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Gano farkon girgizar ƙasa (ET) na iya zama ƙalubale, musamman idan aka bambanta shi da lafiyayyun hanyoyin kula da lafiya (HC) da cutar Parkinson (PD). Kwanan nan, nazarin samfuran bayan gida don ƙwayoyin cuta na hanji da metabolites ɗinsa ya samar da sabbin hanyoyi don gano sabbin alamun cututtukan neurodegenerative. Manyan kitse masu sarkakiya (SCFA), a matsayin babban metabolite na flora na hanji, suna raguwa a cikin najasa a cikin PD. Duk da haka, ba a taɓa yin nazarin SCFA na bayan gida a cikin ET ba. Mun yi niyyar bincika matakan SCFA na bayan gida a cikin ET, tantance alaƙarsu da alamun asibiti da ƙwayoyin cuta na hanji, da kuma tantance yuwuwar iyawar ganewar su. An auna SCFA na bayan gida da ƙwayoyin cuta na hanji a cikin ET 37, sabbin PD 37, da HC 35. An tantance maƙarƙashiya, rashin aiki na autonomic, da tsananin girgiza ta amfani da sikelin. Matakan bayan gida na propionate, butyrate, da isobutyrate sun yi ƙasa a cikin ET fiye da na HC. Haɗin sinadarin propionic, butyric da isobutyric acid da suka bambanta ET daga HC tare da AUC na 0.751 (95% CI: 0.634–0.867). Matakan isovaleric acid na fecal da isobutyric acid sun yi ƙasa a ET fiye da PD. Isovaleric acid da isobutyric acid suna bambanta tsakanin ET da PD tare da AUC na 0.743 (95% CI: 0.629–0.857). Fecal propionate yana da alaƙa da maƙarƙashiya da rashin aiki na autonomic. Isobutyric acid da isovaleric acid suna da alaƙa da tsananin girgiza. Rage yawan SCFA na fecal yana da alaƙa da raguwar yawan Faecalibacterium da Streptobacterium a cikin ET. Don haka, yawan SCFA a cikin najasa yana raguwa a ET kuma yana da alaƙa da tsananin hoton asibiti da canje-canje a cikin microbiota na hanji. Propionic acid, butyric acid, isobutyric acid, da isovaleric acid a cikin najasa na iya zama alamun gano cutar da bambance-bambancen ganewar asali ga ET.
Girgizar Essential (ET) cuta ce mai ci gaba, mai saurin kamuwa da cututtukan jijiyoyi da ke shafar jijiyoyin jiki, wanda kuma zai iya shafar wasu sassan jiki kamar kai, muryoyin murya, da ƙananan gaɓoɓi 1. Siffofin asibiti na ET ba wai kawai sun haɗa da alamun motsi ba, har ma da wasu alamun da ba na motsi ba, gami da cututtukan ciki 2. An gudanar da bincike da yawa don bincika halayen cututtuka da na jiki na girgizar jiki mai mahimmanci, amma ba a gano hanyoyin da ke bayyana cututtuka ba 3,4. Nazarin da aka yi kwanan nan ya nuna cewa rashin aiki na axis na kwakwalwa na microbiota-gut-brain na iya taimakawa wajen haifar da cututtukan jijiyoyi, kuma akwai ƙarin shaida game da yuwuwar haɗin kai tsakanin ƙwayoyin hanji da cututtukan jijiyoyi 5,6. Abin lura, a cikin wani rahoto na shari'a, dashen ƙwayoyin hanji na bahaya ya inganta duka girgizar jiki mai mahimmanci da ciwon hanji mai haushi a cikin majiyyaci, wanda zai iya nuna alaƙar kusanci tsakanin ƙwayoyin hanji da girgizar jiki mai mahimmanci. Bugu da ƙari, mun kuma sami takamaiman canje-canje a cikin ƙwayoyin hanji a cikin marasa lafiya da ET, wanda ke goyon bayan muhimmiyar rawar da dysbiosis na hanji ke takawa a cikin ET8.
Dangane da dysbiosis na hanji a cikin cututtukan neurodegenerative, PD ita ce mafi yawan bincike5. Microbiota mara daidaito na iya ƙara yawan shiga cikin hanji da kunna glia na hanji, wanda ke haifar da alpha-synucleinopathies9,10,11. PD da ET suna da wasu halaye masu haɗuwa, kamar irin wannan mitar girgiza a cikin marasa lafiya da ET da PD, girgizar hutu mai haɗuwa (rawar jiki ta yau da kullun a cikin PD), da girgizar jiki ta postural (galibi ana samunta a cikin marasa lafiya da ET), wanda ke sa ya yi wuya a bambance tsakanin su. matakan farko 12. Saboda haka, muna buƙatar gaggawa mu buɗe taga mai amfani don bambance tsakanin ET da PD. A cikin wannan mahallin, nazarin takamaiman dysbiosis na hanji da canje-canjen metabolite da ke da alaƙa a cikin ET da gano bambance-bambancen su daga PD na iya zama alamun alamun cutar don ganewar asali da ganewar bambance-bambancen ET.
Manyan sinadaran kitse masu gajeru (SCFAs) su ne manyan sinadaran da ke samar da sinadarin fermentation na ƙwayoyin cuta na hanji na zare, kuma ana kyautata zaton suna taka muhimmiyar rawa a hulɗar hanji da kwakwalwa13,14. Kwayoyin hanji suna ɗaukar SCFAs kuma ana jigilar su zuwa hanta ta hanyar tsarin portal venous, kuma wasu SCFAs suna shiga cikin zagayawar jiki. SCFAs suna da tasirin gida akan kiyaye amincin shingen hanji da haɓaka garkuwar jiki a cikin mucosa na hanji15. Hakanan suna da tasirin dogon lokaci akan shingen jini-kwakwalwa (BBB) ​​​​ta hanyar ƙarfafa sunadaran haɗin gwiwa masu ƙarfi da kunna ƙwayoyin jijiyoyi ta hanyar ƙarfafa masu karɓar furotin na G (GPCRs) don haye BBB16. Acetate, propionate, da butyrate sune SCFAs mafi yawa a cikin hanji. Nazarin da aka yi a baya ya nuna raguwar matakan acetic, propionic da butyric acid a cikin marasa lafiya da ke fama da cutar Parkinson17. Duk da haka, ba a taɓa yin nazarin matakan SCFA na najasa a cikin marasa lafiya da ke da ET ba.
Saboda haka, bincikenmu ya yi niyya ne don gano takamaiman canje-canje a cikin najasar SCFA a cikin marasa lafiya da ET da bambance-bambancen su daga marasa lafiya da PD, tantance alaƙar SCFA na najasar tare da alamun asibiti na SCFA da ƙwayoyin cuta na hanji, da kuma gano yuwuwar ganewar asali da bambance-bambancen ikon ganewar samfuran najasar. KZHK. Don magance abubuwan da ke da rikitarwa da ke da alaƙa da magungunan hana PD, mun zaɓi marasa lafiya da ke da cutar Parkinson da ta fara bayyana a matsayin masu kula da cututtuka.
An taƙaita halayen alƙaluma da na asibiti na ETs 37, PDs 37, da HCs 35 a cikin Jadawali na 1. An daidaita ETs, PDs, da HCs ta hanyar shekaru, jinsi, da BMI. Rukuni uku kuma suna da irin wannan rabo na shan taba, shan barasa da shan kofi da shayi. Maki na Wexner (P = 0.004) da maki na HAMD-17 (P = 0.001) na ƙungiyar PD sun fi na ƙungiyar HC girma, kuma maki na HAMA (P = 0.011) da maki na HAMD-17 (P = 0.011) na ƙungiyar ET sun fi na ƙungiyar HC girma. Yanayin cutar a cikin ƙungiyar ET ya fi tsayi fiye da na ƙungiyar PD (P <0.001).
Akwai manyan bambance-bambance a matakan najasa na propionic acid (P = 0.023), acetic acid (P = 0.039), butyric acid (P = 0.020), isovaleric acid (P = 0.045), da isobutyric acid (P = 0.015). . A cikin ƙarin bincike bayan hoc, matakan propionic acid (P = 0.023), butyric acid (P = 0.007), da isobutyric acid (P = 0.040) a cikin rukunin ET sun yi ƙasa sosai fiye da na ƙungiyar HC. Marasa lafiya da ET suna da ƙananan matakan isovalerate (P = 0.014) da isobutyrate (P = 0.005) fiye da marasa lafiya da PD. Bugu da ƙari, matakan acid na najasa (P = 0.013), acetic acid (P = 0.016), da butyric acid (P = 0.041) sun yi ƙasa a cikin marasa lafiya da PD fiye da marasa lafiya da CC (Hoto na 1 da Tebur na Ƙarin 1).
ag yana wakiltar kwatancen rukuni na propionic acid, acetic acid, butyric acid, isovaleric acid, valeric acid, caproic acid da isobutyric acid, bi da bi. Akwai manyan bambance-bambance a cikin matakan fecal propionic acid, acetic acid, butyric acid, isovaleric acid da isobutyric acid tsakanin ƙungiyoyi uku. ET essential tremor, Parkinson's disease, healthy HC control, SCFA. Ana nuna manyan bambance-bambance ta hanyar *P < 0.05 da **P < 0.01.
Idan aka yi la'akari da bambancin da ke tsakanin ƙungiyar ET da ƙungiyar PD, mun gwada marasa lafiya 33 da ke da cutar PD ta farko da kuma marasa lafiya 16 da ke da cutar ET (cutar da ta kai shekaru ≤3) don ƙarin kwatantawa (Jadawali na Ƙarin 2). Sakamakon ya nuna cewa yawan sinadarin ET na fecal propionic acid ya yi ƙasa da na HA sosai (P=0.015). Bambancin da ke tsakanin ET da HC don butyric acid da isobutyric acid bai yi yawa ba, amma har yanzu an lura da wani yanayi (P=0.082). Matakan isobutyrate na fecal sun yi ƙasa sosai a cikin marasa lafiya da ET idan aka kwatanta da marasa lafiya da ke da cutar PD (P=0.030). Bambancin da ke tsakanin ET da PD na isovaleric acid bai yi yawa ba, amma har yanzu akwai wani yanayi (P=0.084). Propionic acid (P = 0.023), acetic acid (P = 0.020), da butyric acid (P = 0.044) sun yi ƙasa sosai a cikin marasa lafiya na PD fiye da marasa lafiya na HC. Waɗannan sakamakon (Karin Hoto na 1) gabaɗaya sun yi daidai da manyan sakamakon. Bambancin da ke tsakanin samfurin gabaɗaya da rukunin marasa lafiya na farko na iya zama saboda ƙaramin girman samfurin a cikin ƙaramin rukuni, wanda ke haifar da ƙarancin ƙarfin ƙididdiga na bayanan.
Mun sake duba ko matakan SCFA na najasa za su iya bambance marasa lafiya da ET daga marasa lafiya da CU ko PD. A cewar binciken ROC, bambancin AUC na matakan propionate shine 0.668 (95% CI: 0.538-0.797), wanda ya ba da damar bambance marasa lafiya da ET daga HC. Ana iya bambanta marasa lafiya da ET da GC ta hanyar matakan butyrate tare da AUC na 0.685 (95% CI: 0.556–0.814). Bambance-bambance a cikin matakan isobutyric acid na iya bambanta marasa lafiya da ET daga HC tare da AUC na 0.655 (95% CI: 0.525–0.786). Lokacin haɗa matakan propionate, butyrate da isobutyrate, an sami mafi girman AUC na 0.751 (95% CI: 0.634–0.867) tare da ƙarfin ji na 74.3% da takamaiman 72.9% (Hoto na 2a). Don bambance tsakanin marasa lafiya da ET da PD, AUC don matakan isovaleric acid shine 0.700 (95% CI: 0.579–0.822) kuma ga matakan isobutyric acid shine 0.718 (95% CI: 0.599–0.836). Haɗin matakan isovaleric acid da isobutyric acid yana da mafi girman AUC na 0.743 (95% CI: 0.629–0.857), ƙarfin ji na 74.3% da takamaiman 62.9% (Hoto na 2b). Bugu da ƙari, mun bincika ko matakan SCFA a cikin najasar marasa lafiya da ke fama da cutar Parkinson sun bambanta da waɗanda aka sarrafa. A cewar binciken ROC, AUC don gano marasa lafiya da ke fama da PD bisa ga bambance-bambancen matakan propionic acid shine 0.687 (95% CI: 0.559-0.814), tare da jin daɗin 68.6% da takamaiman 68.7%. Bambanci a cikin matakan acetate na iya bambanta marasa lafiya da PD daga HCs tare da AUC na 0.674 (95% CI: 0.542–0.805). Marasa lafiya da PD za a iya bambanta su daga CU kawai ta hanyar matakan butyrate tare da AUC na 0.651 (95% CI: 0.515–0.787). Lokacin haɗa matakan propionate, acetate da butyrate, an sami AUC na 0.682 (95% CI: 0.553–0.811) (Hoto na 2c).
Wariya ga Cocin Orthodox na Rasha akan ET da HC; b wariya ga Cocin Orthodox na Rasha akan ET da PD; c Wariya ga ROC akan PD da HC. Girgizar ƙasa mai mahimmanci ta ET, cutar Parkinson, kulawar HC mai lafiya, SCFA.
A cikin marasa lafiya da ke fama da ET, matakan isobutyric acid na hanji sun yi mummunan alaƙa da maki na FTM (r = -0.349, P = 0.034), kuma matakan isovaleric acid na hanji sun yi mummunan alaƙa da maki na FTM (r = -0.421, P = 0.001) da maki na TETRAS. (r = -0.382, P = 0.020). A cikin marasa lafiya da ke fama da ET da PD, matakan propionate na hanji sun yi mummunan alaƙa da maki na SCOPA-AUT (r = −0.236, P = 0.043) (Hoto na 3 da Tebur na Ƙarin 3). Babu wata muhimmiyar alaƙa tsakanin yanayin cutar da SCFA a cikin ƙungiyar ET (P ≥ 0.161) ko ƙungiyar PD (P ≥ 0.246) (Tebur na Ƙarin 4). A cikin marasa lafiya da ke fama da PD, matakan caproic acid na najasa sun kasance suna da alaƙa mai kyau da maki MDS-UPDRS (r = 0.335, P = 0.042). A duk mahalarta, matakan fecal propionate (r = −0.230, P = 0.016) da acetate (r = −0.210, P = 0.029) sun kasance suna da alaƙa mara kyau da maki Wexner (Hoto na 3 da Tebur na Ƙarin 3).
Matakan isobutyric acid na cikin jiki sun yi mu'amala da maki FTM mara kyau, an yi mu'amala da isovaleric acid mara kyau da maki FTM da TETRAS mara kyau, an yi mu'amala da propionic acid mara kyau da maki SCOPA-AUT, an yi mu'amala da caproic acid mara kyau da maki MDS-UPDRS, kuma an yi mu'amala da propionic acid mara kyau da maki FTM da TETRAS mara kyau. TETRAS da acetic acid sun yi mu'amala da maki Wexner mara kyau. Ƙungiyar MDS-UPDRS ta ɗauki nauyin sigar Unified Parkinson's Disease Rating Scale, Mini-Mental State Examination MMSE, Hamilton Depression Rating Scale HAMD-17, abubuwa 17, Hamilton An yi mu'amala da HAMA, HY Hoehn da Yahr stages, SCFA, SCOPA – AUT Parkinson's Autonomic Symptom Outcome Scale, FTM Fana-Tolosa-Marin Clinical Tremor Rating Scale, TETRAS Research Group (TRG) Essential Tremor Rating Scale. Ana nuna manyan bambance-bambance ta hanyar *P < 0.05 da **P < 0.01.
Mun ƙara bincika yanayin wariya na ƙwayoyin cuta na hanji ta amfani da nazarin LEfSE kuma muka zaɓi matakin bayanai na yawan ƙwayoyin cuta na halittar don ƙarin bincike. An yi kwatancen tsakanin ET da HC da kuma tsakanin ET da PD. Daga nan aka yi nazarin hulɗar Spearman akan yawan ƙwayoyin cuta na hanji da matakan SCFA na hanji a cikin ƙungiyoyin kwatantawa guda biyu.
An gano Faecalibacterium (wanda aka haɗa shi da butyric acid, r = 0.408, P < 0.001), Lactobacillus (wanda aka haɗa shi da butyric acid, r = 0.283, P = 0.016), Streptobacterium (wanda aka haɗa shi da propionic acid, r = 0.327) a cikin nazarin ET da CA., P = 0.005; wanda aka haɗa shi da butyric acid, r = 0.374, P = 0.001; yana da alaƙa da isobutyric acid, r = 0.329, P = 0.005), Howardella (yana da alaƙa da propionic acid, r = 0.242, P = 0.041), Raoultella (yana da alaƙa da propionate, r = 0.249, P = 0.035), kuma an gano cewa Candidatus Arthromitus (yana da alaƙa da isobutyric acid, r = 0.302, P = 0.010) ya ragu a cikin ET kuma yana da alaƙa mai kyau da matakan SCFA na najasa. Duk da haka, yawan Stenotropomonas ya ƙaru a cikin ET kuma yana da alaƙa mara kyau da matakan isobutyrate na najasa (r = -0.250, P = 0.034). Bayan daidaitawar FDR, alaƙar da ke tsakanin Faecalibacterium, Catenibacter, da SCFA kawai ta kasance mai mahimmanci (P ≤ 0.045) (Hoto na 4 da Tebur na Ƙarin 5).
Binciken daidaitawar ET da HC. Bayan daidaitawar FDR, an gano cewa yawan Faecalibacterium (wanda ke da alaƙa da butyrate) da Streptobacterium (wanda ke da alaƙa da propionate, butyrate, da isobutyrate) ya ragu a cikin ET kuma yana da alaƙa da matakan SCFA na najasa. b Binciken daidaitawar ET da PD. Bayan daidaitawar FDR, ba a sami wata alaƙa mai mahimmanci ba. Girgizar ET mai mahimmanci, cutar Parkinson, kulawar HC mai lafiya, SCFA. An nuna bambance-bambance masu mahimmanci ta hanyar *P < 0.05 da **P < 0.01.
Lokacin da ake nazarin ET idan aka kwatanta da PD, an gano cewa Clostridium trichophyton ya ƙaru a cikin ET kuma yana da alaƙa da isovaleric acid na hanji (r = -0.238, P = 0.041) da isobutyric acid (r = -0.257, P = 0.027). Bayan daidaitawar FDR, ko dai ya kasance mai mahimmanci (P≥0.295) (Hoto na 4 da Tebur na Ƙarin 5).
Wannan binciken cikakken bincike ne wanda ke bincika matakan SCFA na najasa kuma yana danganta su da canje-canje a cikin ƙwayoyin cuta na hanji da tsananin alamun cutar a cikin marasa lafiya da ET idan aka kwatanta da marasa lafiya da CU da PD. Mun gano cewa matakan SCFA na najasa sun ragu a cikin marasa lafiya da ET kuma suna da alaƙa da tsananin asibiti da canje-canje na musamman a cikin ƙwayoyin cuta na hanji. Matakan tarin kitse na gajerun sarƙoƙi (SCFAs) a cikin najasa sun bambanta ET daga GC da PD.
Idan aka kwatanta da marasa lafiya na GC, marasa lafiya na ET suna da ƙananan matakan najasa na propionic, butyric, da isobutyric acid. Haɗin propionic, butyric da isobutyric acid na iya bambanta tsakanin ET da HC tare da AUC na 0.751 (95% CI: 0.634–0.867), jin daɗin 74.3% da takamaiman 72.9%, yana nuna amfani da su azaman rawar da za a iya takawa a matsayin alamun gano cutar ga ET. Ƙarin bincike ya nuna cewa matakan propionic acid na fecal suna da alaƙa mara kyau da maki Wexner da maki SCOPA-AUT. Matakan isobutyric acid na fecal sun yi daidai da maki FTM. A gefe guda kuma, raguwar matakan butyrate a cikin ET yana da alaƙa da raguwar yawan microbiota masu samar da SCFA, Faecalibacterium, da Categorybacter. Bugu da ƙari, raguwar yawan Catenibacter a cikin ET kuma yana da alaƙa da raguwar matakan propionic da isobutyric acid na fecal.
Yawancin SCFAs da ake samarwa a cikin hanji ana ɗaukar su ta hanyar ƙwayoyin halittar jini musamman ta hanyar jigilar monocarboxylate masu dogaro da H+ ko sodium. Ana amfani da fatty acids masu gajerun sarƙoƙi a matsayin tushen kuzari ga ƙwayoyin halittar jini, yayin da waɗanda ba a haɗa su cikin ƙwayoyin halittar jini ba ana jigilar su zuwa cikin zagayawar portal 18. SCFAs na iya yin tasiri ga motsin hanji, haɓaka aikin shingen hanji, da kuma tasiri ga metabolism na mai masaukin baki da rigakafi19. An gano a baya cewa yawan butyrate, acetate, da propionate ya ragu a cikin najasa a cikin marasa lafiya na PD idan aka kwatanta da HCs17, wanda ya yi daidai da sakamakonmu. Bincikenmu ya gano raguwar SCFA a cikin marasa lafiya da ET, amma ba a san komai game da rawar da SCFA ke takawa a cikin cututtukan ET ba. Butyrate da propionate na iya ɗaurewa da GPCRs kuma suna tasiri ga siginar da ke dogara da GPCR kamar siginar MAPK da NF-κB20. Babban ra'ayin axis na hanji-kwakwalwa shine cewa SCFAs da ƙwayoyin halittar hanji ke fitarwa na iya yin tasiri ga siginar mai masaukin baki, ta haka suna yin tasiri ga aikin hanji da kwakwalwa. Saboda butyrate da propionate suna da tasirin hanawa mai ƙarfi akan aikin histone deacetylase (HDAC)21 kuma butyrate kuma suna iya aiki azaman ligand don abubuwan da ke haifar da rubutu, suna da tasiri mai yawa akan metabolism na mai masaukin baki, bambance-bambance da yaduwa, galibi saboda tasirinsu akan daidaita kwayoyin halitta22. Dangane da shaida daga SCFA da cututtukan neurodegenerative, ana ɗaukar butyrate a matsayin ɗan takarar magani saboda ikonsa na gyara ayyukan HDAC marasa kyau, wanda zai iya magance mutuwar dopaminergic neuron a cikin PD23,24,25. Nazarin dabbobi kuma sun nuna ikon butyric acid don hana lalacewar dopaminergic neuron da inganta rikice-rikicen motsi a cikin samfuran PD26,27. An gano cewa Propionic acid yana iyakance martanin kumburi da kare mutuncin BBB28,29. Nazarin ya nuna cewa propionic acid yana haɓaka rayuwar dopaminergic neurons don mayar da martani ga gubar rotenone a cikin samfuran PD30 kuma cewa shan propionic acid ta baki yana ceton asarar dopaminergic neuron da ƙarancin motsi a cikin beraye tare da PD31. Ba a san komai game da aikin isobutyric acid ba. Duk da haka, wani bincike da aka yi kwanan nan ya gano cewa mamaye beraye tare da B. ovale ya ƙara yawan SCFA na hanji (gami da acetate, propionate, isobutyrate, da isovalerate) da kuma yawan GABA na hanji, yana nuna cewa an kafa alaƙa tsakanin ƙwayoyin cuta na hanji da SCFA na hanji. yawan neurotransmitters32. Ga ET, canje-canje marasa kyau na cututtuka a cikin cerebellum sun haɗa da canje-canje a cikin ƙwayoyin Purkinje da dendrites, ƙaura da asarar ƙwayoyin Purkinje, canje-canje a cikin ƙwayoyin kwandon kwandon, da rashin daidaituwa a cikin haɗin fiber mai hawa zuwa ƙwayoyin Purkinje. nuclei, wanda ke haifar da raguwar fitowar GABAergic daga cerebellum3,4,33. Har yanzu ba a san ko SCFAs suna da alaƙa da neurodegeneration na ƙwayoyin Purkinje da raguwar samar da GABA na cerebellar ba. Sakamakonmu ya nuna alaƙa ta kud da kud tsakanin SCFA da ET; duk da haka, ƙirar binciken da aka yi a kan sassan jiki ba ta ba da damar yanke shawara game da alaƙar da ke tsakanin SCFA da tsarin cutar ET ba. Ana buƙatar ƙarin nazarin bibiya na dogon lokaci, gami da ma'aunin jerin SCFAs na najasa, da kuma nazarin dabbobi da ke bincika hanyoyin.
Ana tsammanin SCFAs suna ƙarfafa ƙanƙantar tsokoki masu santsi na hanji34. Rashin SCFA zai ƙara ta'azzara alamun maƙarƙashiya, kuma ƙarin SCFA na iya inganta alamun maƙarƙashiya PD35. Sakamakonmu kuma yana nuna babban alaƙa tsakanin raguwar yawan SCFA na najasa da ƙaruwar maƙarƙashiya da rashin aiki na autonomic a cikin marasa lafiya da ET. Wani rahoto na shari'a ya gano cewa dashen ƙwayoyin cuta ya inganta rawar jiki mai mahimmanci da ciwon hanji mai haushi a cikin majiyyaci na 7, wanda hakan ya ƙara nuna alaƙar kud da kud tsakanin ƙwayoyin hanji da ET. Saboda haka, mun yi imanin cewa SCFA/microbiota na najasa na iya yin tasiri ga motsi na hanji da aikin tsarin jijiyoyi na autonomic.
Binciken ya gano cewa raguwar matakan SCFAs na najasa a cikin ET yana da alaƙa da raguwar yawan Faecalibacterium (wanda ke da alaƙa da butyrate) da Streptobacterium (wanda ke da alaƙa da propionate, butyrate, da isobutyrate). Bayan gyara FDR, wannan alaƙar ta ci gaba da kasancewa mai mahimmanci. Faecalibacterium da Streptobacterium ƙananan ƙwayoyin cuta ne masu samar da SCFA. An san Faecalibacterium a matsayin ƙananan ƙwayoyin cuta masu samar da butyrate36, yayin da manyan samfuran fermentation na Catenibacterium sune acetate, butyrate da lactic acid37. An gano Faecalibacterium a cikin 100% na ƙungiyoyin ET da HC; Matsakaicin yawan dangi na rukunin ET shine 2.06% kuma na rukunin HC shine 3.28% (LDA 3.870). An gano nau'in ƙwayoyin cuta a cikin 21.6% (8/37) na rukunin HC kuma kawai a cikin samfurin 1 na rukunin ET (1/35). Ragewa da rashin iya gano streptobacteria a cikin ET na iya nuna alaƙa da cututtukan da ke haifar da cutar. Matsakaicin yawan nau'in Catenibacter a cikin rukunin HC shine 0.07% (LDA 2.129). Bugu da ƙari, ƙwayoyin cuta na lactic acid suna da alaƙa da canje-canje a cikin butyrate na najasa (P=0.016, P=0.096 bayan daidaitawar FDR), kuma ɗan takarar amosanin gabbai yana da alaƙa da canje-canje a cikin isobutyrate (P=0.016, P=0.072 bayan daidaitawar FDR). Bayan gyara FDR, yanayin haɗin gwiwa ne kawai ya rage, wanda ba shi da mahimmanci a kididdiga. An kuma san Lactobacilli a matsayin masu samar da SCFA (acetic acid, propionic acid, isobutyric acid, butyric acid) 38 kuma Candidatus Arthromitus takamaiman mai haifar da bambancin ƙwayoyin T mai taimako 17 (Th17), tare da Th1/2 da Tregs da ke da alaƙa da daidaiton garkuwar jiki /Th1739. . Wani bincike da aka yi kwanan nan ya nuna cewa matakan da suka karu na pseudoarthritis na hanji na iya taimakawa wajen kumburin hanji, rashin aikin shingen hanji, da kumburin tsarin jiki 40. An ƙara yawan Clostridium trichophyton a cikin ET idan aka kwatanta da PD. An gano cewa yawan Clostridium trichoides yana da alaƙa da isovaleric acid da isobutyric acid. Bayan daidaitawar FDR, duka sun kasance masu mahimmanci (P≥0.295). Clostridium pilosum wani ƙwayar cuta ce da aka sani da alaƙa da kumburi kuma tana iya ba da gudummawa ga rashin aikin shingen hanji41. Bincikenmu na baya ya ba da rahoton canje-canje a cikin ƙwayoyin cuta na hanji na marasa lafiya da ET8. A nan mun kuma bayar da rahoton canje-canje a cikin ƙwayoyin cuta na hanji na marasa lafiya da ET8. A nan mun kuma bayar da rahoton canje-canje a cikin SCFAs a cikin ET kuma mun gano alaƙa tsakanin dysbiosis na hanji da canje-canje a cikin SCFAs. Rage matakan SCFA suna da alaƙa da dysbiosis na hanji da tsananin girgiza a cikin ET. Sakamakonmu ya nuna cewa axis na hanji-kwakwalwa na iya taka muhimmiyar rawa a cikin pathogenesis na ET, amma ana buƙatar ƙarin bincike a cikin samfuran dabbobi.
Idan aka kwatanta da marasa lafiya da ke fama da PD, marasa lafiya da ke fama da ET suna da ƙarancin matakan isovaleric da isobutyric acid a cikin najasarsu. Haɗin isovaleric acid da isobutyric acid da aka gano ET a cikin PD tare da AUC na 0.743 (95% CI: 0.629–0.857), jin daɗin 74.3% da takamaiman 62.9%, wanda ke nuna yuwuwar rawar da suke takawa a matsayin alamun cutar a cikin ganewar asali na ET. Matakan isovaleric acid na fecal sun yi daidai da maki FTM da TETRAS. Matakan isobutyric acid na fecal sun yi daidai da maki FTM. Rage matakan isobutyric acid yana da alaƙa da raguwar yawan catobacteria. Ba a san komai game da ayyukan isovaleric acid da isobutyric acid ba. Wani bincike da aka yi a baya ya nuna cewa mamaye beraye da ke dauke da Bacteroides ovale ya kara yawan SCFA na hanji (gami da acetate, propionate, isobutyrate, da isovalerate) da kuma yawan GABA na hanji, wanda hakan ya nuna alaƙar hanji tsakanin microbiota da yawan SCFA/neurotransmitter na hanji32. Abin sha'awa, matakan isobutyric acid da aka lura sun yi kama da juna tsakanin kungiyoyin PD da HC, amma sun bambanta tsakanin kungiyoyin ET da PD (ko HC). Isobutyric acid zai iya bambance tsakanin ET da PD tare da AUC na 0.718 (95% CI: 0.599–0.836) da kuma gano ET da NC tare da AUC na 0.655 (95% CI: 0.525–0.786). Bugu da ƙari, matakan isobutyric acid suna da alaƙa da tsananin girgiza, wanda hakan ke ƙara ƙarfafa alaƙarsa da ET. Tambayar ko isobutyric acid na baki zai iya rage tsananin girgiza a cikin marasa lafiya da ET ya cancanci ƙarin bincike.
Saboda haka, yawan sinadarin SCFA na najasa yana raguwa a cikin marasa lafiya da ke fama da ET kuma yana da alaƙa da tsananin ET na asibiti da canje-canje na musamman a cikin ƙwayoyin hanji. Fecal propionate, butyrate, da isobutyrate na iya zama alamun gano cutar ga ET, yayin da isobutyrate da isovalerate na iya zama alamun gano cutar ga ET. Canje-canje a cikin isobutyrate na najasa na iya zama takamaiman ga ET fiye da canje-canje a cikin sauran SCFAs.
Bincikenmu yana da iyakoki da dama. Na farko, tsarin abinci da abubuwan da ake so na abinci na iya yin tasiri ga bayyanar ƙwayoyin cuta, ana buƙatar manyan samfuran bincike a cikin al'ummomi daban-daban, kuma nazarin da za a yi nan gaba ya kamata ya gabatar da cikakken bincike game da abinci mai gina jiki kamar tambayoyin mitar abinci. Na biyu, ƙirar binciken da aka yi a kan ɓangarorin biyu ya hana duk wani ƙarshe game da alaƙar da ke tsakanin SCFAs da haɓaka ET. Ana buƙatar ƙarin nazarin bibiya na dogon lokaci tare da ma'aunin jerin SCFAs na najasa. Na uku, ya kamata a tabbatar da ikon ganewar asali da bambance-bambancen ganewar asali na matakan SCFA na najasa ta amfani da samfuran masu zaman kansu daga ET, HC, da PD. Ya kamata a gwada ƙarin samfuran najasa masu zaman kansu a nan gaba. A ƙarshe, marasa lafiya da PD a cikin ƙungiyarmu sun sami ɗan gajeren lokacin cutar fiye da marasa lafiya da ET. Mun fi daidaita ET, PD da HC ta shekaru, jinsi da BMI. Ganin bambancin yanayin cutar tsakanin ƙungiyar ET da ƙungiyar PD, mun kuma yi nazarin marasa lafiya 33 tare da farkon PD da marasa lafiya 16 tare da ET (tsawon lokacin cuta ≤ shekaru 3) don ƙarin kwatantawa. Bambancin tsakanin rukuni a cikin SCFA gabaɗaya sun yi daidai da bayananmu na farko. Bugu da ƙari, ba mu sami wata alaƙa tsakanin tsawon lokacin cutar da canje-canje a cikin SCFA ba. Duk da haka, a nan gaba, zai fi kyau a ɗauki marasa lafiya da ke da PD da ET a matakin farko tare da ɗan gajeren lokacin cutar don kammala tantancewa a cikin babban samfurin.
Kwamitin ɗa'a na Asibitin Ruijin, wanda ke da alaƙa da Makarantar Likitanci ta Jami'ar Shanghai Jiao Tong (RHEC2018-243) ya amince da yarjejeniyar binciken. An sami izini a rubuce daga dukkan mahalarta.
Tsakanin Janairu 2019 da Disamba 2022, an haɗa mutane 109 (37 ET, 37 PD, da 35 HC) daga Asibitin Cibiyar Rarraba Motsi na Asibitin Ruijin, wanda ke da alaƙa da Makarantar Magunguna ta Jami'ar Shanghai Jiao Tong, a cikin wannan binciken. Sharuɗɗan sune: (1) shekaru 25-85, (2) an gano marasa lafiya da ET bisa ga ka'idojin Ƙungiyar Aiki ta MDS 42 kuma an gano PD bisa ga ka'idojin MDS 43, (3) duk marasa lafiya ba sa shan magungunan hana PD kafin su hau kujera. tattara samfuran. (4) Ƙungiyar ET ta ɗauki β-blockers kawai ko babu magunguna masu alaƙa kafin ta tattara samfuran bayan gida. An kuma zaɓi HCs da suka dace da shekaru, jinsi, da ma'aunin nauyin jiki (BMI). Sharuɗɗan da aka ware su ne: (1) masu cin ganyayyaki, (2) rashin isasshen abinci mai gina jiki, (3) cututtuka na yau da kullun na hanji (gami da cututtukan kumburi na hanji, gyambon ciki ko duodenal), (4) cututtuka masu tsanani na yau da kullun (gami da ciwace-ciwacen daji), gazawar zuciya, gazawar koda, cututtukan jini) (5) Tarihin babban tiyatar ciki, (6) Shan yogurt na yau da kullun ko akai-akai, (7) Amfani da duk wani probiotics ko maganin rigakafi na tsawon wata 1, (8) Amfani da corticosteroids na yau da kullun, hana proton pump, statins, metformin, immunosuppressants ko magungunan hana ciwon daji da kuma (9) mummunan raunin fahimta wanda ke tsoma baki ga gwaje-gwajen asibiti.
Duk waɗanda aka yi wa gwajin sun bayar da tarihin lafiya, bayanai kan nauyi da tsayi don ƙididdige BMI, kuma an yi musu gwajin jijiyoyi da kimantawa ta asibiti kamar Hamilton Anxiety Rating Scale (HAMA) 44, Hamilton Depression Rating Scale-17 (HAMD-17) 45. baƙin ciki, tsananin maƙarƙashiya ta amfani da Wexner Constipation Scale 46 da Bristol Scale 47 da kuma aikin fahimta ta amfani da Mini-Mental State Examination (MMSE) 48. Sikelin Ƙimar Alamomin Cutar Parkinson (SCOPA-AUT) 49 ya binciki rashin lafiyar autonomic a cikin marasa lafiya da ET da PD. Sikelin Ƙimar Tremor Clinical Fan-Tolos-Marin Clinical (FTM) da Essential Tremor Rating Scale (TETRAS) 50 An binciki Ƙungiyar Nazarin Tremor (TRG) 50 a cikin marasa lafiya da ET; An binciki sikelin ƙimar cutar Kinson (MDS-UPDRS) sigar 51 da Hoehn da Yahr (HY) maki 52.
An nemi kowanne mahalarci ya ɗauki samfurin bayan gida da safe ta amfani da akwatin tattara bayan gida. A mayar da kwantena zuwa kankara a adana a -80°C kafin a sarrafa su. An gudanar da binciken SCFA bisa ga ayyukan yau da kullun na Tiangene Biotechnology (Shanghai) Co., Ltd. An tattara 400 MG na sabbin samfuran bayan gida daga kowane mutum kuma an yi nazari ta amfani da SCFAs bayan niƙa da kuma kafin a yi amfani da sonication. An yi nazarin zaɓaɓɓun SCFAs a cikin bayan gida ta amfani da gas chromatography-mass spectrometry (GC-MS) da liquid chromatography-tandem MS (LC-MS/MS).
An cire DNA daga samfuran MG 200 ta amfani da QIAamp® Fast DNA Stool Mini Kit (QIAGEN, Hilden, Jamus) bisa ga umarnin masana'anta. An ƙayyade abun da ke cikin ƙwayoyin cuta ta hanyar jera kwayar halittar S rRNA 16 akan DNA da aka ware daga najasa ta hanyar ƙara girman yankin V3-V4. Gwada DNA ta hanyar gudanar da samfurin akan gel na agarose 1.2%. An yi amfani da haɓakar sarkar polymerase (PCR) na kwayar halittar 16S rRNA ta amfani da firam ɗin ƙwayoyin cuta na duniya (357 F da 806 R) da kuma ɗakin karatu na amplicon mai matakai biyu da aka gina akan dandamalin Novaseq.
Ana bayyana masu canji masu ci gaba a matsayin matsakaicin ± karkacewar daidaito, kuma ana bayyana masu canji na rukuni a matsayin lambobi da kashi. Mun yi amfani da gwajin Levene don gwada daidaiton bambance-bambancen. An yi kwatancen ta amfani da gwaje-gwajen t-t-tailed biyu ko nazarin bambance-bambancen (ANOVA) idan aka saba rarraba masu canji kuma an yi gwaje-gwajen Mann-Whitney U marasa parametric idan an keta ƙa'idodin daidaito ko homoscedasticity. Mun yi amfani da yankin da ke ƙarƙashin lanƙwasa na aikin mai karɓa (ROC) (AUC) don auna aikin ganewar asali na samfurin da kuma bincika ikon SCFA na bambance marasa lafiya da ET daga waɗanda ke da HC ko PD. Don bincika alaƙar da ke tsakanin SCFA da tsananin asibiti, mun yi amfani da nazarin hulɗar Spearman. An gudanar da nazarin ƙididdiga ta amfani da software na SPSS (sigar 22.0; SPSS Inc., Chicago, IL) tare da matakin mahimmanci (gami da ƙimar P da FDR-P) wanda aka saita a 0.05 (gefe biyu).
An yi nazarin jerin S 16 ta amfani da haɗin Trimmomatic (sigar 0.35), Flash (sigar 1.2.11), UPARSE (sigar v8.1.1756), mothur (sigar 1.33.3) da R (sigar 3.6.3). An sarrafa bayanan kwayoyin halitta na rRNA na raw 16S ta amfani da UPARSE don samar da raka'o'in taxonomic na aiki (OTUs) tare da asalin 97%. An ƙayyade taxonomies ta amfani da Silva 128 a matsayin bayanan tunani. An zaɓi matakin janar na bayanai masu yawa na dangi don ƙarin bincike. An yi amfani da nazarin girman tasirin Linear discriminant analysis (LDA) (LEfSE) don kwatantawa tsakanin ƙungiyoyi (ET vs. HC, ET vs. PD) tare da matakin α na 0.05 da matakin girman sakamako na 2.0. An ƙara amfani da nau'ikan rarrabuwa da aka gano ta hanyar nazarin LEfSE don nazarin hulɗar Spearman na SCFA.
Don ƙarin bayani game da tsarin binciken, duba Takaitaccen Rahoton Bincike na Halitta wanda ke da alaƙa da wannan labarin.
Ana adana bayanan jerin 16S na Raw 16S a cikin bayanan Cibiyar Bayar da Bayanai kan Fasahar Halittu ta Ƙasa (NCBI) (SRP438900: PRJNA974928), URL: https://www.ncbi.nlm.nih.gov/Traces/study/?acc= SRP438900&o. =acc_s% 3Aa. Sauran bayanai masu dacewa suna samuwa ga marubucin da ya dace akan buƙata mai ma'ana, kamar haɗin gwiwar kimiyya da musayar ilimi tare da cikakkun ayyukan bincike. Ba a yarda da canja wurin bayanai ga wasu kamfanoni ba tare da izininmu ba.
Buɗe lambar tushe kawai tare da haɗin Trimmomatic (sigar 0.35), Flash (sigar 1.2.11), UPARSE (sigar v8.1.1756), mothur (sigar 1.33.3) da R (sigar 3.6.3), ta amfani da saitunan tsoho ko sashe na "Hanyar". Ana iya ba da ƙarin bayani mai fayyace ga marubucin da ya dace idan an buƙata.
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