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Ama-granule e-Ban-Lan-Gen anciphisa i-dextran sodium sulfate-ebangelwa yi-colitis engapheli ephindaphindayo emagundwini ngokuguqula i-gut microbiota nokubuyisela ukukhiqizwa kwe-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 Haitao21Peking University Shenzhen Hospital Department of Pharmacy, Shenzhen, People's Republic of China; 2Shenzhen University Health Science Center School of Pharmacy, Shenzhen, People's Republic of China; 3Guizhou Medical University Engineering Technology Research Center of Ethnic Medicine and Traditional Chinese Medicine Development and Application Ministry of Education, Guizhou Provincial Key Laboratory of Pharmacy, Guizhou Medical University, Guiyang, People's Republic of China; 4 Department of Gastroenterology, Peking University Shenzhen Hospital, Shenzhen, People's Republic of China; 5 School of Pharmacy, Guizhou Medical University, State Key Laboratory of Medicinal Plant Function and Application, Guiyang; 6 UMnyango Wezokwelapha Zelabhorethri, Isibhedlela sasePeking University iShenzhen, eShenzhen, eShayina [email protected] IShen Xiangchun, Isikole Sekhemisi, IGuizhou Medical University, eGuizhou, IRiphabhulikhi Yabantu baseShayina, 550004, I-imeyili [email protected] Inhloso: Ukwelashwa okusekelwe ku-GLP-1 kuyindlela entsha yokwelapha isifo samathumbu esivuvukalayo. Ama-granules e-Ban-Lan-Gen (BLG) ayifomula eyaziwayo ye-TCM elwa namagciwane ebonisa umsebenzi ongaba khona wokulwa nokuvuvukala ekwelapheni izimo ezahlukahlukene zokuvuvukala. Kodwa-ke, umphumela wayo wokulwa nokuvuvukala ku-colitis kanye nendlela esebenza ngayo akukacaci. IZINDLELA: Ukusungula i-dextran sodium sulfate (DSS) evuvukalayo ebangelwa yi-colitis engapheli evuvukalayo emagundwini. Izinkomba zomsebenzi wesifo, izimpawu zokulimala ze-histological, kanye namazinga e-cytokine avuvukalayo enziwa ukuhlola umphumela wokuvikela we-BLG. Imiphumela ye-BLG ku-gut microbiota kanye namathumbu ibonakaliswe amazinga e-serum GLP-1 kanye nokubonakaliswa kwe-colonic Gcg, GPR41, kanye ne-GRP43, ukwakheka kwe-gut microbiota, indle Amazinga e-SCFA, kanye nokukhululwa kwe-GLP-1 kumaseli e-epithelial e-colonic yegundane eliyinhloko Ukukhiqizwa kwe-GLP-1 okuvela ku-SCFA. Imiphumela: Ukwelashwa kwe-BLG kunciphise kakhulu ukwehla kwesisindo somzimba, i-DAI, ukufinyezwa kwamathumbu amakhulu, ukulimala kwezicubu zamathumbu amakhulu, kanye namazinga e-cytokine abangela ukuvuvukala kwe-TNF-α, IL-1β, kanye ne-IL-6 ezicutshini zamathumbu amakhulu. Ngaphezu kwalokho, ukwelashwa kwe-BLG kungabuyisela kakhulu ukubonakaliswa kwe-Gcg yamathumbu amakhulu, i-GPR41 kanye ne-GRP43 kanye namazinga e-GLP-1 e-serum ezimpukwini ze-colitis, kanye nangokwandisa amabhaktheriya akhiqiza i-SCFA njenge-Akkermansia kanye ne-Prevotellaceae_UCG-001, kanye nokunciphisa ubuningi bamabhaktheriya afana ne-Eubacterium_xylanophilum_group, i-Ruminococcaceae_UCG-014, i-Intestinimonas kanye ne-Oscillibacter. Ngaphezu kwalokho, ukwelashwa kwe-BLG kungakhuphula kakhulu izinga lama-SCFA endle yamagundane e-colitis. Ngesikhathi esifanayo, izivivinyo ze-in vitro zikhombisile nokuthi ukukhishwa kwendle kwamagundane aphathwe nge-BLG kungavuselela kakhulu amaseli amancane e-Murine colonic epithelial akhipha i-GLP-1. Iziphetho: Lokhu okutholakele kusikisela ukuthi i-BLG inomphumela wokulwa ne-colitis. I-BLG inamandla okuthuthukiswa njengokwelapha, okungenani ngokwengxenye ngokuguqula i-gut microbiota nokubuyisela ukukhiqizwa kwe-GLP-1 yamathumbu okususelwa ku-SCFA Imithi ethembisayo ye-colitis ephindaphindayo engapheli. Amagama angukhiye: i-colitis, ama-granules e-Ban-Lan-Gen, i-gut microbiota, ama-fatty acid amafushane, i-GLP-1
I-ulcerative colitis (UC) isifo sokuvuvukala sesikhathi eside samathumbu amakhulu kanye ne-rectum esibonakala ngohudo oluphindaphindayo, ubuhlungu besisu, ukwehla kwesisindo, kanye nendle enegazi e-mucopurulent.1 Muva nje, ukwanda kwe-UC kuye kwanda emazweni ayengenazo izifo eziningi ngaphambili, okuhlanganisa neShayina, kanye nokuthandwa okwandayo kwezindlela zokuphila zaseNtshonalanga.2 Lokhu kwanda kudala izinkinga ezinkulu empilweni yomphakathi futhi kunemiphumela emibi kakhulu ekhonweni leziguli lokusebenza kanye nekhwalithi yokuphila. Okuphawulekayo ukuthi i-pathogenesis ye-UC ayikacaci kahle, kodwa ngokuvamile kuyamukelwa ukuthi izakhi zofuzo, izici zemvelo, i-gut microbiota, kanye nesistimu yomzimba wonke kunegalelo ekuthuthukisweni kwe-UC.3 Ngisho namanje, ayikho ikhambi le-UC, futhi umgomo wokwelashwa ukulawula izimpawu zomtholampilo ngokwezokwelapha, ukukhuthaza nokugcina ukuphulukiswa, ukukhuthaza ukuphulukiswa kwe-mucosal, nokunciphisa ukuphinda kuvele. Ukwelashwa kwakudala kufaka phakathi ama-aminosalicylates, ama-corticosteroids, ama-immunosuppressants, kanye ne-biologics. Kodwa-ke, le mithi ayikwazi ukufeza umphumela oyifunayo ngenxa yemiphumela yayo ehlukahlukene emibi.4 Muva nje, izifundo eziningi zamacala zibonise ukuthi imithi yendabuko yaseShayina (TCM) ibonise amandla amakhulu ekusizeni ukuqeda I-UC enobuthi obuphansi, okuphakamisa ukuthi ukuthuthukiswa kwezindlela zokwelapha ezintsha ze-TCM kuyindlela yokwelapha ethembisayo ye-UC.5-7​​
I-Banlangen Granules (BLG) iyilungiselelo lendabuko lemithi yaseShayina elenziwe ngokukhishwa kwamanzi kwempande ye-Banlangen.8 Ngaphezu kokusebenza kwayo okulwa namagciwane, i-BLG ibonisa umsebenzi ongaba khona wokulwa nokuvuvukala ekwelapheni izimo ezahlukahlukene zokuvuvukala.9,10 Ngaphezu kwalokho, ama-glucosinolates (R,S-goitrin, progoitrin, epiprorubin kanye ne-glucoside ahlukaniswe futhi atholakala ezikhishweni zamanzi ze-Radix isatidis) kanye nama-nucleosides (i-hypoxanthine, i-adenosine, i-uridine kanye ne-guanosine) kanye nama-alkaloid e-indigo afana ne-indigo kanye ne-indirubin.11,12 Izifundo zangaphambilini zibonise kahle ukuthi ama-compounds i-adenosine, i-uridine kanye ne-indirubin abonisa imiphumela enamandla yokulwa ne-colitis kumamodeli ezilwane ahlukene e-colitis.13-17 Kodwa-ke, azikho izifundo ezisekelwe ebufakazini ezenziwe ukuhlola ukusebenza kwe-BLG ku-colitis. Kulesi sifundo samanje, siphenye umphumela wokuvikela we-BLG ku-colitis engapheli ebangelwa yi-dextran sodium sulfate (DSS) ku- Amagundane e-C57BL/6 athola ukuthi ukuphathwa ngomlomo kwe-BLG kunciphisa kakhulu ikholoni engapheli ephindaphindayo ebangelwa yi-DSS kumagundane. Ukuvuvukala, izindlela zayo zokulawula zihlotshaniswa nokuguqulwa kwe-gut microbiota kanye nokubuyiselwa kokukhiqizwa kwe-glucagon-like peptide-1 (GLP-1) etholakala emathunjini.
Ama-granule e-BLG (angenashukela, avunyiwe yi-NMPA yi-Z11020357; i-Beijing Tongrentang Technology Development Co., Ltd., eBeijing, eShayina; inombolo yebhetshi: 20110966) athengwe kumakhemisi. I-DSS (Isisindo sama-Molecular: 36,000–50,000 Daltons) ithengwe kwa-MP Biologicals (Santa Ana, e-USA). I-Sulfasalazine (SASP) (≥ ubumsulwa obungu-98%), i-hematoxylin kanye ne-eosin ithengwe kwa-Sigma-Aldrich (eSt. Louis, MO, e-USA). Ama-mouse TNF-α, IL-1β kanye ne-IL-6 luminex Elisa assay kits athengwe ezinhlelweni ze-R&D (eMinneapolis, MN, e-USA). I-Acetic acid, i-propionic acid, kanye ne-butyric acid ithengwe kwa-Aladdin Industries (eShanghai, eShayina). I-2-Ethylbutyric acid ithengwe kwa-Merck KGaA (eDarmstadt, eJalimane).
Amagundane amaduna angamaviki ayi-6-8 ubudala i-C57BL/6 (isisindo somzimba esingu-18-22 g) athengwe eBeijing Wetahe Laboratory Animal Technology Co., Ltd. (eBeijing, eShayina) futhi agcinwa endaweni engama-22 ± 2 °C ngomjikelezo wokukhanya/omnyama wamahora ayi-12. Amagundane anikwa ukudla okujwayelekile kwamagundane okunokufinyelela mahhala emanzini okuphuza isonto elilodwa ukuze ajwayele indawo entsha. Amagundane abe esehlukaniswa ngokungahleliwe abe amaqembu amane: iqembu lokulawula, iqembu lemodeli ye-DSS, iqembu elenziwe nge-SASP (200 mg/kg, ngomlomo) kanye neqembu elenziwe nge-BLG (1 g/kg, ngomlomo). Njengoba kuboniswe kuMfanekiso 1A, ngokusho kocwaningo lwethu lwangaphambilini, i-colitis ephindaphindayo yokuhlola yabangelwa amagundane ngemijikelezo emithathu ye-1.8% DSS izinsuku ezi-5, kwalandela amanzi acwengekile izinsuku ezi-7, ngokusho kocwaningo lwethu lwangaphambilini.18 Amagundane emaqenjini enziwe nge-SASP kanye ne-BLG aphathwa nge-SASP kanye ne-BLG, ngokulandelana, nsuku zonke kusukela ngosuku lwe-0. Ngokusho kocwaningo lokuqala, umthamo we-BLG ubekwe ku-1 g/kg. Phakathi naleso sikhathi, umthamo we-SASP ubekwe ku-200 mg/Kg ngokusho kwezincwadi.4 Amaqembu emodeli yokulawula kanye ne-DSS athole umthamo ofanayo wamanzi kulo lonke ukuhlolwa.
Isibalo 1 I-BLG ithuthukisa i-colitis engapheli ephindaphindayo ebangelwa yi-DSS emagundwini.(A) Umklamo wokuhlola we-colitis ephindaphindayo engapheli kanye nokwelashwa, (B) ushintsho lwesisindo somzimba, (C) amaphuzu enkomba yomsebenzi wesifo (i-DAI), (D) ubude bekholoni, (E) isithombe esimele ikholoni, (F) Ukufaka umbala kwe-H&E Ikholoni (ukukhulisa, ×100) kanye (G) amaphuzu e-histological. Idatha yethulwa njengesilinganiso ± SEM (n = 6).##p < 0.01 noma ###p < 0.001 vs iqembu lokulawula (i-Con); *p < 0.05 noma **p < 0.01 noma ***p < 0.001 vs iqembu le-DSS.
Isisindo somzimba, ukuqina kwendle, kanye nokopha endulwini kwakuqoshwa nsuku zonke. Inkomba yomsebenzi wesifo (i-DAI) yanqunywa ngokuhlanganisa amaphuzu esisindo somzimba, ukuqina kwendle, kanye nokopha endulwini njengoba kuchaziwe ngaphambilini.19 Ekupheleni kokuhlolwa, wonke amagundane abulawa ngokubulala futhi igazi, indle kanye ne-colon kwaqoqwa ukuze kwenziwe olunye ucwaningo.
Izicubu zekholoni zalungiswa nge-formalin futhi zafakwa ku-paraffin. Izingxenye ze-5-micron zenziwa futhi zagcotshwa nge-hematoxylin-eosin (H&E), zabe seziphuphuthekiswa futhi zafakwa njengoba kuchaziwe ngaphambilini.19
I-RNA ephelele yezicubu zamathumbu ikhishwe yi-Trizol reagent (Invitrogen, Carlsbad, CA), kulandelwe ukukhishwa kwe-cDNA nge-reverse transcriptase (TaKaRa, Kusatsu, Shiga, Japan). I-PCR yokulinganisa yenziwe kusetshenziswa uhlelo lwe-PCR lwesikhathi sangempela nge-SYBR Green Master (Roche, Basel, Switzerland). Ukubhalwa kwezakhi zofuzo okuqondiwe kwalungiswa kwaba yi-β-actin futhi idatha yahlaziywa kusetshenziswa indlela ye-2-ΔΔCT. Ukulandelana kwezakhi zofuzo eziyinhloko kuboniswe kuThebula 1.
Ukuhlukaniswa kwamaseli e-epithelial epithelial egundane eliyinhloko kanye nokukhuliswa kwenziwa njengoba kuchaziwe ngaphambilini.20 Kafushane, amakholoni amagundane anamasonto ayi-6-8 ubudala aqale akhishwa ngemuva kokuhlatshwa ngokuhlukana komlomo wesibeletho, avulwa ngobude, aphathwe nge-Hanks Balanced Salt Solution (HBSS, ngaphandle kwe-calcium ne-magnesium) futhi anqunywa abe yizicucu ezincane ezingama-0.5-1 mm. Ngemva kwalokho, izicubu zagaywa nge-0.4 mg/mL collagenase XI (Sigma, Poole, UK) endaweni ekhululekile ye-DMEM futhi zafakwa ku-centrifuge ku-300 xg imizuzu emi-5 ekushiseni kwegumbi. Phinda umise i-pellet endaweni engaphakathi ye-DMEM (eyengezwe nge-10% ye-fetal bovine serum, ama-Units ayi-100/mL penicillin, kanye ne-100 µg/mL streptomycin) ku-37 °C bese udlula ku-nylon mesh (usayizi we-pore ~250 µm). Ama-Aliquots amaseli e-epithelial ekoloni afakwa ezitsheni ezingaphansi kwengilazi futhi afakwa i-acetic acid, i-propionic acid, i-butyric acid, kanye nezinhlayiya zendle yegundane amahora ama-2 ku-37°C, i-5% CO2.
Izicubu zekholoni zahlanganiswa ne-PBS, futhi amazinga e-cytokines IL-6, TNF-α kanye ne-IL-1β ezicutshini zekholoni atholakala kusetshenziswa ama-luminex ELISA assay kits (izinhlelo ze-R&D, eMinneapolis, MN, e-USA). Ngokufanayo, amazinga e-GLP-1 ku-serum kanye ne-culture medium yamaseli e-epithelial epithelial eyinhloko ye-murine anqunywa nge-ELISA kit (Bioswamp, eWuhan, eShayina) ngokwemiyalelo yomenzi.
I-DNA iyonke endle ikhishwe kusetshenziswa ikhithi yokukhipha i-DNA (eTiangen, eShayina). Ikhwalithi kanye nenani le-DNA kwalinganiswa ngezilinganiso ezingu-260 nm/280 nm kanye no-260 nm/230 nm, ngokulandelana. Ngemva kwalokho, kusetshenziswa i-DNA ngayinye ekhishwe njengethempulethi, kwasetshenziswa ama-primer athile angu-338F (ACTCCTACGGGAGGCAGCAG) kanye no-806R (GGACTACHVGGGTWTCTAAT) ukukhulisa izifunda ze-V3-V4 ze-16S rRNA gene ezindaweni ezahlukene. Imikhiqizo ye-PCR yahlanzwa kusetshenziswa i-QIAquick Gel Extraction Kit (QIAGEN, eJalimane), eyalinganiswa yi-real-time PCR, futhi yahlelwa kusetshenziswa ipulatifomu yokulandelela i-IlluminaMiseq PE300 (Illumina Inc., CA, USA). Ekuhlaziyweni kwe-bioinformatics, ukucutshungulwa kwedatha kwenziwa ngokulandela amaphrothokholi abikiwe ngaphambilini.21,22 Ngamafuphi, sebenzisa i-Cutadapt (V1.9.1) ukuhlunga amafayela aluhlaza asheshayo. Ama-OTU ahlanganiswe ndawonye. kusetshenziswa i-UPARSE (inguqulo 7.0.1001) enesilinganiso sokufana esingu-97%, kanti i-UCHIME yasetshenziswa ukususa ukulandelana kwe-chimeric. Ukuhlaziywa kokwakheka komphakathi kanye nokuhlukaniswa kwenziwa kusetshenziswa i-RDP classifier (http://rdp.cme.msu.edu/) ngokusekelwe kusizindalwazi sezakhi zofuzo se-SILVA ribosomal RNA.
Amazinga ama-fatty acid ama-short-chain (i-acetic acid, i-propionic acid, kanye ne-butyric acid) alinganiswa njengoba kuchaziwe ngaphambilini nguTao et al., kanye nokuguqulwa okuthile.23 Kafushane, i-100 mg yendle yaqala ukulengiswa ku-0.4 mL wamanzi akhishwe i-ion, kwalandela i-0.1 mL ye-50% sulfuric acid kanye ne-0.5 mL ye-2-ethylbutyric acid (izinga langaphakathi), yabe isihlanganiswa futhi yashiswa ku-4°C. I-Centrifuge ngesivinini esingu-12,000 rpm imizuzu eyi-15 ku-C. I-supernatant ikhishwe nge-0.5 mL ye-ether yafakwa ku-GC ukuze ihlaziywe. Ekuhlaziyweni kwe-gas chromatography (GC), amasampula ahlaziywe kusetshenziswa i-GC-2010 Plus gas chromatograph (Shimadzu, Inc.) efakwe i-flame ionization detector (FID). Ukuhlukaniswa kufezwe kusetshenziswa ikholomu ye-ZKAT-624, 30 m × 0.53 mm × 0.3 μm (Lanzhou Zhongke Antai Analytical Technology Co., Ltd., China). Idatha yatholakala kusetshenziswa isofthiwe yesisombululo se-GC (Shimadzu, Inc.). Isilinganiso sokuhlukaniswa sasingu-10:1, igesi ethwalayo yayiyi-nitrogen, kanti izinga lokugeleza laliyi-6 mL/min. Umthamo womjovo wawuyi-1 μL. Izinga lokushisa lomjovo kanye nomjovo lalingu-300°C. Izinga lokushisa le-oven lagcinwa ku-140°C imizuzu eyi-13.5, labe selikhushulwa laya ku-250°C ku- izinga lokushisa liyi-120°C/min; izinga lokushisa ligcinwe imizuzu emi-5.
Idatha yethulwa njengephutha elijwayelekile ± elijwayelekile lesilinganiso (SEM). Ukubaluleka kwedatha kuhlolwe yi-ANOVA yendlela eyodwa kulandelwe ukuhlolwa kukaDuncan kwebanga eliningi. Isofthiwe ye-GraphPad Prism 5.0 (GraphPad Software Inc., eSan Diego, CA, e-USA) yasetshenziswa kuzo zonke izibalo kanti i-p < 0.05 yabhekwa njengebalulekile ngokwezibalo.
Kuyaziwa kahle ukuthi i-UC iyisifo se-colitis esiphindaphindayo esingapheli esinobuhlungu obukhulu besisu, uhudo kanye nokopha. Ngakho-ke, i-colitis ephindaphindayo ephindaphindayo ebangelwa yi-DSS emagundwini yasungulwa ukuze kuhlolwe ukusebenza kahle kwe-BLG yokulwa ne-colitis (Isithombe 1A). Uma kuqhathaniswa neqembu lokulawula, amagundane eqenjini lemodeli ye-DSS ayenciphise kakhulu isisindo somzimba kanye ne-DAI ephezulu, futhi lezi zinguquko zaguqulwa kakhulu ngemva kwezinsuku ezingama-24 zokwelashwa kwe-BLG (Isithombe 1B no-C). Ukufinyezwa kwekholoni kuyisici esibalulekile se-UC. Njengoba kuboniswe kuZithombe 1D no-E, ubude bekholoni yamagundane athola i-DSS bafinyezwa kakhulu, kodwa bancishiswa ukwelashwa kwe-BLG. Ngenxa yalokho, kwenziwa ukuhlaziywa kwe-histopathological ukuhlola ukuvuvukala kwekholoni. Izithombe ezinemibala ye-H&E kanye namaphuzu e-pathological kubonise ukuthi ukuphathwa kwe-DSS kuphazamise kakhulu ukwakheka kwekholoni futhi kwaholela ekubhujisweni kwe-crypt, kanti ukwelashwa kwe-BLG kunciphisa kakhulu ukubhujiswa kwe-crypt kanye namaphuzu e-pathological (Isithombe 1F no-G). Okuphawulekayo ukuthi, umphumela wokuvikela we-BLG ngesilinganiso esingu-1 g/Kg wawufana nowe- I-SASP ngesilinganiso esingu-200 mg/Kg. Ngokubambisana, lokhu okutholakele kusikisela ukuthi i-BLG iyasebenza ekunciphiseni ubunzima be-DSS-relapsing colitis engapheli ebangelwa yi-DSS emagundwini.
I-TNF-α, i-IL-1β kanye ne-IL-6 ziyizimpawu ezibalulekile zokuvuvukala kwamathumbu amakhulu. Njengoba kuboniswe ku-Figure 2A, i-DSS ibangele ukwanda okukhulu kokubonakaliswa kwezakhi zofuzo ze-TNF-α, i-IL-1β kanye ne-IL-6 kumathumbu amakhulu amakhulu uma kuqhathaniswa neqembu lokulawula. Ukuphathwa kwe-BLG kungaguqula kakhulu lezi zinguquko ezibangelwa yi-DSS. Okulandelayo, sisebenzise i-ELISA ukuthola amazinga ama-cytokines okuvuvukala i-TNF-α, i-IL-1β, kanye ne-IL-6 ezicutshini zamathumbu amakhulu. Imiphumela iphinde yabonisa ukuthi amazinga e-TNF-α, i-IL-1β, kanye ne-IL-6 kumathumbu amakhulu akhuliswe kakhulu emagundwini aphathwe nge-DSS, kanti ukwelashwa kwe-BLG kunciphisa lokhu kwanda (Figure 2B).
Isibalo 2 I-BLG ivimbela ukuvezwa kwezakhi zofuzo kanye nokukhiqizwa kwama-cytokines abangela ukuvuvukala i-TNF-α, IL-1β kanye ne-IL-6 emathunjini amagundane aphathwe i-DSS.(A) Ukuvezwa kwezakhi zofuzo ze-Colon ze-TNF-α, IL-1β kanye ne-IL-6; (B) amazinga e-colonic protein e-TNF-α, IL-1β kanye ne-IL-6. Idatha yethulwa njengesilinganiso ± SEM (n = 4–6).#p < 0.05 noma ##p < 0.01 noma ###p < 0.001 vs iqembu lokulawula (Con); *p < 0.05 noma **p < 0.01 vs iqembu le-DSS.
I-dysbiosis yamathumbu ibaluleke kakhulu ekuqaliseni kwe-UC.24 Ukuze kuhlolwe ukuthi i-BLG ilawula yini i-microbiota yamathumbu yamagundane aphathwe nge-DSS, kwenziwa ukulandelana kwe-16S rRNA ukuze kuhlaziywe umphakathi wamagciwane wokuqukethwe kwamathumbu. Umdwebo we-Venn ukhombisa ukuthi amaqembu amathathu abelana ngama-OTU angu-385. Ngesikhathi esifanayo, iqembu ngalinye lalinama-OTU ahlukile (Isithombe 3A). Ngaphezu kwalokho, inkomba ye-Chao1 kanye nenkomba ye-Shannon eboniswe ku-Figure 3B kanye no-C kubonise ukuthi ukuhlukahluka komphakathi kwe-microbiota yamathumbu kuncishisiwe kumagundane aphathwe nge-BLG, njengoba inkomba ye-Shannon yehle kakhulu eqenjini eliphathwe nge-BLG. Ukuhlaziywa kwezingxenye eziyinhloko (i-PCA) kanye nokuhlaziywa kwe-principal coordinate (i-PCoA) kusetshenziswe ukunquma amaphethini okuhlanganisa phakathi kwamaqembu amathathu futhi kubonise ukuthi isakhiwo somphakathi samagundane aphathwe nge-DSS sahlukaniswa ngokusobala ngemva kokwelashwa nge-BLG (Isithombe 3D kanye no-E). Le datha iphakamisa ukuthi ukwelashwa kwe-BLG kuthinte kakhulu isakhiwo somphakathi samagundane ane-DSS-induced colitis.
Isibalo 3 I-BLG ishintsha ukuhlukahluka kwe-gut microbiota kumagundane ane-DSS-induced colitis.(A) Umdwebo we-Venn we-OTU, (B) Inkomba ye-Chao1, (C) Inkomba yokuceba kukaShannon, (D) Isakhiwo samaphuzu e-Principal Component Analysis (PCA) se-OTU, (E) Isibalo se-OTU Principal Coordinate Analysis (PCoA) Isibalo. Idatha yethulwa njengesilinganiso ± SEM (n = 6).**p < 0.01 vs iqembu le-DSS.
Ukuze sihlole izinguquko ezithile ku-fecal microbiota, sihlaziye ukwakheka kwe-gut microbiota kuwo wonke amazinga e-taxonomic. Njengoba kuboniswe ku-Figure 4A, i-phyla eyinhloko kuwo wonke amaqembu kwakuyi-Firmicutes nama-Bacteroidetes, kulandelwe yi-Verrucomicrobia. Ubuningi obuhlobene be-Firmicutes nama-Firmicutes/Bacteroidetes banda kakhulu emiphakathini yamagciwane endle yamagundane aphathwe yi-DSS uma kuqhathaniswa namagundane alawulayo, futhi lezi zinguquko zaguqulwa kakhulu ngemuva kokwelashwa kwe-BLG. Ikakhulukazi, ukwelashwa kwe-BLG kwandise kakhulu ubuningi be-Verrucobacterium endle yamagundane ane-DSS-induced colitis. Ezingeni lekhaya, imiphakathi yamagciwane endle yayihlalwa yi-Lachnospiriaceae, i-Muribaculaceae, i-Akkermansiaceae, i-Ruminococcaceae kanye ne-Prevotellaceae (Isithombe 4B). Uma kuqhathaniswa neqembu le-DSS, ukuncipha kwe-BLG kwandise ubuningi be-Akkermansiaceae, kodwa kunciphisa ubuningi be-Lachnospiraceae kanye ne-Ruminococcaceae. Okuphawulekayo, kuhlobo ezingeni, i-microbiota yendle yayihlalwe yi-Lachnospira_NK4A136_group, i-Akkermansia kanye ne-Prevotellaceae_UCG-001 (Isithombe 4C). Lokhu okutholakele kuphinde kwabonisa ukuthi ukwelashwa kwe-BLG kuguqule ngempumelelo ukungalingani kwe-microbiota ekuphenduleni inselele ye-DSS, ebonakala ngokuncipha kwe-Eubacterium_xylanophilum_group, i-Ruminococcaceae_UCG-014, i-Intestinimonas kanye ne-Oscillibacter, kanye nokwanda kwe-Akkermansia kanye ne-Prevotellaceae_UCG-001.
Isithombe 4 I-BLG ishintsha ubuningi be-gut microbiota kumagundane e-DSS-induced colitis.(A) Ubuningi be-gut microbiota ezingeni le-phylum; (B) Ubuningi be-gut microbiota ezingeni lomndeni; (C) Ubuningi be-gut microbiota ezingeni lohlobo. Idatha yethulwa njengesilinganiso ± SEM (n = 6).#p < 0.05 noma ###p < 0.001 vs iqembu lokulawula (Con); *p < 0.05 noma **p < 0.01 noma ***p < 0.001 vs iqembu le-DSS.
Uma sicabanga ukuthi ama-fatty acid ama-short-chain (ama-SCFA) yiwona ama-metabolites amakhulu e-Akkermansia kanye ne-Prevotellaceae_UCG-001, kuyilapho i-acetate, i-propionate kanye ne-butyrate kuyi-SCFAs eningi kakhulu ku-lumen yamathumbu, sisasesesifundweni sethu. Njengoba kuboniswe kuMfanekiso 5, amazinga e-fecal acetate, i-propionate, kanye ne-butyrate ancishiswe kakhulu eqenjini elashwa yi-DSS, kanti ukwelashwa kwe-BLG kungakucindezela kakhulu lokhu kunciphisa.
Umfanekiso 5. I-BLG inyusa amazinga e-SCFAs endle yamagundane ane-DSS-induced colitis.(A) Okuqukethwe kwe-acetic acid endle; (B) Okuqukethwe kwe-propionic acid endle; (C) Okuqukethwe kwe-butyric acid endle. Idatha yethulwa njengesilinganiso ± SEM (n = 6).#p < 0.05 noma ##p < 0.01 vs iqembu lokulawula (Con); *p < 0.05 noma **p < 0.01 vs iqembu le-DSS.
Siphinde sabala i-coefficient yokuxhumana kwe-Pearson phakathi kwe-genus-level differential SCFA kanye ne-fecal microbiota. Njengoba kuboniswe ku-Figure 6, i-Akkermansia yayihlobene kahle nokukhiqizwa kwe-propionic acid (Pearson = 0.4866) kanye ne-butyric acid (Pearson = 0.6192). Ngokuphambene nalokho, i-Enteromonas kanye ne-Oscillobacter zombili zazihlotshaniswa kabi nokukhiqizwa kwe-acetate, kanye nama-coefficients e-Pearson angu-0.4709 kanye no-0.5104, ngokulandelana. Ngokufanayo, i-Ruminococcaceae_UCG-014 yayihlobene kabi nokukhiqizwa kwe-propionic acid (Pearson = 0.4508) kanye ne-butyric acid (Pearson = 0.5842), ngokulandelana.
Umfanekiso 6 Ukuhlaziywa kobudlelwano be-Pearson phakathi kwama-SCFA ahlukene kanye nama-microbes e-colonic.(A) Ama-Enteromuna ane-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) iwumkhiqizo we-proglucagon (Gcg) osuselwa kuseli onezakhiwo zokulwa nokuvuvukala.28 Njengoba kuboniswe kuMfanekiso 7, i-DSS ibangele ukwehla okukhulu kokubonakaliswa kwe-Gcg mRNA. Ukwelashwa kwe-Colon ne-BLG kungaguqula kakhulu ukwehla kwe-Gcg okubangelwa yi-DSS uma kuqhathaniswa neqembu lokulawula (Umfanekiso 7A). Ngesikhathi esifanayo, izinga le-GLP-1 ku-serum lehlisiwe kakhulu eqenjini eliphathwe yi-DSS, futhi ukwelashwa kwe-BLG kungavimbela kakhulu lokhu kwehla (Umfanekiso 7B). Njengoba ama-fatty acid amafushane angakhuthaza ukukhishwa kwe-GLP-1 ngokusebenzisa i-receptor ehlanganisiwe ye-G-protein 43 (GRP43) kanye ne-receptor ehlanganisiwe ye-G-protein 41 (GRP41), sihlole ne-GPR41 kanye ne-GRP43 emagundwini amagundane e-colitis futhi sathola ukuthi ukubonakaliswa kwe-mRNA ye-colonic ye-GRP43 kanye ne-GPR41 kwehle kakhulu ngemuva kwenselelo ye-DSS, futhi ukwelashwa kwe-BLG kungasindisa ngempumelelo lokhu kwehla (Umfanekiso 7C kanye no-D).
Isibalo 7 I-BLG inyusa amazinga e-serum GLP-1 kanye nokubonakaliswa kwe-mRNA ye-colonic Gcg, GPR41 kanye ne-GRP43 kumagundane aphathwe nge-DSS.(A) Ukubonakaliswa kwe-mRNA ye-Gcg ezicutshini zamathumbu amakhulu; (B) Izinga le-GLP-1 ku-serum; (C) Ukubonakaliswa kwe-mRNA ye-GPR41 ezicutshini zamathumbu amakhulu; (D) Ukubonakaliswa kwe-mRNA ye-GPR43 ezicutshini zamathumbu amakhulu. Idatha yethulwa njengesilinganiso ± SEM (n = 5–6).#p < 0.05 noma ##p < 0.01 vs iqembu lokulawula (Con); *p < 0.05 vs iqembu le-DSS.
Njengoba ukwelashwa kwe-BLG kungakhuphula amazinga e-GLP-1 egazini, ukubonakaliswa kwe-Gcg mRNA yekoloni, kanye namazinga e-fecal SCFA emagundwini aphathwe i-DSS, siphinde sahlola i-acetate, i-propionate, kanye ne-butyrate kanye nokuvela kumagundane alawulwayo (F-Con), i-DSS colitis (F-Con) -DSS) kanye ne-BLG-treated colitis (F-BLG) ekukhululweni kwe-GLP-1 kumaseli e-epithelial epithelial eyinhloko ye-murine colonic. Njengoba kuboniswe ku-Figure 8A, amaseli e-epithelial epithelial eyinhloko yegundane aphathwe nge-2 mM acetic acid, i-propionic acid, kanye ne-butyric acid, ngokulandelana, akhuthaze kakhulu ukukhishwa kwe-GLP-1, okuhambisana nezifundo zangaphambilini.29,30 Ngokufanayo, wonke ama-F-Con, i-F-DSS, kanye ne-F-BLG (okulingana no-0.25 g wendle) akhuthaze kakhulu ukukhishwa kwe-GLP-1 kumaseli e-epithelial eyinhloko yegundane. Okuphawulekayo ukuthi inani le-GLP-1 elikhishwe amaseli e-epithelial eyinhloko yegundane aphathwe i-F-DSS laliphansi kakhulu kunalokho amaseli e-epithelial e-colonic yegundane eliyinhloko aphathwe yi-F-Con kanye ne-F-BLG. (Isithombe 8B). Le mininingwane isikisela ukuthi ukwelashwa kwe-BLG kubuyisele kakhulu ukukhiqizwa kwe-GLP-1 yamathumbu okususelwa ku-SCFA.
Isibalo 8 I-SCFA ethathwe ku-BLG ivuselela ukukhishwa kwe-GLP-1 kumaseli e-epithelial epithelial eyinhloko ye-murine colonic.(A) I-Acetic acid, i-propionic acid, kanye ne-butyric acid kukhuthaze ukukhishwa kwe-GLP-1 kumaseli e-epithelial epithelial eyinhloko ye-murine colonic; (B) iziqeshana zendle Amaseli e-epithelial epithelial eyinhloko ye-murine colonic epithelial ekhuthazwe yi-F-Con, F-DSS kanye ne-F-BLG Inani le-GLP-1 elikhishwe. Ama-quots amaseli e-epithelial e-colonic abekwe ezitsheni ze-petri ezingaphansi kwengilazi futhi aphathwa nge-acetic acid engu-2 mM, i-propionic acid, i-butyric acid, kanye neziqeshana zendle i-F-Con, i-F-DSS, kanye ne-F-BLG (elingana nendle engu-0.25 g), ngokulandelana. Amahora ama-2 ku-37°C, i-5% CO2, ngokulandelana. Inani le-GLP-1 elikhishwe kumaseli e-epithelial epithelial eyinhloko ye-murine colonic litholwe yi-ELISA. Idatha yethulwa njengesilinganiso ± SEM (n = 3).#p < 0.05 noma ##p < 0.01 vs. blank noma F-Con; *p < 0.05 vs. F-DSS.
Izifinyezo: I-Ace, i-acetic acid; i-Pro, i-propionic acid; nokho, i-butyric acid; i-F-Con, i-fecal extract evela kumagundane alawulayo; i-F-DSS, i-fecal extract evela kumagundane e-colitis; i-F-BLG, evela kumathumbu amakhulu aphathwe nge-BLG I-fecal extracts yamagundane avuvukalayo.
Njengoba i-UC ibhalwe ohlwini lwe-World Health Organization njengesifo esingalapheki, iba yingozi emhlabeni wonke; nokho, izindlela ezisebenzayo zokubikezela, ukuvimbela, kanye nokwelapha lesi sifo zisalinganiselwe. Ngakho-ke, kunesidingo esiphuthumayo sokuhlola nokuthuthukisa amasu amasha okwelapha aphephile futhi asebenzayo e-UC. Ukulungiselela imithi yendabuko yaseShayina kuyindlela ethembisayo ngoba amalungiselelo amaningi emithi yendabuko yaseShayina aboniswe ukuthi ayasebenza ekwelapheni i-UC kubantu baseShayina emakhulwini eminyaka, futhi konke kuyizinto eziphilayo eziphilayo kanye nezinto zemvelo ezingenangozi kubantu nasezilwaneni.31,32 Lolu cwaningo luhlose ukufuna ukulungiswa kwemithi yendabuko yaseShayina ephephile futhi ephumelelayo yokwelapha i-UC nokuhlola indlela esebenza ngayo.I-BLG iyifomula yemithi yaseShayina eyaziwayo esetshenziselwa ukwelapha umkhuhlane.8,33 Umsebenzi elabhorethri yethu nakwamanye ukhombisile ukuthi i-indigo, umkhiqizo wemithi yendabuko yaseShayina ocutshungulwe ngezinto ezifanayo zokusetshenziswa njenge-BLG, ubonisa ukusebenza kahle okukhulu ekwelapheni i-UC kubantu nasezilwaneni.4,34 Kodwa-ke, imiphumela ye-BLG yokulwa ne-colitis nemiphumela yayo Indlela yokusebenza ayicacile.Ocwaningweni lwamanje, imiphumela yethu ikhombisa ukuthi i-BLG inciphisa ngempumelelo ukuvuvukala kwamathumbu okubangelwa yi-DSS, okuhlotshaniswa nokuguqulwa kwamathumbu. i-microbiota kanye nokubuyiselwa kokukhiqizwa kwe-GLP-1 okuvela emathunjini.
Kwaziwa kahle ukuthi i-UC ibonakala ngezikhathi zokubuyela emuva ezinezici ezijwayelekile zezokwelapha, njengokwehla kwesisindo, uhudo, ukopha emithanjeni, kanye nomonakalo omkhulu we-mucosal yamathumbu.35 Ngakho-ke, i-colitis ebuyela emuva engapheli yanikezwa ngokunikeza imijikelezo emithathu ye-1.8% DSS izinsuku ezinhlanu, kulandelwe izinsuku eziyisikhombisa zokuphuza amanzi. Njengoba kuboniswe kuMfanekiso 1B, ukwehla kwesisindo okushintshashintshayo kanye namaphuzu e-DAI kwabonisa ukuqaliswa okuphumelelayo kwe-colitis ebuyela emuva engapheli. Amagundane eqenjini aphathwe nge-BLG abonise ukululama kwe-upshift kusukela osukwini lwesi-8, okwakuhluke kakhulu kosuku lwama-24. Izinguquko ezifanayo zabonwa futhi kumaphuzu e-DAI, okuphakamisa ukuthuthuka ekuthuthukisweni kwe-colitis emtholampilo. Ngokuphathelene nokulimala kwamathumbu amakhulu kanye nesimo sokuvuvukala, ubude bamathumbu amakhulu, ukulimala kwezicubu zamathumbu amakhulu, kanye nokubonakaliswa kwezakhi zofuzo kanye nokukhiqizwa kwama-cytokines avuvukalayo i-TNF-α, i-IL-1β, kanye ne-IL-6 ezicutshini zamathumbu amakhulu nakho kwathuthuka kakhulu ngemva kokwelashwa kwe-BLG. Ngokuhlangene, le miphumela ikhombisa ngokusobala ukuthi i-BLG iyasebenza ekwelapheni i-colitis ebuyela emuva engapheli emagundwini.
I-BLG iyisebenzisa kanjani imiphumela yayo yezokwelapha? Izifundo eziningi zangaphambilini zikhombisile ukuthi i-gut microbiota idlala indima ebalulekile ekuthuthukisweni kwe-UC, futhi izindlela zokwelapha ezisekelwe ku-microbiome kanye ne-microbiome eziqondiswe kuvele njengesu elikhangayo kakhulu lokwelapha i-UC. Kulesi sifundo samanje, sibonise ukuthi ukwelashwa kwe-BLG kuholele ekushintsheni okukhulu ekwakhiweni kwe-gut microbiota, okuphakamisa ukuthi umphumela wokuvikela we-BLG ngokumelene ne-DSS-induced colitis uhlobene nokuguqulwa kwe-gut microbiota. Lokhu kuqaphela kuhambisana nomqondo wokuthi ukuhlela kabusha i-homeostasis ye-gut microbiota kuyindlela ebalulekile yokuqonda ukusebenza kahle kwamalungiselelo e-TCM.36,37 Okuphawulekayo ukuthi i-Akkermansia iyigciwane eliyi-Gram-negative futhi eliqinile elingena-anaerobic elihlala ongqimbeni lwe-mucus lwamathumbu, elilimaza ama-mucin, likhiqize i-propionic acid, livuselele ukuhlukaniswa kwamaseli e-goblet, futhi ligcine i-mucosa. umsebenzi wobuqotho bezithiyo.26 Idatha eminingi yezokwelapha neyezilwane iphakamisa ukuthi i-Akkermansia ihlotshaniswa kakhulu ne-mucosa enempilo,38 kanye nokuphathwa ngomlomo kwe-Akkermansia spp. kungathuthukisa kakhulu ukuvuvukala kwe-mucosal.39 Idatha yethu yamanje iphakamisa ukuthi inani elilinganiselwe le-Akkermansia landa kakhulu ngemva kokwelashwa kwe-BLG. Ngaphezu kwalokho, i-Prevotellaceae_UCG-001 iyigciwane elikhiqiza i-SCFA.27 Izifundo eziningi zibonise ukuthi i-Prevotellaceae_UCG-001 itholakale inala elincane endle yezilwane ezine-colitis.40,41 Idatha yethu yamanje ikhombisa nokuthi ukwelashwa kwe-BLG kungandisa kakhulu inani elilinganiselwe le-Prevotellaceae_UCG-001 emathunjini amagundane aphathwe i-DSS. Ngokuphambene nalokho, i-Oscillibacter iyigciwane elihlala li-mesophilic, elingena-anaerobic.42 ibike ukuthi inani elilinganiselwe le-Oscillibacter landa kakhulu emagundwini e-UC futhi lalihlobene kahle kakhulu namazinga e-IL-6 kanye ne-IL-1β kanye namaphuzu e-pathological.43,44 Okuphawulekayo ukuthi ukwelashwa kwe-BLG kunciphisa kakhulu inani elilinganiselwe le-Oscillibacter endle yamagundane aphathwe i-DSS. Okuphawulekayo ukuthi la mabhaktheriya ashintshwe yi-BLG ayengabakhiqizi be-SCFA abaningi kakhulu. amabhaktheriya. Izifundo eziningi zangaphambilini zibonise imiphumela engaba nenzuzo yama-SCFA ekuvuvukeni kwamathumbu amakhulu kanye nokuvikelwa kobuqotho be-epithelial yamathumbu.45,46 Imininingwane yethu yamanje iphinde yabona ukuthi ukugcwala kwe-SCFA acetate, i-propionate, kanye ne-butyrate endle ephathwe yi-DSS kwanda kakhulu emagundwini aphathwe yi-BLG. Uma kuhlanganiswa, lokhu okutholakele kubonisa ngokusobala ukuthi ukwelashwa kwe-BLG kungathuthukisa ngempumelelo amabhaktheriya akhiqiza i-SCFA abangelwa yi-DSS emagundwini ane-colitis ephindaphindayo engapheli.
I-GLP-1 iyi-incretin ekhiqizwa kakhulu ku-ileum kanye ne-colon futhi idlala indima ebalulekile ekubambezeleni ukukhishwa kwesisu kanye nokwehlisa i-glucose yegazi ngemva kokudla.47 Ubufakazi busikisela ukuthi i-dipeptidyl peptidase (DPP)-4, i-agonist ye-GLP-1 receptor, kanye ne-nanomedicine ye-GLP-1 kunganciphisa ngempumelelo ukuvuvukala kwamathumbu emagundwini.48-51 Njengoba kubikiwe ezifundweni zangaphambilini, amazinga aphezulu e-SCFA ahlotshaniswa namazinga e-plasma GLP-1 kubantu nasemagundwini.52 Idatha yethu yamanje ikhombisa ukuthi ngemuva kokwelashwa kwe-BLG, amazinga e-serum GLP-1 kanye nokubonakaliswa kwe-Gcg mRNA kwanda kakhulu. Ngokufanayo, ukukhiqizwa kwe-GLP-1 kwanda kakhulu emasikweni amakoloni ngemuva kokukhuthazwa ngama-extracts endle avela kumagundane e-colitis aphathwe yi-BLG uma kuqhathaniswa nokukhuthazwa ngama-extracts endle avela kumagundane e-colitis aphathwe yi-DSS. Ama-SCFA athinta kanjani ukukhululwa kwe-GLP-1?Gwen Tolhurst et al. ibike ukuthi i-SCFA ingakhuthaza ukukhiqizwa kwe-GLP-1 nge-GRP43 kanye ne-GPR41.29 Idatha yethu yamanje ikhombisa nokuthi ukwelashwa kwe-BLG kukhulisa kakhulu ukuvezwa kwe-mRNA kwe-GRP43 kanye ne-GPR41 emathunjini amagundane aphathwe nge-DSS. Le datha iphakamisa ukuthi ukwelashwa kwe-BLG kungabuyisela ukukhiqizwa kwe-GLP-1 okukhuthazwa yi-SCFA ngokusebenzisa i-GRP43 kanye ne-GPR41.
I-BLG iyisidakamizwa sesikhathi eside esingathengiswa ngaphandle kwemithi kadokotela (i-OTC) eShayina. Umthamo omkhulu we-BLG obekezelelwayo kumagundane aseKunming ungama-80g/Kg, futhi akukho ubuthi obubonakalayo.53 Njengamanje, umthamo onconywayo we-BLG (ngaphandle koshukela) kubantu ungama-9-15 g/ngosuku (kathathu ngosuku). Ucwaningo lwethu lukhombisile ukuthi i-BLG ku-1g/Kg ithuthukise i-DSS-induced chronic relapsing colitis kumagundane. Lo mthamo useduze nomthamo we-BLG osetshenziswa emtholampilo. Ucwaningo lwethu luphinde lwathola ukuthi indlela esebenza ngayo iqondiswa, okungenani ngokwengxenye, yizinguquko kuma-gut microbiota, ikakhulukazi amabhaktheriya akhiqiza i-SCFA, njenge-Akkermansia ne-Prevotellaceae_UCG-001, ukuze kubuyiselwe ukukhiqizwa kwe-GLP-1 okuvela emathunjini. Lokhu okutholakele kusikisela ukuthi i-BLG ifanelwe ukucatshangelwa okwengeziwe njenge-ejenti yokwelapha engaba khona yokwelashwa kwe-clinical colitis. Kodwa-ke, indlela eqondile eguqula ngayo i-gut microbiota isazoqinisekiswa ngamagundane angenayo i-microbiota kanye nokufakelwa kwamagciwane endle.
I-Ace, i-acetic acid; kodwa, i-butyric acid; i-BLG, i-pandan; i-DSS, i-dextran sodium sulfate; i-DAI, inkomba yomsebenzi wesifo; i-DPP, i-dipeptidyl peptidase; i-FID, isitholi se-ionization selangabi; i-F-Con, ukulawula ukukhishwa kwendle kwamagundane; i-F-DSS, ukukhishwa kwendle kwamagundane e-DSS colitis; i-F-BLG, ukukhishwa kwendle kwamagundane e-colitis aphathwe yi-BLG; i-GLP-1, i-peptide efana ne-glucagon-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, ukuhlaziywa kwezingxenye eziyinhloko; i-PCoA, ukuhlaziywa kwe-principal coordinate; i-Pro, i-propionic acid; i-SASP, i-sulfasalazine; i-SCFA, ama-fatty acid amafushane; Imithi yaseShayina, imithi yendabuko yaseShayina; i-UC, i-ulcerative colitis.
Zonke izinqubo zokuhlola zavunywa yiKomidi Lokuziphatha Kwezilwane lasePeking University Shenzhen-Hong Kong University of Science and Technology Medical Center (Shenzhen, China) ngokusho kweZiqondiso Zezikhungo kanye Nemithetho Yezilwane (inombolo yokuziphatha A2020157).
Bonke ababhali benze iminikelo ebalulekile ekuqanjweni nasekuklanyweni, ekutholeni idatha, noma ekuhlaziyweni nasekuchazeni idatha; bahlanganyele ekubhaleni lesi sihloko noma ekubukezeni ngokujulile okuqukethwe okubalulekile kwengqondo; bavumile ukuhambisa umbhalo kumagazini wamanje; ekugcineni bavumile inguqulo yokushicilelwa; Banesibopho sazo zonke izici zomsebenzi.
Lo msebenzi usekelwe yiNational Natural Science Foundation of China (81560676 kanye no-81660479), iphrojekthi yekilasi lokuqala yeShenzhen University (86000000210), iShenzhen Science and Technology Innovation Committee Fund (JCYJ20210324093810026), kanye neGuangdong Provincial Medical Science and Technology Research Fund (A2020157 kanye no-A2020272), iGuizhou Medical University Pharmacy Guizhou Province Funded by Key Laboratory (YWZJ2020-01) kanye nePeking University Shenzhen Hospital (JCYJ2018009).
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