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Ti granules ta Ban-Lan-Gen ti hunguta dextran sodium sulfate-induced chronic relapsing colitis eka timbeva hiku cinca cinca gut microbiota xikan’we naku vuyisela vuhumelerisi bya intestinal SCFA Derived-GLP-1
Jiao 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 Haitao21Yunivhesiti ya Peking Xibedlhele xa Shenzhen Ndzawulo ya Vukhemisi, Shenzhen, Riphabliki ra Vanhu ra China; 2Shenzhen University Health Science Center Xikolo xa Vukhemisi, Shenzhen, Riphabliki ra Vanhu ra China; 3Yunivhesiti ya Vutshunguri ya Guizhou Senthara ya Vulavisisi bya Thekinoloji ya Vuinjhiniyere bya Vutshunguri bya Rixaka na Vutshunguri bya Ndhavuko bya Xichayina Nhluvukiso na Ku Tirhisa Vukorhokeri bya Dyondzo, Laboratori ya Nkoka ya Xifundzha xa Guizhou ya Khemisi, Yunivhesiti ya Vutshunguri ya Guizhou , Guiyang, Riphabliki ra Vanhu ra China; 4 Ndzawulo ya Gastroenterology, Xibedlhele xa Shenzhen xa Yunivhesiti ya Peking, Shenzhen, Riphabliki ra Vanhu ra China; 5 Xikolo xa Vukhemisi, Yunivhesiti ya Vutshunguri ya Guizhou, Laboratori ya Nkoka ya Mfumo ya Ntirho na ku Tirhisa Swimilana swa Mirhi, Guiyang; 6 Ndzawulo ya Vutshunguri bya Laboratori, Yunivhesiti ya Peking Xibedlhele xa Shenzhen, Shenzhen, China [email protected] Shen Xiangchun, Xikolo xa Vukhemisi, Yunivhesiti ya Vutshunguri ya Guizhou, Guizhou, Riphabliki ra Vanhu ra China, 550004, Imeyili [email protected] Xikongomelo: Vutshunguri lebyi sekeriweke eka GLP-1 i ndlela leyintshwa ya vutshunguri bya vuvabyi bya marhumbu lebyi pfimbaka.Ban-Lan-Gen (BLG) ti granules i xivumbeko xa TCM xa antiviral lexi tivekaka lexi kombisaka ntirho lowu nga vaka kona wo lwisana na ku pfimba eka vutshunguri bya swiyimo swo hambana swa ku pfimba.Hambiswiritano, mbuyelo wa yona wo lwisana na ku pfimba eka colitis na endlelo ra yona ro tirha swa ha ri erivaleni.MAENDLELO: Ku simeka dextran sodium sulfate (DSS)-induced chronic relapsing colitis eka timbeva.Disease activity indices, histological markers ya ku vaviseka, na ti levele ta proinflammatory cytokine swi endliwile ku kambela mbuyelo wo sirhelela wa BLG.Vuyelo bya BLG eka microbiota ya marhumbu na marhumbu byi tiveka hi ti levele ta serum GLP-1 na colonic Gcg, GPR41, na GRP43 expression, gut microbiota composition, fecal SCFAs levels, na GLP-1 release kusuka eka primary mouse colonic epithelial tisele SCFA-derived GLP-1 production.Mimbuyelo: Vutshunguri bya BLG byi hungute swinene ku lahlekeriwa hi ntiko wa miri, DAI, ku koma ka kholokholo, ku onhaka ka tinyama ta kholokholo, na swiyimo swa proinflammatory cytokine swa TNF-α, IL-1β, na IL-6 eka tinyama ta kholokholo.Ku engetela kwalaho, vutshunguri bya BLG byi nga vuyisela swinene ku paluxiwa ka Gcg, GPR41 na GRP43 ya kholoni na swiyimo swa serum GLP-1 eka colitis mice, naswona hiku engetela ti bacteria leti humesaka SCFA tofana na Akkermansia na Prevotellaceae_UCG-001, naku hunguta nhlayo ya ti bacteria tofana na Eubacterium_xylanophilum_group, Ruminococcaceae_UCG-014, Intestinimonas na Oscillibacter. Ku engetela kwalano, vutshunguri bya BLG byinga engetela swinene levele ya SCFAs eka manyoro ya ti colitis mice. Hi nkarhi lowu fanaka, swikambelo swa in vitro switlhele swikombisa leswaku fecal extract ya BLG-treated mice yinga hlohletela swinene primary small Murine colonic colonic epithelial cells leyi humesaka GLP-1. Mahetelelo: Swikumiwa leswi swi ringanyeta leswaku BLG yi na mbuyelo wo lwisana na vuvabyi bya colitis. BLG yi na vuswikoti byo tumbuluxiwa tanihi vutshunguri, hi xiphemu hi ku cinca-cinca microbiota ya le malungwini na ku vuyisela vuhumelerisi bya GLP-1 lebyi humaka eka SCFA bya le malungwini Mirhi leyi tshembisaka eka vuvabyi bya colitis lebyi tlhelelaka endzhaku lebyi nga heriki. Marito ya nkoka: colitis, ti granules ta Ban-Lan-Gen, microbiota ya marhumbu, ti fatty acids ta ti chain to koma, GLP-1
Ulcerative colitis (UC) i vuvabyi bya nkarhi wo leha bya ku pfimba ka kholokholo na rectum lebyi tivekaka hi ku tlhela ku va na ku pfimba ka khwiri, ku vava ka khwiri, ku lahlekeriwa hi ntiko, na manyoro lama nga na ngati ya mucopurulent.1 Sweswinyana, ku hangalaka ka UC ku vile ku andza ematikweni lawa khale a ma nga ri na mavabyi ya le hansi, ku katsa na China, hi ku andza ka ku duma ka vutomi bya le Vupeladyambu.2 Ku tlakuka loku ku tisa swiphiqo leswikulu eka vaaki rihanyo naswona swi na switandzhaku leswikulu eka vuswikoti bya vavabyi byo tirha na khwalithi ya vutomi.Lexi xiyekaka, pathogenesis ya UC ya ha ri erivaleni ngopfu, kambe hi ntolovelo swa amukeriwa leswaku ti genetics, swilo swa mbango, gut microbiota, na masocha ya miri hinkwaswo swi hoxa xandla eka ku kula ka UC.3 Hambi ku ri sweswi, a ku na murhi wa UC, naswona xikongomelo xa vutshunguri i ku lawula swikombiso swa tliliniki, ku hlohlotela na ku hlayisa remission, promote mucosal healing, and reduce recurrence.Vutshunguri bya xikhale byi katsa aminosalicylates , corticosteroids, immunosuppressants, na biologics.Hambiswiritano, mirhi leyi a yi nge fikeleli mbuyelo lowu lavekaka hikwalaho ka switandzhaku swa yona swo hambana.4 Sweswinyana, tidyondzo to tala ta timhaka ti kombisile leswaku mirhi ya ndhavuko ya Machayina (TCM) yi kombisile vuswikoti lebyikulu byo pfuneta ku hunguta UC hi chefu ya le hansi, leswi ringanyetaka leswaku ku tumbuluxiwa ka vutshunguri lebyintshwa bya TCM i maqhinga ya vutshunguri lama tshembisaka eka UC.5-7
Banlangen Granules (BLG) i murhi wa ndhavuko wa murhi wa China lowu endliweke kusuka eka mati lawa ya humesiweke ya rimitsu ra Banlangen.8 Ku engetela eka ku tirha ka yona ka antiviral, BLG yi kombisa ntirho lowu nga vaka kona wo lwisana na ku pfimba eka vutshunguri bya swiyimo swo hambana swa ku pfimba.9,10 Ku engetela kwalaho, ti glucosinolates (R,S-goitrin, progoitrin, epiprorubin na glucoside swi hambanisiwile no tiviwa kusuka eka swiphemu swa mati swa Radix isatidis) na ti nucleosides (hypoxanthine, adenosine, uridine na guanosine) na ti alkaloids ta indigo to fana na indigo na indirubin.11,12 Mindzavisiso ya khale yi tsarile kahle leswaku swihlanganisi swa adenosine, uridine na indirubin swi kombisa mbuyelo wa matimba wo lwisana na colitis eka timodeli to hambana ta swiharhi swa colitis.13-17 Hambiswiritano, a ku na tidyondzo leti simekiweke eka vumbhoni ti endliwile ku kambela ku tirha kahle ka BLG eka colitis.Eka dyondzo ya sweswi, hi lavisisile mbuyelo wo sirhelela wa BLG eka dextran sodium sulfate (DSS)-induced chronic relapsing colitis eka timbeva ta C57BL/6 naswona hi kumile leswaku vulawuri bya nomu bya BLG byi hungute swinene DSS-induced chronic relapsing colon eka timbeva Ku pfimba, tindlela ta yona to lawula ti fambelanisiwa na ku cinca cinca ka microbiota ya marhumbu xikan’we naku vuyiseriwa ka vuhumelerisi bya glucagon-like peptide-1 (GLP-1) leyi humaka eka marhumbu.
Ti granules ta BLG (ti nga ri na chukele, leti pfumeleriweke hi NMPA Z11020357; Beijing Tongrentang Technology Development Co., Ltd., Beijing, China; nomboro ya ntlawa: 20110966) ti xaviwile eka tikhemisi.DSS (Ntiko wa Molekhuli: 36,000–50,000 Daltons) yi xaviwile eka MP Biologicals (Santa Ana, USA).Sulfasalazine (SASP) (≥ 98% ya vutengi), hematoxylin na eosin swi xaviwile kusuka eka Sigma-Aldrich (St. Louis, MO, USA).Ti mouse TNF-α, IL-1β na IL-6 luminex Elisa assay kits ti xaviwile kusuka eka tisisiteme ta R&D (Minneapolis, MN, USA).Acetic acid, propionic acid, na butyric acid swi xaviwile kusuka eka Aladdin Tiindasitiri (Shanghai, China).2-Ethylbutyric acid yi xaviwile kusuka eka Merck KGaA (Darmstadt, Germany).
Timbeva ta xinuna ta 6-8 wa mavhiki ta C57BL/6 (ndzilo wa miri wa 18-22 g) ti xaviwile kusuka eka Beijing Wetahe Laboratory Animal Technology Co., Ltd. (Beijing, China) naswona ti vekiwile eka ndzhawu ya 22 ± 2 °C na 12 h light/ dark cycle.Timbeva ti phameriwile swakudya swa standard rodent leswingana mfikelelo wa mahala eka mati yo nwa kuringana vhiki rin’we kuva ti tolovela ndzhawu leyintshwa.The timbeva ti tlhele ti avanyisiwile hi ku landzelelana hi mintlawa ya mune: ntlawa wa vulawuri, ntlawa wa modele wa DSS, ntlawa lowu tshunguriweke hi SASP (200 mg/kg, hi nomu) na ntlawa lowu tshunguriweke hi BLG (1 g/kg, hi nomu).Hilaha swi kombisiweke hakona eka Xifaniso 1A, hi ku ya hi dyondzo ya hina ya khale, experimental chronic relapsing colitis yi hlohloteriwile eka timbeva hi swirhendzevutani swinharhu swa 1.8% DSS ku ringana masiku ya 5, ku landzela mati lama distilled ku ringana 7 masiku, hi ku ya hi dyondzo ya hina ya khale.18 Timbeva eka mintlawa leyi tshunguriweke hi SASP na BLG ti tshunguriwile hi SASP na BLG, hi ku landzelelana, siku rin’wana na rin’wana ku sukela hi siku ra 0.Hi ku ya hi swikambelo swo sungula, mpimo wa BLG wu vekiwile eka 1 g/kg.Hi nkarhi wolowo, mpimo wa SASP wu vekiwile eka 200 mg/Kg ku ya hi matsalwa.4 Mintlawa ya modele ya vulawuri na DSS yi amukerile leswi fanaka vholumo ya mati eka xikambelo hinkwaxo.
Xifaniso 1 BLG yi antswisa DSS-induced chronic relapsing colitis eka timbeva.(A) Dizayini ya swikambelo ya chronic recurrent colitis na vutshunguri, (B) ku cinca ka ntiko wa miri, (C) xikoro xa index ya migingiriko ya mavabyi (DAI), (D) ku leha ka kholoni, (E) xifaniso lexi yimelaka kholoni, (F) H&E staining Colon (ku kurisiwa, ×100) na (G) histological xikoro.Data yi nyikeriwa tanihi xiringaniso ± SEM (n = 6).##p < 0.01 kumbe ###p < 0.001 vs ntlawa wa vulawuri (Con); *p < 0.05 kumbe **p < 0.01 kumbe ***p < 0.001 ku hambana na ntlawa wa DSS.
Ndzilo wa miri, ku nga cinci ka manyoro, na ku huma ngati ya le khwirini swi rhekhodiwile siku na siku.Disease activity index (DAI) yi kumiwile hi ku hlanganisa swikoweto swa ntiko wa miri, ku nga cinci ka manyoro, na ku huma ngati ya rectal tanihilaha swi hlamuseriweke hakona khale.19 Eku heleni ka xikambelo, timbeva hinkwato ti dlayiwile naswona ngati, manyoro na kholokholo swi hlengeletiwile ku endla swikambelo swin’wana.
Tinyama ta kholokholo ti vekiwile hi formalin naswona ti nghenisiwile eka paraffin.Swiyenge swa 5-micron swi endliwile no pendiwa hi hematoxylin-eosin (H&E), kutani swi pfala mahlo no nyikiwa swikoweto tani hi leswi swi hlamuseriweke khale.19
RNA hinkwayo ya tissue ya colon yi humesiwile hi Trizol reagent (Invitrogen, Carlsbad, CA), ku landzela ku humesiwa ka cDNA hi reverse transcriptase (TaKaRa, Kusatsu, Shiga, Japan).Quantitative PCR yi endliwile hiku tirhisa real-time PCR system na SYBR Green Master (Roche, Basel, Switzerland).Target gene transcripts yi normalised eka β-actin naswona data yi kamberiwile hi ku tirhisa ndlela ya 2-ΔΔCT.Ntlhandlamano wa ti gene primer wu kombisiwile eka Tafula ra 1.
Primary mouse colonic epithelial cell isolation na culture swi endliwile tani hileswi swinga hlamuseriwa khale.20 Hiku komisa, ti colons ta mice ya 6-8 wa mavhiki tisungule ku tsemiwa endzhaku ka ku endliwa magandzelo hi cervical dislocation, kutani ti pfuriwa hiku leha, ti tshunguriwa hi Hanks Balanced Salt Solution (HBSS, handle ka calcium na magnesium) kutani ti tsemiwa kuva 0.5-1 mm ya leswintsongo swiphemu.Endzhaku ka sweswo, ti tissues ti gayiwile hi 0.4 mg/mL collagenase XI (Sigma, Poole, UK) eka free DMEM medium naswona ti centrifuged eka 300 xg kuringana 5 min eka mahiselo ya kamara.Resuspend pellet eka DMEM medium (yi engeteriwile hi 10% fetal bovine serum, 100 Units/mL penicillin, na 100 μg/mL streptomycin) eka 37 °C naswona yi hundza eka nylon mesh (pore size ~250 μm).Ti aliquots ta ti cells ta colonic epithelial ti vekiwile eka ti glass-bottom dishes naswona ti pfaleriwile na acetic acid, propionic acid, butyric acid, na mouse fecal extracts kuringana 2 wa tiawara eka 37°C, 5% CO2.
Tinyama ta kholokholo ti homogenized na PBS, naswona ti levele ta ti cytokines IL-6, TNF-α na IL-1β eka tissue ya colon ti kumiwile hiku tirhisa luminex ELISA assay kits (R&D systems, Minneapolis, MN, USA).Hilaha ku fanaka, ti levele ta GLP-1 eka serum na culture medium ya primary murine colonic epithelial cells tikumiwile hi ELISA kit (Bioswamp, Wuhan, China) kuya hi swiletelo swa muendli.
DNA hinkwayo kusuka eka manyoro yi humesiwile hiku tirhisa DNA extraction kit (Tiangen, China).Khwalithi na nhlayo ya DNA swipimiwile eka ti ratios ta 260 nm/280 nm na 260 nm/230 nm, hiku landzelelana.Endzhaku ka sweswo, hiku tirhisa DNA yin’wana na yin’wana leyi humesiweke tani hi template, specific primers 338F (ACTCCTACGGGGAGGCAGCAG) na 806R (GGACTACHVGGGTWTCTAAT) ti tirhisiwile ku kurisa swifundzha swa V3-V4 swa jini ya 16S rRNA eka swifundzha swo hambana.Swikumiwa swa PCR swi basisiwile hi ku tirhisa QIAquick Gel Extraction Kit (QIAGEN, Germany), swi pimiwile hi nkarhi wa xiviri hi PCR, naswona swi landzelerisiwile hi ku tirhisa pulatifomo ya ku landzelelana ya IlluminaMiseq PE300 (Illumina Inc., CA, USA).Ku kuma bioinformatics, data ku lulamisiwa ku endliwile hi ku landzelela tiphrothokholi leti vikiweke khale.21,22 Hi ku komisa, tirhisa Cutadapt (V1.9.1) ku sefa tifayela ta raw express.Ti-OTU ti hlengeletiwile hi ku tirhisa UPARSE (version 7.0.1001) hi ku tsemiwa ka ku fana ka 97%, naswona UCHIME yi tirhisiwile ku susa ntlhandlamano wa chimeric.Nxopaxopo wa vuhlanganisi bya vaaki na ku hlawuriwa swi endliwile hi ku tirhisa xihlawulekisi xa RDP (http://rdp.cme.msu.edu/) leyi sekeriweke eka database ya tijini ta SILVA ribosomal RNA.
Ti levele ta ti short-chain fatty acids (acetic acid, propionic acid, na butyric acid) ti pimiwe tani hileswi swinga hlamuseriwa khale hi Tao et al., na ku cinca kun’wana.23 Hiku komisa, 100 mg ya manyoro yisungule ku yimisiwa eka 0.4 mL ya mati lawa yanga deionized, ku landzela 0.1 mL ya 50% sulfuric acid na 0.5 mL ya 2-ethylbutyric acid (internal standard), kutani yi homogenized kutani yi hisiwa eka 4°C. Centrifuge eka 12,000 rpm kuringana 15 wa timinete eka C.Supernatant yi humesiwile hi 0.5 mL ya ether kutani yi cheriwa eka GC kuva yi kamberiwa.Eka nxopaxopo wa gas chromatography (GC), tisampulu ti kamberiwile hiku tirhisa GC-2010 Plus gas chromatograph (Shimadzu, Inc.) leyi hlomisiweke hi flame ionization detector (FID).Ku hambanisiwa ku fikeleleriwile hi ku tirhisa kholomo ya ZKAT-624, 30 m × 0.53 mm × 0.3 μm (Lanzhou Zhongke Antai Analytical Technology Co., Ltd., China).Data yi kumiwile hi ku tirhisa software ya GC solution (Shimadzu, Inc.).Nhlayo ya ku avanyisa a yi ri 10:1, gasi yo rhwala a yi ri nayitrojini, naswona mpimo wa ku khuluka a wu ri 6 mL/min.Vholumo ya ku cheriwa a yi ri 1 μL.Mahiselo ya injector na detector akuri 300°C.Mahiselo ya oven ya khomiwile eka 140°C kuringana 13.5 wa timinete, kutani ya tlakusiwa kuya eka 250°C hi rivilo ra 120°C/min; mahiselo ya khomiwile kuringana 5 wa timinete.
Data yi nyikiwile tanihi xiringaniso ± xihoxo xa ntolovelo xa xiringaniso (SEM).Nkoka wa datha wu kamberiwile hi ANOVA ya ndlela yin’we leyi landzeriweke hi xikambelo xa Duncan xa swiyenge swo tala.GraphPad Prism 5.0 software (GraphPad Software Inc., San Diego, CA, USA) yi tirhisiwile eka swibalo hinkwaswo naswona p < 0.05 yi tekiwile yi ri ya nkoka hi tlhelo ra tinhlayo.
Swi tiveka kahle leswaku UC i vuvabyi bya colitis lebyi tlhelelaka endzhaku lebyi nga heriki lebyi nga na ku vava lokukulu ka khwiri, ku pfimba ka khwiri na ku huma ngati.Hikokwalaho, DSS-induced chronic relapsing colitis eka timbeva yi simekiwile ku kambela ku tirha kahle ka anti-colitis ka BLG (Fig. 1A).Loko ku pimanisiwa na ntlawa wa vulawuri, timbeva eka ntlawa wa modele wa DSS a ti hungute ngopfu ntiko wa miri na DAI yale henhla, naswona ku cinca loku ku tlheriseriwe endzhaku swinene endzhaku ka masiku ya 24 ya vutshunguri bya BLG (Xifaniso 1B na C).Ku koma ka kholokholo i xikombiso xa nkoka xa UC.Hilaha swi kombisiweke hakona eka Swifaniso 1D na E, ku leha ka kholoni ya timbeva leti amukeleke DSS ku hungutiwile swinene, kambe ku ntshunxiwile hi vutshunguri bya BLG.Endzhaku ka sweswo, nxopaxopo wa histopathological wu endliwile eka assess colonic inflammation.H&E stained images na swikoweto swa pathological swi kombisile leswaku vulawuri bya DSS byi kavanyetile swinene architecture ya colonic naswona swi endle leswaku ku va na ku onhiwa ka crypt, kasi vutshunguri bya BLG byi hungute swinene ku onhiwa ka crypt na swikoweto swa pathological (Xifaniso 1F na G).Lexi xiyekaka, mbuyelo wo sirhelela wa BLG eka mpimo wa 1 g/Kg a wu ringanisiwa na wa SASP eka mpimo wa 200 mg/Kg.Hi ku hlangana, swikumiwa leswi swi ringanyeta leswaku BLG yi tirha kahle eku hunguteni ka ku tika ka DSS-induced chronic relapsing colitis eka timbeva.
TNF-α, IL-1β na IL-6 i swikombiso swa nkoka swa ku pfimba swa ku pfimba ka kholokholo.Hilaha swi kombisiweke hakona eka Xifaniso 2A, DSS yi hlohlotele ku tlakuka lokukulu eka ku paluxiwa ka tijini ta TNF-α, IL-1β na IL-6 eka kholokholo loko ku pimanisiwa na ntlawa wa vulawuri.Ku nyikiwa ka BLG swi nga tlherisela endzhaku swinene ku cinca loku ku kongomisiwaka hi DSS.Ku landzela, hi tirhise ELISA ku kumisisa swiyimo swa ku pfimba cytokines TNF-α, IL-1β, na IL-6 eka tissue ya colon.Mimbuyelo yi tlhele yi kombisa leswaku ti levele ta colonic ta TNF-α, IL-1β, na IL-6 ti tlakukile swinene eka timbeva leti tshunguriweke hi DSS, kasi vutshunguri bya BLG byi hungute ku tlakuka loku (Xifaniso 2B).
Xifaniso 2 BLG yi sivela ku paluxiwa ka tijini na vuhumelerisi bya ti-cytokines ta proinflammatory TNF-α, IL-1β na IL-6 eka kholokholo ya timbeva leti tshunguriweke hi DSS.(A) Ku paluxiwa ka tijini ta kholoni ta TNF-α, IL-1β na IL-6; (B) swiyimo swa tiphrotheyini ta kholoni ta TNF-α, IL-1β na IL-6.Data yi nyikeriwile tanihi xiringaniso ± SEM (n = 4–6).#p < 0.05 kumbe ##p < 0.01 kumbe ###p < 0.001 vs ntlawa wa vulawuri (Con); *p < 0.05 kumbe **p < 0.01 vs ntlawa wa DSS.
Intestinal dysbiosis i ya nkoka swinene eka pathogenesis ya UC.24 Ku lavisisa loko BLG yi cinca cinca microbiota ya marhumbu ya timbeva leti tshunguriweke hi DSS, 16S rRNA sequencing yi endliwile ku xopaxopa vaaki va tibakteriya ta leswi nga endzeni ka marhumbu.Xifaniso xa Venn xi kombisa leswaku mintlawa yinharhu yi avelana 385 wa ti-OTU.Hi nkarhi lowu fanaka, ntlawa wun’wana na wun’wana a wu ri na ti-OTU to hlawuleka (Fig. 3A).Ku ya emahlweni, Chao1 index na Shannon index leswi kombisiweke eka Xifaniso xa 3B na C swi kombisile leswaku ku hambana ka vaaki ka microbiota ya marhumbu swi hungutiwile eka timbeva leti tshunguriweke hi BLG, tanihileswi Shannon index yi hungutekeke swinene eka ntlawa lowu tshunguriweke hi BLG.Principal component analysis (PCA) na principal coordinate analysis (PCoA) swi tirhisiwile ku kumisisa swivumbeko swa ku hlengeleta exikarhi ka mintlawa yinharhu na yi kombisile leswaku xivumbeko xa vaaki xa timbeva leti tshunguriweke hi DSS xi hambanisiwile kahle endzhaku ka vutshunguri bya BLG (Xifaniso 3D na E).Data leyi yi ringanyeta leswaku vutshunguri bya BLG byi khumbe swinene xivumbeko xa vaaki xa timbeva leti nga na vuvabyi bya colitis lebyi hlohloteriwaka hi DSS.
Xifaniso 3 BLG yi cinca ku hambana ka microbiota ya marhumbu eka timbeva leti nga na DSS-induced colitis.(A) Xifaniso xa Venn xa OTU, (B) Chao1 index, (C) Shannon’s richness index, (D) Principal Component Analysis (PCA) score plot of OTU, (E) OTU Principal Coordinate Analysis (PCoA) score Figure. Data yi nyikeriwile tanihi xiringaniso ± SEM (n = 6).**p < 0.01 vs ntlawa wa DSS.
Ku kambela ku cinca ko karhi eka microbiota ya manyoro, hi kambisisile xivumbeko xa microbiota ya marhumbu eka swiyimo hinkwaswo swa taxonomic.Hilaha swi kombisiweke hakona eka Xifaniso xa 4A, phyla leyikulu eka mintlawa hinkwayo a ku ri Firmicutes na Bacteroidetes, yi landzeriwa hi Verrucomicrobia.The relative abundances of Firmicutes and Firmicutes/Bacteroidetes ratios were significantly increased in the miganga ya switsongwatsongwana swa manyoro ya timbeva leti tshunguriweke hi DSS loko ku pimanisiwa na timbeva leti lawuriwaka, naswona ku cinca loku ku tlheriseriwe endzhaku swinene endzhaku ka vutshunguri bya BLG .Ngopfu-ngopfu, vutshunguri bya BLG byi engetele swinene ku tala loku ringanaka ka Verrucobacterium eka manyoro ya timbeva leti nga na colitis leyi hlohloteriwaka hi DSS.Eka xiyimo xa le kaya, miganga ya switsongwatsongwana swa manyoro a yi tshama hi Lachnospiriaceae, . Muribaculaceae, Akkermansiaceae, Ruminococcaceae na Prevotellaceae (Fig. 4B).Loko ku pimanisiwa na ntlawa wa DSS, ku hela ka BLG swi engetele nhlayo ya Akkermansiaceae, kambe swi hungute nhlayo ya Lachnospiraceae na Ruminococcaceae.Lexi xiyekaka, eka xiyimo xa genus, fecal microbiota ayi tshama hi Lachnospira_NK4A136_group, Akkermansia na Prevotellaceae_UCG-001 (Fig. 4C).Ku kumiwa loku ku tlhele ku kombisa leswaku vutshunguri bya BLG byi tlherisele endzhaku hi ndlela leyinene ku nga ringani ka microbiota ku hlamula eka ntlhontlho wa DSS, lowu tivekaka hi ku hunguteka ka Eubacterium_xylanophilum_group, Ruminococcaceae_UCG-014, Intestinimonas na Oscillibacter, na ku tlakuka ka Akkermansia na Prevotellaceae_UCG-001.
Xifaniso xa 4 BLG yi cinca ku tala ka microbiota ya le malungwini eka timbeva ta colitis leti hlohloteriweke hi DSS.(A) Ku tala ka microbiota ya le malungwini eka xiyimo xa phylum; (B) Ku tala ka microbiota ya marhumbu eka xiyimo xa ndyangu; (C) Ku tala ka microbiota ya marhumbu eka xiyimo xa genus.Data yi nyikeriwile tanihi xiringaniso ± SEM (n = 6).#p < 0.05 kumbe ###p < 0.001 vs ntlawa wa vulawuri (Con); *p < 0.05 kumbe **p < 0.01 kumbe ***p < 0.001 ku hambana na ntlawa wa DSS.
Loko hi tekela enhlokweni leswaku ti short-chain fatty acids (SCFAs) i ti metabolites letikulu ta Akkermansia na Prevotellaceae_UCG-001, kasi acetate, propionate na butyrate hi tona ti SCFA leti nga tala swinene eka lumen ya marhumbu, 25-27 ha ha ri eka dyondzo ya hina.Hilaha swi kombisiweke hakona eka Xifaniso xa 5, fecal acetate, propionate, na butyrate concentrations a swi ri tano swi hungutekile swinene eka ntlawa lowu tshunguriweke hi DSS, kasi vutshunguri bya BLG byi nga tshikilela ngopfu ku hunguteka loku.
Xifaniso 5. BLG yi engetela ti levele ta SCFAs eka manyoro ya timbeva leti nga na DSS-induced colitis.(A) Nhlayo ya acetic acid eka manyoro; (B) nhlayo ya propionic acid eka manyoro; (C) nhlayo ya butyric acid eka manyoro.Data yi nyikeriwile tanihi xiringaniso ± SEM (n = 6).#p < 0.05 kumbe ##p < 0.01 vs ntlawa wa vulawuri (Con); *p < 0.05 kumbe **p < 0.01 vs ntlawa wa DSS.
Hi tlhele hi hlayela Pearson correlation coefficient exikarhi ka genus-level differential SCFA na fecal microbiota.Hilaha swi kombisiweke hakona eka Xifaniso xa 6, Akkermansia yi fambelanisiwile kahle na vuhumelerisi bya propionic acid (Pearson = 0.4866) na butyric acid (Pearson = 0.6192).Ku hambana na sweswo, Enteromonas na Oscillobacter hivumbirhi bya swona a swi fambelanisiwa hi ndlela yo biha na acetate vuhumelerisi, na ti Pearson coefficients ta 0.4709 na 0.5104, hiku landzelelana.Hilaha ku fanaka, Ruminococcaceae_UCG-014 yi fambelanisiwile hi ndlela yo biha na vuhumelerisi bya propionic acid (Pearson = 0.4508) na butyric acid (Pearson = 0.5842), hiku landzelelana.
Xifaniso 6 Nxopaxopo wa ku yelana ka Pearson exikarhi ka ti-SCFA to hambana na switsongwatsongwana swa kholokholo.(A) Enteromonas na acetic acid; (B) Bacillus ya concussion leyi nga na acetic acid; (C) Akkermansia vs asidi ya propionic; (D) Ruminococcus_UCG-014 leyi nga na asidi ya propionic; (E) Akkermansia leyi nga ni asidi ya butyric; (F) ) Ruminococcus _UCG-014 leyi nga na asidi ya butyric.
Glucagon-like peptide-1 (GLP-1) i xiendliwa xa muxaka wa sele xo karhi xa le ndzhaku ka vuhundzuluxi xa proglucagon (Gcg) lexi nga na swivumbeko swo lwisana na ku pfimba.28 Hilaha swi kombisiweke hakona eka Xifaniso xa 7, DSS yi hlohlotele ku hunguteka lokukulu eka ku paluxiwa ka Gcg mRNA.Vutshunguri bya kholokholo na BLG byi nga tlherisela endzhaku swinene ku hunguteka ka Gcg loku hlohloteriweke hi DSS loko ku pimanisiwa na ntlawa wa vulawuri (Fig. 7A).Hi nkarhi lowu fanaka, mpimo wa GLP-1 eka serum wu hungutiwile swinene eka ntlawa lowu tshunguriweke hi DSS, naswona vutshunguri bya BLG byi nga sivela ngopfu ku hunguteka loku (Fig. 7B).Tanihi leswi tiasidi ta mafurha ta tikhetane to koma ti nga hlohlotelaka ku humesiwa ka GLP-1 hi ku tirhisa G-protein-coupled receptor 43 (GRP43) na G-protein-coupled receptor 41 (GRP41) activation, hi va tlhele va kambisisa GPR41 na GRP43 eka kholokholo ya timbeva ta colitis naswona va kumile leswaku ku paluxiwa ka mRNA ya kholokholo ya GRP43 na GPR41 ku hungutekile swinene endzhaku ka ntlhontlho wa DSS, naswona vutshunguri bya BLG byi nga ponisa hi ndlela leyinene ku hunguteka loku (Xifaniso 7C na D).
Xifaniso 7 BLG yi engetela ti levele ta serum GLP-1 na ku paluxiwa ka Gcg ya kholoni, GPR41 na GRP43 mRNA eka timbeva leti tshunguriweke hi DSS.(A) Ku paluxiwa ka Gcg mRNA eka tinyama ta kholokholo; (B) Level ya GLP-1 eka serum; (C) Ku paluxiwa ka mRNA ya GPR41 eka tinyama ta kholokholo; (D) Ku paluxiwa ka GPR43 mRNA eka tinyama ta kholokholo.Data yi nyikeriwile tanihi xiringaniso ± SEM (n = 5–6).#p < 0.05 kumbe ##p < 0.01 vs ntlawa wa vulawuri (Con); *p < 0.05 vs ntlawa wa DSS.
Tanihi leswi vutshunguri bya BLG byi nga engetelaka ti levele ta serum GLP-1, colonic Gcg mRNA expression, na fecal SCFA levels eka timbeva leti tshunguriweke hi DSS, hi tlhele hi kambisisa acetate, propionate, na butyrate xikan’we na ku suka eka control (F-Con), DSS colitis (F-Con) -DSS) na BLG-treated colitis (F-BLG) mice eka ku humesiwa ka GLP-1 kusuka eka primary murine tisele ta epithelial ta kholoni.Hilaha swi kombisiweke hakona eka Xifaniso xa 8A, tisele ta epithelial ta kholoni ta mbeva to sungula leti tshunguriweke hi 2 mM acetic acid, propionic acid, na butyric acid, hi ku landzelelana, ti hlohlotele swinene ku humesiwa ka GLP-1, leswi fambelanaka na tidyondzo ta khale.29,30 Hilaha ku fanaka, hinkwaswo F-Con, F-DSS, na F-BLG (leswi ringanaka na 0.25 g ya manyoro) swi hlohlotele swinene ku humesiwa ka GLP-1 ku suka eka tisele ta primary murine colonic epithelial cells.Lexi xiyekaka, nhlayo ya GLP-1 leyi humesiweke hi F-DSS-treated primary mouse colonic epithelial cells a yi ri ehansi swinene ku tlula ya F-Con na F-BLG-treated primary mouse colonic epithelial cells.(Xifaniso 8B).Data leyi yi ringanyeta leswaku vutshunguri bya BLG byi vuyisele swinene vuhumelerisi bya GLP-1 lebyi humaka eka SCFA bya le malungwini.
Xifaniso 8 SCFA leyi humaka eka BLG yi hlohlotela ku humesiwa ka GLP-1 ku suka eka tisele ta epithelial ta kholoni ta murine to sungula.(A) Acetic acid, propionic acid, na butyric acid swi hlohlotele ku humesiwa ka GLP-1 ku suka eka tisele ta epithelial ta kholoni ta murine to sungula; (B) swiphemu swa manyoro F-Con, F-DSS na F-BLG swi hlohlotele tisele ta primary murine colonic epithelial Nhlayo ya GLP-1 leyi humesiweke.Ti aliquots ta tisele ta colonic epithelial ti vekiwile eka ti glass-bottom petri dishes naswona ti tshunguriwile hi 2 mM acetic acid, propionic acid, butyric acid, na ti fecal extracts F-Con, F-DSS, na F-BLG (leyi ringanaka na 0.25 g ya manyoro), hiku landzelelana. 2 wa tiawara eka 37°C, 5% CO2, hi ku landzelelana.Nhlayo ya GLP-1 leyi humesiweke kusuka eka tisele ta primary murine colonic epithelial yi kumiwile hi ELISA.Data yi nyikeriwile tani hi mean ± SEM (n = 3).#p < 0.05 kumbe ##p < 0.01 vs. blank kumbe F-Con; *p < 0.05 ku hambana na F-DSS.
Swifunengeto: Ace, asidi ya acetic; Pro, asidi ya propionic; hambiswiritano, asidi ya butyric; F-Con, fecal extract kusuka eka ti control mice; F-DSS, xiphemu xa manyoro kusuka eka timbeva ta colitis; F-BLG, kusuka eka BLG-treated colon Fecal extracts ya timbeva leti pfimbaka.
Leswi yi xaxametiweke hi Nhlangano wa Rihanyo wa Misava Hinkwayo tanihi vuvabyi lebyi nga tshungulekiki, UC yi hundzuka khombo ra misava hinkwayo; hambiswiritano, tindlela leti tirhaka to vhumbha, ku sivela, na ku tshungula vuvabyi lebyi ta ha ri titsongo.Hikokwalaho, ku na xilaveko xa xihatla xo lavisisa na ku tumbuluxa tindlela letintshwa ta vutshunguri leti hlayisekeke na leti tirhaka ta UC.Malunghiselelo ya mirhi ya ndhavuko ya Xichayina i ndlela leyi tshembisaka hikuva malunghiselelo yo tala ya mirhi ya ndhavuko ya Xichayina ya kombisiwile ku va ya tirha eka vutshunguri bya UC eka vaaki va Machayina eka malembe xidzana, naswona hinkwaswo i swilo swa biological organics na switirhisiwa swa ntumbuluko leti ngopfu-ngopfu ti nga riki na khombo eka vanhu na swiharhi.31,32 Dyondzo leyi a yi kongomisiwile ku lava malunghiselelo ya mirhi ya ndhavuko ya Xichayina leyi hlayisekeke no tirha kahle eka vutshunguri bya UC na ku lavisisa endlelo ra yona ro tirha.BLG i fomula ya mirhi ya Xichayina leyi tivekaka swinene leyi tirhisiwaka ku tshungula mukhuhlwana.8,33 Ntirho eka laboratori ya hina na van’wana wu kombisile leswaku indigo, xiendliwa xa mirhi ya ndhavuko ya Xichayina lexi lulamisiweke ku suka eka swilo leswi fanaka na BLG, yi kombisa ku tirha lokukulu eka vutshunguri bya UC eka vanhu na swiharhi.4,34 Hambiswiritano, vuyelo bya anti-colitis bya BLG na vuyelo bya yona Endlelo a ri le rivaleni.Eka dyondzo ya sweswi, mimbuyelo ya hina yi kombisa leswaku BLG yi hunguta hi ndlela leyinene ku pfimba ka kholokholo loku hlohloteriwaka hi DSS, loku fambelanaka na ku cinca-cinca ka microbiota ya marhumbu na ku vuyiseriwa ka vuhumelerisi bya GLP-1 leyi humaka eka marhumbu.
Swi tiveka kahle leswaku UC yi tiveka hi ku tlhelela endzhaku ka minkarhi leyi nga na swihlawulekisi swa tliliniki leswi tolovelekeke, swo fana na ku lahlekeriwa hi ntiko, ku pfimba ka khwiri, ku huma ngati ya le khwirini, na ku onhaka lokukulu ka mucosal ya kholokholo.35 Xisweswo, chronic relapsing colitis yi nyikiwile hi ku nyika swirhendzevutani swinharhu swa 1.8% DSS ku ringana masiku ya ntlhanu, ku landzela masiku ya nkombo ya mati yo nwa.Hilaha swi kombisiweke hakona eka Xifaniso 1B, ku cinca-cinca ka ku lahlekeriwa hi ntiko na swikoweto swa DAI swi kombisile ku humelela ka induction ya chronic relapsing colitis.Timbeva eka ntlawa lowu tshunguriweke hi BLG ti kombisile ku hola ka upshift ku sukela hi siku ra 8, leswi a swi hambanile swinene na siku ra 24.Ku cinca loku fanaka ku tlhele ku voniwa eka xikoro xa DAI, leswi ringanyetaka ku antswisiwa eka ku antswisiwa ka tliliniki ka colitis.Hi mayelana na ku vaviseka ka kholokholo na xiyimo xa ku pfimba, ku leha, ku onhaka ka tinyama ta kholokholo, na ku paluxiwa ka tijini na vuhumelerisi bya ti-cytokines ta proinflammatory TNF-α, IL-1β, na IL-6 eka tinyama ta kholokholo na swona swi antswisiwile swinene endzhaku ka vutshunguri bya BLG.Hi ku hlangana, mimbuyelo leyi yi kombisa kahle leswaku BLG yi tirha kahle eka vutshunguri bya chronic relapsing colitis eka timbeva.
Xana BLG yi tirhisa njhani vuyelo bya yona bya mirhi?Mindzavisiso yo tala ya khale yi kombisile leswaku microbiota ya le malungwini yi tlanga xiave xa nkoka eka pathogenesis ya UC, naswona vutshunguri lebyi sekeriweke eka microbiome na lebyi kongomisiweke eka microbiome byi humelerile tanihi maqhinga yo koka rinoko swinene eka vutshunguri bya UC.Eka dyondzo ya sweswi, hi kombisile leswaku vutshunguri bya BLG byi endle leswaku ku va na ku cinca lokukulu eka xivumbeko xa microbiota ya marhumbu, leswi ringanyetaka leswaku mbuyelo wo sirhelela wa BLG eka colitis leyi hlohloteriwaka hi DSS wu fambelana na ku cinca cinca ka microbiota ya marhumbu.Ku xiyisisiwa loku ku fambisana na mianakanyo ya leswaku ku tlhela ku phurogirema homeostasis ya microbiota ya marhumbu i ndlela ya nkoka yo twisisa ku tirha kahle ka malunghiselelo ya TCM.36,37 Lexi xiyekaka, Akkermansia i Gram-negative na strictly anaerobic bacterium leyi hanyaka eka mucus leyara ya marhumbu, leyi onhaka ti mucins, yi humesa propionic acid, yi hlohletela ku hambana ka tisele ta goblet naswona yi hlayisa mucosa. function of barrier integrity.26 Data yo tala ya tliliniki na ya swiharhi yi ringanyeta leswaku Akkermansia yi fambelanisiwa swinene na mucosa leyi hanyeke kahle,38 na vulawuri bya nomu bya Akkermansia spp. swi nga antswisa swinene ku pfimba ka mucosal.39 Data ya hina ya sweswi yi ringanyeta leswaku nhlayo ya xiringaniso ya Akkermansia yi engeteleka swinene endzhaku ka vutshunguri bya BLG.Ku engetela kwalaho, Prevotellaceae_UCG-001 i xitsongwatsongwana lexi humesaka SCFA.27 Mindzavisiso yo tala yi kombisile leswaku Prevotellaceae_UCG-001 yi ​​kumiwile hi nhlayo ya le hansi ya xiringaniso eka manyoro ya swifuwo leswi nga na colitis.40,41 Data ya hina ya sweswi yi tlhela yi kombisa leswaku vutshunguri bya BLG byi nga engetela swinene nhlayo ya xiringaniso ya Prevotellaceae_UCG-001 eka kholokholo ya timbeva leti tshunguriweke hi DSS.Ku hambana na sweswo, Oscillibacter i xitsongwatsongwana xa mesophilic, strictly anaerobic.42 yi vikile leswaku nhlayo ya xiringaniso ya Oscillibacter yi tlakuke swinene eka timbeva ta UC naswona a yi ri ya nkoka swinene swi fambelanisiwa kahle na swiyimo swa IL-6 na IL-1β na swikoweto swa vuvabyi.43,44 Lexi xiyekaka, vutshunguri bya BLG byi hungute swinene ku tala loku ringanaka ka Oscillibacter eka manyoro ya timbeva leti tshunguriweke hi DSS.Lexi xiyekaka, tibakteriya leti cinciweke hi BLG a ku ri tona tibakteriya leti humesaka SCFA swinene.Mindzavisiso yo tala ya khale yi kombisile vuyelo lebyi nga pfunaka bya ti-SCFA eka kholokholo ku pfimba na nsirhelelo wa vutshembeki bya epithelial ya marhumbu.45,46 Data ya hina ya sweswi yi tlhele yi xiya leswaku nhlayo ya SCFA acetate, propionate, na butyrate eka manyoro lama tshunguriweke hi DSS yi engeteriwile swinene eka timbeva leti tshunguriweke hi BLG. Loko swi tekiwa swin’we, swikumiwa leswi swi kombisa kahle leswaku vutshunguri bya BLG byi nga ndlandlamuxa hi ndlela leyinene tibakteriya leti humelerisaka SCFA leti hlohloteriweke hi DSS eka timbeva leti nga na nkarhi wo leha vuvabyi bya colitis lebyi tlhelelaka endzhaku.
GLP-1 i incretin leyi humelerisiwaka ngopfu eka ileum na kholokholo naswona yi tlanga xiave xa nkoka eka ku hlwela ku pfumala nchumu ka le khwirini na ku hunguta glucose ya ngati endzhaku ka swakudya.47 Vumbhoni byi ringanyeta leswaku dipeptidyl peptidase (DPP)-4, GLP-1 receptor agonist, na GLP-1 nanomedicine swi nga hunguta hi ndlela leyinene ku pfimba ka marhumbu eka timbeva.48-51 Hilaha swi vikiweke hakona eka tidyondzo ta khale, nhlayo yale henhla ya SCFA yi fambelanisiwile na ti levele ta plasma GLP-1 eka vanhu na timbeva. 52 Data ya hina ya sweswi yi kombisa leswaku endzhaku ka vutshunguri bya BLG, swiyimo swa serum GLP-1 na ku paluxiwa ka Gcg mRNA swi engeteriwile swinene.Hilaha ku fanaka, ku humesiwa ka GLP-1 ku engeteriwile swinene eka mindhavuko ya kholoni endzhaku ka ku hlohloteriwa hi swiphemu swa manyoro ku suka eka timbeva ta colitis leti tshunguriweke hi BLG loko ku pimanisiwa na ku hlohloteriwa hi swiphemu swa manyoro ku suka eka timbeva ta colitis leti tshunguriweke hi DSS.Xana ti SCFA ti khumba njhani ku humesiwa ka GLP-1?Gwen Tolhurst na van'wana. va vikile leswaku SCFA yi nga hlohlotela ku humesiwa ka GLP-1 hi ku tirhisa GRP43 na GPR41.29 Data ya hina ya sweswi yi tlhela yi kombisa leswaku vutshunguri bya BLG byi engetela swinene ku paluxiwa ka mRNA ya GRP43 na GPR41 eka kholokholo ya timbeva leti tshunguriweke hi DSS.Data leyi yi ringanyeta leswaku vutshunguri bya BLG byi nga vuyisela vuhumelerisi bya GLP-1 lebyi hlohloteriweke hi SCFA hi ku tirhisa GRP43 na GPR41.
BLG i murhi wa nkarhi wo leha lowu nga xavisiwiki hi dokodela (OTC) eChina. Mpimo lowukulu lowu tiyiseleriwaka wa BLG eka timbeva ta Kunming i 80g/Kg, naswona ku hava chefu ya xihatla leyi voniweke.53 Sweswi, mpimo lowu ringanyetiweke wa BLG (handle ka chukele) eka vanhu i 9-15 g/siku (3 times a day).Dyondzo ya hina yi kombisile leswaku BLG eka 1g/Kg yi antswise DSS-induced chronic relapsing colitis eka mice.Dose leyi yi le kusuhi na mpimo wa BLG lowu tirhisiwaka hi tlhelo ra tliliniki.Dyondzo ya hina yi tlhele yi kuma leswaku endlelo ra yona ra ntirho ri kongomisiwa, hi xiphemu, hi ku cinca eka microbiota ya marhumbu, ngopfungopfu tibakteriya leti humesaka SCFA, ku fana na Akkermansia na Prevotellaceae_UCG-001, ku vuyisela vuhumelerisi bya GLP-1 lebyi humaka eka marhumbu.Swikumiwa leswi swi ringanyeta leswaku BLG yi faneriwa hi ku ya emahlweni ku tekeriwa enhlokweni tanihi xiaki lexi nga kotekaka xa vutshunguri bya vutshunguri bya colitis ya tliliniki.Hambiswiritano, endlelo leri kongomeke leri yi cincaka microbiota ya le malungwini ha rona ya ha fanele ku tiyisisiwa hi timbeva leti pfumalaka microbiota na ku rhumeriwa ka tibakteriya ta manyoro.
Ace, asidi ya acetic; kambe, asidi ya butyric; BLG, ku nga pandan; DSS, ku nga sodiyamu sulfate ya dextran; DAI, xikombiso xa migingiriko ya mavabyi; DPP, ku nga dipeptidyl peptidase; FID, xitivi xa ionization ya malangavi; F-Con, vulawuri Ti Fecal extracts ta timbeva; F-DSS, swiphemu swa manyoro swa timbeva ta DSS colitis; F-BLG, swiphemu swa manyoro swa timbeva ta colitis leti tshunguriweke hi BLG; GLP-1, peptide-1 leyi fanaka na glucagon; Gcg, ku nga glucagon; chromatography ya gasi, chromatography ya gasi; GRP43, G xirho lexi hlanganisiweke na tiphrotheyini 43; GRP41, G xirho lexi hlanganisiweke na tiphrotheyini 41; H&E, hematoxylin-eosin, ku nga hematokisilini-eosin; HBSS, Xitshunxo xa Munyu lexi ringaniseriweke xa Hanks ; OTC, OTC, hi ku tirhisa swilo leswi nga riki swa nkoka; PCA, nxopaxopo wa swiphemu leswikulu; PCoA, nxopaxopo wa vuhlanganisi bya nkoka; Pro, asidi ya propionic; SASP, xitsongwatsongwana xa sulfasalazine; SCFA, ti- fatty acid ta tikhetane to koma; Vutshunguri bya Xichayina, vutshunguri bya ndhavuko bya Xichayina; UC, vuvabyi bya khwiri lebyi nga ni swilondza.
Tiphurothokholo hinkwato ta swikambelo ti amukeriwile hi Komiti ya Mahanyelo ya Swiharhi ya Yunivhesiti ya Peking Yunivhesiti ya Shenzhen-Hong Kong ya Sayense na Thekinoloji Medical Center (Shenzhen, China) hi ku ya hi Swiletelo swa Nhlangano na Milawu ya Swiharhi (nomboro ya mahanyelo ya A2020157).
Vatsari hinkwavo va hoxe xandla swinene eka ku ehleketa na ku dizayina, ku kuma datha, kumbe nxopaxopo na nhlamuselo ya datha; u nghenelerile eku tsaleni ka atikili kumbe ku pfuxeta hi vukheta nhundzu ya nkoka ya vutlhari; va pfumerile ku yisa tsalwa ra voko eka magazini wa sweswi; eku heteleleni u pasisile vuhundzuluxeri lebyi leswaku byi kandziyisiwa; Ku va na vutihlamuleri eka swiyenge hinkwaswo swa ntirho.
Ntirho lowu wu seketeriwile hi National Natural Science Foundation of China (81560676 na 81660479), phurojeke ya xiyimo xo sungula ya Yunivhesiti ya Shenzhen (86000000210), Nkwama wa Komiti ya Vumaki bya Sayense na Thekinoloji ya Shenzhen (JCYJ20210324093810026), na Nkwama wa Vulavisisi bya Sayense na Thekinoloji ya Xifundzha xa Guangdong (A2020157 na A2020272), Khemisi ya Yunivhesiti ya Vutshunguri ya Guizhou Xifundzha xa Guizhou leyi seketeriwaka hi timali hi Laboratori ya Nkoka (YWZJ2020-01) na Xibedlhele xa Yunivhesiti ya Peking ya Shenzhen (JCYJ2018009).
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