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Hiki ke paʻakikī ka ʻike mua ʻana i ka essential tremor (ET), ʻoiai ke hoʻokaʻawale ʻia mai nā kaohi olakino (HC) a me ka maʻi Parkinson (PD). I kēia manawa, ua hāʻawi ka nānā ʻana i nā hāpana ʻōpala no ka microbiota ʻōpū a me kāna mau metabolites i nā ʻano hana hou no ka ʻike ʻana i nā biomarkers hou o nā maʻi neurodegenerative. ʻO nā waikawa momona kaulahao pōkole (SCFA), ma ke ʻano he metabolite nui o ka flora ʻōpū, ua hoʻemi ʻia i loko o nā feces ma PD. Eia nō naʻe, ʻaʻole i aʻo ʻia ka fecal SCFA ma ET. Ua manaʻo mākou e noiʻi i nā pae fecal o SCFAs ma ET, e loiloi i ko lākou pilina me nā hōʻailona lapaʻau a me ka microbiota ʻōpū, a hoʻoholo i ko lākou hiki ke diagnostic. Ua ana ʻia ka Fecal SCFA a me ka gut microbiota ma 37 ETs, 37 PDs hou, a me 35 HCs. Ua loiloi ʻia ka constipation, autonomic dysfunction, a me ke koʻikoʻi o ka tremor me ka hoʻohana ʻana i nā unahi. ʻOi aku ka haʻahaʻa o nā pae fecal o ka propionate, butyrate, a me isobutyrate ma ET ma mua o HC. ʻO ka hui pū ʻana o nā waikawa propionic, butyric a me isobutyric i hoʻokaʻawale iā ET mai HC me ka AUC o 0.751 (95% CI: 0.634–0.867). ʻOi aku ka haʻahaʻa o ka waikawa isovaleric fecal a me nā pae waikawa isobutyric ma ET ma mua o PD. Hoʻokaʻawale ka waikawa Isovaleric a me ka waikawa isobutyric ma waena o ET a me PD me ka AUC o 0.743 (95% CI: 0.629–0.857). Hoʻopili ʻia ka fecal propionate me ka constipation a me ka autonomic dysfunction. Hoʻopili ʻia ka waikawa Isobutyric a me ka waikawa isovaleric i ka koʻikoʻi o ka haʻalulu. Ua pili ka emi ʻana o nā SCFA fecal me ka emi ʻana o ka nui o Faecalibacterium a me Streptobacterium i loko o ka ET. No laila, emi ka nui o SCFA i loko o nā feces i loko o ET a pili pū me ke koʻikoʻi o ke kiʻi lapaʻau a me nā loli i ka microbiota ʻōpū. ʻO ka fecal propionate, butyrate, isobutyrate, a me ka isovalerate paha nā biomarkers diagnostics kūpono no ka ET.
ʻO ka essential tremor (ET) kahi maʻi neurodegenerative holomua a mau loa i hōʻike ʻia e ka haʻalulu o nā ʻaoʻao o luna, hiki ke hoʻopilikia i nā ʻāpana ʻē aʻe o ke kino e like me ke poʻo, nā kaula leo, a me nā ʻaoʻao haʻahaʻa 1. ʻO nā hiʻohiʻona lapaʻau o ET ʻaʻole wale nā ​​​​hōʻailona motor akā ʻo kekahi mau hōʻailona non-motor, me ka maʻi gastrointestinal 2. Ua hana ʻia nā haʻawina he nui e nānā i nā ʻano pathological a me physiological o ka essential tremor, akā ʻaʻole i ʻike ʻia nā ʻano pathophysiological maopopo3,4; Hōʻike nā haʻawina hou e hiki i ka hana ʻole o ka microbiota-gut-brain axis ke kōkua i nā maʻi neurodegenerative, a ke ulu nei nā hōʻike no kahi pilina bidirectional ma waena o ka gut microbiota a me nā maʻi neurodegenerative5,6. ʻIke ʻia, ma kahi hōʻike hihia hoʻokahi, ua hoʻomaikaʻi ka transplantation fecal microbiota i ka essential tremor a me ka irritable bowel syndrome i kahi maʻi, kahi e hōʻike ai i kahi pilina pili ma waena o ka gut microbiota a me ka essential tremor. Eia kekahi, ua ʻike mākou i nā loli kikoʻī i ka gut microbiota i nā maʻi me ET, kahi e kākoʻo ikaika ai i ke kuleana koʻikoʻi o ka gut dysbiosis ma ET8.
E pili ana i ka dysbiosis ʻōpū i nā maʻi neurodegenerative, ʻo PD ka mea i aʻo nui ʻia5. Hiki i kahi microbiota kaulike ʻole ke hoʻonui i ka permeability ʻōpū a hoʻāla i ka glia ʻōpū, e alakaʻi ana i nā alpha-synucleinopathies9,10,11. Loaʻa iā PD a me ET kekahi mau hiʻohiʻona maʻamau, e like me ke alapine like o ka haʻalulu i nā maʻi ET a me PD, ka haʻalulu hoʻomaha overlapping (haʻalulu maʻamau i PD), a me ka haʻalulu postural (loaʻa pinepine i nā maʻi ET), e paʻakikī ai ke hoʻokaʻawale ma waena o lākou. nā pae mua 12. No laila, pono mākou e wehe i kahi puka makani pono e hoʻokaʻawale ma waena o ET a me PD. Ma kēia ʻano, ʻo ke aʻo ʻana i ka dysbiosis ʻōpū kikoʻī a me nā loli metabolite pili i ET a me ka ʻike ʻana i ko lākou ʻokoʻa mai PD e lilo i mau biomarkers kūpono no ka hōʻailona a me ka hōʻailona ʻokoʻa o ET.
ʻO nā waikawa momona kaulahao pōkole (SCFA) nā metabolites nui i hana ʻia e ka fermentation bacteria intestinal o ka fiber dietary a ua manaʻo ʻia he kuleana koʻikoʻi lākou i nā pilina ʻōpū-lolo13,14. Lawe ʻia nā SCFA e nā cell colon a lawe ʻia i ke akepaʻa ma o ka ʻōnaehana venous portal, a komo kekahi mau SCFA i ke kaʻapuni systemic. Loaʻa i nā SCFA nā hopena kūloko i ka mālama ʻana i ka pono o ka pale ʻōpū a me ka hoʻolaha ʻana i ka pale kūlohelohe i loko o ka mucosa ʻōpū15. Loaʻa iā lākou nā hopena lōʻihi ma ka pale koko-lolo (BBB) ​​​​ma ka hoʻoulu ʻana i nā protein junction tight a me ka hoʻoulu ʻana i nā neurons ma ka hoʻoulu ʻana i nā mea loaʻa G protein-coupled (GPCRs) e hele i ka BBB16. ʻO Acetate, propionate, a me butyrate nā SCFA nui loa i loko o ka colon. Ua hōʻike nā haʻawina mua i ka emi ʻana o nā pae fecal o nā waikawa acetic, propionic a me butyric i nā poʻe maʻi me ka maʻi Parkinson17. Eia nō naʻe, ʻaʻole i aʻo ʻia nā pae fecal o SCFAs i nā poʻe maʻi me ET.
No laila, ua kuhikuhi ʻia kā mākou noiʻi e ʻike i nā loli kikoʻī i ka fecal SCFA i nā poʻe maʻi me ET a me ko lākou ʻokoʻa mai nā poʻe maʻi me PD, e loiloi ana i ka pilina o ka fecal SCFA me nā hōʻailona lapaʻau o ET a me ka microbiota ʻōpū, a me ka hoʻoholo ʻana i nā hiki ke hōʻoia a me nā ʻokoʻa diagnostic o nā laʻana fecal. KZhK. No ka hoʻoponopono ʻana i nā mea hoʻohuihui e pili ana i nā lāʻau anti-PD, ua koho mākou i nā poʻe maʻi me ka maʻi Parkinson hou e like me nā kaohi maʻi.
Ua hōʻuluʻulu ʻia nā ʻano demographic a me nā ʻano lapaʻau o nā 37 ET, 37 PD, a me 35 HC ma ka Papa 1. Ua hoʻohālikelike ʻia nā ET, PD, a me HC e ka makahiki, ke kāne, a me ka BMI. Loaʻa i nā hui ʻekolu nā ʻāpana like o ka puhipaka, ka inu ʻana i ka waiʻona a me ka inu ʻana i ke kofe a me ke kī. ʻOi aku ka kiʻekiʻe o ka helu Wexner (P = 0.004) a me ka helu HAMD-17 (P = 0.001) o ka hui PD ma mua o ka hui HC, a ʻoi aku ka kiʻekiʻe o ka helu HAMA (P = 0.011) a me ka helu HAMD-17 (P = 0.011) o ka hui ET ma mua o ka hui HC. ʻOi aku ka lōʻihi o ke ala o ka maʻi ma ka hui ET ma mua o ka hui PD (P<0.001).
Aia nā ʻokoʻa koʻikoʻi i nā pae fecal o ka waikawa propionic fecal (P = 0.023), waikawa acetic (P = 0.039), waikawa butyric (P = 0.020), waikawa isovaleric (P = 0.045), a me ka waikawa isobutyric (P = 0.015). . I ka loiloi post hoc hou aʻe, ʻoi aku ka haʻahaʻa o nā pae o ka waikawa propionic (P = 0.023), ka waikawa butyric (P = 0.007), a me ka waikawa isobutyric (P = 0.040) i ka hui ET ma mua o ka poʻe i ka hui HC. ʻOi aku ka haʻahaʻa o nā pae o ka isovalerate (P = 0.014) a me ka isobutyrate (P = 0.005) o nā maʻi me ET ma mua o nā maʻi me PD. Eia kekahi, ʻoi aku ka haʻahaʻa o nā pae o ka fecal propionic acid (P = 0.013), acetic acid (P = 0.016), a me ka butyric acid (P = 0.041) i nā maʻi me PD ma mua o nā maʻi me CC (Kiʻi 1 a me ka Papa Hoʻohui 1).
Hōʻike ʻo ag i kahi hoʻohālikelike hui o ka waikawa propionic, ka waikawa acetic, ka waikawa butyric, ka waikawa isovaleric, ka waikawa valeric, ka waikawa caproic a me ka waikawa isobutyric. Aia nā ʻokoʻa koʻikoʻi ma nā pae o ka waikawa propionic fecal, ka waikawa acetic, ka waikawa butyric, ka waikawa isovaleric a me ka waikawa isobutyric ma waena o nā hui ʻekolu. ET haʻalulu koʻikoʻi, ka maʻi Parkinson, ka mana HC olakino, SCFA. Hōʻike ʻia nā ʻokoʻa koʻikoʻi e *P < 0.05 a me **P < 0.01.
Ma ka noʻonoʻo ʻana i ka ʻokoʻa o ke kaʻina o ka maʻi ma waena o ka hui ET a me ka hui PD, ua aʻo mākou i 33 mau maʻi me ka PD mua a me 16 mau maʻi me ET (kaʻina o ka maʻi <3 mau makahiki) no ka hoʻohālikelike hou aku (Papa Hoʻohui 2). Ua hōʻike nā hopena ua haʻahaʻa loa ka nui o ka waikawa propionic fecal o ET ma mua o HA (P=0.015). ʻAʻole koʻikoʻi ka ʻokoʻa ma waena o ET a me HC no ka waikawa butyric a me ka waikawa isobutyric, akā ua ʻike ʻia kekahi ʻano (P = 0.082). ʻOi aku ka haʻahaʻa o nā pae isobutyrate fecal i nā maʻi me ET i hoʻohālikelike ʻia me nā maʻi me PD (P = 0.030). ʻAʻole koʻikoʻi ka ʻokoʻa ma waena o ET a me PD o ka waikawa isovaleric, akā aia nō kekahi ʻano (P = 0.084). ʻOi aku ka haʻahaʻa o ka waikawa propionic (P = 0.023), ka waikawa acetic (P = 0.020), a me ka waikawa butyric (P = 0.044) i nā maʻi PD ma mua o nā maʻi HC. ʻO kēia mau hopena (Kiʻi Hoʻohui 1) e kūlike me nā hopena nui. ʻO ka ʻokoʻa o nā hopena ma waena o ka laʻana holoʻokoʻa a me ka hui maʻi mua ma muli paha o ka liʻiliʻi o ka laʻana i loko o ka hui, e hopena ana i ka mana helu haʻahaʻa o ka ʻikepili.
Ua nānā hou mākou inā hiki i nā pae SCFA fecal ke hoʻokaʻawale i nā maʻi me ET mai nā maʻi me CU a i ʻole PD. Wahi a ka loiloi ROC, ʻo ka ʻokoʻa ma AUC o nā pae propionate he 0.668 (95% CI: 0.538-0.797), ka mea i hiki ai ke hoʻokaʻawale i nā maʻi me ET mai HC. Hiki ke hoʻokaʻawale ʻia nā maʻi me ET a me GC e nā pae butyrate me ka AUC o 0.685 (95% CI: 0.556–0.814). ʻO nā ʻokoʻa ma nā pae waikawa isobutyric e hoʻokaʻawale i nā maʻi me ET mai HC me ka AUC o 0.655 (95% CI: 0.525–0.786). I ka hoʻohui ʻana i nā pae propionate, butyrate a me isobutyrate, ua loaʻa kahi AUC kiʻekiʻe o 0.751 (95% CI: 0.634–0.867) me ka ʻike o 74.3% a me ka kikoʻī o 72.9% (Kiʻi 2a). No ka hoʻokaʻawale ʻana ma waena o nā maʻi ET a me PD, ʻo ka AUC no nā pae waikawa isovaleric he 0.700 (95% CI: 0.579–0.822) a no nā pae waikawa isobutyric he 0.718 (95% CI: 0.599–0.836). ʻO ka hui pū ʻana o ka waikawa isovaleric a me nā pae waikawa isobutyric he AUC kiʻekiʻe o 0.743 (95% CI: 0.629–0.857), ʻike o 74.3% a me ka kikoʻī o 62.9% (Kiʻi 2b). Eia kekahi, ua nānā mākou inā ʻokoʻa nā pae SCFA i loko o nā feces o nā maʻi me ka maʻi Parkinson mai nā kaohi. Wahi a ka loiloi ROC, ʻo ka AUC no ka ʻike ʻana i nā maʻi me PD ma muli o nā ʻokoʻa o nā pae waikawa propionic he 0.687 (95% CI: 0.559-0.814), me ka ʻike o 68.6% a me ka kikoʻī o 68.7%. Hiki i nā ʻokoʻa o nā pae acetate ke hoʻokaʻawale i nā maʻi PD mai nā HC me ka AUC o 0.674 (95% CI: 0.542–0.805). Hiki ke hoʻokaʻawale ʻia nā maʻi me PD mai CU wale nō ma o nā pae butyrate me ka AUC o 0.651 (95% CI: 0.515–0.787). I ka hui pū ʻana o nā pae propionate, acetate a me butyrate, ua loaʻa kahi AUC o 0.682 (95% CI: 0.553–0.811) (Kiʻi 2c).
ka hoʻokae ʻana e ka Ekalesia Orthodox Lūkini e kūʻē iā ET a me HC; b ka hoʻokae ʻana o ROC e kūʻē iā ET a me PD; c ka hoʻokae ʻana o ROC e kūʻē iā PD a me HC; ka haʻalulu koʻikoʻi o ET, ka maʻi o Parkinson, ka kaohi HC olakino, SCFA.
I nā poʻe maʻi me ET, ua pili maikaʻi ʻole ka pae o ka waikawa isobutyric fecal me ka helu FTM (r = -0.349, P = 0.034), a ua pili maikaʻi ʻole ka pae o ka waikawa isovaleric fecal me ka helu FTM (r = -0.421, P = 0.001) a me ka helu TETRAS. (r = -0.382, P = 0.020). I nā poʻe maʻi me ET a me PD, ua pili maikaʻi ʻole nā ​​pae o ka propionate fecal me nā helu SCOPA-AUT (r = −0.236, P = 0.043) (Kiʻi 3 a me ka Papa Hoʻohui 3). ʻAʻohe pilina koʻikoʻi ma waena o ke ʻano o ka maʻi a me SCFA i loko o ka hui ET (P ≥ 0.161) a i ʻole ka hui PD (P ≥ 0.246) (Papa Hoʻohui 4). I nā poʻe maʻi me PD, ua pili pono nā pae waikawa caproic fecal me nā helu MDS-UPDRS (r = 0.335, P = 0.042). Ma waena o nā mea komo a pau, ua pili maikaʻi ʻole nā ​​pae fecal propionate (r = −0.230, P = 0.016) a me acetate (r = −0.210, P = 0.029) me nā helu Wexner (Kiʻi 3 a me ka Papa Hoʻohui 3).
Ua pili maikaʻi ʻole nā ​​pae waikawa isobutyric fecal me nā helu FTM, ua pili maikaʻi ʻole ka waikawa isovaleric me nā helu FTM a me TETRAS, ua pili maikaʻi ʻole ka waikawa propionic me nā helu SCOPA-AUT, ua pili maikaʻi ʻia ka waikawa caproic me nā helu MDS-UPDRS, a ua pili maikaʻi ʻole ka waikawa propionic me nā helu FTM a me TETRAS. Ua pili maikaʻi ʻole ʻo TETRAS a me ka waikawa acetic me ka helu Wexner. Mana kākoʻo ʻia e ka MDS-UPDRS Association o ka Unified Parkinson's Disease Rating Scale, Mini-Mental State Examination MMSE, Hamilton Depression Rating Scale HAMD-17, 17 mau mea, Hamilton Anxiety Rating Scale HAMA, HY Hoehn a me 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. Hōʻike ʻia nā ʻokoʻa koʻikoʻi e *P < 0.05 a me **P < 0.01.
Ua ʻimi hou mākou i ke ʻano hoʻokaʻawale o ka microbiota ʻōpū me ka hoʻohana ʻana i ka loiloi LEfSE a ua koho i ka pae ʻikepili nui o ka genus no ka loiloi hou aku. Ua hana ʻia nā hoʻohālikelike ma waena o ET a me HC a ma waena o ET a me PD. A laila ua hana ʻia ka loiloi pilina Spearman ma ka nui o ka microbiota ʻōpū a me nā pae SCFA fecal i nā hui hoʻohālikelike ʻelua.
ʻO Faecalibacterium (pili me ka waikawa butyric, r = 0.408, P < 0.001), Lactobacillus (pili me ka waikawa butyric, r = 0.283, P = 0.016), Streptobacterium (pili me ka waikawa propionic, r = 0.327) i loaʻa i ka loiloi o ET a me CA. , P = 0.005; pili me ka waikawa butyric, r = 0.374, P = 0.001; pili me ka waikawa isobutyric, r = 0.329, P = 0.005), Howardella (pili me ka waikawa propionic, r = 0.242, P = 0.041), Raoultella (pili me ka propionate, r = 0.249, P = 0.035), a me Candidatus Arthromitus (pili me ka waikawa isobutyric, r = 0.302, P = 0.010) e emi ana ma ET a pili pono me nā pae SCFA fecal. Eia nō naʻe, ua piʻi ka nui o Stenotropomonas ma ET a ua pili maikaʻi ʻole me nā pae isobutyrate fecal (r = -0.250, P = 0.034). Ma hope o ka hoʻoponopono ʻana o FDR, ʻo ka pilina ma waena o Faecalibacterium, Catenibacter, a me SCFA wale nō i koe koʻikoʻi (P ≤ 0.045) (Kiʻi 4 a me ka Papa Hoʻohui 5).
ʻO ka loiloi pilina o ET a me HC. Ma hope o ka hoʻoponopono ʻana o FDR, ua ʻike ʻia ka nui o Faecalibacterium (pili maikaʻi me ka butyrate) a me Streptobacterium (pili maikaʻi me ka propionate, butyrate, a me isobutyrate) ua emi iho ma ET a pili maikaʻi me nā pae SCFA fecal. b ʻO ka loiloi pilina o ET a me PD. Ma hope o ka hoʻoponopono ʻana o FDR, ʻaʻohe pilina koʻikoʻi i loaʻa. ET haʻalulu koʻikoʻi, ka maʻi Parkinson, ka mana HC olakino, SCFA. Hōʻike ʻia nā ʻokoʻa koʻikoʻi e *P < 0.05 a me **P < 0.01.
I ka nānā ʻana i ka ET e kūʻē i ka PD, ua ʻike ʻia ua hoʻonui ʻia ka Clostridium trichophyton ma ET a ua pili pū me ka waikawa isovaleric fecal (r = -0.238, P = 0.041) a me ka waikawa isobutyric (r = -0.257, P = 0.027). ). Ma hope o ka hoʻoponopono ʻana o FDR, ua noho koʻikoʻi kekahi o lākou (P≥0.295) (Kiʻi 4 a me ka Papa Hoʻohui 5).
He haʻawina piha kēia e nānā ana i nā pae SCFA fecal a hoʻopili iā lākou me nā loli i ka microbiota ʻōpū a me ke koʻikoʻi o nā hōʻailona i nā poʻe maʻi me ET i hoʻohālikelike ʻia me nā poʻe maʻi me CU a me PD. Ua ʻike mākou ua hoʻemi ʻia nā pae SCFA fecal i nā poʻe maʻi me ET a ua pili pū me ke koʻikoʻi o ke olakino a me nā loli kikoʻī i ka microbiota ʻōpū. ʻO nā pae fecal cumulative o nā waikawa momona kaulahao pōkole (SCFAs) e hoʻokaʻawale iā ET mai GC a me PD.
Ke hoʻohālikelike ʻia me nā maʻi GC, ʻoi aku ka haʻahaʻa o nā pae fecal o nā waikawa propionic, butyric, a me isobutyric i nā maʻi ET. ʻO ka hui pū ʻana o nā waikawa propionic, butyric a me isobutyric i hoʻokaʻawale iā ET a me HC me ka AUC o 0.751 (95% CI: 0.634–0.867), ka ʻike o 74.3% a me ka kikoʻī o 72.9%, e hōʻike ana i kā lākou hoʻohana ʻana ma ke ʻano he biomarkers diagnostic no ke kuleana hiki o ET. Ua hōʻike ʻia ka loiloi hou aku ua pili maikaʻi ʻole nā ​​​​paepae waikawa propionic fecal me ka helu Wexner a me ka helu SCOPA-AUT. Ua pili pono nā paepae waikawa isobutyric fecal me nā helu FTM. Ma ka ʻaoʻao ʻē aʻe, ua pili ka emi ʻana o nā pae butyrate ma ET me ka emi ʻana o ka nui o ka microbiota hana SCFA, Faecalibacterium, a me Categorybacter. Eia kekahi, ua pili pū ka emi ʻana o ka nui o Catenibacter ma ET me ka emi ʻana o nā paepae waikawa propionic a me isobutyric fecal.
ʻO ka hapa nui o nā SCFA i hana ʻia i loko o ka colon e lawe ʻia e nā colonocytes ma o nā mea lawe monocarboxylate H+-dependent a i ʻole sodium-dependent. Hoʻohana ʻia nā waikawa momona kaulahao pōkole i omo ʻia ma ke ʻano he kumu ikehu no nā colonocytes, ʻoiai ʻo nā mea i hoʻoheheʻe ʻole ʻia i loko o nā colonocytes e lawe ʻia i loko o ke kahe ʻana o ka puka 18. Hiki i nā SCFA ke hoʻohuli i ka neʻe ʻana o ka ʻōpū, hoʻonui i ka hana pale ʻōpū, a hoʻohuli i ka metabolism host a me ka pale ʻana19. Ua ʻike mua ʻia ua hoʻemi ʻia nā ʻano fecal o ka butyrate, acetate, a me ka propionate i nā maʻi PD i hoʻohālikelike ʻia me HCs17, kahi mea e kūlike me kā mākou mau hopena. Ua ʻike kā mākou noiʻi i ka emi ʻana o nā SCFA i nā maʻi me ET, akā ʻaʻole ʻike nui ʻia e pili ana i ke kuleana o SCFAs i ka pathology o ET. Hiki i ka Butyrate a me ka propionate ke hoʻopaʻa i nā GPCRs a hoʻohuli i ka hōʻailona GPCR-dependent e like me MAPK a me NF-κB20 signaling. ʻO ke kumu nui o ka axis gut-brain ʻo ia ka hiki i nā SCFAs i hūnā ʻia e nā microbes gut ke hoʻohuli i ka hōʻailona host, no laila e hoʻohuli i ka hana gut a me ka lolo. Ma muli o ka hopena ikaika o ka butyrate a me ka propionate i ka hana histone deacetylase (HDAC)21 a hiki i ka butyrate ke hana ma ke ʻano he ligand no nā mea hoʻololi, loaʻa iā lākou nā hopena ākea i ka metabolism host, differentiation a me ka proliferation, ma muli o ko lākou mana ma ka hoʻoponopono gene22. Ma muli o nā hōʻike mai SCFA a me nā maʻi neurodegenerative, ua manaʻo ʻia ʻo butyrate he moho therapeutic ma muli o kona hiki ke hoʻoponopono i ka hana HDAC impaired, hiki ke hoʻoponopono i ka make neuron dopaminergic ma PD23,24,25. Ua hōʻike pū nā haʻawina holoholona i ka hiki o ka waikawa butyric ke pale aku i ka degeneration neuron dopaminergic a hoʻomaikaʻi i nā maʻi neʻe i nā hiʻohiʻona PD26,27. Ua ʻike ʻia ka waikawa propionic e kaupalena i nā pane mumū a pale i ka pono o ka BBB28,29. Ua hōʻike nā haʻawina e hoʻolaha ka waikawa propionic i ke ola ʻana o nā neurons dopaminergic i ka pane ʻana i ka rotenone toxicity i nā hiʻohiʻona PD 30 a ʻo ka lawelawe waha o ka waikawa propionic e hoʻopakele i ka nalowale o ka neuron dopaminergic a me nā hemahema motor i nā ʻiole me PD 31. ʻAʻole ʻike nui ʻia e pili ana i ka hana o ka waikawa isobutyric. Eia nō naʻe, ua ʻike ʻia kahi noiʻi hou i ka hoʻonui ʻana o ka koloni ʻana o nā ʻiole me B. ovale i ka nui o ka SCFA ʻōpū (me ka acetate, propionate, isobutyrate, a me isovalerate) a me ka nui o ka GABA ʻōpū, e hōʻike ana ua hoʻokumu ʻia kahi loulou ma waena o ka microbiota ʻōpū a me ka nui o nā neurotransmitters32. I loko o ET, ʻo nā loli pathological maʻamau ʻole i loko o ka cerebellum e pili ana i nā loli i nā axons cell Purkinje a me nā dendrites, ka neʻe ʻana a me ka nalowale ʻana o nā cell Purkinje, nā loli i nā axons cell hīnaʻi, nā ʻano ʻē i nā pilina fiber piʻi me ka hoʻolaha cell Purkinje, a me nā loli i nā mea loaʻa GABA i ka iwi dentate. nuclei, kahi e alakaʻi ai i ka emi ʻana o ka puka GABAergic mai ka cerebellum3,4,33. ʻAʻole maopopo inā pili nā SCFA me ka neurodegeneration cell Purkinje a ua emi ka hana ʻana o ka cerebellar GABA. Hōʻike kā mākou mau hopena i kahi pilina ikaika ma waena o SCFA a me ET, akā ʻaʻole ʻae ka hoʻolālā haʻawina cross-sectional i nā hopena e pili ana i ka pilina kumu ma waena o SCFA a me ke kaʻina maʻi o ET; Pono nā haʻawina hoʻomau lōʻihi hou aʻe, me nā ana ʻana o nā SCFA fecal, a me nā haʻawina holoholona e nānā ana i nā ʻano hana.
Manaʻo ʻia nā SCFA e hoʻoulu i ka ʻūlū ʻana o nā ʻiʻo laumania o ka colon34. ʻO ka nele o SCFA e hoʻonui i nā hōʻailona o ka constipation, a ʻo ka hoʻohui ʻana me SCFA e hoʻomaikaʻi paha i nā hōʻailona o ka constipation PD35. Hōʻike pū kā mākou mau hopena i kahi pilina koʻikoʻi ma waena o ka emi ʻana o ka nui o ka fecal SCFA a me ka hoʻonui ʻia o ka constipation a me ka hana autonomic i nā maʻi me ET. Ua ʻike ʻia kekahi hōʻike hihia ua hoʻomaikaʻi ka hoʻoili ʻana o ka microbiota i ka essential tremor a me ka irritable bowel syndrome i ka maʻi 7, e hōʻike hou ana i kahi pilina pili ma waena o ka gut microbiota a me ET. No laila, ke manaʻoʻiʻo nei mākou e hiki i ka fecal SCFA/microbiota ke hoʻopilikia i ka neʻe ʻana o ka ʻōpū host a me ka hana o ka ʻōnaehana nerve autonomic.
Ua ʻike ʻia ma ke aʻo ʻana ua pili ka emi ʻana o nā pae o nā SCFA fecal ma ET me ka emi ʻana o ka nui o Faecalibacterium (e pili ana me ka butyrate) a me Streptobacterium (e pili ana me ka propionate, butyrate, a me isobutyrate). Ma hope o ka hoʻoponopono ʻana o FDR, ua mau kēia pilina koʻikoʻi. ʻO Faecalibacterium lāua ʻo Streptobacterium nā microorganisms e hana ana i ka SCFA. Ua ʻike ʻia ʻo Faecalibacterium he microorganism e hana ana i ka butyrate36, ʻoiai ʻo nā huahana nui o ka fermentation Catenibacter he acetate, butyrate a me ka lactic acid37. Ua ʻike ʻia ʻo Faecalibacterium ma 100% o nā hui ET a me HC; ʻo ka nui waena o ka hui ET he 2.06% a ʻo ka hui HC he 3.28% (LDA 3.870). Ua ʻike ʻia ka bacteria mahele ma 21.6% (8/37) o ka hui HC a ma 1 laʻana wale nō o ka hui ET (1/35). ʻO ka emi ʻana a me ka ʻike ʻole ʻia o ka streptobacteria ma ET e hōʻike paha i kahi pilina me ka pathogenicity o ka maʻi. ʻO ka nui waena o nā ʻano Catenibacter i ka hui HC he 0.07% (LDA 2.129). Eia kekahi, ua pili nā bacteria lactic acid me nā loli i ka fecal butyrate (P = 0.016, P = 0.096 ma hope o ka hoʻoponopono ʻana o FDR), a ua pili ka moho arthritis me nā loli i ka isobutyrate (P = 0.016, P = 0.072 ma hope o ka hoʻoponopono ʻana o FDR). Ma hope o ka hoʻoponopono ʻana o FDR, ʻo ke ʻano pilina wale nō i koe, ʻaʻole ia he koʻikoʻi helu. Ua ʻike ʻia ʻo Lactobacilli he mau mea hana SCFA (acetic acid, propionic acid, isobutyric acid, butyric acid) 38 a ʻo Candidatus Arthromitus kahi mea hoʻoulu kikoʻī o ka hoʻokaʻawale ʻana o nā cell T helper 17 (Th17), me Th1 / 2 a me Tregs e pili ana me ke kaulike pale /Th1739. . Ua hōʻike ʻia kahi noiʻi hou e hiki i nā pae kiʻekiʻe o ka fecal pseudoarthritis ke kōkua i ka mumū o ka colonic, ka hana ʻole o ka pale ʻōpū, a me ka mumū ʻōnaehana 40. Ua hoʻonui ʻia nā pae o Clostridium trichoides ma ET i hoʻohālikelike ʻia me PD. Ua ʻike ʻia ka nui o Clostridium trichoides he pilina maikaʻi ʻole me ka isovaleric acid a me ka isobutyric acid. Ma hope o ka hoʻoponopono ʻana o FDR, ua noho koʻikoʻi nā mea ʻelua (P≥0.295). ʻO Clostridium pilosum kahi bacteria i ʻike ʻia e pili ana i ka mumū a hiki ke kōkua i ka hana ʻole o ka pale ʻōpū41. Ua hōʻike kā mākou noiʻi mua i nā loli i ka microbiota gut o nā maʻi me ET8. Maanei mākou e hōʻike pū nei i nā loli i ka SCFA ma ET a ʻike i kahi pilina ma waena o ka dysbiosis gut a me nā loli i ka SCFA. ʻO ka emi ʻana o nā pae SCFA e pili pono ana me ka dysbiosis gut a me ka haʻalulu koʻikoʻi ma ET. Hōʻike kā mākou mau hopena e hiki i ka axis gut-brain ke pāʻani i kahi kuleana koʻikoʻi i ka pathogenesis o ET, akā pono nā noiʻi hou aʻe i nā hiʻohiʻona holoholona.
Ke hoʻohālikelike ʻia me nā poʻe maʻi me PD, ʻoi aku ka haʻahaʻa o nā pae isovaleric a me isobutyric acids i loko o kā lākou feces i nā poʻe maʻi me ET. ʻO ka hui pū ʻana o ka isovaleric acid a me ka isobutyric acid i ʻike ʻia ʻo ET ma PD me ka AUC o 0.743 (95% CI: 0.629–0.857), ka ʻike o 74.3% a me ka specificity o 62.9%, e hōʻike ana i ko lākou kuleana hiki ke lilo i biomarkers i ka ʻike ʻokoʻa o ET. . Ua pili pono nā pae isovaleric acid fecal me nā helu FTM a me TETRAS. Ua pili pono nā pae isobutyric acid fecal me nā helu FTM. Ua pili ka emi ʻana o nā pae isobutyric acid me ka emi ʻana o ka nui o nā catobacteria. ʻAʻole ʻike nui ʻia e pili ana i nā hana o ka isovaleric acid a me ka isobutyric acid. Ua hōʻike ʻia ma kahi noiʻi mua ua hoʻonui ka noho ʻana o nā ʻiole me B. ovale i ka nui o nā SCFA ʻōpū (me ka acetate, propionate, isobutyrate, a me isovalerate) a me nā ʻano GABA ʻōpū, e hōʻike ana i ka pilina ʻōpū ma waena o ka microbiota a me nā ʻano SCFA/neurotransmitter ʻōpū32. ʻO ka mea hoihoi, ua like nā pae waikawa isobutyric i ʻike ʻia ma waena o nā hui PD a me HC, akā ʻokoʻa ma waena o nā hui ET a me PD (a i ʻole HC). Hiki i ka waikawa Isobutyric ke hoʻokaʻawale ma waena o ET a me PD me ka AUC o 0.718 (95% CI: 0.599–0.836) a ʻike iā ET a me NC me ka AUC o 0.655 (95% CI: 0.525–0.786). Eia kekahi, pili nā pae waikawa isobutyric me ka koʻikoʻi o ka haʻalulu, e hoʻoikaika hou ana i kona pilina me ET. ʻO ka nīnau inā hiki i ka waikawa isobutyric waha ke hōʻemi i ka koʻikoʻi o ka haʻalulu i nā poʻe maʻi me ET e pono ai ke aʻo hou ʻia.
No laila, ua hoʻemi ʻia ka nui o ka SCFA fecal i nā poʻe maʻi me ET a pili pū me ke koʻikoʻi o ka ET a me nā loli kikoʻī i loko o ka microbiota ʻōpū. ʻO ka fecal propionate, butyrate, a me ka isobutyrate paha he mau biomarkers diagnostic no ET, ʻoiai ʻo isobutyrate a me isovalerate paha he mau biomarkers diagnostic ʻokoʻa no ET. ʻOi aku ka kikoʻī o nā loli i ka fecal isobutyrate no ET ma mua o nā loli i nā SCFA ʻē aʻe.
He nui nā palena o kā mākou noiʻi. ʻO ka mea mua, hiki i nā ʻano meaʻai a me nā makemake meaʻai ke hoʻohuli i ka hōʻike ʻana o ka microbiota, pono nā laʻana noiʻi nui aʻe i nā heluna kanaka like ʻole, a pono e hoʻolauna nā noiʻi e hiki mai ana i nā noiʻi meaʻai piha a ʻōnaehana e like me nā nīnau nīnau pinepine meaʻai. ʻO ka lua, ʻo ka hoʻolālā noiʻi cross-sectional e pale i nā hopena e pili ana i ka pilina kumu ma waena o SCFA a me ke kaʻina hana maʻi o ET. Pono nā noiʻi hahai lōʻihi hou aʻe me nā ana serial o nā SCFA fecal. ʻO ke kolu, pono e hōʻoia ʻia nā hiki ke hōʻoia a me ka ʻokoʻa o nā pae SCFA fecal me ka hoʻohana ʻana i nā laʻana kūʻokoʻa mai ET, HC, a me PD. Pono e hoʻāʻo ʻia nā laʻana ʻōpala kūʻokoʻa hou aʻe i ka wā e hiki mai ana. ʻO ka mea hope loa, ʻoi aku ka pōkole o ka lōʻihi o ka maʻi o nā maʻi me PD i kā mākou cohort ma mua o nā maʻi me ET. Ua hoʻohālikelike nui mākou iā ET, PD a me HC ma ka makahiki, ke kāne a me ka BMI. Ma muli o ka ʻokoʻa o ke kaʻina maʻi ma waena o ka hui ET a me ka hui PD, ua aʻo pū mākou i 33 mau maʻi me PD mua a me 16 mau maʻi me ET (ka lōʻihi o ka maʻi ≤3 mau makahiki) no ka hoʻohālikelike hou aku. ʻO nā ʻokoʻa ma waena o ka hui ma SCFA ua kūlike me kā mākou ʻikepili mua. Eia kekahi, ʻaʻole mākou i ʻike i ka pilina ma waena o ka lōʻihi o ka maʻi a me nā loli i ka SCFA. Eia nō naʻe, i ka wā e hiki mai ana, ʻoi aku ka maikaʻi o ka hoʻolimalima ʻana i nā maʻi me PD a me ET i kahi wā mua me ka lōʻihi o ka maʻi e hoʻopau ai i ka hōʻoia ʻana i kahi hāpana nui aʻe.
Ua ʻāpono ʻia ke kaʻina hana noiʻi e ke Kōmike Hoʻopono o ka Halemai ʻo Ruijin e pili ana i ke Kula Lapaʻau o ke Kulanui ʻo Shanghai Jiao Tong (RHEC2018-243). Ua loaʻa ka ʻae i kākau ʻia mai nā mea komo a pau.
Ma waena o Ianuali 2019 a me Dekemaba 2022, ua hoʻokomo ʻia nā kumuhana 109 (37 ET, 37 PD, a me 35 HC) mai ka Movement Disorder Center Clinic o ka Halemai ʻo Ruijin, e pili ana i ke Kula Lapaʻau o ke Kulanui ʻo Shanghai Jiao Tong, i loko o kēia noiʻi. ʻO nā pae hoʻohālikelike: (1) makahiki 25-85, (2) ua ʻike ʻia nā maʻi me ET e like me nā pae hoʻohālikelike o ka MDS Working Group 42 a ua ʻike ʻia ka PD e like me nā pae hoʻohālikelike o ka MDS 43, (3) ʻaʻole i lawe nā maʻi āpau i nā lāʻau anti-PD ma mua o ka hōʻiliʻili ʻana i nā laʻana. (4) Ua lawe wale ka hui ET i nā β-blockers a i ʻole nā ​​​​lāʻau lapaʻau pili ʻole ma mua o ka hōʻiliʻili ʻana i nā laʻana ʻōpala. Ua koho pū ʻia nā HC i kūlike i ka makahiki, ke kāne, a me ka helu helu kino (BMI). ʻO nā pae hoʻokaʻawale: (1) ka poʻe ʻai mea kanu, (2) ka ʻai pono ʻole, (3) nā maʻi mau o ke ala gastrointestinal (me ka maʻi mumū o ka ʻōpū, nā ʻōpū gastric a i ʻole duodenal), (4) nā maʻi mau koʻikoʻi (me nā ʻōpū malignant), ka hāʻule ʻana o ka puʻuwai, ka hāʻule ʻana o ka renal, nā maʻi hematological) (5) Mōʻaukala o ke ʻoki kino nui o ka gastrointestinal, (6) Ka ʻai mau ʻana i ka yogurt, (7) Ka hoʻohana ʻana i kekahi probiotics a i ʻole antibiotics no 1 mahina, (8) Ka hoʻohana mau ʻana i nā corticosteroids, nā mea hoʻopaʻa proton pump, statins, metformin, immunosuppressants a i ʻole nā ​​​​lāʻau anticancer a me (9) ka hōʻino koʻikoʻi o ka noʻonoʻo e hoʻopilikia ai i nā hoʻokolohua lapaʻau.
Ua hāʻawi nā kumuhana āpau i ka mōʻaukala lapaʻau, ke kaumaha a me ka ʻike kiʻekiʻe e helu ai i ka BMI, a ua hana ʻia kahi hoʻokolohua neurological a me ka loiloi lapaʻau e like me ka Hamilton Anxiety Rating Scale (HAMA) 44 anxiety score, ka Hamilton Depression Rating Scale-17 score (HAMD-17) 45. kaumaha, koʻikoʻi o ka constipation me ka hoʻohana ʻana i ka Wexner Constipation Scale 46 a me ka Bristol Stool Scale 47 a me ka hana cognitive me ka hoʻohana ʻana i ka Mini-Mental State Examination (MMSE) 48. Ua nānā ka Scale for the Assessment of Autonomic Symptoms of Parkinson's Disease (SCOPA-AUT) 49 i ka autonomic dysfunction i nā maʻi me ET a me PD. Ua nānā ʻia ka Fana-Tolos-Marin Clinical Tremor Rating Scale (FTM) a me ka Essential Tremor Rating Scale (TETRAS) 50. Ua nānā ʻia ka Tremor Study Group (TRG) 50 i nā maʻi me ET; ka Kinson's Disease Rating Scale (MDS-), i kākoʻo ʻia e ka United Parkinson's Disease Association; Ua nānā ʻia ka UPDRS mana 51 a me Hoehn lāua ʻo Yahr (HY) mana 52.
Ua noi ʻia kēlā me kēia mea komo e hōʻiliʻili i kahi hāpana ʻōpala i ke kakahiaka me ka hoʻohana ʻana i kahi pahu hōʻiliʻili ʻōpala. E hoʻololi i nā pahu i ka hau a mālama ma -80°C ma mua o ka hana ʻana. Ua hana ʻia ka loiloi SCFA e like me nā hana maʻamau o Tiangene Biotechnology (Shanghai) Co., Ltd. Ua hōʻiliʻili ʻia he 400 mg o nā hāpana ʻōpala hou mai kēlā me kēia kumuhana a ua kālailai ʻia me ka hoʻohana ʻana i nā SCFA ma hope o ka wili ʻana a me ka sonication. Ua kālailai ʻia nā SCFA i koho ʻia i loko o nā ʻōpala me ka hoʻohana ʻana i ka gas chromatography-mass spectrometry (GC-MS) a me ka liquid chromatography-tandem MS (LC-MS/MS).
Ua unuhi ʻia ka DNA mai nā laʻana 200 mg me ka hoʻohana ʻana i ka QIAamp® Fast DNA Stool Mini Kit (QIAGEN, Hilden, Kelemānia) e like me nā kuhikuhi a ka mea hana. Ua hoʻoholo ʻia ka haku mele microbial ma ka hoʻonohonoho ʻana i ka gene 16 S rRNA ma ka DNA i hoʻokaʻawale ʻia mai nā feces ma ka hoʻonui ʻana i ka ʻāpana V3-V4. E hoʻāʻo i ka DNA ma ka holo ʻana i ka laʻana ma kahi gel agarose 1.2%. Ua hana ʻia ka hoʻonui ʻana o ka polymerase chain reaction (PCR) o ka gene 16S rRNA me ka hoʻohana ʻana i nā primers bacterial universal (357 F a me 806 R) a me kahi waihona amplicon ʻelua-ʻanuʻu i kūkulu ʻia ma ka paepae Novaseq.
Hōʻike ʻia nā loli hoʻomau ma ke ʻano he awelika ± ʻokoʻa maʻamau, a hōʻike ʻia nā loli mahele ma ke ʻano he helu a me nā pakeneka. Ua hoʻohana mākou i ka hoʻāʻo a Levene e hoʻāʻo i ka homogeneity o nā variances. Ua hana ʻia nā hoʻohālikelike me ka hoʻohana ʻana i nā hoʻāʻo t ʻelua-tailed a i ʻole ka nānā ʻana o ka variance (ANOVA) inā ua hoʻolaha maʻamau ʻia nā loli, a me nā hoʻāʻo Mann-Whitney U nonparametric inā ua uhaki ʻia nā manaʻo normality a i ʻole homoscedasticity. Ua hoʻohana mākou i ka ʻāpana ma lalo o ke kiʻikuhi hana hoʻokipa (ROC) (AUC) e helu i ka hana diagnostic o ke kumu hoʻohālike a nānā i ka hiki o SCFA ke hoʻokaʻawale i nā maʻi me ET mai ka poʻe me HC a i ʻole PD. No ka nānā ʻana i ka pilina ma waena o SCFA a me ke koʻikoʻi o ka maʻi, ua hoʻohana mākou i ka nānā ʻana o ka pilina Spearman. Ua hana ʻia ka nānā ʻana i ka helu me ka hoʻohana ʻana i ka polokalamu SPSS (mana 22.0; SPSS Inc., Chicago, IL) me ka pae koʻikoʻi (me ka waiwai P a me FDR-P) i hoʻonohonoho ʻia ma 0.05 (ʻaoʻao ʻelua).
Ua kālailai ʻia nā moʻo 16 S me ka hoʻohana ʻana i ka hui pū ʻana o Trimmomatic (mana 0.35), Flash (mana 1.2.11), UPARSE (mana v8.1.1756), mothur (mana 1.33.3) a me R (mana 3.6.3) polokalamu. Ua hana ʻia nā ʻikepili gene 16S rRNA maka me ka hoʻohana ʻana iā UPARSE e hana i nā ʻāpana taxonomic hana (OTU) me 97% ʻike. Ua kuhikuhi ʻia nā taxonomies me ka hoʻohana ʻana iā Silva 128 ma ke ʻano he waihona ʻikepili kuhikuhi. Ua koho ʻia ka pae generic o ka ʻikepili nui pili no ka nānā hou aku. Ua hoʻohana ʻia ka loiloi nui hopena linear discriminant (LDA) (LEfSE) no nā hoʻohālikelike ma waena o nā hui (ET vs. HC, ET vs. PD) me ka paepae α o 0.05 a me ka paepae nui hopena o 2.0. Ua hoʻohana hou ʻia nā genera discriminant i ʻike ʻia e ka loiloi LEfSE no ka loiloi correlation Spearman o SCFA.
No ka ʻike hou aku e pili ana i ka hoʻolālā noiʻi, e ʻike i ka Natural Research Report Abstract e pili ana me kēia ʻatikala.
Mālama ʻia nā ʻikepili hoʻonohonoho maka 16S ma ka waihona ʻikepili BioProject o ke Kikowaena ʻIke Biotechnology (NCBI) National Center for Biotechnology Information (SRP438900: PRJNA974928), URL: https://www.ncbi.nlm.nih.gov/Traces/study/?acc= SRP438900&o. =acc_s% 3Aa. Loaʻa nā ʻikepili pili ʻē aʻe i ka mea kākau pili ma ke noi kūpono, e like me nā hana like ʻepekema a me nā hoʻololi hoʻonaʻauao me nā papahana noiʻi piha. ʻAʻole ʻae ʻia ka hoʻoili ʻana o ka ʻikepili i nā ʻaoʻao ʻekolu me ka ʻole o kā mākou ʻae.
ʻO ke code kumu wehe wale nō me ka hui pū ʻana o Trimmomatic (mana 0.35), Flash (mana 1.2.11), UPARSE (mana v8.1.1756), mothur (mana 1.33.3) a me R (mana 3.6.3), me ka hoʻohana ʻana i nā hoʻonohonoho paʻamau a i ʻole ka ʻāpana "Method". Hiki ke hāʻawi ʻia ka ʻike wehewehe hou aku i ka mea kākau pili ma ke noi kūpono.
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