Nature.com i tlawh avangin lawmthu kan sawi e. I hman mek browser version hian CSS support a nei tlem hle. A tha ber tur chuan i browser version thar zawk hmang turin kan fuih a che (or Internet Explorer-a Compatibility Mode kha disable rawh). Chutih lai chuan support kal zel tur chuan styling emaw JavaScript emaw tel lovin site hi kan entir a ni.
Essential tremor (ET) hriat hmasak hi a harsa thei hle a, a bik takin healthy controls (HC) leh Parkinson’s disease (PD) atanga thliar hran a nih chuan a harsa thei hle. Tun hnaiah gut microbiota leh a metabolites te stool sample an zirchiannaah hian neurodegenerative diseases biomarker thar hmuhchhuahna kawng thar a awm ta a ni. PD-ah hian intestinal flora-a metabolite ber atan short-chain fatty acids (SCFA) a tlahniam a. Mahse, fecal SCFA hi ET-ah hian zirchian a la ni ngai lo. ET-a SCFAs fecal levels chhui a, clinical symptoms leh gut microbiota nena an inzawmna teh a, an diagnostic ability awm thei te hriat chian kan tum a ni. Fecal SCFA leh gut microbiota te chu ET 37, PD thar 37, leh HC 35 ah te teh a ni. Constipation, autonomic dysfunction, leh tremor severity te chu scale hmangin an zirchiang a ni. ET-ah hian HC aiin propionate, butyrate leh isobutyrate te fecal level a hniam zawk a ni. Propionic, butyric leh isobutyric acids te inzawmkhawm chuan ET leh HC a thliar hrang a, AUC chu 0.751 (95% CI: 0.634–0.867) a ni. Fecal isovaleric acid leh isobutyric acid level chu ET-ah hian PD aiin a hniam zawk a ni. Isovaleric acid leh isobutyric acid hian ET leh PD te hi an thliar hrang a, AUC chu 0.743 (95% CI: 0.629–0.857) a ni. Fecal propionate hi inverse takin constipation leh autonomic dysfunction nen a inzawm tlat a ni. Isobutyric acid leh isovaleric acid te hi tremor severity nen hian inverse takin an inzawm a ni. Fecal SCFA content tlahniam hi ET-a Faecalibacterium leh Streptobacterium tamna tlahniam nen a inzawm tih hmuhchhuah a ni. Chutiang chuan bawlhhlawh chhunga SCFA awm zat chu ET-ah a tlahniam a, clinical picture nasat dan leh intestinal microbiota inthlak danglamna nen a inzawm a ni. Feces-a propionic acid, butyric acid, isobutyric acid, leh isovaleric acid te hi ET tana diagnostic leh differential diagnostic biomarker awm thei an ni thei.
Essential tremor (ET) hi neurodegenerative disorder kal zel, chronic a ni a, a bul berah chuan a ke ruh chunglam a nghing a, chu chuan taksa peng dang, lu, vocal cord leh a ke hnuai lam te pawh a nghawng thei bawk ET clinical features-ah hian motor symptoms chauh ni lovin non-motor sign thenkhat, gastrointestinal disease 2 te pawh a tel. Essential tremor-a pathological leh physiological characteristics zirchian nan zirchianna tam tak neih a ni tawh a, mahse pathophysiological mechanism chiang tak erawh hmuhchhuah a la ni lo3, Tun hnaia zirchianna hrang hrangah chuan microbiota-gut-brain axis hnathawh that lohna hian neurodegenerative diseases a thlen thei tih a tarlang a, gut microbiota leh neurodegenerative diseases inkara bidirectional link awm thei tur finfiahna a pung zel bawk Hriat tur pawimawh tak chu case report pakhatah chuan fecal microbiota transplantation hian damlo pakhatah essential tremor leh irritable bowel syndrome pahnih a ti tha a, hei hian gut microbiota leh essential tremor inzawmna nghet tak a awm tih a tilang thei a ni. Chu bakah, ET vei damlote gut microbiota-ah pawh danglamna chiang tak kan hmu bawk a, hei hian ET8-a gut dysbiosis chanvo pawimawh tak chu nasa takin a thlawp a ni.
Neurodegenerative diseases-a gut dysbiosis chungchangah chuan PD hi zirchian tam ber a ni5. Microbiota inthlau tak chuan intestinal permeability a tipung thei a, intestinal glia a tichak thei a, chu chuan alpha-synucleinopathies a thlen thei9,10,11. PD leh ET hian thil chi hrang hrang inzawmkhawm (overlapping characteristics) an nei a, chu chu ET leh PD vei te zingah tremor awm tam dan inang, overlapping resting tremor (PD-a tremor pangngai), leh postural tremor (ET vei zingah hmuh tam ber) te hi a ni a, hei vang hian an inthliarna a harsa hle. early stages 12. Chuvangin ET leh PD inthliarna tur window tangkai tak kan hawn vat a ngai a ni. Hemi kawngah hian ET-a specific intestinal dysbiosis leh a kaihhnawih metabolite inthlak danglamna zirchianna leh PD atanga an danglamna hriatchhuah hi ET diagnosis leh differential diagnosis atana biomarker awm thei a ni thei.
Short-chain fatty acids (SCFAs) hi dietary fiber intestinal bacterial fermentation atanga siam metabolite lian ber a ni a, gut-brain inzawmnaah pawh hmun pawimawh tak a chang nia ngaih a ni13, SCFAs hi colon cells ten an la a, portal venous system kaltlangin liver ah an phur lut a, SCFA thenkhat chu systemic circulation ah an lut bawk. SCFAs hian intestinal barrier integrity vawng reng tur leh intestinal mucosa-a innate immunity tihhmasawn kawngah local effect a nei a ni15. Tin, blood-brain barrier (BBB)-ah hun rei tak chhung nghawng an nei bawk a, tight junction proteins te an tichak a, BBB16 paltlang turin G protein-coupled receptor (GPCRs) te tichakin neurons te an tichak bawk. Acetate, propionate, leh butyrate te hi colon chhunga SCFA awm tam ber an ni. Tun hmaa zirchianna hrang hrangah chuan Parkinson natna vei te zingah acetic, propionic leh butyric acids te fecal level a tlahniam tih hmuhchhuah a ni17. Mahse, ET vei zingah hian fecal SCFA level hi zirchian a la ni ngai lo.
Chutiang chuan kan zirchianna hian ET vei damlote fecal SCFA-a inthlak danglamna bik leh PD vei te nena an danglamna hriatchhuah a tum a, fecal SCFA leh SCFA leh intestinal microbiota clinical symptoms inzawmna tehna te, fecal sample-te diagnostic leh differential diagnostic theihna awm thei te hriatchhuah a tum bawk. KZHK. Anti-PD damdawi nena inzawm thil buaithlak tak takte sutkian nan, Parkinson’s natna lo chhuak thar nei damlote chu natna control atan kan thlang a.
ET 37, PD 37, leh HC 35 te demographic leh clinical characteristics chu Table 1-ah hian tarlan a ni a, ETs, PDs, leh HCs te chu kum, sex leh BMI hmangin an inmil a ni. Group pathumte hian meizuk, zu in leh coffee leh tea in zat inang an nei bawk. PD group-a Wexner score (P = 0.004) leh HAMD-17 score (P = 0.001) chu HC group aiin a sang zawk a, ET group-a HAMA score (P = 0.011) leh HAMD-17 score (P = 0.011) chu HC group aiin a sang zawk bawk. ET group-a natna kal dan hi PD group aiin a rei zawk tih a chiang hle (P<0.001).
Fecal level-ah hian fecal propionic acid (P = 0.023), acetic acid (P = 0.039), butyric acid (P = 0.020), isovaleric acid (P = 0.045), leh isobutyric acid (P = 0.015) te chu a inang lo hle. . Post hoc analysis dang an neih leh chuan ET group-a propionic acid (P = 0.023), butyric acid (P = 0.007), leh isobutyric acid (P = 0.040) level chu HC group aiin a hniam zawk tih a chiang hle. ET vei damlote chu PD vei damlote aiin isovalerate (P = 0.014) leh isobutyrate (P = 0.005) level a hniam zawk a ni. Tin, PD vei te zingah hian CC vei te aiin fecal propionic acid (P = 0.013), acetic acid (P = 0.016), leh butyric acid (P = 0.041) level a hniam zawk bawk (Fig. 1 leh Supplementary Table 1)
ag hian propionic acid, acetic acid, butyric acid, isovaleric acid, valeric acid, caproic acid leh isobutyric acid te group comparison a entir a ni. Group pathumte zingah hian fecal propionic acid, acetic acid, butyric acid, isovaleric acid leh isobutyric acid level-ah danglamna nasa tak a awm a ni. ET essential tremor, Parkinson natna, HC hrisel control, SCFA te a ni. Inthlauhna lian tak chu *P < 0.05 leh **P < 0.01 te hian a tarlang.
ET group leh PD group inkara natna kal dan inang lo ngaihtuah chuan PD hmasa ber nei damlo 33 leh ET vei 16 (natna course ≤3 years) te chu tehkhin belh turin kan test a (Supplementary Table 2). Results atanga a lan dan chuan ET-a fecal propionic acid awm zat chu HA aiin a hniam zawk tih a chiang hle (P=0.015). Butyric acid leh isobutyric acid tan ET leh HC inthlauhna hi a langsar lo hle a, mahse trend a la awm tho (P = 0.082). ET vei zingah hian PD vei te nen khaikhin chuan fecal isobutyrate level a hniam zawk tih a chiang hle (P = 0.030). Isovaleric acid ET leh PD inthlauhna hi a langsar lo hle a, mahse trend a la awm tho (P = 0.084). PD vei zingah hian HC vei aiin propionic acid (P = 0.023), acetic acid (P = 0.020), leh butyric acid (P = 0.044) te chu a hniam zawk tih a chiang hle. Heng result (Supplementary Figure 1) te hi a tlangpuiin result bulpui nen a inmil hle. Sample pumpui leh damlo subgroup hmasa ber result inang lo hi subgroup-a sample size tlem vang a ni thei a, chu chuan data-a statistical power a tihhniam phah a ni.
A dawtah chuan fecal SCFA level hian ET vei leh CU emaw PD vei te a thliar hrang thei em tih kan enfiah leh a. ROC analysis atanga a lan dan chuan propionate level AUC inthlauhna chu 0.668 (95% CI: 0.538-0.797) a ni a, hei hian ET vei leh HC vei te chu a thliar hrang thei a ni. ET leh GC vei damlote chu butyrate level hmangin an thliar hrang thei a, AUC chu 0.685 (95% CI: 0.556–0.814) a ni. Isobutyric acid level danglamna hian ET vei leh HC nei te chu a thliar hrang thei a, AUC chu 0.655 (95% CI: 0.525–0.786) a ni. Propionate, butyrate leh isobutyrate level te an inzawm khawm chuan AUC sang zawk 0.751 (95% CI: 0.634–0.867) a ni a, sensitivity 74.3% leh specificity 72.9% a ni (Fig. 2a). ET leh PD vei te thliar hran nan isovaleric acid level AUC chu 0.700 (95% CI: 0.579–0.822) a ni a, isobutyric acid level tan 0.718 (95% CI: 0.599–0.836) a ni. Isovaleric acid leh isobutyric acid level inzawmkhawm hian AUC sang zawk 0.743 (95% CI: 0.629–0.857), sensitivity 74.3% leh specificity 62.9% a nei sang zawk (Fig. 2b). Tin, Parkinson natna vei damlote ek-a SCFA level chu control-te nen a danglam em tih kan enfiah bawk. ROC analysis atanga a lan dan chuan propionic acid level inang lo atanga PD vei te hriatchhuahna atana AUC chu 0.687 (95% CI: 0.559-0.814) a ni a, sensitivity 68.6% leh specificity 68.7% a ni. Acetate level inang lo hian PD vei leh AUC 0.674 (95% CI: 0.542–0.805) nei HC te chu a thliar hrang thei a ni. PD vei damlote chu CU atanga thliar hran theih an ni a, butyrate level chauhvin AUC 0.651 (95% CI: 0.515–0.787) a nei a ni. Propionate, acetate leh butyrate level te an inzawm khawm chuan AUC 0.682 (95% CI: 0.553–0.811) a ni (Fig. 2c).
Russian Orthodox Kohhran ET leh HC-te thliar hranna; b Russian Orthodox Kohhranin ET leh PD an laka inthliarna; c ROC-in PD leh HC a thliar hranna. ET essential tremor, Parkinson natna, HC hrisel control, SCFA te a ni.
ET vei damlote zingah chuan fecal isobutyric acid level chu FTM score (r = -0.349, P = 0.034) nen a inzawm tha lo hle a, fecal isovaleric acid level chu FTM score (r = -0.421, P = 0.001) leh TETRAS score nen a inzawm tha lo hle bawk. (r = -0.382, P = 0.020) a ni. ET leh PD vei damlote zingah chuan fecal propionate level chu SCOPA-AUT score nen a inzawm tha lo hle (r = −0.236, P = 0.043) (Fig. 3 leh Supplementary Table 3). ET group (P ≥ 0.161) emaw PD group (P ≥ 0.246) emaw-ah pawh natna kal dan leh SCFA inkarah inzawmna lian tham a awm lo (Supplementary Table 4). PD vei damlote zingah chuan fecal caproic acid level hi MDS-UPDRS score nen a inzawm tha hle (r = 0.335, P = 0.042). Mi zawng zawng zingah fecal propionate (r = −0.230, P = 0.016) leh acetate (r = −0.210, P = 0.029) level te chu Wexner score nen a inzawm tha lo hle (Fig. 3 leh Supplementary Table 3).
Fecal isobutyric acid level chu FTM score nen a inzawm tha lo a, isovaleric acid chu FTM leh TETRAS score nen a inzawm tha lo a, propionic acid chu SCOPA-AUT score nen a inzawm tha lo a, caproic acid chu MDS-UPDRS score nen a inzawm tha lo a, propionic acid chu FTM leh TETRAS score nen a inzawm tha lo hle bawk. TETRAS leh acetic acid te hi Wexner score nen hian a inzawm tha lo hle. MDS-UPDRS Association sponsored version of Unified Parkinson’s Disease Rating Scale, Mini-Mental State Examination MMSE, Hamilton Depression Rating Scale HAMD-17, item 17, Hamilton Anxiety Rating Scale HAMA, HY Hoehn leh Yahr stages, SCFA, SCOPA – AUT Parkinson’s Disease Autonomic Symptom Outcome Scale, FTM te chu a hlawhtling hle Fana-Tolosa-Marin Clinical Tremor Rating Scale, TETRAS Research Group (TRG)-in a pawimawh ber chu Tremor Rating Scale hmanga siam a ni. Inthlauhna lian tak chu *P < 0.05 leh **P < 0.01 te hian a tarlang.
LEfSE analysis hmangin gut microbiota discriminatory nature kan zirchiang lehzual a, genus relative abundance data level chu analysis dang neih belh nan kan thlang a ni. ET leh HC leh ET leh PD te khaikhin a ni. Chumi hnuah Spearman correlation analysis chu comparison group pahnih-a gut microbiota leh fecal SCFA level relative abundance-ah an ti a.
ET leh CA te zirchiannaah hian Faecalibacterium (butyric acid nena inzawm, r = 0.408, P < 0.001), Lactobacillus (butyric acid nena inzawm, r = 0.283, P = 0.016), Streptobacterium (propionic acid nena inzawm, r = 0.327) te an awm a ni. , P = 0.005 a ni a; butyric acid nen a inzawm a, r = 0.374, P = 0.001; isobutyric acid nen a inzawm a, r = 0.329, P = 0.005), Howardella (propionic acid nen a inzawm, r = 0.242, P = 0.041), Raoultella (propionate nen a inzawm a, r = 0.249, P = 0.035), leh Candidatus Arthromitus (isobutyric acid nen a inzawm, r = 0.302, P = 0.010) chu ET-ah a tlahniam tih hmuhchhuah a ni a, fecal SCFA level nen pawh a inzawm tha hle. Mahse, Stenotropomonas tamna chu ET-ah a pung a, fecal isobutyrate level nen a inzawm tha lo hle (r = -0.250, P = 0.034). FDR adjustment hnuah pawh Faecalibacterium, Catenibacter, leh SCFA te inzawmna chauh a langsar hle (P ≤ 0.045) (Fig. 4 leh Supplementary Table 5).
ET leh HC te inzawmna (correlation analysis) a ni. FDR adjustment hnuah ET-ah Faecalibacterium (butyrate nena inzawm tha) leh Streptobacterium (propionate, butyrate, leh isobutyrate nena inzawm tha) tamna chu a tlahniam tih hmuhchhuah a ni a, fecal SCFA level nen pawh a inzawm tha hle tih hmuhchhuah a ni. b ET leh PD te inzawmna (correlation analysis) a ni. FDR adjustment hnuah pawh inzawmna lian tham hmuh tur a awm lo. ET essential tremor, Parkinson natna, HC hrisel control, SCFA te a ni. Inthlauhna lian tak chu *P < 0.05 leh **P < 0.01 te hian a tarlang.
ET leh PD an zirchian chuan ET-ah Clostridium trichophyton a pung tih hmuhchhuah a ni a, fecal isovaleric acid (r = -0.238, P = 0.041) leh isobutyric acid (r = -0.257, P = 0.027) nen a inzawm tih hmuhchhuah a ni. ). FDR siamthat hnuah pawh pakhat zawk chu a langsar reng (P≥0.295) (Figure 4 leh Supplementary Table 5).
He zirchianna hi zirchianna zau tak a ni a, fecal SCFA levels a enfiah a, ET vei te CU leh PD vei te nena khaikhin chuan gut microbiota leh symptom severity inthlak danglamna nen a inzawm tir a ni. ET vei damlote zingah fecal SCFA level a tlahniam tih kan hmu a, clinical severity leh gut microbiota-a specific changes nen a inzawm tih kan hmuchhuak bawk. Feces-a short-chain fatty acids (SCFAs) level awm zat (cumulative level) hian ET leh GC leh PD a danglamna a siam a ni.
GC vei te nen khaikhin chuan ET vei te hian fecal level ah propionic, butyric, leh isobutyric acids an nei tlem zawk a ni. Propionic, butyric leh isobutyric acids te inzawmkhawm hian ET leh HC te hi AUC 0.751 (95% CI: 0.634–0.867), sensitivity 74.3% leh specificity 72.9% neiin a danglam thei a, hei hian ET tana diagnostic biomarker atana potential role anga hman an nih thu a tarlang. An zirchiannaah chuan fecal propionic acid level chu Wexner score leh SCOPA-AUT score nen a inzawm tha lo tih hmuhchhuah a ni. Fecal isobutyric acid level chu FTM score nen inverse takin a inzawm a ni. A lehlamah chuan ET-a butyrate level tlahniam hi SCFA siamtu microbiota, Faecalibacterium leh Categorybacter tamna tlahniam nen a inzawm tih an hmuchhuak bawk. Hei bakah hian ET-a Catenibacter tamna tlahniam hi fecal propionic leh isobutyric acid level tlahniam nen pawh a inzawm tih hmuhchhuah a ni bawk.
Colon-a SCFA siam tam zawk hi colonocyte-te chuan H+-dependent emaw sodium-dependent monocarboxylate transporter hmangin an la lut ber a ni. Absorbed short-chain fatty acids hi colonocytes tan energy source atan hman a ni a, colonocytes-a metabolized lote erawh chu portal circulation-ah an phur lut thung SCFAs hian intestinal motility a nghawng thei a, intestinal barrier function a tichak thei a, host metabolism leh immunity a nghawng thei bawk19. Tun hmain PD vei zingah HCs17 nena khaikhin chuan butyrate, acetate, leh propionate fecal concentration a tlahniam tih hmuhchhuah a ni a, hei hi kan result nen a inmil hle. Kan zirchiannaah hian ET vei damlote zingah SCFA tlahniam tih hmuhchhuah a ni a, mahse ET pathology-a SCFA chanvo chungchang erawh hriat tur a tlem hle. Butyrate leh propionate te hian GPCR te hi an inzawm khawm thei a, GPCR-a innghat signaling MAPK leh NF-κB20 signaling te an nghawng thei bawk. Gut-brain axis concept bulpui ber chu gut microbes atanga SCFAs chhuak te hian host signaling a nghawng thei a, chu chuan gut leh thluak hnathawh a nghawng thei a ni. Butyrate leh propionate hian histone deacetylase (HDAC) activity-ah inhibitory effect nasa tak an neih avangin21 leh butyrate hian transcription factors tan ligand angin a thawk thei bawk a, host metabolism, differentiation leh proliferation-ah nghawng zau tak an nei a, a chhan ber chu gene regulation-a an nghawng vang a ni SCFA leh neurodegenerative diseases atanga evidence atanga a lan dan chuan butyrate hi HDAC activity tihchhiat a siamthat theih avangin therapeutic candidate anga ngaih a ni a, hei hian PD23,24,25 ah dopaminergic neuron thihna a mediate thei a ni. Ran zirchiannaah pawh butyric acid hian dopaminergic neuron degeneration a veng thei a, PD model-ah movement disorder a ti tha thei tih hmuhchhuah a ni bawk26,27. Propionic acid hian inflammatory response a tihtlem bakah BBB integrity a humhim tih hmuhchhuah a ni28,29. Zirna hrang hrangah chuan propionic acid hian PD model 30 ah rotenone toxicity chhanna atan dopaminergic neurons te dam khawchhuahna a tichak tih hmuhchhuah a ni a 31 ah propionic acid oral administration hian PD vei mice te dopaminergic neuron hloh leh motor deficit te a chhanchhuak tih hmuhchhuah a ni bawk. Isobutyric acid hnathawh dan hi hriat tur a tlem hle. Mahse, tun hnaia zirchianna pakhatah chuan B. ovale hmanga mice colonization hian intestinal SCFA content (acetate, propionate, isobutyrate, leh isovalerate te pawh tel) leh intestinal GABA concentration a tipung tih hmuhchhuah a ni a, hei hian gut microbiota leh intestinal SCFA inzawmna a awm tih a tilang chiang hle. neurotransmitters concentration hrang hrang32. ET tan chuan cerebellum-a pathological change pangngai lo awmte chu Purkinje cell axons leh dendrites inthlak danglamna, Purkinje cells inthlak danglam leh hloh, basket cell axons inthlak danglamna, leh Purkinje cells nena ascending fiber connection inthlak danglamna te a ni. nuclei, chu chuan cerebellum atanga GABAergic output tlahniam a thlen thin3,4,33. SCFAs hi Purkinje cell neurodegeneration leh cerebellar GABA production tlahniam nen a inzawm em tih erawh hriat chian a la ni lo. Kan result hian SCFA leh ET te hi inzawmna nghet tak a nei tih a tilang a; mahse, cross-sectional study design chuan SCFA leh ET natna kalphung inzawmna (causal relationship) chungchangah thutlukna siam a phal lo. Longitudinal follow-up study dang neih belh a ngai a, chutah chuan fecal SCFAs serial measurement te, rannung zirchianna mechanisms enfiah te pawh a tel a ni.
SCFAs hian colonic smooth muscle contractility a tichak niin an ngai34. SCFA tlakchhamna hian constipation symptoms a ti na zual ang a, SCFA supplementation hian constipation symptoms PD35 a ti tha thei bawk. Kan result hian ET vei te zingah fecal SCFA content tlahniam leh constipation leh autonomic dysfunction tihpun te hi inzawmna lian tak a awm tih a tarlang bawk. Case report pakhatah chuan microbiota transplantation hian damlo 7-ah essential tremor leh irritable bowel syndrome pahnih a ti \ha tih hmuhchhuah a ni a, hei hian gut microbiota leh ET inzawmna nghet tak a awm tih a tilang lehzual a ni. Chuvangin, fecal SCFA/microbiota hian host intestinal motility leh autonomic nervous system function a nghawng thei niin kan ring.
He zirchianna hian ET-a fecal SCFAs level tlahniam hi Faecalibacterium (butyrate nena inzawm) leh Streptobacterium (propionate, butyrate, leh isobutyrate nena inzawm) tamna tlahniam nen a inzawm tih hmuhchhuah a ni. FDR siamthat hnuah pawh he inzawmna hi a langsar reng a ni. Faecalibacterium leh Streptobacterium te hi SCFA siamtu microorganism an ni. Faecalibacterium hi butyrate siamtu microorganism a nih thu hriat a ni36 a, Catenibacter fermentation atanga thil siam chhuah ber chu acetate, butyrate leh lactic acid te an ni ET leh HC group pahnih zinga 100%-ah Faecalibacterium hmuhchhuah a ni a; ET group-a median relative abundance chu 2.06% a ni a, HC group-a median relative abundance chu 3.28% a ni (LDA 3.870). Category bacterium hi HC group 21.6% (8/37) ah hmuhchhuah a ni a, ET group sample 1 (1/35) ah chauh hmuhchhuah a ni. ET-a streptobacteria tlahniam leh hmuh theih loh hian natna thlentu (pathogenicity) nen pawh inzawmna a nei tih a tilang thei bawk. HC group-a Catenibacter chi hrang hrangte median relative abundance chu 0.07% a ni (LDA 2.129). Tin, lactic acid bacteria te hi fecal butyrate inthlak danglamna nen a inzawm tih hmuhchhuah a ni bawk (FDR adjustment hnuah P=0.016, P=0.096), arthritis candidate chu isobutyrate inthlak danglamna nen a inzawm bawk (P=0.016, FDR adjustment hnuah P=0.072). FDR siamthat hnuah chuan correlation trend chauh a la awm a, hei hi statistically significant a ni lo. Lactobacilli hi SCFA (acetic acid, propionic acid, isobutyric acid, butyric acid) siamtu nia hriat a ni bawk 38 leh Candidatus Arthromitus hi T helper 17 (Th17) cell differentiation tirtu bik a ni a, Th1/2 leh Tregs te hi immune balance /Th1739 nena inzawm a ni. . Tun hnaia zirchianna pakhat chuan fecal pseudoarthritis level sang chuan colonic inflammation, intestinal barrier dysfunction, leh systemic inflammation a thlen thei tih a tarlang ET-ah hian PD nen khaikhin chuan Clostridium trichophyton a pung a ni. Clostridium trichoides tamna hi isovaleric acid leh isobutyric acid nen a inzawm tha lo tih hmuhchhuah a ni. FDR adjustment hnuah pawh an pahnih hian an langsar reng (P≥0.295). Clostridium pilosum hi inflammation nena inzawm nia hriat a ni a, intestinal barrier dysfunction a thlen thei a ni41. Kan zirchianna hmasaah khan ET8 vei damlote gut microbiota a inthlak danglam tih kan hmuchhuak a. Hetah hian ET-a SCFAs inthlak danglamna kan report bawk a, gut dysbiosis leh SCFAs inthlak danglamna inzawmna kan hmuchhuak bawk. SCFA level tlahniam hi ET-a intestinal dysbiosis leh tremor severity nen a inzawm tlat a ni. Kan result hian ET pathogenesis-ah hian gut-brain axis hian hmun pawimawh tak a chang thei tih a tilang a, mahse animal model-a zirchianna neih belh a ngai a ni.
PD vei te nen khaikhin chuan ET vei te hian an bawlhhlawh ah isovaleric leh isobutyric acids an nei tlem zawk a ni. Isovaleric acid leh isobutyric acid inzawmkhawm hian PD-ah ET a hmuchhuak a, AUC chu 0.743 (95% CI: 0.629–0.857), sensitivity 74.3% leh specificity 62.9% a ni a, hei hian ET differential diagnosis-a biomarker anga an chanvo a neih theih thu a tilang a ni. . Fecal isovaleric acid level chu FTM leh TETRAS score nen inverse takin a inzawm a ni. Fecal isobutyric acid level chu FTM score nen inverse takin a inzawm a ni. Isobutyric acid level tlahniam hi catobacteria tamna tlahniam nen a inzawm tih an hmuchhuak. Isovaleric acid leh isobutyric acid hnathawh dan hi hriat tur a tlem hle. Tun hmaa zirchianna pakhatah chuan Bacteroides ovale hmanga mice colonization hian intestinal SCFA content (acetate, propionate, isobutyrate, leh isovalerate te pawh tel) leh intestinal GABA concentration a tipung tih hmuhchhuah a ni a, hei hian microbiota leh intestinal SCFA/neurotransmitter concentration inkara intestinal link a tarlang a ni Ngaihven awm tak chu, isobutyric acid level hmuhchhuah chu PD leh HC group-ah a inang a, mahse ET leh PD (or HC) group-ah erawh a danglam thung. Isobutyric acid hian ET leh PD chu AUC 0.718 (95% CI: 0.599–0.836) neiin a thliar hrang thei a, ET leh NC chu AUC 0.655 (95% CI: 0.525–0.786) neiin a hriat theih bawk. Tin, isobutyric acid level hi tremor severity nen a inzawm a, hei hian ET nena a inzawmna a tichak zual hle. ET vei damlote zingah oral isobutyric acid hian tremor natna a tihziaawm thei em tih zawhna hi zirchian belh a ngai a ni.
Chutiang chuan ET vei damlote zingah fecal SCFA content a tlahniam a, ET clinical severity leh intestinal microbiota-a specific changes nen a inzawm a ni. Fecal propionate, butyrate, leh isobutyrate te hi ET tan chuan diagnostic biomarker an ni thei a, isobutyrate leh isovalrate te erawh chu ET tan chuan differential diagnostic biomarker an ni thei thung. Fecal isobutyrate inthlak danglamna hi SCFA dang inthlak danglamna aiin ET tan a chiang zawk thei.
Kan zirlai hian tihkhawtlai engemaw zat a nei a. Pakhatnaah chuan, ei leh in dan leh ei duh dan hian microbiota expression a nghawng thei a, population hrang hranga study sample lian zawk lak a ngai a, nakin lawka zirchiannaah chuan ei leh in chungchanga survey kimchang leh mumal tak, food frequency questionnaire ang chi te hman a ngai a ni. Pahnihnaah chuan, cross-sectional study design hian SCFAs leh ET lo awm dan inzawmna (causal relationship) chungchangah thutlukna siam a khap tlat a ni. Fecal SCFAs serial measurement hmanga hun rei tak chhunga follow-up study neih belh a ngai a ni. Pathumnaah chuan, fecal SCFA level-a diagnostic leh differential diagnostic theihna chu ET, HC, leh PD atanga independent sample hmanga validate tur a ni. Nakin lawkah independent fecal sample tam zawk test a ngai a ni. A tawp berah chuan kan cohort-a PD vei te hian ET vei te aiin natna an rei zawk tih a chiang hle. Kum, sex leh BMI hmangin ET, PD leh HC te kan match ber a ni. ET group leh PD group inkara natna kal dan inang lo tak takte ngaihtuah chuan, PD hmasa ber nei mi 33 leh ET (natna hun chhung ≤3 years) vei 16 te chu tehkhin belh turin kan zirchiang bawk. SCFA-a group hrang hrangte inthlauhna chu a tlangpuiin kan primary data nen a inmil hle. Tin, natna rei zawng leh SCFA inthlak danglamna inkarah hian inzawmna kan hmu lo. Mahse, nakin lawkah chuan sample lian zawka validation tihfel theih nan PD leh ET vei damlote chu a tir lamah natna hun rei lo zawka lak luh a tha ber ang.
He zirchianna protocol hi Shanghai Jiao Tong University School of Medicine (RHEC2018-243) nena inzawm Ruijin Hospital-a ethics committee chuan a pawm a ni. He huna tel zawng zawngte hnen atangin written informed consent lak vek a ni.
January 2019 leh December 2022 inkar khan Shanghai Jiao Tong University School of Medicine nena inzawm Ruijin Hospital-a Movement Disorder Center Clinic atanga subject 109 (37 ET, 37 PD, leh 35 HC) te chu he zirchiannaah hian an tel a ni. Criteria chu: (1) kum 25–85 inkar, (2) ET vei damlote chu MDS Working Group criteria 42 angin hmuhchhuah an ni a, PD chu MDS criteria 43 angin hmuhchhuah an ni a, (3) damlo zawng zawngte chu chair hmain anti-PD damdawi an ei lo. sample lakkhawm a ni. (4) ET group hian stool sample an lak hmain β-blockers chauh emaw, a kaihhnawih damdawi engmah emaw an ei lo. Kum, mipa leh hmeichhia, leh body mass index (BMI) nena inmil HC te pawh thlan an ni bawk. Exclusion criteria chu: (1) vegetarians, (2) ei leh in tha lo, (3) gastrointestinal tract-a natna khirh tak tak (inflammatory bowel disease, gastric emaw duodenal ulcers te pawh tel), (4) natna khirh tak tak (malignant tumors te pawh tel), heart failure, renal failure, hematological diseases nei tawh) (5) History of major gastrointestinal diseases te a ni surgery, (6) Yogurt ei rei emaw, ei fo emaw, (7) Thla 1 chhung probiotics emaw antibiotics emaw eng pawh hman, (8 ) Corticosteroid, proton pump inhibitor, statin, metformin, immunosuppressant emaw cancer dona damdawi hman rei tak leh (9) clinical trial tibuaitu hriatna lama harsatna nasa tak neih.
Subject zawng zawngte hian BMI chhiar nan medical history, weight leh height information an pe vek a, neurological examination leh clinical assessment te an nei a, chungte chu Hamilton Anxiety Rating Scale (HAMA) 44 anxiety score, Hamilton Depression Rating Scale-17 score (HAMD-17) 45. depression, severity of constipation using the Wexner Constipation Scale 46 leh Bristol te an ni Stool Scale 47 leh Mini-Mental State Examination (MMSE) hmanga hriatna lama thawh dan 48 . Scale for the Assessment of Autonomic Symptoms of Parkinson’s Disease (SCOPA-AUT) 49 chuan ET leh PD vei te autonomic dysfunction an enfiah a. ET vei damlote chu Fan-Tolos-Marin Clinical Tremor Rating Scale (FTM) leh Essential Tremor Rating Scale (TETRAS) 50 Tremor Study Group (TRG) 50 te enfiah a ni a; United Parkinson’s Disease Association-in a buatsaih Kinson’s disease rating scale (MDS- UPDRS) version 51 leh Hoehn leh Yahr (HY) grade 52 te enfiah a ni.
He huna tel tinte chu zing lamah stool collection container hmangin stool sample lak turin an ti a. Container te chu ice ah dah la, process hmain -80°C ah dah rawh. SCFA analysis hi Tiangene Biotechnology (Shanghai) Co., Ltd. routine operations angin tih a ni a, subject tin atanga fecal sample thar 400 mg lakkhawm niin, grinding leh pre-sonication hnuah SCFAs hmangin analyze a ni. Feces-a SCFA thlan chhuah te chu gas chromatography-mass spectrometry (GC-MS) leh liquid chromatography-tandem MS (LC-MS/MS) hmangin an zirchiang a.
DNA chu siamtu thupek angin QIAamp® Fast DNA Stool Mini Kit (QIAGEN, Hilden, Germany) hmangin 200 mg sample atanga lakchhuah a ni. Microbial composition chu 16 S rRNA gene chu bawlhhlawh atanga DNA lakchhuahah V3-V4 region amplify a, sequencing hmangin an chhut a ni. DNA chu 1.2% agarose gel-a sample run-in test rawh. 16S rRNA gene polymerase chain reaction (PCR) amplification chu universal bacterial primers (357 F leh 806 R) leh Novaseq platform-a siam two-step amplicon library hmangin an ti a ni.
Continuous variable te chu mean ± standard deviation anga tarlan a ni a, categorical variable te chu number leh percentage anga tarlan a ni bawk. Variances homogeneity test nan Levene’s test kan hmang a. Variable-te chu normal-a sem chhuah a nih chuan two-tailed t test emaw analysis of variance (ANOVA) emaw hmangin tehkhin a ni a, normality emaw homoscedasticity assumption bawhchhiat a nih chuan nonparametric Mann-Whitney U test hmangin tehkhin a ni. Receiver operating characteristic (ROC) curve (AUC) hnuaia area chu model-a diagnostic performance quantified nan kan hmang a, SCFA-in ET vei leh HC emaw PD vei te a thliar hrang theih dan kan enfiah bawk. SCFA leh clinical severity inzawmna enfiah nan Spearman correlation analysis kan hmang a. Statistical analysis chu SPSS software (version 22.0; SPSS Inc., Chicago, IL) hmangin an ti a, significance level (P value leh FDR-P telin) chu 0.05 (two-sided)-ah dah a ni.
S sequence 16 te hi Trimmomatic (version 0.35), Flash (version 1.2.11), UPARSE (version v8.1.1756), mothur (version 1.33.3) leh R (version 3.6.3) software hmanga zirchian a ni. Raw 16S rRNA gene data chu UPARSE hmangin process a ni a, 97% identity nei operational taxonomic unit (OTU) siam a ni. Taxonomies te chu reference database atan Silva 128 hmangin an tarlang a ni. Relative abundance data generic level chu zirchian belh zel nan thlan a ni. Group hrang hrang (ET vs. HC, ET vs. PD) tehkhin nan linear discriminant analysis (LDA) effect size analysis (LEfSE) hman a ni a, α threshold 0.05 leh effect size threshold 2.0 a ni. LEfSE analysis hmanga discriminant genera hmuhchhuah te chu SCFA-a Spearman correlation analysis atan hman belh a ni.
Study design chungchang hriat belh duh chuan he thuziak nena inzawm Natural Research Report Abstract hi en la.
Raw 16S sequencing data hi National Center for Biotechnology Information (NCBI) BioProject database (SRP438900: PRJNA974928), URL: https://www.ncbi.nlm.nih.gov/Traces/study/?acc= SRP438900&o-ah dah a ni. =acc_s% 3Aa a ni. Data dangte chu a kaihhnawih ziaktu hnenah a remchan dan anga dilna a awm a, chu chu scientific lama thawhhona leh research project kimchang nena zirna lama inthlengna te hi a ni. Kan remtihna tel lo chuan third party hnenah data transfer phal a ni lo.
Open source code chu Trimmomatic (version 0.35), Flash (version 1.2.11), UPARSE (version v8.1.1756), mothur (version 1.33.3) leh R (version 3.6.3) te inzawmkhawm chauh hmangin, default settings emaw section “Method” hmangin. Thu chiang zawk chu a ziaktu hnenah a remchan dan anga dilna a awm chuan pek theih a ni.
Pradeep S leh Mehanna R. Hyperkinetic movement lama harsatna leh ataxia-a chaw kawng natna. Parkinson natna nen a inzawm. rilru tibuai. 90, 125–133 (2021) ah a tarlang bawk.
Louis, ED leh Faust, PL Pathology of essential tremor: neurodegeneration leh neuronal connection te insiam thar lehna. Nat. Pastor Nirol chuan a rawn ti a. 16, 69–83 (2020) ah a tarlang bawk.
Gironell, A. Essential tremor hi Gaba dysfunction natna bulpui ber a ni em? Awle. internationality a ni. Rev. Neuroscience lam a ni. 163, 259–284 (2022) ah a tarlang bawk.
Dogra N., Mani RJ leh Katara DP Gut-brain axis: Parkinson natnaah hian signaling mode pahnih. Cell chhunga molecule awmte. Neurobiology chungchang zir chianna. 42, 315–332 (2022) ah a tarlang bawk.
Quigley-a chuan EMM. Microbiota-brain-gut axis leh neurodegenerative natna te hi a ni. tun. Nellore a ni. Neuroscience lam a ni. Report 17, 94 (2017) a ni.
Liu, XJ, Wu, LH, Xie, WR leh He, XX Fecal microbiota transplantation hian a rualin damlote chu essential tremor leh irritable bowel syndrome a ti tha a ni. A rilru a hah lutuk chuan a rilru a buai em em a. 20, 796–798 (2020).
Zhang P. leh a thawhpuiten an sawi. Essential tremor-a intestinal microbiota-a inthlak danglamna bik leh Parkinson natna atanga an danglamna. NPJ Parkinson natna a ni. 8, 98 (2022)-ah tarlan a ni.
Luo S, Zhu H, Zhang J leh Wang D. Neuronal-glial-epithelial units regulation-a microbiota chanvo pawimawh tak. Infection laka inven theihna. 14, 5613–5628 (2021) ah a tarlang bawk.
Emin A. leh a thawhpuiten an sawi. Parkinson natna zual zel zingah duodenal alpha-synuclein leh intestinal gliosis awm dan. che. rilru tibuai. A rilru a hah lutuk chuan a rilru a buai em em a. 29358 (2023).
Skorvanek M. leh a thawhpuiten an sawi. Alpha-synuclein 5G4 dotu antibodies hian colon mucosa-ah hian overt Parkinson’s disease leh prodromal Parkinson’s disease a hre thei a ni. che. rilru tibuai. 33, 1366–1368 (2018) ah a tarlang bawk.
Algarni M leh Fasano A. Essential tremor leh Parkinson natna vei inmilna. Parkinson natna nen a inzawm. rilru tibuai. 46, С101–С104 (2018) ah a tarlang bawk.
Sampson, TR leh a thawhpuiten an ziak a. Gut microbiota hian Parkinson natna model-ah motor deficit leh neuroinflammation a tidanglam thei a ni. A rilru a hah lutuk chuan a rilru a buai em em a. 1469–1480.e1412 (2016).
Unger, MM leh a thawhpuiten an ziak a ni. Parkinson natna vei leh kum inang control-te zingah hian short-chain fatty acid leh gut microbiota hi a inang lo hle. Parkinson natna nen a inzawm. rilru tibuai. 32, 66–72 (2016) ah a tarlang bawk.
Bleacher E, Levy M, Tatirovsky E leh Elinav E. Host immune interface-a microbiome-in a enkawl metabolites te. J. Immunology chungchang. 198, 572–580 (2017) ah a tarlang bawk.