quigley, EMM. Imiterere y'imikorobe, ubwonko, amara n'indwara zo kwangirika kw'imitsi. ikoranabuhanga. Nellore. Ubumenyi bw'ubwonko. Raporo 17, 94 (2017).
Liu, XJ, Wu, LH, Xie, WR na He, XX Gutera microbiota y'amafi icyarimwe binoza uburyohe bw'indwara y'amara n'indwara y'imitsi iterwa n'ingufu mu barwayi. Geriatric Psychology 20, 796–798 (2020).
Zhang P. n'abandi. Impinduka zihariye mu mikorobe y'amara mu gutitira kw'ingenzi n'itandukaniro ryazo n'indwara ya Parkinson. Indwara ya NPJ Parkinson. 8, 98 (2022).
Luo S, Zhu H, Zhang J na Wang D. Uruhare rw'ingenzi rwa mikorobe mu kugenzura ibice by'imitsi ya neuronal-glial-epithelial. Ubudahangarwa ku byanduza. 14, 5613–5628 (2021).
Emin A. n'abandi. Pathology ya duodenal alpha-synuclein na intestine gliosis mu ndwara ya Parkinson ikomeza. move. confusion. https://doi.org/10.1002/mds.29358 (2023).
Skorvanek M. n'abandi. Utunyangingo twa alpha-synuclein 5G4 tumenya indwara ya Parkinson n'indwara ya Parkinson yo mu mara. move. confusion. 33, 1366–1368 (2018).
Algarni M na Fasano A. Guhurirana kw'indwara yo gutigita kw'ingenzi n'indwara ya Parkinson. Bifitanye isano n'indwara ya Parkinson. urujijo. 46, С101–С104 (2018).
Sampson, TR n'abandi. Mikorobe zo mu nda zihindura imiterere y'imitsi n'ubwivumbure mu mikorere y'indwara ya Parkinson. Cell 167, 1469–1480.e1412 (2016).
Unger, MM n'abandi. Aside y'ibinure by'uruhererekane rugufi na mikorobe zo mu nda bitandukanye hagati y'abarwayi ba Parkinson n'ababana n'imyaka isa. Bifitanye isano n'indwara ya Parkinson. urujijo. 32, 66–72 (2016).
Bleacher E, Levy M, Tatirovsky E na Elinav E. Metabolites zigenzurwa na mikorobe ziri ku gice cy’ubudahangarwa bw’umubiri. J. Immunology. 198, 572–580 (2017).