Ngā mihi nui ki a koe mō tō toro mai ki Nature.com. He iti noa te tautoko CSS mō te putanga o te pūtirotiro e whakamahia ana e koe. Mō ngā hua pai rawa atu, ka tūtohu mātou kia whakamahia e koe tētahi putanga hou ake o tō pūtirotiro (kāore rānei e mono i te Aratau Hototahi i roto i te Internet Explorer). I tēnei wā, hei whakarite i te tautoko tonu, kei te whakaatu mātou i te pae me te kore he momo kāhua, he JavaScript rānei.
He uaua pea te tautuhi wawe i te wiri nui (ET), inā koa ka wehewehea mai i ngā mana hauora (HC) me te mate a Parkinson (PD). Nō nā tata nei, kua whakaratohia e te tātaritanga o ngā tauira paru mō ngā microbiota puku me ōna matūkai ngā tikanga hou mō te kimi i ngā tohu koiora hou o ngā mate neurodegenerative. Ko ngā waikawa ngako mekameka-poto (SCFA), hei matūkai matua o ngā tipu puku, ka heke i roto i ngā paru i roto i te PD. Heoi, kāore anō kia rangahaua te SCFA paru i roto i te ET. Ko tā mātou whāinga he tirotiro i ngā taumata paru o ngā SCFA i roto i te ET, aromatawai i tō rātou whanaungatanga ki ngā tohu haumanu me ngā microbiota puku, me te whakatau i tō rātou kaha tātaritanga pea. I inehia te SCFA paru me te microbiota puku i roto i te 37 ET, 37 PD hou, me te 35 HC. I aromatawaihia te mate kōroke, te ngoikore o te pūnaha autonomic, me te kaha o te wiri mā te whakamahi i ngā tauine. He iti ake ngā taumata paru o te propionate, butyrate, me te isobutyrate i roto i te ET i tō te HC. Nā te huinga o ngā waikawa propionic, butyric me te isobutyric i wehewehe te ET mai i te HC me te AUC o te 0.751 (95% CI: 0.634–0.867). He iti ake ngā taumata o te waikawa isovaleric fecal me te waikawa isobutyric i roto i te ET i tērā i roto i te PD. Ka wehewehe te waikawa isovaleric me te waikawa isobutyric i waenga i te ET me te PD me te AUC o te 0.743 (95% CI: 0.629–0.857). He hononga whakahurihuri te propionate fecal ki te mate puku me te ngoikore o te pūnaha autonomic. He hononga whakahurihuri te waikawa isobutyric me te waikawa isovaleric ki te kaha o te wiri. Ko te hekenga o te ihirangi SCFA fecal i hono atu ki te hekenga o te nui o Faecalibacterium me Streptobacterium i roto i te ET. Nō reira, ka heke te ihirangi o te SCFA i roto i te paru i roto i te ET, ā, e hono ana ki te kaha o te pikitia haumanu me ngā huringa o te microbiota whekau. Ko te waikawa propionic, te waikawa butyric, te waikawa isobutyric, me te waikawa isovaleric i roto i ngā tūtae pea hei tohu tautuhi me te tautuhi rerekētanga mō te ET.
Ko te wiri nui (ET) he mate neurodegenerative ahu whakamua, mau tonu e tohuhia ana e te wiri o ngā pito o runga, ka pā pea ki ētahi atu wāhanga o te tinana pēnei i te mahunga, ngā taura reo, me ngā pito o raro 1. Ko ngā āhuatanga haumanu o te ET ehara i te mea ko ngā tohu nekehanga anake engari ko ētahi tohu kore-nekehanga, tae atu ki te mate puku 2. He maha ngā rangahau kua mahia hei tirotiro i ngā āhuatanga pathological me te physiological o te wiri nui, engari kāore anō kia tautuhia ngā tikanga pathophysiological mārama3,4. E kī ana ngā rangahau tata nei ko te ngoikore o te microbiota-puku-roro ka whai wāhi pea ki ngā mate neurodegenerative, ā, kei te piki haere te taunakitanga mō te hononga rua-ara pea i waenga i te microbiota puku me ngā mate neurodegenerative5,6. He mea nui, i roto i tētahi pūrongo take, i whakapai ake te whakawhitinga microbiota paru i te wiri nui me te mate puku irritable i roto i tētahi tūroro, e tohu ana pea i te whanaungatanga tata i waenga i te microbiota puku me te wiri nui. Hei tāpiri, i kitea hoki e mātou ngā huringa motuhake i roto i te microbiota puku i roto i ngā tūroro me te ET, e tautoko kaha ana i te tūranga nui o te dysbiosis puku i roto i te ET8.
Mō te dysbiosis puku i roto i ngā mate neurodegenerative, ko te PD te mea tino whānuitia te rangahau5. Ka taea e te microbiota kore taurite te whakanui ake i te urunga o te puku me te whakahohe i te glia puku, ka arahi ki te alpha-synucleinopathies9,10,11. He āhuatanga taupatupatu a te PD me te ET, pērā i te auau rite o te wiri i roto i ngā tūroro ET me te PD, te wiri okioki taupatupatu (te wiri noa i roto i te PD), me te wiri tū (te nuinga o te wā ka kitea i roto i ngā tūroro ET), he uaua ki te wehewehe i waenga i a rāua. ngā wāhanga tōmua 12. Nō reira, me whakatuwhera wawe tātou i tētahi matapihi whai hua hei wehewehe i waenga i te ET me te PD. I roto i tēnei horopaki, ko te ako i te dysbiosis puku motuhake me ngā huringa metabolite e pā ana ki te ET me te tautuhi i ō rātou rerekētanga mai i te PD ka noho hei tohu koiora pea mō te tātaritanga me te tātaritanga rerekē o te ET.
Ko ngā waikawa ngako mekameka-poto (SCFA) ngā matū matū nui i hangaia e te whakapūtanga huakita puku o te muka kai, ā, e whakaarohia ana he mahi nui tā rātou i roto i ngā taunekeneke puku-roro13,14. Ka tangohia ngā SCFA e ngā pūtau koroni ka haria ki te ate mā te pūnaha uaua tomokanga, ā, ka uru ētahi SCFA ki te tohanga pūnaha. He pānga ā-rohe ngā SCFA ki te pupuri i te pono o te ārai puku me te whakatairanga i te ārai mate ā-roto i roto i te mucosa puku15. He pānga roa anō hoki tā rātou ki te ārai toto-roro (BBB) ​​mā te whakaoho i ngā pūmua hononga piri me te whakahohe i ngā neuron mā te whakaoho i ngā kaiwhakawhiwhi hononga pūmua G (GPCR) kia whiti i te BBB16. Ko te Acetate, te propionate, me te butyrate ngā SCFA tino nui i roto i te koroni. Kua whakaatuhia e ngā rangahau o mua te hekenga o ngā taumata paru o ngā waikawa acetic, propionic me te butyric i roto i ngā tūroro e mate ana a Parkinson17. Heoi, kāore anō kia rangahauhia ngā taumata SCFA paru i roto i ngā tūroro e mate ana a ET.
Nō reira, ko te whāinga o tā mātou rangahau he tautuhi i ngā huringa motuhake o te SCFA paru i roto i ngā tūroro me te ET me ō rātou rerekētanga mai i ngā tūroro me te PD, te aromatawai i te whanaungatanga o te SCFA paru ki ngā tohu haumanu o te SCFA me ngā microbiota puku, me te tautuhi i ngā kaha tātaritanga me te tātaritanga rerekē pea o ngā tauira paru. KZHK. Hei aro ki ngā āhuatanga whakararuraru e pā ana ki ngā rongoā anti-PD, i whiriwhiria e mātou ngā tūroro me te mate a Parkinson hou hei mana whakahaere mate.
Kei te Ripanga 1 ngā āhuatanga taupori me ngā āhuatanga haumanu o ngā ET 37, ngā PD 37, me ngā HC 35. I tauritehia ngā ET, ngā PD, me ngā HC e ai ki te tau, te ira tangata, me te BMI. He rite tonu te ōwehenga o te kai paipa, te inu waipiro me te inu kawhe me te tī o ngā rōpū e toru. He teitei ake te kaute Wexner (P = 0.004) me te kaute HAMD-17 (P = 0.001) o te rōpū PD i ērā o te rōpū HC, ā, he teitei ake te kaute HAMA (P = 0.011) me te kaute HAMD-17 (P = 0.011) o te rōpū ET i ērā o te rōpū HC. He roa ake te haere o te mate i roto i te rōpū ET i ērā o te rōpū PD (P<0.001).
He rerekētanga nui ngā taumata o te waikawa propionic (P = 0.023), te waikawa acetic (P = 0.039), te waikawa butyric (P = 0.020), te waikawa isovaleric (P = 0.045), me te waikawa isobutyric (P = 0.015) i roto i te paru. I roto i ngā tātaritanga muri-hoc, he iti iho ngā taumata o te waikawa propionic (P = 0.023), te waikawa butyric (P = 0.007), me te waikawa isobutyric (P = 0.040) i roto i te rōpū ET i ērā i roto i te rōpū HC. He iti ake ngā taumata o te isovalerate (P = 0.014) me te isobutyrate (P = 0.005) o ngā tūroro ET i ngā tūroro PD. Hei tāpiritanga, he iti iho ngā taumata o te waikawa propionic fecal (P = 0.013), te waikawa acetic (P = 0.016), me te waikawa butyric (P = 0.041) i roto i ngā tūroro PD i ngā tūroro CC (Pikitia 1 me te Ripanga Tāpiri 1).
Ko te ag he whakataurite rōpū o te waikawa propionic, te waikawa acetic, te waikawa butyric, te waikawa isovaleric, te waikawa valeric, te waikawa caproic me te waikawa isobutyric. He rerekētanga nui i roto i ngā taumata o te waikawa propionic fecal, te waikawa acetic, te waikawa butyric, te waikawa isovaleric me te waikawa isobutyric i waenga i ngā rōpū e toru. Te wiri nui o te ET, te mate a Parkinson, te mana whakahaere HC hauora, SCFA. Ko ngā rerekētanga nui e tohuhia ana e *P < 0.05 me **P < 0.01.
I runga i te rerekētanga o te rerenga mate i waenga i te rōpū ET me te rōpū PD, i whakamatautauria e mātou he 33 ngā tūroro me te PD wawe me te 16 ngā tūroro me te ET (rerenga mate ≤3 tau) hei whakataurite atu (Ripanga Tāpiri 2). I whakaatuhia e ngā hua he iti iho te ihirangi waikawa propionic fecal o te ET i tērā o te HA (P=0.015). Kāore i te nui te rerekētanga i waenga i te ET me te HC mō te waikawa butyric me te waikawa isobutyric, engari i kitea tonu he ia (P = 0.082). He iti iho ngā taumata isobutyrate fecal i roto i ngā tūroro me te ET ki te whakaritea ki ngā tūroro me te PD (P = 0.030). Kāore i te nui te rerekētanga i waenga i te ET me te PD o te waikawa isovaleric, engari i mau tonu te ia (P = 0.084). He iti iho te waikawa propionic (P = 0.023), te waikawa acetic (P = 0.020), me te waikawa butyric (P = 0.044) i roto i ngā tūroro PD i ngā tūroro HC. Ko ēnei hua (Pikitia Tāpiri 1) he rite tonu ki ngā hua matua. Ko te rerekētanga o ngā hua i waenga i te tauira whānui me te rōpū tūroro tōmua pea nā te iti o te tauira i roto i te rōpū, ka hua ake he iti ake te mana tatauranga o ngā raraunga.
I muri mai ka tirotirohia e mātou mēnā ka taea e ngā taumata SCFA paru te wehewehe i ngā tūroro me te ET mai i ngā tūroro me te CU, te PD rānei. E ai ki te tātaritanga ROC, ko te rerekētanga o te AUC o ngā taumata propionate he 0.668 (95% CI: 0.538-0.797), nā reira i taea ai te wehewehe i ngā tūroro me te ET mai i te HC. Ka taea te wehewehe i ngā tūroro me te ET me te GC mā ngā taumata butyrate me te AUC o te 0.685 (95% CI: 0.556–0.814). Mā ngā rerekētanga o ngā taumata waikawa isobutyric ka taea te wehewehe i ngā tūroro me te ET mai i te HC me te AUC o te 0.655 (95% CI: 0.525–0.786). I te whakakotahitanga o ngā taumata propionate, butyrate me isobutyrate, i whiwhihia he AUC teitei ake o te 0.751 (95% CI: 0.634–0.867) me te aro o te 74.3% me te motuhaketanga o te 72.9% (Pikitia 2a). Hei wehewehe i waenga i ngā tūroro ET me te PD, ko te AUC mō ngā taumata waikawa isovaleric he 0.700 (95% CI: 0.579–0.822) ā, mō ngā taumata waikawa isobutyric he 0.718 (95% CI: 0.599–0.836). Ko te whakakotahitanga o ngā taumata waikawa isovaleric me te waikawa isobutyric he AUC teitei ake o te 0.743 (95% CI: 0.629–0.857), te aro o te 74.3% me te motuhaketanga o te 62.9% (Pikitia 2b). Hei tāpiritanga, i tirotirohia e mātou mēnā he rerekē ngā taumata SCFA i roto i ngā paru o ngā tūroro e pangia ana e te mate a Parkinson mai i ngā mana whakahaere. E ai ki te tātaritanga ROC, ko te AUC mō te tautuhi i ngā tūroro e pangia ana e te PD i runga i ngā rerekētanga o ngā taumata waikawa propionic he 0.687 (95% CI: 0.559-0.814), me te aro o te 68.6% me te motuhake o te 68.7%. Mā ngā rerekētanga o ngā taumata acetate ka taea te wehewehe i ngā tūroro PD mai i ngā HC me te AUC o te 0.674 (95% CI: 0.542–0.805). Ka taea te wehewehe i ngā tūroro e pangia ana e te PD mai i te CU mā ngā taumata butyrate anake me te AUC o te 0.651 (95% CI: 0.515–0.787). I te whakakotahitanga o ngā taumata propionate, acetate me te butyrate, i whiwhihia he AUC o te 0.682 (95% CI: 0.553–0.811) (Pikitia 2c).
Te whakahāwea o te Hāhi Orthodox o Ruhia ki te ET me te HC; b te whakahāwea o te Hāhi Orthodox o Ruhia ki te ET me te PD; c te whakahāwea o te ROC ki te PD me te HC. Te wiri nui o te ET, te mate a Parkinson, te whakahaere HC hauora, SCFA.
I roto i ngā tūroro me te ET, he hononga kino ngā taumata waikawa isobutyric fecal ki te kaute FTM (r = -0.349, P = 0.034), ā, he hononga kino ngā taumata waikawa isovaleric fecal ki te kaute FTM (r = -0.421, P = 0.001) me te kaute TETRAS. (r = -0.382, P = 0.020). I roto i ngā tūroro me te ET me te PD, he hononga kino ngā taumata propionate fecal ki ngā kaute SCOPA-AUT (r = −0.236, P = 0.043) (Pikitia 3 me te Ripanga Tāpiri 3). Kāore he hononga nui i waenga i te haerenga o te mate me te SCFA i roto i te rōpū ET (P ≥ 0.161) i te rōpū PD rānei (P ≥ 0.246) (Ripanga Tāpiri 4). I roto i ngā tūroro he PD, he hononga pai ngā taumata waikawa caproic fecal ki ngā kaute MDS-UPDRS (r = 0.335, P = 0.042). Mō ngā kaiuru katoa, he hononga kino ngā taumata propionate fecal (r = −0.230, P = 0.016) me te acetate (r = −0.210, P = 0.029) ki ngā kaute Wexner (Pikitia 3 me te Ripanga Tāpiri 3).
He hononga kino ngā taumata waikawa isobutyric paru ki ngā kaute FTM, he hononga kino te waikawa isovaleric ki ngā kaute FTM me TETRAS, he hononga kino te waikawa propionic ki ngā kaute SCOPA-AUT, he hononga pai te waikawa caproic ki ngā kaute MDS-UPDRS, ā, he hononga kino te waikawa propionic ki ngā kaute FTM me TETRAS. He hononga kino te TETRAS me te waikawa acetic ki te kaute Wexner. Ko te putanga tautoko a te MDS-UPDRS Association o te Unified Parkinson's Disease Rating Scale, Mini-Mental State Examination MMSE, Hamilton Depression Rating Scale HAMD-17, 17 ngā tūemi, Hamilton Anxiety Rating Scale HAMA, HY Hoehn and 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. Ko ngā rerekētanga nui e tohuhia ana e *P < 0.05 me **P < 0.01.
I tūhuratia anō e mātou te āhua wehewehe o ngā moroiti puku mā te whakamahi i te tātaritanga LEfSE, ā, i tīpakohia te taumata raraunga nui whanaunga o te ira mō te tātaritanga atu. I whakaritea ngā whakataurite i waenga i te ET me te HC, me te ET me te PD. I muri mai, i whakahaerehia te tātaritanga hononga Spearman ki te nui whanaunga o ngā moroiti puku me ngā taumata SCFA paru i roto i ngā rōpū whakataurite e rua.
I kitea i roto i te tātaritanga o ET me CA ko Faecalibacterium (e pā ana ki te waikawa butyric, r = 0.408, P < 0.001), Lactobacillus (e pā ana ki te waikawa butyric, r = 0.283, P = 0.016), Streptobacterium (e pā ana ki te waikawa propionic, r = 0.327). , P = 0.005; e pā ana ki te waikawa butyric, r = 0.374, P = 0.001; e pā ana ki te waikawa isobutyric, r = 0.329, P = 0.005), Howardella (e pā ana ki te waikawa propionic, r = 0.242, P = 0.041), Raoultella (e pā ana ki te propionate, r = 0.249, P = 0.035), me Candidatus Arthromitus (e pā ana ki te waikawa isobutyric, r = 0.302, P = 0.010) i kitea he iti iho i roto i te ET, ā, he pai te hononga ki ngā taumata SCFA paru. Heoi, i piki ake te nui o Stenotropomonas i roto i te ET, ā, he kino te hononga ki ngā taumata isobutyrate paru (r = -0.250, P = 0.034). I muri i te whakatikatika FDR, ko ngā hononga anake i waenga i te Faecalibacterium, Catenibacter, me te SCFA i noho nui (P ≤ 0.045) (Pikitia 4 me te Ripanga Tāpiri 5).
Tātari hononga o ET me HC. Whai muri i te whakatikatika FDR, i kitea te hekenga o te nui o Faecalibacterium (he hononga pai ki te butyrate) me Streptobacterium (he hononga pai ki te propionate, butyrate, me te isobutyrate) i roto i te ET, ā, he hononga pai ki ngā taumata SCFA paru. b Tātari hononga o ET me PD. Whai muri i te whakatikatika FDR, kāore i kitea he hononga nui. Te wiri nui o ET, te mate a Parkinson, te mana whakahaere HC hauora, SCFA. Ko ngā rerekētanga nui e tohuhia ana e *P < 0.05 me **P < 0.01.
I te tātaritanga o te ET me te PD, i kitea he pikinga ake o te Clostridium trichophyton i roto i te ET, ā, he hononga ki te waikawa isovaleric fecal (r = -0.238, P = 0.041) me te waikawa isobutyric (r = -0.257, P = 0.027). ). I muri i te whakatikatikanga FDR, i noho nui tonu tetahi o ēnei (P≥0.295) (Pikitia 4 me te Ripanga Tāpiri 5).
He rangahau whānui tēnei e tirotiro ana i ngā taumata SCFA paru, ā, e hono ana i ēnei ki ngā huringa o ngā microbiota puku me te kaha o ngā tohu i roto i ngā tūroro me te ET ki te whakaritea ki ngā tūroro me te CU me te PD. I kitea e mātou kua heke ngā taumata SCFA paru i roto i ngā tūroro me te ET, ā, e hono ana ki te kaha haumanu me ngā huringa motuhake i roto i ngā microbiota puku. Ko ngā taumata kohikohi o ngā waikawa ngako mekameka-poto (SCFA) i roto i ngā paru ka wehewehe i te ET mai i te GC me te PD.
Ki te whakaritea ki ngā tūroro GC, he iti ake ngā taumata paru o ngā waikawa propionic, butyric, me te isobutyric i roto i te paru o ngā tūroro ET. Mā te whakakotahitanga o ngā waikawa propionic, butyric me te isobutyric ka taea te wehewehe i waenga i te ET me te HC me te AUC o te 0.751 (95% CI: 0.634–0.867), te aro o te 74.3% me te motuhake o te 72.9%, e tohu ana i tō rātou whakamahinga hei tūranga pea hei tohu tohu mō te ET. I whakaatuhia e ngā tātaritanga anō he hononga kino ngā taumata waikawa propionic fecal ki te kaute Wexner me te kaute SCOPA-AUT. He hononga whakahurihuri ngā taumata waikawa isobutyric fecal ki ngā kaute FTM. I tētahi atu taha, ko te hekenga o ngā taumata butyrate i roto i te ET i honoa ki te hekenga o te nui o ngā microbiota whakaputa SCFA, Faecalibacterium, me Categorybacter. Hei tāpiri, ko te hekenga o te nui o Catenibacter i roto i te ET i honoa hoki ki te hekenga o ngā taumata waikawa propionic me te isobutyric fecal.
Ko te nuinga o ngā SCFA i hangaia i roto i te koroni ka tangohia e ngā pūtau koroni mā roto i ngā kaikawe monocarboxylate e whakawhirinaki ana ki te H+, e whakawhirinaki ana rānei ki te konutai. Ko ngā waikawa ngako mekameka poto e mimitihia ana ka whakamahia hei puna pūngao mō ngā pūtau koroni, ko ngā mea kāore i te whakapūngaohia i roto i ngā pūtau koroni ka haria ki roto i te tohanga toto 18. Ka taea e ngā SCFA te awe i te nekehanga o te puku, te whakarei ake i te mahi ārai puku, me te awe i te pākia o te tinana me te ārai mate19. I kitea i mua ko ngā kukū paru o te butyrate, acetate, me te propionate i whakaitihia i roto i ngā tūroro PD ki te whakaritea ki ngā HCs17, he rite tonu ki ā mātou hua. I kitea e tā mātou rangahau he iti iho te SCFA i roto i ngā tūroro me te ET, engari he iti noa te mōhiotia mō te tūranga o te SCFA i roto i te mate o te ET. Ka taea e te butyrate me te propionate te here ki ngā GPCR me te awe i te tohu GPCR e whakawhirinaki ana ki te GPCR pērā i te tohu MAPK me te NF-κB20. Ko te ariā taketake o te tuaka puku-roro ko ngā SCFA i tukuna e ngā moroiti puku ka awe i te tohu tinana, ā, ka awe i te mahi o te puku me te roro. Nā te mea he kaha ngā pānga aukati o te butyrate me te propionate ki te mahi histone deacetylase (HDAC)21, ā, ka taea hoki e te butyrate te mahi hei ligand mō ngā take whakawhiti, he whānuitia ō rātou pānga ki te pākia o te tinana, te rerekētanga me te tipu, nā te mea nui i runga i te whakahaere ira22. I runga i ngā taunakitanga mai i te SCFA me ngā mate neurodegenerative, e kiia ana te butyrate he kaitono rongoā nā tōna kaha ki te whakatika i te ngoikore o te mahi HDAC, ka taea te āwhina i te mate o ngā neuron dopaminergic i roto i te PD23,24,25. Kua whakaatuhia hoki e ngā rangahau kararehe te kaha o te waikawa butyric ki te aukati i te pirau o ngā neuron dopaminergic me te whakapai ake i ngā mate nekehanga i roto i ngā tauira PD26,27. Kua kitea te waikawa propionic ka whakawhāiti i ngā urupare mumura me te tiaki i te pono o te BBB28,29. Kua whakaatuhia e ngā rangahau ka whakatairanga te waikawa propionic i te oranga o ngā neuron dopaminergic hei whakautu ki te paitini rotenone i roto i ngā tauira PD 30, ā, ko te whakahaere ā-waha o te waikawa propionic ka whakaora i te ngaronga o ngā neuron dopaminergic me ngā ngoikoretanga nekeneke i roto i ngā kiore me te PD 31. He iti noa te mōhiotanga mō te mahi a te waikawa isobutyric. Heoi, i kitea i roto i tētahi rangahau tata nei ko te noho tahi o ngā kiore me te B. ovale i whakanui ake i te nui o te SCFA puku (tae atu ki te acetate, propionate, isobutyrate, me te isovalerate) me te kukū GABA puku, e whakaatu ana kua whakatūria he hononga i waenga i ngā microbiota puku me ngā kukū neurotransmitters SCFA puku32. Mō te ET, ko ngā huringa pathological rerekē i roto i te cerebellum ko ngā huringa o ngā axons me ngā dendrites pūtau Purkinje, te nekehanga me te ngaronga o ngā pūtau Purkinje, ngā huringa o ngā axons pūtau kete, me ngā rerekētanga o ngā hononga muka piki ki ngā pūtau Purkinje. ka heke te putanga GABAergic mai i te cerebellum3,4,33. Kāore anō kia mārama mēnā kei te hono ngā SCFA ki te neurodegeneration pūtau Purkinje me te heke o te hanga GABA cerebellar. E kī ana ā mātou hua he hononga tata i waenga i te SCFA me te ET; heoi, kāore te hoahoa rangahau whakawhiti-wāhanga e whakaae ki tētahi whakatau mō te whanaungatanga take i waenga i te SCFA me te tukanga mate ET. Me whai ake ngā rangahau whai muri roa, tae atu ki ngā inenga raupapa o ngā SCFA paru, me ngā rangahau kararehe e tirotiro ana i ngā tikanga.
E whakaarohia ana ka whakaoho te SCFA i te kaha o te uaua maeneene o te koroni34. Mā te kore o te SCFA ka kino ake ngā tohu o te mate puku, ā, mā te tāpiritanga ki te SCFA ka pai ake pea ngā tohu o te mate puku PD35. E whakaatu ana hoki ā mātou hua i tētahi hononga nui i waenga i te hekenga o te ihirangi SCFA paru me te pikinga o te mate puku me te ngoikore o te pūnaha autonomic i roto i ngā tūroro me te ET. I kitea i tētahi pūrongo take he pai ake te wiri nui me te mate puku irritable i roto i te tūroro 7 nā te whakawhitinga microbiota, e whakaatu ana i tētahi hononga tata i waenga i te microbiota puku me te ET. Nō reira, e whakapono ana mātou ka pā pea te SCFA/microbiota paru ki te nekehanga o te whekau o te tangata me te mahi a te pūnaha io autonomic.
I kitea i roto i te rangahau ko te hekenga o ngā taumata o ngā SCFA paru i roto i te ET i hono atu ki te hekenga o te nui o Faecalibacterium (e hono ana ki te butyrate) me Streptobacterium (e hono ana ki te propionate, butyrate, me te isobutyrate). Whai muri i te whakatikatika FDR, he mea nui tonu tēnei whanaungatanga. Ko Faecalibacterium me Streptobacterium he moroiti whakaputa SCFA. E mōhiotia ana ko Faecalibacterium he moroiti whakaputa butyrate36, ko ngā hua matua o te whakapūtanga Catenibacter ko te acetate, te butyrate me te waikawa lactic37. I kitea te Faecalibacterium i roto i te 100% o ngā rōpū ET me te HC; Ko te nui toharite o te rōpū ET he 2.06%, ā, ko te rōpū HC he 3.28% (LDA 3.870). I kitea te huakita kāwai i roto i te 21.6% (8/37) o te rōpū HC, ā, i roto i te tauira kotahi anake o te rōpū ET (1/35). Ko te hekenga me te kore e kitea o ngā streptobacter i roto i te ET ka tohu pea i te hononga ki te mate o te mate. Ko te nui toharite o ngā momo Catenibacter i roto i te rōpū HC he 0.07% (LDA 2.129). Hei tāpiri, i honoa ngā huakita waikawa lactic ki ngā huringa o te butyrate paru (P=0.016, P=0.096 i muri i te whakatikatika FDR), ā, i honoa ngā mate rumatiki ki ngā huringa o te isobutyrate (P=0.016, P=0.072 i muri i te whakatikatika FDR). I muri i te whakatikatika FDR, ko te ia o te hononga anake e toe ana, kāore i te tino hiranga i te tatauranga. E mōhiotia ana hoki ko ngā Lactobacilli he kaihanga SCFA (waikawa acetic, waikawa propionic, waikawa isobutyric, waikawa butyric) 38 ā, ko Candidatus Arthromitus he kaiwhakaoho motuhake i te rerekētanga pūtau T helper 17 (Th17), me Th1/2 me Tregs e hono ana ki te taurite ārai mate /Th1739. E whakaatu ana tētahi rangahau hou ko te nui o te pseudoarthritis fecal ka whai wāhi pea ki te mumura o te koroni, te ngoikore o te arai whekau, me te mumura pūnaha 40. I piki ake te Clostridium trichophyton i roto i te ET ki te whakataurite ki te PD. I kitea he hononga kino te nui o te Clostridium trichoides ki te waikawa isovaleric me te waikawa isobutyric. Whai muri i te whakatikatika FDR, i noho nui tonu ngā mea e rua (P≥0.295). Ko te Clostridium pilosum he huakita e mōhiotia ana e hono ana ki te mumura, ā, ka whai wāhi pea ki te ngoikore o te arai whekau41. I kōrerohia e tā mātou rangahau o mua ngā huringa o te microbiota puku o ngā tūroro me te ET8. I konei ka kōrerohia hoki e mātou ngā huringa o ngā SCFA i roto i te ET me te tautuhi i te hononga i waenga i te dysbiosis puku me ngā huringa o ngā SCFA. Ko te hekenga o ngā taumata SCFA e hono tata ana ki te dysbiosis puku me te kaha o te wiri i roto i te ET. E kī ana ā mātou hua he mahi nui pea te tuaka puku-roro i roto i te pathogenesis o te ET, engari me whai atu rangahau i roto i ngā tauira kararehe.
Ki te whakaritea ki ngā tūroro he PD, he iti ake ngā taumata o ngā waikawa isovaleric me te isobutyric i roto i ngā paru o ngā tūroro he ET. Nā te whakakotahitanga o te waikawa isovaleric me te waikawa isobutyric i tautuhia te ET i roto i te PD me te AUC o te 0.743 (95% CI: 0.629–0.857), te aro o te 74.3% me te motuhake o te 62.9%, e whakaatu ana i tō rātou tūranga pea hei tohu koiora i roto i te tautuhi rerekētanga o te ET. He hononga whakahurihuri ngā taumata waikawa isovaleric paru ki ngā kaute FTM me TETRAS. He hononga whakahurihuri ngā taumata waikawa isobutyric paru ki ngā kaute FTM. Ko te hekenga o ngā taumata waikawa isobutyric i honoa ki te hekenga o te nui o ngā catobacteria. He iti noa te mōhiotia mō ngā mahi a te waikawa isovaleric me te waikawa isobutyric. I whakaatuhia e tētahi rangahau o mua ko te noho tahi o ngā kiore me te Bacteroides ovale i roto i ngā kiore i whakanui ake i te nui o te SCFA puku (tae atu ki te acetate, propionate, isobutyrate, me te isovalerate) me ngā kukū GABA puku, e whakaatu ana i te hononga puku i waenga i te microbiota me ngā kukū SCFA/neurotransmitter puku32. He mea whakamīharo, he rite tonu ngā taumata waikawa isobutyric i kitea i waenga i ngā rōpū PD me HC, engari he rerekē i waenga i ngā rōpū ET me PD (HC rānei). Ka taea e te waikawa Isobutyric te wehewehe i waenga i te ET me te PD me te AUC o te 0.718 (95% CI: 0.599–0.836) me te tautuhi i te ET me te NC me te AUC o te 0.655 (95% CI: 0.525–0.786). Hei tāpiri, he hononga ngā taumata waikawa isobutyric ki te kaha o te wiri, e whakapakari ake ana i tōna hononga ki te ET. Me rangahau anō te pātai mēnā ka taea e te waikawa isobutyric ā-waha te whakaiti i te kaha o te wiri i roto i ngā tūroro me te ET.
Nō reira, ka whakaitihia te nui o te SCFA i roto i te paru i roto i ngā tūroro e pāngia ana e te ET, ā, e pā ana ki te kaha o te ET me ngā huringa motuhake i roto i ngā huakita puku. Ko te propionate paru, te butyrate, me te isobutyrate pea he tohu koiora tātaritanga mō te ET, engari ko te isobutyrate me te isovalerate pea he tohu koiora tātaritanga rerekē mō te ET. Tērā pea he motuhake ake ngā huringa o te isobutyrate paru mō te ET i ngā huringa o ētahi atu SCFA.
He maha ngā herenga o tā mātou rangahau. Tuatahi, ko ngā tauira kai me ngā manakohanga kai ka pā ki te whakaaturanga o ngā microbiota, me nui ake ngā tauira rangahau i roto i ngā taupori rerekē, ā, me whakauru e ngā rangahau ā muri ake nei ngā rangahau kai whānui me te pūnaha pēnei i ngā pātai auau kai. Tuarua, ka ārai te hoahoa rangahau whakawhiti-wāhanga i ngā whakatau mō te whanaungatanga take i waenga i ngā SCFA me te whanaketanga o te ET. Me whai ake ngā rangahau whai muri mō te wā roa me ngā ine raupapa o ngā SCFA paru. Tuatoru, me whakamana ngā āheinga tātaritanga me te tātaritanga rerekē o ngā taumata SCFA paru mā te whakamahi i ngā tauira motuhake mai i te ET, HC, me te PD. Me whakamātautau ake ngā tauira paru motuhake a muri ake nei. Hei whakamutunga, he poto ake te roa o te mate o ngā tūroro whai PD i roto i tā mātou rōpū i ngā tūroro whai ET. I taurite te nuinga o te ET, PD me te HC mā te tau, te ira tangata me te BMI. I runga i te rerekētanga o te haerenga o te mate i waenga i te rōpū ET me te rōpū PD, i akohia hoki e mātou he 33 ngā tūroro whai PD wawe me te 16 ngā tūroro whai ET (te roa o te mate ≤3 tau) hei whakataurite atu. Ko ngā rerekētanga i waenga i te rōpū i roto i te SCFA he rite tonu ki ā mātou raraunga tuatahi. Hei tāpiritanga, kāore i kitea he hononga i waenga i te roa o te mate me ngā huringa o te SCFA. Heoi, i te heke mai, he pai ake te kimi i ngā tūroro whai PD me ET i te wā tōmua me te roa poto o te mate hei whakaoti i te whakamana i roto i tētahi tauira nui ake.
I whakaaetia te kawa o te rangahau e te komiti matatika o te Hōhipera Ruijin, e hono ana ki te Kura Rongoā o te Whare Wānanga o Shanghai Jiao Tong (RHEC2018-243). I whiwhi whakaaetanga ā-tuhi mai i ngā kaiuru katoa.
I waenganui i a Hānuere 2019 me Tīhema 2022, 109 ngā tāngata (37 ET, 37 PD, me te 35 HC) mai i te Movement Disorder Center Clinic o te Hōhipera Ruijin, e hono ana ki te Kura Rongoā o te Whare Wānanga o Shanghai Jiao Tong, i whakaurua ki tēnei rangahau. Ko ngā paearu ko: (1) te pakeke 25–85 tau, (2) i tātaritatia ngā tūroro me te ET e ai ki ngā paearu a te Rōpū Mahi MDS 42 me te PD e ai ki ngā paearu MDS 43, (3) kāore ngā tūroro katoa i tango i ngā rongoā anti-PD i mua i te kohi tauira. (4) Ko ngā β-blockers anake i tangohia e te rōpū ET, kāore rānei he rongoā e pā ana i mua i te kohi tauira paru. I tīpakohia hoki ngā HC i taurite ki te pakeke, te ira tangata, me te taupū taumaha tinana (BMI). Ko ngā paearu whakakore ko: (1) te hunga kaiwhenua, (2) te kai koretake, (3) ngā mate pūmau o te ara kai (tae atu ki te mate mumura o te puku, te mate puku, te mate duodenal rānei), (4) ngā mate pūmau kino (tae atu ki ngā pukupuku kino), te ngoikore o te ngākau, te ngoikore o te whatukuhu, ngā mate toto) (5) He hītori o te pokanga nui o te puku, (6) Te kai miraka kawa mō te wā roa, te kai auau rānei i te miraka kawa, (7) Te whakamahi i ngā probiotics, i ngā paturopi rānei mō te 1 marama, (8) Te whakamahi pūmau i ngā corticosteroids, ngā aukati papu proton, ngā statins, te metformin, ngā immunosuppressants, ngā rongoā anticancer rānei, me te (9) te ngoikore nui o te hinengaro e whakararuraru ana i ngā whakamātautau haumanu.
I whakaratohia e ngā kaupapa katoa ngā hītori hauora, te taumaha me ngā mōhiohio teitei hei tatau i te BMI, ā, i whai whakamātautau neurological me te aromatawai haumanu pērā i te Hamilton Anxiety Rating Scale (HAMA) 44 anxiety score, te Hamilton Depression Rating Scale-17 score (HAMD-17) 45. I tirotirohia te pouri, te kaha o te mate puku mā te whakamahi i te Wexner Constipation Scale 46 me te Bristol Stool Scale 47 me te mahi hinengaro mā te whakamahi i te Mini-Mental State Examination (MMSE) 48. I tirotirohia e te Scale for the Assessment of Autonomic Symptoms of Parkinson's Disease (SCOPA-AUT) 49 te ngoikore o te pūnaha autonomic i roto i ngā tūroro me te ET me te PD. I tirotirohia te Fan-Tolos-Marin Clinical Tremor Rating Scale (FTM) me te Essential Tremor Rating Scale (TETRAS) 50 me te Tremor Study Group (TRG) 50 i roto i ngā tūroro me te ET; i tirotirohia te United Parkinson's Disease's Disease rating scale (MDS-UPDRS) putanga 51 me te Hoehn and Yahr (HY) grade 52.
I tonoa ia kaiuru ki te kohi i tētahi tauira paru i te ata mā te whakamahi i tētahi ipu kohi paru. Whakawhitihia ngā ipu ki te hukapapa ka rongoa ki te -80°C i mua i te tukatuka. I whakahaerehia te tātaritanga SCFA i runga anō i ngā mahi o ia rā a Tiangene Biotechnology (Shanghai) Co., Ltd. I kohia he 400 mg o ngā tauira paru hou mai i ia kaupapa, ā, i tātarihia mā te whakamahi i ngā SCFA i muri i te huri me te whakapūtanga i mua i te tangi. I tātarihia ngā SCFA i tīpakohia i roto i ngā paru mā te whakamahi i te hau chromatography-mass spectrometry (GC-MS) me te wai chromatography-tandem MS (LC-MS/MS).
I tangohia te DNA mai i ngā tauira 200 mg mā te whakamahi i te QIAamp® Fast DNA Stool Mini Kit (QIAGEN, Hilden, Tiamana) e ai ki ngā tohutohu a te kaihanga. I whakatauhia te hanganga moroiti mā te raupapatanga i te ira 16 S rRNA i runga i te DNA i wehea mai i ngā paru mā te whakanui i te rohe V3-V4. Whakamātauria te DNA mā te whakahaere i te tauira ki runga i te 1.2% agarose gel. I mahia te whakanui i te polymerase chain reaction (PCR) o te ira 16S rRNA mā te whakamahi i ngā primers huakita whānui (357 F me 806 R) me te whare pukapuka amplicon e rua-taahiraa i hangaia i runga i te tūāpapa Novaseq.
Ka whakaatuhia ngā taurangi tonu hei toharite ± paerewa rerekētanga, ā, ka whakaatuhia ngā taurangi kāwai hei tau me te ōrau. I whakamahia e mātou te whakamātautau a Levene hei whakamātautau i te ōritetanga o ngā rerekētanga. I whakaritea ngā whakatairite mā te whakamahi i ngā whakamātautau-t e rua-hiku, te tātari rerekētanga rānei (ANOVA) mēnā he tohatoha noa ngā taurangi, me ngā whakamātautau U Mann-Whitney kore-taurite mēnā i takahia ngā whakaaro ōritetanga, ōritetanga rānei. I whakamahia e mātou te rohe i raro i te pihi āhuatanga whakahaere kaiwhiwhi (ROC) (AUC) hei ine i te mahi tātaritanga o te tauira me te tirotiro i te kaha o te SCFA ki te wehewehe i ngā tūroro me te ET mai i te hunga he HC, he PD rānei. Hei tirotiro i te whanaungatanga i waenga i te SCFA me te kaha haumanu, i whakamahia e mātou te tātari hononga Spearman. I mahia te tātari tatauranga mā te whakamahi i te pūmanawa SPSS (putanga 22.0; SPSS Inc., Chicago, IL) me te taumata hiranga (tae atu ki te uara P me te FDR-P) i whakatakotoria ki te 0.05 (taha-rua).
I tātarihia ngā raupapatanga S 16 mā te whakamahi i te huinga o te pūmanawa Trimmomatic (putanga 0.35), Flash (putanga 1.2.11), UPARSE (putanga v8.1.1756), mothur (putanga 1.33.3) me te R (putanga 3.6.3). I tukatukahia ngā raraunga ira rRNA 16S mata mā te whakamahi i te UPARSE hei whakaputa i ngā waeine whakarōpū mahi (OTU) me te 97% tuakiri. I tohua ngā whakarōpū mā te whakamahi i te Silva 128 hei pātengi raraunga tohutoro. I tīpakohia te taumata whānui o ngā raraunga nui whanaunga mō te tātari atu. I whakamahia te tātari rahi pānga tātari wehewehe rārangi (LDA) (LEfSE) mō ngā whakatairite i waenga i ngā rōpū (ET vs. HC, ET vs. PD) me te paepae α o te 0.05 me te paepae rahi pānga o te 2.0. Ko ngā momo wehewehe i tautuhia e te tātari LEfSE i whakamahia anō mō ​​te tātari hononga Spearman o te SCFA.
Mō ētahi atu kōrero e pā ana ki te hoahoa o te rangahau, tirohia te Whakarāpopototanga o te Pūrongo Rangahau Taiao e pā ana ki tēnei tuhinga.
Kei roto i te pātengi raraunga BioProject o te National Center for Biotechnology Information (NCBI) (SRP438900: PRJNA974928) ngā raraunga mata o te raupapatanga 16S, URL: https://www.ncbi.nlm.nih.gov/Traces/study/?acc= SRP438900&o. =acc_s% 3Aa. Kei te wātea ētahi atu raraunga e tika ana ki te kaituhi e pā ana mēnā he tono tika, pērā i ngā mahi tahi pūtaiao me ngā whakawhitiwhiti mātauranga me ngā kaupapa rangahau katoa. Kāore e whakaaetia te whakawhiti raraunga ki ngā rōpū tuatoru me te kore e whakaaetia e mātou.
Waehere pūtake tuwhera anake me te huinga o Trimmomatic (putanga 0.35), Flash (putanga 1.2.11), UPARSE (putanga v8.1.1756), mothur (putanga 1.33.3) me R (putanga 3.6.3), mā te whakamahi i ngā tautuhinga taunoa, i te wāhanga "Tikanga" rānei. Ka taea te tuku atu i ētahi atu mōhiohio whakamārama ki te kaituhi e pā ana mēnā he tono tika.
Pradeep S me Mehanna R. Ngā mate puku i roto i ngā mate nekehanga hyperkinetic me te ataxia. E pā ana ki te mate a Parkinson. pōhēhētanga. 90, 125–133 (2021).
Louis, ED me Faust, PL Te mate o te wiri nui: te neurodegeneration me te whakaritenga anō o ngā hononga neuronal. Nat. Pastor Nirol. 16, 69–83 (2020).
Gironell, A. He mate matua rānei te wiri nui o te ngoikore o te roro o Gaba? Ae. internationality. Rev. Neuroscience. 163, 259–284 (2022).
Dogra N., Mani RJ me Katara DP Te tuaka puku-roro: ngā momo tohu e rua i roto i te mate a Parkinson. Ngā ngota pūtau. Neurobiology. 42, 315–332 (2022).
Quigley, EMM. Te tuaka o te microbiota-roro-puku me ngā mate neurodegenerative. o nāianei. Nellore. Neuroscience. Ngā pūrongo 17, 94 (2017).
Liu, XJ, Wu, LH, Xie, WR me He, XX Ka whakapai ake te whakawhitinga microbiota paru i te wiri nui me te mate puku irritable i roto i ngā tūroro i te wā kotahi. Geriatric Psychology 20, 796–798 (2020).
Zhang P. et al. Ngā huringa motuhake o ngā microbiota puku i roto i te wiri nui me tō rātou rerekētanga mai i te mate a Parkinson. NPJ Parkinson's disease. 8, 98 (2022).
Luo S, Zhu H, Zhang J me Wang D. Te tūranga nui o ngā microbiota i roto i te whakahaere i ngā wae neuronal-glial-epithelial. Te ātete ki ngā mate. 14, 5613–5628 (2021).
Emin A. et al. Te mate o te duodenal alpha-synuclein me te gliosis whekau i roto i te mate a Parkinson e ahu whakamua ana. nekehanga. pōhēhētanga. https://doi.org/10.1002/mds.29358 (2023).
Skorvanek M. et al. Ka kitea e ngā paturopi ki te alpha-synuclein 5G4 te mate a Parkinson me te mate a Parkinson prodromal i roto i te mucosa koroni. nekehanga. pōhēhētanga. 33, 1366–1368 (2018).
Algarni M me Fasano A. Te tūponotanga o te wiri nui me te mate a Parkinson. E pā ana ki te mate a Parkinson. te pōhēhē. 46, С101–С104 (2018).
Sampson, TR me ētahi atu. Ka whakatikatikahia e ngā microbiota puku ngā ngoikoretanga nekeneke me te mumura roro i roto i ngā tauira o te mate a Parkinson. Pūtau 167, 1469–1480.e1412 (2016).
Unger, MM et al. He rerekē ngā waikawa ngako mekameka-poto me ngā microbiota puku i waenga i ngā tūroro e pāngia ana e te mate a Parkinson me ngā mana whakahaere taurite. E pā ana ki te mate a Parkinson. whakapoauau. 32, 66–72 (2016).
Bleacher E, Levy M, Tatirovsky E me Elinav E. Ngā matūkai e whakahaeretia ana e te microbiome i te atanga ārai mate o te kaihautū. J. Immunology. 198, 572–580 (2017).