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Nchọpụta mbụ nke ịma jijiji dị mkpa (ET) nwere ike isi ike, ọkachasị mgbe a na-ekewapụ ya na njikwa ahụike (HC) na ọrịa Parkinson (PD). N'oge na-adịbeghị anya, nyocha nke ihe nlele stool maka microbiota eriri afọ na metabolites ya enyela ụzọ ọhụrụ maka ịchọpụta ihe ndị na-egosi ọrịa neurodegenerative ọhụrụ. A na-ebelata abụba dị mkpụmkpụ (SCFA), dị ka metabolite bụ isi nke flora eriri afọ, na nsị na PD. Agbanyeghị, a mụọbeghị SCFA na ET. Ebumnuche anyị bụ inyocha ọkwa SCFAs nke nsị na ET, nyochaa mmekọrịta ha na mgbaàmà ahụike na microbiota eriri afọ, ma chọpụta ikike nchọpụta ha nwere ike. A tụrụ SCFA na microbiota eriri afọ na ET 37, PD 37 ọhụrụ, na HC 35. Ejiri scales nyochaa afọ ntachi, nsogbu autonomic, na oke ịma jijiji. Ọkwa nsị nke propionate, butyrate, na isobutyrate dị ala na ET karịa na HC. Nchikota nke propionic, butyric na isobutyric acid dị iche na ET na HC yana AUC nke 0.751 (95% CI: 0.634–0.867). Ọkwa isovaleric acid na isobutyric acid dị ala na ET karịa na PD. Isovaleric acid na isobutyric acid na-ekewa n'etiti ET na PD na AUC nke 0.743 (95% CI: 0.629–0.857). Fecal propionate na-ejikọta ya na afọ ntachi na nsogbu autonomic. Isobutyric acid na isovaleric acid nwere njikọ megide oke ịma jijiji. Mbelata na fecal SCFAs jikọtara ya na mbelata na ụba nke Faecalibacterium na Streptobacterium na ET. Ya mere, ọdịnaya nke SCFA na nsị na-ebelata na ET ma jikọtara ya na oke nke foto ahụike na mgbanwe na microbiota eriri afọ. Fecal propionate, butyrate, isobutyrate, na isovalerate nwere ike ịbụ ihe ngosi nchọpụta na nchọpụta dị iche iche maka ET.
Ma jijiji dị mkpa (ET) bụ ọrịa neurodegenerative na-aga n'ihu, nke na-adịghị ala ala nke a na-ahụkarị site na ịma jijiji nke akụkụ elu, nke nwekwara ike imetụta akụkụ ahụ ndị ọzọ dịka isi, eriri olu, na akụkụ ala 1. Njirimara ahụike nke ET gụnyere ọ bụghị naanị mgbaàmà moto kamakwa ụfọdụ ihe ịrịba ama na-abụghị moto, gụnyere ọrịa afọ 2. Emeela ọtụtụ ọmụmụ ihe iji nyochaa njirimara ọrịa na nke anụ ahụ nke ịma jijiji dị mkpa, mana achọpụtabeghị usoro pathophysiological doro anya3,4; Ọmụmụ ihe ndị na-adịbeghị anya na-egosi na enweghị ọrụ nke microbiota-gut-brain axis nwere ike itinye aka na ọrịa neurodegenerative, enwerekwa ihe akaebe na-eto eto maka njikọ nwere ike ịbụ n'etiti microbiota eriri afọ na ọrịa neurodegenerative5,6. N'ụzọ dị mkpa, n'otu akụkọ ikpe, ntinye ọgwụ nje fecal microbiota mekwara ka ọrịa ịma jijiji dị mkpa na ọrịa eriri afọ na-ewe iwe dị mma n'ime onye ọrịa, nke nwere ike igosi mmekọrịta chiri anya n'etiti microbiota eriri afọ na ịma jijiji dị mkpa. Na mgbakwunye, anyị hụkwara mgbanwe kpọmkwem na microbiota eriri afọ na ndị ọrịa nwere ET, nke na-akwado ọrụ dị mkpa nke dysbiosis eriri afọ na ET8.
Banyere ọrịa eriri afọ na-adịghị mma n'ọrịa neurodegenerative, PD bụ nke a na-amụkarị nke ọma5. Microbiota na-adịghị mma nwere ike ime ka eriri afọ na-abanye ma mee ka glia eriri afọ rụọ ọrụ, na-eduga na alpha-synucleinopathies9,10,11. PD na ET nwere ụfọdụ ihe ndị a na-ahụkarị, dịka ugboro ole ịma jijiji yiri nke ahụ na ndị ọrịa ET na PD, ịma jijiji ezumike na-ekpuchi (ọmarịcha nkịtị na PD), na ịma jijiji postural (nke a na-ahụkarị na ndị ọrịa ET), na-eme ka o sie ike ịmata ọdịiche dị n'etiti ha. mmalite 12. Ya mere, anyị kwesịrị imepe windo bara uru ngwa ngwa iji mata ọdịiche dị n'etiti ET na PD. N'ọnọdụ a, ịmụ banyere dysbiosis eriri afọ kpọmkwem na mgbanwe metabolite metụtara na ET na ịchọpụta ọdịiche ha na PD nwere ike ịghọ ihe ngosi ihe nwere ike ịbụ maka nchọpụta na nchọpụta dị iche iche nke ET.
Asịd abụba dị mkpụmkpụ (SCFAs) bụ ihe ndị bụ isi sitere na nje bacteria na-agbaze eriri afọ nke eriri nri, a na-echekwa na ha na-arụ ọrụ dị mkpa na mmekọrịta eriri afọ na ụbụrụ13,14. A na-ebuga SCFAs site na mkpụrụ ndụ eriri afọ ma bufee ha na imeju site na sistemụ portal venous, ụfọdụ SCFAs na-abanyekwa na mgbasa ozi sistemụ. SCFAs nwere mmetụta mpaghara na ịnọgide na-eguzosi ike n'ezi ihe nke ihe mgbochi eriri afọ na ịkwalite mgbochi ebumpụta ụwa na mucosa eriri afọ15. Ha nwekwara mmetụta ogologo oge na ihe mgbochi ụbụrụ ọbara (BBB) ​​site na ịkpalite protein njikọ tight na ịgbalite neurons site na ịkpalite ndị nnata G protein-coupled (GPCRs) ịgafe BBB16. Acetate, propionate, na butyrate bụ SCFAs kachasị baa ụba na eriri afọ. Ọmụmụ ihe ndị gara aga egosila mbelata ọkwa acetic, propionic na butyric acid na ndị ọrịa nwere ọrịa Parkinson17. Agbanyeghị, a mụọbeghị ọkwa SCFAs na ndị ọrịa nwere ET.
Ya mere, nnyocha anyị bụ ịchọpụta mgbanwe ụfọdụ na nsị SCFA n'ime ndị ọrịa nwere ET na ọdịiche ha na ndị ọrịa nwere PD, inyocha mmekọrịta dị n'etiti nsị SCFA na mgbaàmà ahụike nke ET na microbiota eriri afọ, yana ịchọpụta ikike nchọpụta na nchọpụta dị iche iche nke ihe nlele nsị. KZhK. Iji lebara ihe ndị na-agbagwoju anya metụtara ọgwụ mgbochi PD anya, anyị họpụtara ndị ọrịa nwere ọrịa Parkinson ọhụrụ ka ha bụrụ njikwa ọrịa.
A chịkọtara njirimara mmadụ na ahụike nke ET 37, PD 37, na HC 35 na Tebụl 1. E jikọtara ET, PD, na HC site na afọ, okike, na BMI. Otu atọ ahụ nwekwara nha nha nke ise siga, ịṅụ mmanya na ịṅụ kọfị na tii. Akara Wexner (P = 0.004) na akara HAMD-17 (P = 0.001) nke otu PD dị elu karịa nke otu HC, akara HAMA (P = 0.011) na akara HAMD-17 (P = 0.011) nke otu ET dị elu karịa nke otu HC. Usoro ọrịa ahụ na otu ET dị ogologo karịa nke otu PD (P <0.001).
E nwere nnukwu ọdịiche dị na ọkwa nsị nke fecal propionic acid (P = 0.023), acetic acid (P = 0.039), butyric acid (P = 0.020), isovaleric acid (P = 0.045), na isobutyric acid (P = 0.015). . Na nyocha hoc ọzọ, ọkwa nke propionic acid (P = 0.023), butyric acid (P = 0.007), na isobutyric acid (P = 0.040) na otu ET dị ala nke ukwuu karịa ndị nọ na otu HC. Ndị ọrịa nwere ET nwere obere ọkwa nke isovalerate (P = 0.014) na isobutyrate (P = 0.005) karịa ndị ọrịa nwere PD. Tinyere nke ahụ, ọkwa nke fecal propionic acid (P = 0.013), acetic acid (P = 0.016), na butyric acid (P = 0.041) dị ala karịa na ndị ọrịa nwere PD karịa na ndị ọrịa nwere CC (Fig. 1 na Tebụl Mgbakwunye 1).
ag na-anọchite anya ntụnyere otu nke propionic acid, acetic acid, butyric acid, isovaleric acid, valeric acid, caproic acid na isobutyric acid, n'otu n'otu. E nwere nnukwu ọdịiche dị na ọkwa fecal propionic acid, acetic acid, butyric acid, isovaleric acid na isobutyric acid n'etiti otu atọ ahụ. ET essential tremor, Parkinson's disease, healthy HC control, SCFA. E gosipụtara nnukwu ọdịiche site na *P < 0.05 na **P < 0.01.
N'ịtụle ọdịiche dị n'usoro ọrịa dị n'etiti otu ET na otu PD, anyị mụrụ ndị ọrịa 33 nwere PD mbụ na ndị ọrịa 16 nwere ET (usoro ọrịa ihe na-erughị afọ 3) maka ntụnyere ọzọ (Tebụl Mgbakwunye 2). Nsonaazụ gosiri na ọdịnaya fecal propionic acid dị na ET dị ala karịa nke HA (P=0.015). Ọdịiche dị n'etiti ET na HC maka butyric acid na isobutyric acid abụghị ihe dị mkpa, mana a ka hụrụ usoro (P= 0.082). Ọkwa isobutyrate fecal dị ala nke ukwuu na ndị ọrịa nwere ET ma e jiri ya tụnyere ndị ọrịa nwere PD (P= 0.030). Ọdịiche dị n'etiti ET na PD nke isovaleric acid abụghị ihe dị mkpa, mana enwere usoro (P= 0.084). Propionic acid (P= 0.023), acetic acid (P= 0.020), na butyric acid (P= 0.044) dị ala nke ukwuu na ndị ọrịa PD karịa na ndị ọrịa HC. Nsonaazụ ndị a (Foto mgbakwunye 1) na-adaba na nsonaazụ ndị bụ isi. Ihe dị iche na nsonaazụ dị n'etiti ihe nlele ahụ dum na obere ndị ọrịa mbụ nwere ike ịbụ n'ihi obere nha ihe nlele ahụ na obere obere, nke na-ebute obere ike ọnụọgụgụ nke data ahụ.
Anyị lere anya ọzọ ma ọkwa SCFA nke nsị nwere ike ịmata ọdịiche dị n'etiti ndị ọrịa nwere ET na ndị ọrịa nwere CU ma ọ bụ PD. Dịka nyocha ROC si kwuo, ọdịiche dị na ọkwa propionate nke AUC bụ 0.668 (95% CI: 0.538-0.797), nke mere ka o kwe omume ịmata ọdịiche dị n'etiti ndị ọrịa nwere ET na HC. Enwere ike ịmata ọdịiche dị n'etiti ndị ọrịa nwere ET na GC site na ọkwa butyrate na AUC nke 0.685 (95% CI: 0.556–0.814). Ọdịiche dị na ọkwa isobutyric acid nwere ike ịmata ọdịiche dị n'etiti ndị ọrịa nwere ET na HC na AUC nke 0.655 (95% CI: 0.525–0.786). Mgbe ejikọtara ọkwa propionate, butyrate na isobutyrate, enwetara AUC dị elu nke 0.751 (95% CI: 0.634–0.867) na mmetụta nke 74.3% na nkọwapụta nke 72.9% (Foto 2a). Iji mata ọdịiche dị n'etiti ndị ọrịa ET na PD, AUC maka ọkwa isovaleric acid bụ 0.700 (95% CI: 0.579–0.822) na maka ọkwa isobutyric acid bụ 0.718 (95% CI: 0.599–0.836). Njikọta nke ọkwa isovaleric acid na isobutyric acid nwere AUC dị elu nke 0.743 (95% CI: 0.629–0.857), mmetụta nke 74.3% na nkọwapụta nke 62.9% (Foto 2b). Tinyere nke a, anyị lere anya ma ọkwa SCFA dị na nsị nke ndị ọrịa nwere ọrịa Parkinson dị iche na nke ndị a na-achịkwa. Dịka nyocha ROC si kwuo, AUC maka ịchọpụta ndị ọrịa nwere PD dabere na ọdịiche dị na ọkwa propionic acid bụ 0.687 (95% CI: 0.559-0.814), yana mmetụta nke 68.6% na nkọwapụta nke 68.7%. Ọdịiche dị na ọkwa acetate nwere ike ịmata ọdịiche dị n'etiti ndị ọrịa PD na HC nwere AUC nke 0.674 (95% CI: 0.542–0.805). Enwere ike ịmata ọdịiche dị n'etiti ndị ọrịa nwere PD na CU naanị site na ọkwa butyrate na AUC nke 0.651 (95% CI: 0.515–0.787). Mgbe ejikọtara ọkwa propionate, acetate na butyrate, enwetara AUC nke 0.682 (95% CI: 0.553–0.811) (Foto 2c).
ịkpa ókè site n'aka Chọọchị Ọtọdọks nke Russia megide ET na HC; b ịkpa ókè ROC megide ET na PD; c ịkpa ókè ROC megide PD na HC; ET dị mkpa ịma jijiji, ọrịa Parkinson, njikwa HC dị mma, SCFA.
N'ime ndị ọrịa nwere ET, ọkwa isobutyric acid nke fecal jikọtara ya na akara FTM (r = -0.349, P = 0.034), ọkwa isovaleric acid nke fecal jikọtara ya na akara FTM (r = -0.421, P = 0.001) na akara TETRAS. (r = -0.382, P = 0.020). N'ime ndị ọrịa nwere ET na PD, ọkwa propionate nke fecal jikọtara ya na akara SCOPA-AUT (r = −0.236, P = 0.043) (Fig. 3 na Tebụl Mgbakwunye 3). Enweghị njikọ dị mkpa n'etiti usoro ọrịa na SCFA n'ime otu ET (P ≥ 0.161) ma ọ bụ otu PD (P ≥ 0.246) (Tebụl Mgbakwunye 4). N'ime ndị ọrịa nwere PD, ọkwa fecal caproic acid jikọtara nke ọma na akara MDS-UPDRS (r = 0.335, P = 0.042). N'ime ndị niile sonyere, ọkwa fecal propionate (r = −0.230, P = 0.016) na acetate (r = −0.210, P = 0.029) nwere njikọ na-adịghị mma na akara Wexner (Foto nke 3 na Tebụl Mgbakwunye 3).
E jikọtara ọkwa fecal isobutyric acid na akara FTM n'ụzọ na-adịghị mma, e jikọtara isovaleric acid na akara FTM na TETRAS n'ụzọ na-adịghị mma, e jikọtara propionic acid na akara SCOPA-AUT n'ụzọ na-adịghị mma, e jikọtara caproic acid na akara MDS-UPDRS n'ụzọ dị mma, e jikọtara propionic acid na akara FTM na TETRAS n'ụzọ na-adịghị mma. E jikọtara TETRAS na acetic acid na akara Wexner n'ụzọ na-adịghị mma. MDS-UPDRS Association kwadoro ụdị nke Unified Parkinson's Disease Rating Scale, Mini-Mental State Examination MMSE, Hamilton Depression Rating Scale HAMD-17, ihe 17, Hamilton Anxiety Rating Scale HAMA, HY Hoehn na Yahr stages, SCFA, SCOPA – AUT Parkinson's Disease Autonomic Symptom Result Scale, FTM Fana-Tolosa-Marin Clinical Tremor Rating Scale, TETRAS Research Group (TRG) Essential Tremor Rating Scale. E gosipụtara ọdịiche dị mkpa site na *P < 0.05 na **P < 0.01.
Anyị nyochakwara ụdị ịkpa ókè nke nje bacteria afọ site na iji nyocha LEfSE wee họrọ ọkwa data oke ọnụọgụgụ mkpụrụ ndụ ihe nketa maka nyocha ọzọ. E mere ntụnyere n'etiti ET na HC na n'etiti ET na PD. Emechara nyocha mmekọrịta Spearman na oke ọnụọgụgụ microbiota eriri afọ na ọkwa SCFA n'ime otu ntụnyere abụọ ahụ.
Faecalibacterium (ejikọtara ya na butyric acid, r = 0.408, P < 0.001), Lactobacillus (ejikọtara ya na butyric acid, r = 0.283, P = 0.016), Streptobacterium (ejikọtara ya na propionic acid, r = 0.327) dị na nyocha nke ET na CA., P = 0.005; ejikọtara ya na butyric acid, r = 0.374, P = 0.001; na-ejikọta ya na isobutyric acid, r = 0.329, P = 0.005), Howardella (na-ejikọta ya na propionic acid, r = 0.242, P = 0.041), Raoultella (na-ejikọta ya na propionate, r = 0.249, P = 0.035), na Candidatus Arthromitus (na-ejikọta ya na isobutyric acid, r = 0.302, P = 0.010) na-ebelata na ET ma na-ejikọta ya na ọkwa SCFA nke nsị. Agbanyeghị, mmụba Stenotropomonas mụbara na ET ma na-ejikọta ya na ọkwa isobutyrate nke nsị (r = -0.250, P = 0.034). Mgbe mgbanwe FDR gasịrị, naanị njikọ dị n'etiti Faecalibacterium, Catenibacter, na SCFA ka dị mkpa (P ≤ 0.045) (Foto 4 na Tebụl Mgbakwunye 5).
Nyocha njikọ nke ET na HC. Mgbe mgbanwe FDR gasịrị, achọpụtara na ọnụọgụ Faecalibacterium (nke nwere njikọ dị mma na butyrate) na Streptobacterium (nke nwere njikọ dị mma na propionate, butyrate, na isobutyrate) belatara na ET ma nwee njikọ dị mma na ọkwa SCFA nke nsị. b Nyocha njikọ nke ET na PD. Mgbe mgbanwe FDR gasịrị, achọpụtaghị njikọ dị mkpa. ET dị mkpa ịma jijiji, ọrịa Parkinson, njikwa HC dị mma, SCFA. E gosipụtara ọdịiche dị mkpa site na *P < 0.05 na **P < 0.01.
Mgbe a na-enyocha ET megide PD, a chọpụtara na Clostridium trichophyton mụbara na ET ma jikọta ya na fecal isovaleric acid (r = -0.238, P = 0.041) na isobutyric acid (r = -0.257, P = 0.027). Mgbe mgbanwe FDR gasịrị, nke ọ bụla ka dị mkpa (P≥0.295) (Foto 4 na Tebụl Mgbakwunye 5).
Ọmụmụ ihe a bụ ọmụmụ zuru oke nke na-enyocha ọkwa SCFA nke nsị ma jikọta ha na mgbanwe na microbiota eriri afọ na oke mgbaàmà na ndị ọrịa nwere ET ma e jiri ya tụnyere ndị ọrịa nwere CU na PD. Anyị chọpụtara na ọkwa SCFA nke nsị belatara na ndị ọrịa nwere ET ma jikọta ya na oke ahụike na mgbanwe kpọmkwem na microbiota eriri afọ. Ngụkọta ọkwa fatty acids dị mkpụmkpụ (SCFAs) na-eme ka ET dị iche na GC na PD.
Ma e jiri ya tụnyere ndị ọrịa GC, ndị ọrịa ET nwere obere ọkwa propionic, butyric, na isobutyric acid. Njikọta nke propionic, butyric na isobutyric acid ndị a ma ama dịka ET na HC na AUC nke 0.751 (95% CI: 0.634–0.867), mmetụta nke 74.3% na nkọwapụta nke 72.9%, na-egosi ojiji ha dị ka ihe nrịbama nchọpụta maka ọrụ ET nwere ike ịrụ. Nyocha ndị ọzọ gosiri na ọkwa fecal propionic acid jikọtara ya na akara Wexner na akara SCOPA-AUT. Ọkwa fecal isobutyric acid jikọtara ya na akara FTM. N'aka nke ọzọ, mbelata na ọkwa butyrate na ET jikọtara ya na mbelata na ọnụọgụ microbiota na-emepụta SCFA, Faecalibacterium, na Categorybacter. Na mgbakwunye, mbelata na oke Catenibacter na ET jikọtara ya na mbelata na ọkwa fecal propionic na isobutyric acid.
Ọtụtụ SCFAs emepụtara na eriri afọ na-eji site na ndị na-ebuga monocarboxylate nke dabere na sodium. A na-eji obere abụba ndị a na-amịkọrọ eme ihe dị ka isi iyi ike maka eriri afọ, ebe ndị na-anaghị emejupụta na eriri afọ na-ebuga na mgbasa ozi ọnụ ụzọ 18. SCFAs nwere ike imetụta mmegharị eriri afọ, melite ọrụ mgbochi eriri afọ, ma metụta metabolism na mgbochi ndị ọbịa19. Achọpụtara na mbụ na njupụta nke butyrate, acetate, na propionate belatara na ndị ọrịa PD ma e jiri ya tụnyere HCs17, nke kwekọrọ na nsonaazụ anyị. Ọmụmụ ihe anyị chọpụtara mbelata na SCFAs na ndị ọrịa nwere ET, mana a maghị ihe dị ukwuu gbasara ọrụ SCFAs na pathology nke ET. Butyrate na propionate nwere ike ijikọ na GPCRs ma metụta akara GPCR dị ka MAPK na NF-κB20 signaling. Echiche bụ isi nke eriri afọ-ụbụrụ bụ na SCFAs nke nje bacteria na-emepụta nwere ike imetụta akara nnabata, si otú a na-emetụta ọrụ eriri afọ na ụbụrụ. Ebe ọ bụ na butyrate na propionate nwere mmetụta dị ike na ọrụ histone deacetylase (HDAC)21 na butyrate nwekwara ike ịrụ ọrụ dị ka ligand maka ihe ndị na-egosi ihe, ha nwere mmetụta sara mbara na metabolism nke ndị ọbịa, ọdịiche na mmụba, nke bụ isi n'ihi mmetụta ha na nhazi mkpụrụ ndụ ihe nketa22. Dabere na ihe akaebe sitere na SCFA na ọrịa neurodegenerative, a na-ewere butyrate dị ka onye na-achọ ọgwụgwọ n'ihi ikike ya idozi ọrụ HDAC na-adịghị mma, nke nwere ike ime ka ọnwụ dopaminergic neuron dị na PD23,24,25. Ọmụmụ anụmanụ egosikwala ike nke butyric acid iji gbochie mmebi neuron dopaminergic ma melite nsogbu mmegharị na ụdị PD26,27. Achọpụtala na Propionic acid na-egbochi nzaghachi mkpali ma chebe iguzosi ike n'ezi ihe nke BBB28,29. Ọmụmụ ihe egosila na propionic acid na-akwalite ndụ nke dopaminergic neurons na nzaghachi maka nsị rotenone na ụdị PD 30 na nchịkwa ọnụ nke propionic acid na-azọpụta mfu dopaminergic neuron na ụkọ moto na òké nwere PD31. Amaghị ihe gbasara ọrụ nke isobutyric acid. Agbanyeghị, otu nnyocha e mere n'oge na-adịbeghị anya chọpụtara na ime ka òké ndị nwere B. ovale dị n'ime eriri afọ mụbaa ọdịnaya SCFA n'ime eriri afọ (gụnyere acetate, propionate, isobutyrate, na isovalerate) na mkpokọta GABA n'ime eriri afọ, na-egosi na e guzobela njikọ n'etiti microbiota eriri afọ na SCFA n'ime eriri afọ. mkpokọta nke neurotransmitters32. Na ET, mgbanwe ọrịa na-adịghị mma na cerebellum gụnyere mgbanwe na axons na dendrites nke mkpụrụ ndụ Purkinje, mwepụ na mfu nke mkpụrụ ndụ Purkinje, mgbanwe na axons nke mkpụrụ ndụ basket, nsogbu na njikọ eriri na-arị elu na nkesa mkpụrụ ndụ Purkinje, na mgbanwe na ndị na-anabata GABA na ọkpụkpụ dentate. nuclei, nke na-eduga na mbelata na mmepụta GABAergic site na cerebellum3,4,33. Ọ ka edoghị anya ma SCFAs jikọtara ya na neurodegeneration nke mkpụrụ ndụ Purkinje na mbelata mmepụta GABA cerebellar. Nsonaazụ anyị na-egosi njikọ siri ike n'etiti SCFA na ET, mana nhazi ọmụmụ ihe nkebi anaghị ekwe ka nkwubi okwu ọ bụla gbasara mmekọrịta kpatara ya n'etiti SCFA na usoro ọrịa nke ET; A chọrọ ọmụmụ ihe ndị ọzọ gbasara nleba anya ogologo oge, gụnyere nha usoro nke SCFAs nke nsị, yana ọmụmụ anụmanụ na-enyocha usoro.
A na-eche na SCFAs na-akpali mkpụkọ akwara dị nro nke eriri afọ34. Enweghị SCFA ga-eme ka ihe mgbaàmà nke afọ ntachi ka njọ, mgbakwunye na SCFA nwere ike ime ka ihe mgbaàmà nke afọ ntachi PD35 ka mma. Nsonaazụ anyị na-egosikwa njikọ dị ukwuu n'etiti mbelata ọdịnaya SCFA na nsị na mmụba nke afọ ntachi na nsogbu autonomic na ndị ọrịa nwere ET. Otu akụkọ ikpe chọpụtara na ntinye microbiota mekwara ka ma ịma jijiji dị mkpa na ọrịa eriri afọ iwe dịkwuo mma na onye ọrịa 7, na-egosikwa mmekọrịta chiri anya n'etiti microbiota eriri afọ na ET. Ya mere, anyị kwenyere na SCFA/microbiota fecal nwere ike imetụta mmegharị eriri afọ na ọrụ sistemụ akwara autonomic.
Nnyocha ahụ chọpụtara na mbelata nke ọkwa SCFAs nke nsị na ET jikọtara ya na mbelata nke Faecalibacterium (ejikọtara na butyrate) na Streptobacterium (ejikọtara na propionate, butyrate, na isobutyrate). Mgbe edozichara FDR, mmekọrịta a ka dị mkpa. Faecalibacterium na Streptobacterium bụ nje ndị na-emepụta SCFA. A maara Faecalibacterium dị ka nje na-emepụta butyrate36, ebe isi ihe ndị sitere na Catenibacter fermentation bụ acetate, butyrate na lactic acid37. A chọpụtara Faecalibacterium na 100% nke ma otu ET na HC; ọnụọgụ dị n'etiti nke otu ET bụ 2.06% na nke otu HC bụ 3.28% (LDA 3.870). A chọpụtara nje bacteria dị na 21.6% (8/37) nke otu HC na naanị na otu ihe atụ nke otu ET (1/35). Mbelata na enweghị ike ịchọpụta streptobacteria na ET nwekwara ike igosi njikọ na ọrịa ahụ. Ọnụ ọgụgụ dị n'etiti ụdị Catenibacter na otu HC bụ 0.07% (LDA 2.129). Na mgbakwunye, nje bacteria lactic acid jikọtara ya na mgbanwe na fecal butyrate (P=0.016, P=0.096 mgbe mgbanwe FDR gasịrị), a jikọtara onye nwere ọrịa ogbu na nkwonkwo na mgbanwe na isobutyrate (P=0.016, P=0.072 mgbe mgbanwe FDR gasịrị). Mgbe edozichara FDR, naanị usoro njikọ ahụ ka dị, nke na-adịghị mkpa na ọnụọgụgụ. A makwaara Lactobacilli dị ka ndị na-emepụta SCFA (acetic acid, propionic acid, isobutyric acid, butyric acid) 38 na Candidatus Arthromitus bụ ihe na-akpali kpọmkwem nke T helper 17 (Th17) cell difference, yana Th1/2 na Tregs jikọtara ya na nhazi ahụ ike /Th1739. . Nnyocha e mere n'oge na-adịbeghị anya na-egosi na ọkwa dị elu nke pseudoarthritis nke fecal nwere ike itinye aka na mbufụt nke eriri afọ, nsogbu mgbochi eriri afọ, na mbufụt sistemụ 40. E mụbara ọkwa Clostridium trichoides na ET ma e jiri ya tụnyere PD. A chọpụtara na ọnụọgụ Clostridium trichoides nwere njikọ na-adịghị mma na isovaleric acid na isobutyric acid. Mgbe mgbanwe FDR gasịrị, ha abụọ ka dị mkpa (P≥0.295). Clostridium pilosum bụ nje bacteria a maara na ọ na-ejikọta ya na mbufụt ma nwee ike itinye aka na nsogbu mgbochi eriri afọ41. Ọmụmụ ihe anyị gara aga kọrọ mgbanwe na microbiota eriri afọ nke ndị ọrịa nwere ET8. N'ebe a, anyị na-akọkwa mgbanwe na SCFA na ET ma chọpụta njikọ dị n'etiti dysbiosis eriri afọ na mgbanwe na SCFA. Mbelata ọkwa SCFA na-ejikọta nke ọma na dysbiosis eriri afọ na oke ịma jijiji na ET. Nsonaazụ anyị na-egosi na eriri afọ-ụbụrụ nwere ike ịrụ ọrụ dị mkpa na pathogenesis nke ET, mana ọ dị mkpa ka a mụọ ihe ndị ọzọ na ụdị anụmanụ.
Ma e jiri ya tụnyere ndị ọrịa nwere PD, ndị ọrịa nwere ET nwere obere ọkwa nke isovaleric na isobutyric acid n'ime nsị ha. Nchikota nke isovaleric acid na isobutyric acid achọpụtara ET na PD yana AUC nke 0.743 (95% CI: 0.629–0.857), mmetụta nke 74.3% na nkọwapụta nke 62.9%, na-egosi ọrụ ha nwere ike dị ka ihe nrịbama na nchọpụta differential nke ET. Ọkwa isovaleric acid fecal nwere njikọ chiri anya na akara FTM na TETRAS. Ọkwa isobutyric acid fecal nwere njikọ chiri anya na akara FTM. Mbelata nke ọkwa isobutyric acid jikọtara ya na mbelata nke ọtụtụ catobacteria. A maghị ihe gbasara ọrụ nke isovaleric acid na isobutyric acid. Nnyocha gara aga gosiri na ịmịnye oke ndị nwere B. ovale n'ime ahụ mụbara ọnụọgụ SCFAs nke eriri afọ (gụnyere acetate, propionate, isobutyrate, na isovalerate) na mkpokọta GABA nke eriri afọ, na-egosipụta njikọ dị n'etiti microbiota na mkpokọta SCFA/neurotransmitter nke eriri afọ32. Ọ dị mma ịmara na ọkwa isobutyric acid a hụrụ yiri nke ahụ n'etiti otu PD na HC, mana ọ dị iche n'etiti otu ET na PD (ma ọ bụ HC). Isobutyric acid nwere ike ịmata ọdịiche dị n'etiti ET na PD na AUC nke 0.718 (95% CI: 0.599–0.836) ma chọpụta ET na NC na AUC nke 0.655 (95% CI: 0.525–0.786). Na mgbakwunye, ọkwa isobutyric acid na-ejikọta na oke ịma jijiji, na-eme ka njikọ ya na ET sikwuo ike. Ajụjụ nke ma isobutyric acid ọnụ nwere ike ibelata oke ịma jijiji na ndị ọrịa nwere ET kwesịrị ịmụ ihe ọzọ.
Ya mere, a na-ebelata ọdịnaya SCFA nke nsị n'ime ndị ọrịa nwere ET ma jikọta ya na oke ahụike nke ET na mgbanwe ụfọdụ na microbiota eriri afọ. Fecal propionate, butyrate, na isobutyrate nwere ike ịbụ ihe ngosi nchọpụta maka ET, ebe isobutyrate na isovalerate nwere ike ịbụ ihe ngosi nchọpụta dị iche iche maka ET. Mgbanwe na isobutyrate nke nsị n'ime nwere ike ịbụ ihe akọwapụtara maka ET karịa mgbanwe na SCFA ndị ọzọ.
Ọmụmụ ihe anyị nwere ọtụtụ ihe mgbochi. Nke mbụ, usoro nri na mmasị nri nwere ike imetụta ngosipụta microbiota, a chọrọ ihe nlele ọmụmụ buru ibu n'ọtụtụ mmadụ dị iche iche, ọmụmụ ihe ndị ga-eme n'ọdịnihu kwesịrị iwebata nyocha nri zuru oke na nke usoro dịka ajụjụ ugboro ugboro nri. Nke abụọ, nhazi ọmụmụ ihe nkewa na-egbochi nkwubi okwu ọ bụla gbasara mmekọrịta dị n'etiti SCFA na usoro ọrịa nke ET. A chọrọ ọmụmụ ihe ndị ọzọ na-esochi ogologo oge yana nha usoro nke SCFAs nke nsị. Nke atọ, a ga-enyocha ikike nchọpụta na nchọpụta dị iche iche nke ọkwa SCFA nke nsị site na iji ihe nlele onwe ha sitere na ET, HC, na PD. A ga-anwale ihe nlele nsị ndị ọzọ n'ọdịnihu. N'ikpeazụ, ndị ọrịa nwere PD n'ime otu anyị nwere oge ọrịa dị mkpụmkpụ karịa ndị ọrịa nwere ET. Anyị na-ejikọtakarị ET, PD na HC site na afọ, okike na BMI. N'ihi ọdịiche dị na usoro ọrịa n'etiti otu ET na otu PD, anyị mụkwara ndị ọrịa 33 nwere PD mbụ na ndị ọrịa 16 nwere ET (oge ọrịa ≤ afọ 3) maka ntụnyere ọzọ. Ọdịiche dị n'etiti otu na SCFA kwekọrọ na data mbụ anyị. Tinyere nke a, anyị ahụghị njikọ ọ bụla n'etiti oge ọrịa na mgbanwe na SCFA. Agbanyeghị, n'ọdịnihu, ọ ga-akacha mma ịkpọbata ndị ọrịa nwere PD na ET n'oge mbụ nwere obere oge ọrịa iji mezue nkwenye ahụ na nnukwu ihe nlele.
Kọmitii Omume nke Ụlọ Ọgwụ Ruijin nke jikọtara ya na Ụlọ Akwụkwọ Ọgwụ Mahadum Shanghai Jiao Tong (RHEC2018-243) kwadoro usoro ọmụmụ ihe a. E nwetara nkwenye ederede site n'aka ndị niile sonyere.
N'agbata Jenụwarị 2019 na Disemba 2022, e tinyere mmadụ 109 (37 ET, 37 PD, na 35 HC) site na Movement Disorder Center Clinic nke Ụlọ Ọgwụ Ruijin, nke jikọtara na Shanghai Jiao Tong University School of Medicine, na ọmụmụ ihe a. Ihe ndị a chọrọ bụ: (1) afọ 25–85, (2) a chọpụtara ndị ọrịa nwere ET dịka ụkpụrụ MDS Working Group si dị 42, a chọpụtakwara PD dịka ụkpụrụ MDS 43 si dị, (3) ndị ọrịa niile anaghị aṅụ ọgwụ mgbochi PD tupu ha agaa oche. nchịkọta nke ihe nlele. (4) Ndị otu ET were naanị β-blockers ma ọ bụ ọgwụ ndị metụtara ya tupu ha anakọta ihe nlele nsị. A họrọkwara HCs ndị kwekọrọ na afọ, okike, na ọnụọgụ ahụ (BMI). Ihe ndị a na-ewepụ n'ọrụ bụ: (1) ndị anaghị eri anụ, (2) nri na-adịghị mma, (3) ọrịa ndị na-adịghị ala ala nke eriri afọ (gụnyere ọrịa eriri afọ mbufụt, ọnya afọ ma ọ bụ duodenal), (4) ọrịa ndị na-adịghị ala ala siri ike (gụnyere etuto ọjọọ), nkụda obi, ọdịda akụrụ, ọrịa ọbara) (5) Akụkọ ihe mere eme nke nnukwu ịwa ahụ afọ, (6) Iri yogọt ogologo oge ma ọ bụ mgbe niile, (7) Iji probiotics ma ọ bụ ọgwụ nje ọ bụla ruo otu ọnwa, (8) Iji corticosteroids, proton pump inhibitors, statins, metformin, immunosuppressants ma ọ bụ ọgwụ mgbochi kansa eme ihe ogologo oge na (9) nnukwu nsogbu nghọta nke na-egbochi nnwale ụlọ ọgwụ.
Ndị niile e nyere akụkọ ahụike, ibu na ịdị elu ha nyere akụkọ ihe mere eme ahụike, ozi ibu na ịdị elu iji gbakọọ BMI, ma mee nyocha akwara na nyocha ahụike dịka Hamilton Anxiety Rating Scale (HAMA) 44, Hamilton Depression Rating Scale-17 akara (HAMD-17) 45. ịda mbà n'obi, oke afọ ntachi site na iji Wexner Constipation Scale 46 na Bristol Stool Scale 47 na arụmọrụ nghọta site na iji Mini-Mental State Examination (MMSE) 48. Scale maka Nyocha nke Autonomic Symptoms of Parkinson's Disease (SCOPA-AUT) 49 lere anya na ọrịa autonomic na ndị ọrịa nwere ET na PD. E lere otu nnyocha Tremor Clinical Fana-Tolos-Marin Clinical (FTM) na Essential Tremor Rating Scale (TETRAS) 50. E lere otu nnyocha Tremor (TRG) 50 anya na ndị ọrịa nwere ET; Kinson's Disease Rating Scale (MDS-), nke United Parkinson's Disease Association kwadoro; UPDRS version 51 na Hoehn na Yahr (HY) version 52.
A gwara onye ọ bụla so na ya ka o were ihe nlele stool n'ụtụtụ site na iji ihe e ji anakọta stool. Bufee akpa ndị ahụ na ice ma chekwaa ha na -80°C tupu e mee ha. Emere nyocha SCFA dịka ọrụ Tiangene Biotechnology (Shanghai) Co., Ltd si dị. E si n'otu onye chịkọta ihe nlele 400 mg nke nsị ọhụrụ wee nyochaa ha site na iji SCFAs mgbe e gweri ma sonication. E jiri gas chromatography-mass spectrometry (GC-MS) na liquid chromatography-tandem MS (LC-MS/MS) nyochaa SCFAs ahọpụtara na nsị.
E si na ihe nlele 200 mg nke QIAamp® Fast DNA Stool Mini Kit (QIAGEN, Hilden, Germany) wepụta DNA dịka ntuziaka onye nrụpụta si dị. A chọpụtara nhazi nke microbial site na usoro mkpụrụ ndụ ihe nketa 16 S rRNA na DNA nke e kewapụrụ site na nsị site na ime ka mpaghara V3-V4 dịkwuo elu. Nwalee DNA ahụ site na ịgba ihe nlele ahụ na gel agarose 1.2%. Ejiri ihe mgbakwunye Polymerase chain reaction (PCR) mee mmụba nke mkpụrụ ndụ ihe nketa 16S rRNA site na iji ihe mgbakwunye nje bacteria zuru ụwa ọnụ (357 F na 806 R) na ọbá akwụkwọ amplicon nzọụkwụ abụọ nke e wuru na ikpo okwu Novaseq.
A na-egosipụta mgbanwe ndị na-aga n'ihu dị ka nkezi ± ọkọlọtọ nkewa, a na-egosipụtakwa mgbanwe dị iche iche dị ka ọnụọgụgụ na pasentị. Anyị jiri ule Levene nwalee otu ụdị nke mgbanwe. E jiri ule t abụọ ma ọ bụ nyocha nke mgbanwe (ANOVA) tụnyere ya ma ọ bụrụ na a na-ekesa mgbanwe ndị a na-emekarị, yana ule Mann-Whitney U na-abụghị parametric ma ọ bụrụ na emebiri echiche nkịtị ma ọ bụ homoscedasticity. Anyị jiri mpaghara dị n'okpuru usoro njirimara ọrụ nnata (ROC) (AUC) tụọ arụmọrụ nchọpụta nke ihe nlereanya ahụ ma lelee ikike nke SCFA iji mata ndị ọrịa nwere ET na ndị nwere HC ma ọ bụ PD. Iji nyochaa mmekọrịta dị n'etiti SCFA na oke ahụike, anyị jiri nyocha mmekọrịta Spearman. E jiri ngwanrọ SPSS (mbipụta 22.0; SPSS Inc., Chicago, IL) mee nyocha ọnụọgụgụ yana ọkwa dị mkpa (gụnyere uru P na FDR-P) nke edobere na 0.05 (akụkụ abụọ).
E jiri ngwakọta nke Trimmomatic (mbipụta 0.35), Flash (mbipụta 1.2.11), UPARSE (mbipụta v8.1.1756), mothur (mbipụta 1.33.3) na R (mbipụta 3.6.3) nyochaa usoro S 16 ahụ. E jiri UPARSE hazie data mkpụrụ ndụ ihe nketa rRNA Raw 16S iji mepụta nkeji taxonomic arụmọrụ (OTUs) nwere njirimara 97%. E ji Silva 128 kọwaa taxonomies dị ka nchekwa data ntụaka. A họọrọ ọkwa zuru oke nke data oke ihe metụtara maka nyocha ọzọ. E jiri nyocha nha mmetụta Linear discriminant analysis (LDA) (LEfSE) mee ihe maka ntụnyere n'etiti otu (ET vs. HC, ET vs. PD) nwere oke α nke 0.05 na oke nha mmetụta nke 2.0. E jirikwa ụdị dị iche iche nke nyocha LEfSE chọpụtara mee ihe maka nyocha njikọ Spearman nke SCFA.
Maka ozi ndị ọzọ gbasara nhazi ọmụmụ ihe a, lee Nchịkọta Akụkọ Nnyocha Okike nke metụtara akụkọ a.
A na-echekwa data usoro 16S Raw na nchekwa data BioProject nke National Center for Biotechnology Information (NCBI) (SRP438900: PRJNA974928), URL: https://www.ncbi.nlm.nih.gov/Traces/study/?acc= SRP438900&o. =acc_s% 3Aa. Enwere ike ịnweta data ndị ọzọ dị mkpa nye onye dere ya ma ọ bụrụ na ọ rịọ maka ezi uche dị na ya, dịka mmekorita sayensị na mgbanwe agụmakwụkwọ na ọrụ nyocha zuru oke. Agaghị ekwe ka e nyefee data nye ndị ọzọ na-enweghị nkwenye anyị.
Koodu isi mmalite mepere emepe naanị site na iji ngwakọta nke Trimmomatic (mbipụta 0.35), Flash (mbipụta 1.2.11), UPARSE (mbipụta v8.1.1756), mothur (mbipụta 1.33.3) na R (mbipụta 3.6.3), site na iji ntọala ndabara ma ọ bụ ngalaba "Ụzọ". Enwere ike inye onye edemede kwekọrọ ozi nkọwa ndị ọzọ mgbe a rịọrọ ya nke ọma.
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