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Iigranules zeBan-Lan-Gen zinciphisa i-dextran sodium sulfate-induced chronic relapsing colitis kwiimpuku ngokuguqula i-gut microbiota kunye nokubuyisela imveliso ye-SCFA Derived-GLP-1 yamathumbu
UJiao Peng,1-3,*Li Xi,4,*Zheng Lin,3,5 Duan Lifang,1 Gao Zhengxian,2,5 Diehu,1 Li Jie,6 Li Xiaofeng,6 Shen Xiangchun,5 Xiao Haitao21 Isibhedlele sasePeking University Shenzhen Isebe leKhemesti, eShenzhen, kwiRiphabliki yabantu baseTshayina; 2 IZiko leSayensi yezeMpilo kwiYunivesithi yaseShenzhen Isikolo seKhemesti, eShenzhen, kwiRiphabliki yabantu baseTshayina; 3 IZiko loPhando loBunjineli beYunivesithi yezoNyango yaseGuizhou Medical Technology lezonyango lobuhlanga kunye nophuhliso kunye nokusetyenziswa kwezonyango zesiTshayina zemveli UMphathiswa weMfundo, iLebhu ephambili yePhondo laseGuizhou yeKhemesti, kwiYunivesithi yezoNyango yaseGuizhou, eGuiyang, kwiRiphabliki yabantu baseTshayina; 4 ISebe leGastroenterology, iSibhedlele saseShenzhen kwiYunivesithi yasePeking, eShenzhen, kwiRiphabliki yabantu baseTshayina; 5 Isikolo seKhemesti, iYunivesithi yezoNyango yaseGuizhou, iLebhu ephambili yeLizwe yeZityalo zeMithi kunye nokusebenza, eGuiyang; 6 ISebe lezonyango leLebhu, iYunivesithi yasePeking iSibhedlele saseShenzhen, eShenzhen, eTshayina [email protected] IShen Xiangchun, iSikolo seKhemisti, iYunivesithi yezoNyango yaseGuizhou, eGuizhou, kwiRiphabliki yabantu baseTshayina, 550004, I-imeyile [email protected] Injongo: Unyango olusekelwe kwi-GLP-1 lukhetho olutsha lonyango lwesifo samathumbu esidumbileyo. Iigranules zeBan-Lan-Gen (BLG) ziyindlela eyaziwayo ye-TCM yokulwa neentsholongwane ebonisa umsebenzi onokuthi ulwe nokuvuvukala kunyango lweemeko ezahlukeneyo zokudumba. Nangona kunjalo, isiphumo sayo sokulwa nokuvuvukala kwi-colitis kunye nendlela esebenza ngayo azikacaci. IINDLELA: Ukumisela i-dextran sodium sulfate (DSS) ebangelwa yi-colitis engapheliyo ephindaphindayo kwiimpuku. Izalathisi zomsebenzi wesifo, iimpawu ze-histological zokulimala, kunye namanqanaba e-cytokine ebangela ukuvuvukala zenziwe ukuvavanya isiphumo sokukhusela se-BLG. Imiphumo ye-BLG kwi-gut microbiota kunye namathumbu ibonakaliswe ngamanqanaba e-serum GLP-1 kunye nokubonakaliswa kwe-colonic Gcg, GPR41, kunye ne-GRP43, ukwakheka kwe-gut microbiota, indle Amanqanaba e-SCFA, kunye nokukhululwa kwe-GLP-1 kwiiseli ze-epithelial ze-mouse eziphambili Ukuveliswa kwe-GLP-1 evela kwi-SCFA. Iziphumo: Unyango lwe-BLG lunciphise kakhulu ukulahleka kobunzima bomzimba, i-DAI, ukufinyeza kwamathumbu amakhulu, umonakalo wezicubu zamathumbu amakhulu, kunye namanqanaba e-cytokine e-proinflammatory ye-TNF-α, IL-1β, kunye ne-IL-6 kwizicubu zamathumbu amakhulu. Ukongeza, unyango lwe-BLG lunokubuyisela kakhulu i-Gcg yamathumbu amakhulu, i-GPR41 kunye ne-GRP43 expression kunye namanqanaba e-GLP-1 kwi-serum kwiimpuku ze-colitis, nangokwandisa iibhaktheriya ezivelisa i-SCFA ezifana ne-Akkermansia kunye ne-Prevotellaceae_UCG-001, kunye nokunciphisa ubuninzi beebhaktheriya ezifana ne-Eubacterium_xylanophilum_group, i-Ruminococcaceae_UCG-014, i-Intestinimonas kunye ne-Oscillibacter. Ukongeza, unyango lwe-BLG lunokunyusa kakhulu inqanaba le-SCFA kwindle yeempuku ze-colitis. Kwangaxeshanye, uvavanyo lwe-in vitro lukwabonise ukuba i-extract yelindle yeempuku eziphathwe nge-BLG inokukhuthaza kakhulu iiseli ze-epithelial ze-Murine colonic ezincinci ezikhupha i-GLP-1. Izigqibo: Ezi ziphumo zibonisa ukuba i-BLG inefuthe lokulwa ne-colitis. I-BLG inamandla okuphuhliswa njengonyango, ubuncinane ngokuyinxenye ngokuguqula i-gut microbiota kunye nokubuyisela imveliso ye-GLP-1 yamathumbu ephuma kwi-SCFA. Amayeza athembisayo kwi-colitis engapheliyo ephinda ibuyele. Amagama angundoqo: i-colitis, ii-granules ze-Ban-Lan-Gen, i-gut microbiota, ii-fatty acids ezimfutshane, i-GLP-1
I-ulcerative colitis (UC) sisifo sokudumba esihlala ixesha elide kwi-colon kunye ne-rectum esibonakaliswa kurhudo oluphindaphindayo, iintlungu zesisu, ukwehla kobunzima, kunye nendle enegazi eliphuma kwi-mucopurulent.1 Kutshanje, ukuxhaphaka kwe-UC kuye kwanda kumazwe awayengenazo izifo kangako ngaphambili, kuquka neTshayina, kunye nokuthandwa okukhulayo kwendlela yokuphila yaseNtshona.2 Oku kwanda kubangela iingxaki ezinkulu kwimpilo yoluntu kwaye kunemiphumo emibi kumandla ezigulane okusebenza kunye nomgangatho wobomi. Okuphawulekayo kukuba, i-pathogenesis ye-UC ayikacaci kangako, kodwa kuyavunywa ngokubanzi ukuba i-genetics, izinto ezingqongileyo, i-gut microbiota, kunye ne-immune system zonke zinegalelo ekuphuhlisweni kwe-UC.3 Kwanangoku, akukho nyango lwe-UC, kwaye injongo yonyango kukulawula iimpawu zeklinikhi ngokwezonyango, ukukhuthaza nokugcina ukuxolelwa, ukukhuthaza ukuphiliswa kwe-mucosal, kunye nokunciphisa ukuphinda kuvele. Unyango lweklasikhi luquka i-aminosalicylates, ii-corticosteroids, ii-immunosuppressants, kunye ne-biologics. Nangona kunjalo, la mayeza awakwazi ukufikelela kwisiphumo esifunekayo ngenxa yeziphumo zawo ezahlukeneyo.4 Kutshanje, izifundo ezininzi zibonise ukuba amayeza emveli aseTshayina (TCM) abonakalise amandla amakhulu ekuncedeni ukunciphisa I-UC enetyhefu ephantsi, nto leyo ebonisa ukuba uphuhliso lwezonyango ezintsha ze-TCM lucebo lonyango oluthembisayo lwe-UC.5-7
I-Banlangen Granules (BLG) sisilungiselelo semveli samayeza aseTshayina esenziwe ngesicatshulwa samanzi seengcambu zeBanlangen.8 Ukongeza ekusebenzeni kwayo njenge-antiviral, i-BLG ibonisa umsebenzi onokuthi ulwe nokudumba ekunyangeni iimeko ezahlukeneyo zokudumba.9,10 Ukongeza, ii-glucosinolates (R,S-goitrin, progoitrin, epiprorubin kunye ne-glucoside ziye zahlulwa zaza zachongwa kwiimveliso zamanzi zeRadix isatidis) kunye nee-nucleosides (hypoxanthine, adenosine, uridine kunye ne-guanosine) kunye nee-alkaloids ze-indigo ezifana ne-indigo kunye ne-indirubin.11,12 Izifundo zangaphambili zibonise kakuhle ukuba iikhompawundi ze-adenosine, uridine kunye ne-indirubin zibonisa iziphumo ezinamandla zokulwa ne-colitis kwiimodeli ezahlukeneyo zezilwanyana ze-colitis.13-17 Nangona kunjalo, akukho zifundo ezisekelwe kubungqina ezenziweyo ukuvavanya ukusebenza kwe-BLG kwi-colitis. Kolu phononongo, siphande ngesiphumo sokukhusela se-BLG kwi-colitis engapheliyo ebangelwa yi-dextran sodium sulfate (DSS) kwi-colitis engapheliyo ephindaphindayo kwi- C57BL/6 iimpuku kwaye zafumanisa ukuba ukunikwa ngomlomo kwe-BLG kuyinciphise kakhulu i-DSS-induced chronic relapsing colon kwiimpuku. Ukuvuvukala, iindlela zayo zokulawula zidibene nokuguqulwa kwe-gut microbiota kunye nokubuyiselwa kwemveliso ye-glucagon-like peptide-1 (GLP-1) evela kwisisu.
Iigranule ze-BLG (ezingenaswekile, ezivunyiweyo yi-NMPA yi-Z11020357; iBeijing Tongrentang Technology Development Co., Ltd., eBeijing, eTshayina; inombolo yebhetshi: 20110966) zithengwe kwiikhemesti. I-DSS (Ubunzima beMolecular: 36,000–50,000 Daltons) ithengwe kwi-MP Biologicals (eSanta Ana, eMelika). I-Sulfasalazine (SASP) (≥ 98% ubumsulwa), i-hematoxylin kunye ne-eosin zithengwe kwi-Sigma-Aldrich (eSt. Louis, MO, eMelika). Iikiti zovavanyo lwe-mouse TNF-α, IL-1β kunye ne-IL-6 luminex Elisa zithengwe kwiinkqubo ze-R&D (eMinneapolis, eMelika, eMelika). I-Acetic acid, i-propionic acid, kunye ne-butyric acid zithengwe kwi-Aladdin Industries (eShanghai, eTshayina). I-2-Ethylbutyric acid ithengwe kwi-Merck KGaA (eDarmstadt, eJamani).
Iimpuku ezingamadoda ezineeveki ezi-6-8 ubudala ze-C57BL/6 (ubunzima bomzimba obuyi-18-22 g) zithengwe eBeijing Wetahe Laboratory Animal Technology Co., Ltd. (eBeijing, eTshayina) zaza zagcinwa kwindawo engama-22 ± 2 °C kunye nomjikelo wokukhanya/omnyama weeyure ezili-12. Iimpuku zondliwa ukutya okuqhelekileyo kweempuku kunye nokufikelela simahla emanzini okusela iveki enye ukuze ziqhelane nendawo entsha. Iimpuku zahlulwahlulwa ngokungacwangciswanga zaba ngamaqela amane: iqela lolawulo, iqela lemodeli ye-DSS, iqela elinyangwa yi-SASP (200 mg/kg, ngomlomo) kunye neqela elinyangwa yi-BLG (1 g/kg, ngomlomo). Njengoko kubonisiwe kuMfanekiso 1A, ngokwesifundo sethu sangaphambili, isifo sokuvuvukala esingapheliyo esiphindaphindayo sovavanyo sabangelwa kwiimpuku ngemijikelo emithathu ye-1.8% DSS kangangeentsuku ezi-5, kulandele amanzi acociweyo kangangeentsuku ezi-7, ngokwesifundo sethu sangaphambili.18 Iimpuku kumaqela anyangwa yi-SASP kunye ne-BLG zanyangwa nge-SASP kunye ne-BLG, ngokwahlukeneyo, yonke imihla ukususela ngomhla we-0. Ngokwezilingo zokuqala, idosi ye-BLG imiselwe kwi-1 g/kg. Okwangoku, idosi ye-SASP imiselwe kwi-200 mg/Kg ngokweencwadi.4 Amaqela olawulo kunye neemodeli ze-DSS afumene umthamo ofanayo wamanzi kulo lonke uvavanyo.
Umfanekiso 1 I-BLG ilungisa i-colitis engapheliyo ephindaphindayo ebangelwa yi-DSS kwiimpuku. (A) Uyilo lovavanyo lwe-colitis engapheliyo ephindaphindayo kunye nonyango, (B) utshintsho lobunzima bomzimba, (C) amanqaku esalathisi somsebenzi wesifo (i-DAI), (D) ubude bekholoni, (E) umfanekiso omele ikholoni, (F) i-H&E staining Colon (ukukhulisa, ×100) kunye (G) amanqaku e-histological. Idatha iboniswa njenge-avareji ± SEM (n = 6).##p < 0.01 okanye ###p < 0.001 vs iqela lolawulo (Con); *p < 0.05 okanye **p < 0.01 okanye ***p < 0.001 vs iqela le-DSS.
Ubunzima bomzimba, ukuqina kwendle, kunye nokopha emqolo kwakurekhodwa yonke imihla. Isalathisi somsebenzi wesifo (i-DAI) sachongwa ngokuhlanganisa amanqaku obunzima bomzimba, ukuqina kwendle, kunye nokopha emqolo njengoko kuchaziwe ngaphambili.19 Ekupheleni kovavanyo, zonke iimpuku zabulawa kwaye igazi, ilindle kunye ne-colon zaqokelelwa ukuze kwenziwe uvavanyo olongezelelweyo.
Izicubu zekholoni zilungisiwe zaza zafakwa kwiparafini. Amacandelo e-5-micron enziwe aza adaywa nge-hematoxylin-eosin (H&E), emva koko afiphazwa kwaye afakwa amanqaku njengoko kuchaziwe ngaphambili.19
I-RNA iyonke yezicubu zamathumbu ikhutshwe yi-Trizol reagent (Invitrogen, Carlsbad, CA), ilandelwa kukukhutshwa kwe-cDNA nge-reverse transcriptase (TaKaRa, Kusatsu, Shiga, Japan). I-PCR yobungakanani yenziwe kusetyenziswa inkqubo ye-PCR yexesha langempela ene-SYBR Green Master (Roche, Basel, Switzerland). Ii-Target gene transcripts zenziwe zalungelelaniswa kwi-β-actin kwaye idatha yahlalutywa kusetyenziswa indlela ye-2-ΔΔCT. I-gene primer sequences iboniswe kwiTheyibhile 1.
Ukwahlulwa kweeseli ze-epithelial ze-colonic yegundane kunye nokulima kwenziwa njengoko kuchaziwe ngaphambili.20 Ngokufutshane, iikholoni zeempuku ezineeveki ezi-6-8 ubudala zaqala zasuswa emva kokuba zibulawe ngokusasazeka komlomo wesibeleko, zaza zavulwa ixesha elide, zanyangwa ngeHanks Balanced Salt Solution (HBSS, ngaphandle kwecalcium kunye ne-magnesium) zaza zanqunyulwa zaba ziingceba ezincinci eziyi-0.5-1 mm. Emva koko, izicubu zagaywa nge-0.4 mg/mL collagenase XI (Sigma, Poole, UK) kwi-free DMEM medium zaza zafakwa kwi-centrifuge kwi-300 xg kangangemizuzu emi-5 kubushushu begumbi. Phinda uxhome i-pellet kwi-DMEM medium (yongezwe nge-10% ye-fetal bovine serum, iiYunithi ezili-100/mL penicillin, kunye ne-100 µg/mL streptomycin) kwi-37 °C kwaye zidlule kwi-nylon mesh (ubukhulu be-pore ~250 µm). Ii-Aliquots zeeseli ze-epithelial ze-colonic zafakwa kwizitya ezisezantsi kweglasi zaza zafakwa kwi-acetic acid, i-propionic acid, i-asidi ye-butyric, kunye nezicatshulwa zelindle lempuku iiyure ezi-2 kwi-37°C, i-5% ye-CO2.
Izicubu zekholoni zadityaniswa ne-PBS, kwaye amanqanaba e-cytokines IL-6, TNF-α kunye ne-IL-1β kwizicubu zekholoni afunyaniswa kusetyenziswa izixhobo zovavanyo lwe-luminex ELISA (iinkqubo ze-R&D, eMinneapolis, MN, e-USA). Ngokufanayo, amanqanaba e-GLP-1 kwi-serum kunye ne-culture medium yeeseli ze-epithelial ze-murine colonic eziphambili amiselwa nge-ELISA kit (eBioswamp, eWuhan, eTshayina) ngokwemiyalelo yomenzi.
I-DNA iyonke ephuma kwindle ikhutshwe kusetyenziswa i-DNA extraction kit (eTiangen, eTshayina). Umgangatho kunye nobungakanani be-DNA bulinganiswe kwi-ratios ye-260 nm/280 nm kunye ne-260 nm/230 nm, ngokwahlukeneyo. Emva koko, kusetyenziswa i-DNA nganye ekhutshiweyo njengetemplate, ii-primers ezithile ze-338F (ACTCCTACGGGAGGCAGCAG) kunye ne-806R (GGACTACHVGGGTWTCTAAT) zisetyenzisiwe ukukhulisa iindawo ze-V3-V4 ze-16S rRNA gene kwiindawo ezahlukeneyo. Iimveliso ze-PCR zicociwe kusetyenziswa i-QIAquick Gel Extraction Kit (QIAGEN, eJamani), ezilinganiswe yi-real-time PCR, kwaye zalandelelaniswa kusetyenziswa i-IlluminaMiseq PE300 sequencing platform (Illumina Inc., CA, USA). Uhlalutyo lwe-bioinformatics, ukucutshungulwa kwedatha kwenziwe ngokulandela iiprotokholi ezixeliweyo ngaphambili.21,22 Ngamafutshane, sebenzisa i-Cutaptate (V1.9.1) ukucoca iifayile ze-raw express. Ii-OTU zadityaniswa kusetyenziswa i-UPARSE (inguqulelo 7.0.1001) ene-cutoff efanayo ye-97%, kwaye i-UCHIME yasetyenziswa ukususa ulandelelwano lwe-chimeric. Uhlalutyo lokwakheka koluntu kunye nokuhlelwa lwenziwe kusetyenziswa i-RDP classifier (http://rdp.cme.msu.edu/) ngokusekelwe kwi-database ye-SILVA ribosomal RNA gene.
Amanqanaba e-short-chain fatty acids (i-acetic acid, i-propionic acid, kunye ne-butyric acid) alinganiswe njengoko kuchaziwe ngaphambili nguTao et al., kunye notshintsho oluthile.23 Ngamafutshane, i-100 mg yendle yaqala yaxhonywa kwi-0.4 mL yamanzi acocekileyo, yalandelwa yi-0.1 mL ye-50% ye-sulfuric acid kunye ne-0.5 mL ye-2-ethylbutyric acid (umgangatho wangaphakathi), emva koko yaguqulwa yaza yafudunyezwa kwi-4°C. I-Centrifuge kwi-12,000 rpm imizuzu eli-15 kwi-C. I-supernatant ikhutshwe nge-0.5 mL ye-ether yaza yafakwa kwi-GC ukuze ihlalutywe. Kwi-gas chromatography (GC) analysis, iisampulu zahlalutywa kusetyenziswa i-GC-2010 Plus gas chromatograph (Shimadzu, Inc.) exhotyiswe nge-flame ionization detector (FID). Ukwahlula kufezekiswe kusetyenziswa ikholamu ye-ZKAT-624, 30 m × 0.53 mm × 0.3 μm (Lanzhou Zhongke Antai Analytical Technology Co., Ltd., China). Idatha ifunyenwe kusetyenziswa isoftware yesisombululo se-GC (Shimadzu, Inc.). Umlinganiselo wokwahlulwa ube yi-10:1, igesi ethwalayo yayiyi-nitrogen, kwaye izinga lokuhamba kwayo libe yi-6 mL/min. Umthamo we-injection ube yi-1 μL. Ubushushu be-injector kunye ne-detector bebuyi-300°C. Ubushushu be-oven bubanjwe kwi-140°C imizuzu eli-13.5, emva koko banda baya kwi-250°C kwi-a izinga lobushushu le-120°C/min; ubushushu bugcinwe imizuzu emi-5.
Idatha iboniswa njengempazamo eqhelekileyo ye-± ye-mean (SEM). Ukubaluleka kwedatha kuhlolwe yi-ANOVA yendlela enye kulandele uvavanyo lukaDuncan lwe-multiple range. Isoftware yeGraphPad Prism 5.0 (GraphPad Software Inc., eSan Diego, CA, e-USA) isetyenzisiwe kuzo zonke izibalo kwaye i-p < 0.05 ithathwa njengebalulekileyo ngokwezibalo.
Kuyaziwa ukuba i-UC sisifo se-colitis esingapheliyo esiphinda sibuye esineentlungu eziqatha zesisu, urhudo kunye nokopha. Ngenxa yoko, i-colitis engapheliyo ephinda ibuye ebangelwe yi-DSS kwiimpuku yasekwa ukuze kuvavanywe ukusebenza kwe-BLG yokulwa ne-colitis (Umzobo 1A). Xa kuthelekiswa neqela lolawulo, iimpuku kwiqela lemodeli ye-DSS zazinobunzima bomzimba obuphantsi kakhulu kunye ne-DAI ephezulu, kwaye olu tshintsho lwaguqulwa kakhulu emva kweentsuku ezingama-24 zonyango lwe-BLG (Umfanekiso 1B kunye no-C). Ukunciphisa ikholoni luphawu olubalulekileyo lwe-UC. Njengoko kubonisiwe kwiMifanekiso 1D kunye no-E, ubude bekholoni yeempuku ezafumana i-DSS bancitshiswa kakhulu, kodwa bancitshiswa lunyango lwe-BLG. Emva koko, uhlalutyo lwe-histopathological lwenziwa ukuvavanya ukudumba kwekholoni. Imifanekiso enemibala ye-H&E kunye namanqaku e-pathological abonise ukuba ulawulo lwe-DSS luphazamise kakhulu uyilo lwekholoni kwaye lwabangela ukutshatyalaliswa kwe-crypt, ngelixa unyango lwe-BLG lunciphise kakhulu ukutshatyalaliswa kwe-crypt kunye namanqaku e-pathological (Umfanekiso 1F kunye no-G). Ngokuphawulekayo, isiphumo sokukhusela se-BLG kwidosi ye-1 g/Kg sasifana neso se I-SASP ngedosi ye-200 mg/Kg. Ezi ziphumo zibonisa ukuba i-BLG iyasebenza ekunciphiseni ubunzima be-DSS-induced chronic relapsing colitis kwiimpuku.
I-TNF-α, i-IL-1β kunye ne-IL-6 ziimpawu ezibalulekileyo zokudumba kokuvuvukala kwamathumbu amakhulu. Njengoko kubonisiwe kuMfanekiso 2A, i-DSS ibangele ukwanda okukhulu kokubonakaliswa kwezakhi zofuzo ze-TNF-α, i-IL-1β kunye ne-IL-6 kumathumbu amakhulu amakhulu xa kuthelekiswa neqela lolawulo. Ulawulo lwe-BLG lunokuguqula kakhulu olu tshintsho olubangelwa yi-DSS. Okulandelayo, sisebenzise i-ELISA ukumisela amanqanaba ee-cytokines ezivuvukalayo ze-TNF-α, i-IL-1β, kunye ne-IL-6 kwizicubu zamathumbu amakhulu. Iziphumo zikwabonise ukuba amanqanaba e-TNF-α, i-IL-1β, kunye ne-IL-6 kumathumbu amakhulu anyuswe kakhulu kwiimpuku ezinyangwe nge-DSS, ngelixa unyango lwe-BLG lunciphise oku kunyuka (Umfanekiso 2B).
Umfanekiso 2 I-BLG ithintela ukubonakaliswa kwezakhi zofuzo kunye nokuveliswa kwee-cytokines ezibangela ukuvuvukala i-TNF-α, IL-1β kunye ne-IL-6 kwikholoni yeempuku eziphathwe yi-DSS.(A) Ukubonakaliswa kwezakhi zofuzo zekholoni ze-TNF-α, IL-1β kunye ne-IL-6; (B) amanqanaba eprotheyini yekholoni ye-TNF-α, IL-1β kunye ne-IL-6. Idatha iboniswa njenge-avareji ± SEM (n = 4–6).#p < 0.05 okanye ##p < 0.01 okanye ###p < 0.001 vs iqela lolawulo (Con); *p < 0.05 okanye **p < 0.01 vs iqela le-DSS.
I-dysbiosis yamathumbu ibaluleke kakhulu kwi-pathogenesis ye-UC.24 Ukuphanda ukuba i-BLG iyayilawula na i-microbiota yamathumbu eempuku eziphathwe yi-DSS, kwenziwe ulandelelwano lwe-16S rRNA ukuhlalutya uluntu lwebhaktiriya lwezinto eziqulethwe ngamathumbu. Umzobo weVenn ubonisa ukuba la maqela mathathu abelana ngee-OTU ezingama-385. Kwangaxeshanye, iqela ngalinye lalinee-OTU ezizodwa (Umzobo 3A). Ngaphezu koko, i-Chao1 index kunye ne-Shannon index eziboniswe kuMfanekiso 3B kunye no-C zibonise ukuba ukwahluka koluntu lwe-microbiota yamathumbu kuncitshisiwe kwiimpuku eziphathwe yi-BLG, njengoko i-Shannon index yehle kakhulu kwiqela eliphathwe yi-BLG. Uhlalutyo lwecandelo eliphambili (i-PCA) kunye nohlalutyo oluphambili (i-PCoA) zisetyenzisiwe ukumisela iipatheni zokudibanisa phakathi kwamaqela amathathu kwaye zibonise ukuba ulwakhiwo loluntu lweempuku eziphathwe yi-DSS lwahlulwe ngokucacileyo emva konyango lwe-BLG (Umfanekiso 3D kunye no-E). Ezi datha zibonisa ukuba unyango lwe-BLG luchaphazele kakhulu ulwakhiwo loluntu lweempuku ezine-DSS-induced colitis.
Umfanekiso 3 I-BLG itshintsha ulwahlulo lwe-gut microbiota kwiimpuku ezine-DSS-induced colitis.(A) Umzobo weVenn we-OTU, (B) Isalathisi seChao1, (C) Isalathisi sobutyebi bukaShannon, (D) Isicwangciso samanqaku e-Principal Component Analysis (PCA) se-OTU, (E) Isiphumo se-OTU Principal Coordinate Analysis (PCoA) Umfanekiso. Idatha iboniswe njenge-mean ± SEM (n = 6).**p < 0.01 vs iqela le-DSS.
Ukuvavanya utshintsho oluthile kwi-fecal microbiota, sihlalutye ukwakheka kwe-gut microbiota kuwo onke amanqanaba e-taxonomic. Njengoko kubonisiwe kuMfanekiso 4A, i-phyla ephambili kuwo onke amaqela yayiyiFirmicutes kunye neBacteroidetes, ilandelwa yiVerrucomicrobia. Ubuninzi be-Firmicutes kunye neFirmicutes/Bacteroidetes ratios bande kakhulu kuluntu lwe-fecal microbial lweempuku eziphathwe yi-DSS xa kuthelekiswa neempuku zolawulo, kwaye olu tshintsho lwaguqulwa kakhulu emva konyango lwe-BLG. Ngokukodwa, unyango lwe-BLG lonyuse kakhulu ubuninzi be-Verrucobacterium kwindle yeempuku ezine-DSS-induced colitis. Kwinqanaba lekhaya, uluntu lwe-fecal microbial lwaluhlalwa yiLachnospiriaceae, iMuribaculaceae, i-Akkermansiaceae, iRuminococcaceae kunye nePrevotellaceae (Umzobo 4B). Xa kuthelekiswa neqela le-DSS, ukuncipha kwe-BLG kwandisa ubuninzi be-Akkermansiaceae, kodwa kunciphisa ubuninzi be-Lachnospiraceae kunye neRuminococcaceae. Ngokukodwa, kwi-genus kwinqanaba, i-microbiota yendle yayihlalwe yiLachnospira_NK4A136_group, iAkkermansia kunye nePrevotellaceae_UCG-001 (Umzobo 4C). Olu phando lukwabonise ukuba unyango lwe-BLG luguqule ngempumelelo ukungalingani kwe-microbiota ukuphendula umngeni we-DSS, obonakaliswe kukwehla kwe-Eubacterium_xylanophilum_group, iRuminococcaceae_UCG-014, i-Intestinimonas kunye ne-Oscillibacter, kunye nokwanda kwe-Akkermansia kunye nePrevotellaceae_UCG-001.
Umfanekiso 4 I-BLG itshintsha ubuninzi be-gut microbiota kwiimpuku ze-DSS-induced colitis.(A) Ubuninzi be-gut microbiota kwinqanaba le-phylum; (B) Ubuninzi be-gut microbiota kwinqanaba losapho; (C) Ubuninzi be-gut microbiota kwinqanaba lohlobo. Idatha iboniswa njenge-avareji ± SEM (n = 6).#p < 0.05 okanye ###p < 0.001 vs iqela lolawulo (Con); *p < 0.05 okanye **p < 0.01 okanye ***p < 0.001 vs iqela le-DSS.
Xa sicinga ukuba ii-fatty acids ezimfutshane (ii-SCFA) zezona metabolites ziphambili ze-Akkermansia kunye ne-Prevotellaceae_UCG-001, ngelixa i-acetate, i-propionate kunye ne-butyrate zezona SCFA zininzi kakhulu kwi-intestinal lumen, sisafunda kwi-25-27. Njengoko kubonisiwe kuMfanekiso 5, amanqanaba e-fecal acetate, i-propionate, kunye ne-butyrate ancitshiswe kakhulu kwiqela eliphathwe yi-DSS, ngelixa unyango lwe-BLG lunokuthintela kakhulu oku kuncipha.
Umfanekiso 5. I-BLG yonyusa amanqanaba e-SCFAs kwindle yeempuku ezine-DSS-induced colitis.(A) Umxholo we-acetic acid kwindle; (B) umxholo we-propionic acid kwindle; (C) umxholo we-butyric acid kwindle. Idatha iboniswa njenge-avareji ± SEM (n = 6).#p < 0.05 okanye ##p < 0.01 vs iqela lolawulo (Con); *p < 0.05 okanye **p < 0.01 vs iqela le-DSS.
Siphinde sabala i-coefficient yolwalamano lwePearson phakathi kwe-SCFA yokwahluka kwe-genus-level kunye ne-fecal microbiota. Njengoko kubonisiwe kuMfanekiso 6, i-Akkermansia yayinxulumene kakuhle nokuveliswa kwe-propionic acid (Pearson = 0.4866) kunye ne-butyric acid (Pearson = 0.6192). Ngokwahlukileyo koko, zombini i-Enteromonas kunye ne-Oscillobacter zazinxulumene kakubi nokuveliswa kwe-acetate, kunye ne-Pearson coefficients ye-0.4709 kunye ne-0.5104, ngokwahlukeneyo. Ngokufanayo, i-Ruminococcaceae_UCG-014 yayinxulumene kakubi nokuveliswa kwe-propionic acid (Pearson = 0.4508) kunye ne-butyric acid (Pearson = 0.5842), ngokwahlukeneyo.
Umfanekiso 6 Uhlalutyo lolwalamano lwePearson phakathi kwee-SCFA ezahlukeneyo kunye neentsholongwane zekoloni.(A) I-Enteromonas ene-acetic acid; (B) I-Concussion bacillus ene-acetic acid; (C) I-Akkermansia vs i-propionic acid; (D) I-Ruminococcus_UCG-014 ene-propionic acid; (E) I-Akkermansia ene-butyric acid; (F) ) I-Ruminococcus _UCG-014 ene-butyric acid.
I-peptide efana ne-Glucagon-1 (GLP-1) yimveliso yeseli ethile emva kokuguqulwa kwe-proglucagon (Gcg) eneempawu zokulwa nokuvuvukala.28 Njengoko kubonisiwe kuMfanekiso 7, i-DSS ibangele ukwehla okukhulu kokubonakaliswa kwe-Gcg mRNA. Unyango lwe-Colon kunye ne-BLG lunokuguqula kakhulu ukwehla kwe-Gcg okubangelwa yi-DSS xa kuthelekiswa neqela lolawulo (Umfanekiso 7A). Kwangaxeshanye, inqanaba le-GLP-1 kwi-serum lincitshisiwe kakhulu kwiqela eliphathwe yi-DSS, kwaye unyango lwe-BLG lunokuthintela kakhulu oku kuncipha (Umfanekiso 7B). Ekubeni ii-fatty acids ezimfutshane zinokuvuselela ukukhutshwa kwe-GLP-1 nge-receptor edibeneyo ye-G-protein 43 (GRP43) kunye ne-receptor edibeneyo ye-G-protein 41 (GRP41), sikwahlolisise i-GPR41 kunye ne-GRP43 kwi-colon ye-colitis mice kwaye safumanisa ukuba ukubonakaliswa kwe-mRNA ye-colonic ye-GRP43 kunye ne-GPR41 kwehle kakhulu emva komngeni we-DSS, kwaye unyango lwe-BLG lunokusindisa ngempumelelo oku kuncipha (Umfanekiso 7C kunye no-D).
Umfanekiso 7 I-BLG yonyusa amanqanaba e-GLP-1 kwi-serum kunye nokubonakaliswa kwe-mRNA ye-Gcg, GPR41 kunye ne-GRP43 kwiimpuku eziphathwe yi-DSS.(A) Ukubonakaliswa kwe-mRNA ye-Gcg kwizicubu ze-colon; (B) Inqanaba le-GLP-1 kwi-serum; (C) Ukubonakaliswa kwe-mRNA ye-GPR41 kwizicubu ze-colon; (D) Ukubonakaliswa kwe-mRNA ye-GPR43 kwizicubu ze-colon. Idatha iboniswa njenge-avareji ± SEM (n = 5–6).#p < 0.05 okanye ##p < 0.01 vs iqela lolawulo (Con); *p < 0.05 vs iqela le-DSS.
Ekubeni unyango lwe-BLG lunokunyusa amanqanaba e-GLP-1 kwi-serum, ukubonakaliswa kwe-colonic Gcg mRNA, kunye namanqanaba e-fecal SCFA kwiimpuku eziphathwe yi-DSS, sihlolisise ngakumbi i-acetate, i-propionate, kunye ne-butyrate kunye ne-control (F-Con), i-DSS colitis (F-Con) -DSS) kunye ne-BLG-treated colitis (F-BLG) iimpuku ekukhutshweni kwe-GLP-1 kwiiseli ze-epithelial ze-murine colonic eziphambili. Njengoko kubonisiwe kuMfanekiso 8A, iiseli ze-epithelial ze-mouse eziphambili eziphathwe nge-2 mM acetic acid, i-propionic acid, kunye ne-butyric acid, ngokulandelanayo, zikhuthaze kakhulu ukukhululwa kwe-GLP-1, ngokuhambelana nezifundo zangaphambili.29,30 Ngokufanayo, zonke ii-F-Con, i-F-DSS, kunye ne-F-BLG (ezilingana ne-0.25 g yendle) zikhuthaze kakhulu ukukhululwa kwe-GLP-1 kwiiseli ze-epithelial ze-murine colonic eziphambili. Okuphawulekayo kukuba, inani le-GLP-1 elikhutshwe ziiseli ze-epithelial ze-epithelial ze-murine colonic eziphambili eziphathwe yi-F-DSS laliphantsi kakhulu kunelo iiseli ze-epithelial ze-mouse eziphambili eziphathwe yi-F-Con kunye ne-F-BLG. (Umfanekiso 8B). Ezi datha zibonisa ukuba unyango lwe-BLG lubuyisele kakhulu imveliso ye-GLP-1 yamathumbu evela kwi-SCFA.
Umfanekiso 8 I-SCFA evela kwi-BLG ivuselela ukukhululwa kwe-GLP-1 kwiiseli ze-epithelial ze-murine colonic eziphambili.(A) I-Acetic acid, i-propionic acid, kunye ne-butyric acid zikhuthaze ukukhululwa kwe-GLP-1 kwiiseli ze-epithelial ze-murine colonic eziphambili; (B) ii-extracts zefecal F-Con, F-DSS kunye ne-F-BLG ezivuselele iiseli ze-epithelial ze-murine colonic eziphambili Inani le-GLP-1 likhutshiwe. Ii-Aliquots zeeseli ze-epithelial ze-colonic zibekwe kwizitya ze-petri ezisezantsi kweglasi kwaye zanyangwa nge-2 mM acetic acid, i-propionic acid, i-butyric acid, kunye nee-extracts ze-fecal F-Con, F-DSS, kunye ne-F-BLG (ezilingana ne-0.25 g yendle), ngokwahlukeneyo. Iiyure ezi-2 kwi-37°C, i-5% CO2, ngokulandelelana. Ubungakanani be-GLP-1 ekhutshwe kwiiseli ze-epithelial ze-murine colonic ezisisiseko bufunyenwe yi-ELISA. Idatha iboniswa njenge-avareji ± SEM (n = 3).#p < 0.05 okanye ##p < 0.01 vs. blank okanye F-Con; *p < 0.05 vs. F-DSS.
Izifinyezo: I-Ace, i-acetic acid; i-Pro, i-propionic acid; nangona kunjalo, i-butyric acid; i-F-Con, isicatshulwa sendle esivela kwiimpuku zolawulo; i-F-DSS, isicatshulwa sendle esivela kwiimpuku ze-colitis; i-F-BLG, evela kwikholoni enyangwa yi-BLG Isicatshulwa sendle seempuku ezivuvukalayo.
I-UC, ebhalwe yi-World Health Organization njengesifo esinganyangekiyo, i-UC iba yingozi kwihlabathi liphela; nangona kunjalo, iindlela ezisebenzayo zokuqikelela, ukuthintela, kunye nokunyanga esi sifo zisanqongophele. Ke ngoko, kukho imfuneko engxamisekileyo yokuphonononga nokuphuhlisa amaqhinga amatsha akhuselekileyo nasebenzayo okunyanga i-UC. Amalungiselelo amayeza emveli aseTshayina lukhetho oluthembisayo kuba amayeza amaninzi emveli aseTshayina abonakalisiwe ukuba ayasebenza kunyango lwe-UC kubemi baseTshayina kwiinkulungwane ezidlulileyo, kwaye onke ayizinto eziphilayo kunye nezinto zendalo ezingenabungozi ebantwini nakwizilwanyana.31,32 Olu phononongo lujolise ekufuneni amalungiselelo amayeza emveli aseTshayina akhuselekileyo nasebenzayo kunyango lwe-UC kunye nokuphonononga indlela esebenza ngayo.I-BLG yifomyula eyaziwayo yaseTshayina esetyenziselwa ukunyanga umkhuhlane.8,33 Umsebenzi kwilabhoratri yethu nakwamanye ubonise ukuba i-indigo, imveliso yamayeza emveli aseTshayina ecutshungulweyo evela kwizinto ezifanayo ne-BLG, ibonisa ukusebenza okubonakalayo kunyango lwe-UC ebantwini nakwizilwanyana.4,34 Nangona kunjalo, iziphumo ze-BLG zokulwa ne-colitis kunye nemiphumo yayo Indlela ayicacanga.Kuphononongo lwangoku, iziphumo zethu zibonisa ukuba i-BLG inciphisa ngempumelelo ukudumba kwamathumbu okubangelwa yi-DSS, okunxulunyaniswa nokuguqulwa kwamathumbu. i-microbiota kunye nokubuyiselwa kwemveliso ye-GLP-1 ephuma emathunjini.
Kuyaziwa ukuba i-UC ibonakaliswa ngamaxesha okubuyela umva aneempawu eziqhelekileyo zeklinikhi, ezinje ngokuncipha kobunzima, urhudo, ukopha emqolo, kunye nomonakalo omkhulu we-mucosal yamathumbu.35 Ngoko ke, i-colitis engapheliyo ebuyela umva yanikwa ngokunika imijikelo emithathu ye-1.8% DSS kangangeentsuku ezintlanu, kulandele iintsuku ezisixhenxe zokusela amanzi. Njengoko kubonisiwe kuMfanekiso 1B, ukwehla kobunzima okuguqukayo kunye namanqaku e-DAI abonise ukuqaliswa ngempumelelo kwe-colitis engapheliyo ebuyela umva. Iimpuku kwiqela elanyangwa nge-BLG zibonise ukuchacha okuphezulu ukusuka ngomhla wesi-8, okwahluke kakhulu kumhla wama-24. Utshintsho olufanayo lubonwe nakwinqaku le-DAI, nto leyo ebonisa ukuphucuka kophuculo lweklinikhi lwe-colitis. Ngokuphathelele ukwenzakala kwamathumbu amakhulu kunye nesimo sokudumba, ubude bamathumbu amakhulu, umonakalo wezicubu zamathumbu amakhulu, kunye nokubonakaliswa kwezakhi zofuzo kunye nokuveliswa kwee-cytokines ezibangela ukuvuvukala i-TNF-α, IL-1β, kunye ne-IL-6 kwizicubu zamathumbu amakhulu nazo ziphuculwe kakhulu emva konyango lwe-BLG. Ngokudibeneyo, ezi ziphumo zibonisa ngokucacileyo ukuba i-BLG iyasebenza kunyango lwe-colitis engapheliyo ebuyela umva kwiimpuku.
I-BLG iyisebenzisa njani imiphumo yayo yezonyango? Izifundo ezininzi zangaphambili zibonise ukuba i-gut microbiota idlala indima ebalulekileyo kwi-pathogenesis ye-UC, kwaye unyango olusekelwe kwi-microbiome kunye nolwe-microbiome luye lwavela njengecebo elinomtsalane kakhulu lokunyanga i-UC. Kolu phononongo lwangoku, sibonise ukuba unyango lwe-BLG lubangele utshintsho olukhulu kulwakhiwo lwe-gut microbiota, nto leyo ebonisa ukuba isiphumo sokukhusela se-BLG nxamnye ne-DSS-induced colitis sinxulumene nokuguqulwa kwe-gut microbiota. Olu phononongo luhambelana nengcamango yokuba ukuphinda ucwangcise i-homeostasis ye-gut microbiota yindlela ebalulekileyo yokuqonda ukusebenza kakuhle kwamalungiselelo e-TCM.36,37 Okuphawulekayo kukuba, i-Akkermansia yintsholongwane ye-Gram-negative kwaye ayina-anaerobic ehlala kumaleko we-mucus yamathumbu, eyonakalisa i-mucins, ivelise i-propionic acid, ivuselela ukwahluka kweeseli ze-goblet, kwaye igcina i-mucosa. umsebenzi wobungqingqwa bomqobo.26 Idatha emininzi yezonyango neyezilwanyana ibonisa ukuba i-Akkermansia inxulunyaniswa kakhulu ne-mucosa esempilweni,38 kunye nokufakwa ngomlomo kwe-Akkermansia spp. inokuphucula kakhulu ukudumba kwe-mucosal.39 Idatha yethu yangoku ibonisa ukuba ubuninzi be-Akkermansia buyanda kakhulu emva konyango lwe-BLG. Ukongeza, i-Prevotellaceae_UCG-001 yibhaktiriya evelisa i-SCFA.27 Izifundo ezininzi zibonise ukuba i-Prevotellaceae_UCG-001 ifunyenwe ngobuninzi obuphantsi kwindle yezilwanyana ezine-colitis.40,41 Idatha yethu yangoku ikwabonisa ukuba unyango lwe-BLG lunokunyusa kakhulu ubuninzi be-Prevotellaceae_UCG-001 kwikholoni yeempuku eziphathwe yi-DSS. Ngokwahlukileyo koko, i-Oscillibacter yibhaktiriya ethanda i-mesophilic, engathathi hlangothi kwi-anaerobic.42 ibike ukuba ubuninzi be-Oscillibacter bunyuke kakhulu kwiimpuku ze-UC kwaye bunxulumene kakuhle namanqanaba e-IL-6 kunye ne-IL-1β kunye namanqaku e-pathological.43,44 Ngokuphawulekayo, unyango lwe-BLG lunciphise kakhulu ubuninzi be-Oscillibacter kwindle yeempuku eziphathwe yi-DSS. Ngokuphawulekayo, ezi ntsholongwane eziguqulwe yi-BLG zezona zivelisa kakhulu i-SCFA. iintsholongwane. Izifundo ezininzi zangaphambili zibonise iziphumo eziluncedo ze-SCFAs ekuvuvukeni kwamathumbu amakhulu kunye nokukhuselwa kobungqingqwa be-epithelial yamathumbu.45,46 Idatha yethu yangoku ikwabonise ukuba ukugxila kwe-SCFA acetate, i-propionate, kunye ne-butyrate kwindle ephathwe yi-DSS kwandiswe kakhulu kwiimpuku eziphathwe yi-BLG. Xa zizonke, ezi ziphumo zibonisa ngokucacileyo ukuba unyango lwe-BLG lunokuphucula ngempumelelo iintsholongwane ezivelisa i-SCFA ezibangelwa yi-DSS kwiimpuku ezine-colitis engapheliyo.
I-GLP-1 yi-incretin eveliswa kakhulu kwi-ileum nakwi-colon kwaye idlala indima ebalulekileyo ekulibaziseni ukukhupha isisu kunye nokunciphisa i-glucose yegazi emva kokutya.47 Ubungqina bubonisa ukuba i-dipeptidyl peptidase (DPP)-4, i-agonist ye-GLP-1 receptor, kunye ne-nanomedicine ye-GLP-1 inokunciphisa ngempumelelo ukudumba kwamathumbu kwiimpuku.48-51 Njengoko kubikwe kwizifundo zangaphambili, ubuninzi be-SCFA budibene namanqanaba e-plasma GLP-1 ebantwini nakwiimpuku.52 Idatha yethu yangoku ibonisa ukuba emva konyango lwe-BLG, amanqanaba e-serum GLP-1 kunye nokubonakaliswa kwe-Gcg mRNA kwandiswe kakhulu. Ngokufanayo, ukukhutshwa kwe-GLP-1 kwandiswe kakhulu kwiinkcubeko zekoloni emva kokuvuselelwa ngee-extracts zendle ezivela kwiimpuku ze-colitis eziphathwe yi-BLG xa kuthelekiswa nokuvuselelwa ngee-extracts zendle ezivela kwiimpuku ze-colitis eziphathwe yi-DSS. Ii-SCFA zichaphazela njani ukukhululwa kwe-GLP-1?Gwen Tolhurst et al. Ixelile ukuba i-SCFA inokukhuthaza ukukhutshwa kwe-GLP-1 nge-GRP43 kunye ne-GPR41.29 Idatha yethu yangoku ikwabonisa ukuba unyango lwe-BLG luyandisa kakhulu ukubonakaliswa kwe-mRNA kwe-GRP43 kunye ne-GPR41 kumathumbu amakhulu eempuku eziphathwe yi-DSS. Ezi datha zibonisa ukuba unyango lwe-BLG lunokubuyisela imveliso ye-GLP-1 ekhuthazwa yi-SCFA ngokusebenzisa i-GRP43 kunye ne-GPR41.
I-BLG liyeza lexesha elide elingathengiswayo eTshayina (i-OTC). Idosi ephezulu ye-BLG enyanyezelwayo kwiimpuku zaseKunming yi-80g/Kg, kwaye akukho tyhefu ibonakalayo.53 Okwangoku, idosi ecetyiswayo ye-BLG (engenaswekile) ebantwini yi-9-15 g/ngosuku (kathathu ngemini). Uphononongo lwethu lubonise ukuba i-BLG kwi-1g/Kg iphucule i-DSS-induced chronic relapsing colitis kwiimpuku. Le dosi isondele kwidosi ye-BLG esetyenziswa eklinikhi. Uphononongo lwethu lukwafumanise ukuba indlela esebenza ngayo ilawulwa, ubuncinane ngokuyinxenye, lutshintsho kwi-gut microbiota, ngakumbi iibhaktheriya ezivelisa i-SCFA, ezifana ne-Akkermansia kunye ne-Prevotellaceae_UCG-001, ukubuyisela imveliso ye-GLP-1 evela emathunjini. Ezi ziphumo zibonisa ukuba i-BLG ifanelwe ukuqwalaselwa ngakumbi njengeyeza elinokubakho lonyango lwe-clinical colitis. Nangona kunjalo, indlela echanekileyo eguqula ngayo i-gut microbiota isaza kuqinisekiswa ziimpuku ezingenayo i-microbiota kunye nokufakelwa kwebhaktheriya yendle.
I-Ace, i-acetic acid; kodwa, i-butyric acid; i-BLG, i-pandan; i-DSS, i-dextran sodium sulfate; i-DAI, isalathisi somsebenzi wesifo; i-DPP, i-dipeptidyl peptidase; i-FID, isixhobo sokufumanisa i-ionization yelangatye; i-F-Con, ulawulo lwe-Fecal extracts yeempuku; i-F-DSS, i-fecal extracts yeempuku ze-DSS colitis; i-F-BLG, i-fecal extracts yeempuku ze-colitis eziphathwe yi-BLG; i-GLP-1, i-glucagon-like peptide-1; i-Gcg, i-glucagon; i-gas chromatography, i-gas chromatography; i-GRP43, i-G protein-coupled receptor 43; i-GRP41, i-G protein-coupled receptor 41; i-H&E, i-hematoxylin-eosin; i-HBSS, i-Hanks' Balanced Salt Solution; i-OTC, i-OTC; i-PCA, uhlalutyo lwecandelo eliphambili; i-PCoA, uhlalutyo oluphambili lwe-coordinate; i-Pro, i-propionic acid; i-SASP, i-sulfasalazine; i-SCFA, ii-short-chain fatty acids; Amayeza aseTshayina, amayeza emveli aseTshayina; i-UC, i-ulcerative colitis.
Zonke iindlela zovavanyo zivunyiwe yiKomiti yeZimilo zeZilwanyana kwiYunivesithi yasePeking iShenzhen-Hong Kong University of Science and Technology Medical Center (eShenzhen, eTshayina) ngokweZikhokelo zeZiko kunye neMimiselo yeZilwanyana (inombolo yokuziphatha A2020157).
Bonke ababhali benze igalelo elikhulu ekucingeni nasekuyileni, ekufumaneni idatha, okanye ekuhlalutyeni nasekutolikeni idatha; bathathe inxaxheba ekubhaleni inqaku okanye ekuhlaziyeni ngokunzulu umxholo obalulekileyo wengqondo; bavumile ukuhambisa umbhalo-ngqangi kwijenali yangoku; ekugqibeleni bavumile inguqulelo ukuba ipapashwe; Banoxanduva lwazo zonke iinkalo zomsebenzi.
Lo msebenzi uxhaswe yiNational Natural Science Foundation yaseTshayina (81560676 kunye ne-81660479), iprojekthi yeklasi yokuqala yeYunivesithi yaseShenzhen (86000000210), iShenzhen Science and Technology Innovation Committee Fund (JCYJ20210324093810026), kunye neGuangdong Provincial Medical Science and Technology Research Fund (A2020157 kunye ne-A2020272), iGuizhou Medical University Pharmacy Guizhou Province exhaswa yiKey Laboratory (YWZJ2020-01) kunye nePeking University Shenzhen Hospital (JCYJ2018009).
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