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Ban-Lan-Gen granules attenuate dextran sodium sulfate-induced chronic relapsing colitis in mice by modulating gut microbiota and restoring intestinal SCFA Derived-GLP-1 production
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 Haitao21Peking University Shenzhen Hospital Department of Pharmacy, Shenzhen, Republics 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 Dipatmen mi Gastroenterology, Peking University Shenzhen Hospital, Shenzhen, People's Republic of China; 5 Sukuru mi yath, Guizhou Medical University, State Key Laboratory of Medicical Plant Function and Application, Guiyang; 6 Dipatmen mi Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen, China [email protected] Shen Xiangchun, School of Pharmacy, Guizhou Medical University, Guizhou, People's Republic of China, 550004, Email [email protected] Lembe ma pire tek: GLP-1-based therapy ubedo yore manyen mi thieth pa two ma mako ic. (BLG) granules ubedo yath ma julwongo ni antiviral TCM ma nyutho tic ma copo jwigo wang i kum two matung tung. Ento, tic pare mi jwigo wang i kum colitis man kite ma etiyo kudu podi ungeyere ngo. YORE: Mi ketho dextran sodium sulfate (DSS)-induced chronic colpsing activity i remo ma rac. indices, histological markers of injury, and proinflammatory cytokine levels were done to assess protective effect of BLG. Adwogi pa BLG ikum gut microbiota man gut juporo ku serum GLP-1 levels man colonic Gcg, GPR41, man GRP43 expression, gut microbiota composition, fecal SC levels, man primary mouse releases from mouse colonic epithelial cells SCFA-derived GLP-1 production.Adwogi: BLG treatment udwoko piny pek pa kum, DAI, colon shortening, colon tissue damage, man proinflammatory cytokine levels pa TNF-α, IL-1β, man IL-6 in colon tissue. I medo, BLG treatment copo dwoko piny GPR14. man GRP43 nyuthu man rwom pa GLP-1 i rimo pa oyo ma colitis, man ku medo SCFA-producing bacteria calu Akkermansia man Prevotellaceae_UCG-001, man dwoko piny wel pa bacteria calu Eubacterium_xylanophilum_group, Ruminococcaceae_UCG-104, Imonantes man Ocilicbaliter. Mi medo, yath pa BLG copo medo rwom pa SCFAs i ic pa oyo ma two colitis. I saa marom, lembe ma jutimo in vitro de unyutho nia piny ma juwodho kud i ic pa oyo ma jutiyo kudu ku BLG copo ketho GLP-1 i Murine colonic epithelial cells. I ajiki: Lembe ma junwango nyuthu nia BLG utiye ku tic mi juku two ic. BLG utiye ku copo mi yubu calu yath, kadi nya yore moko ni loko gut microbiota man dwoko SCFA-derived GLP-1 ma nwang i ic. Yath maber pi two ma mako ic. Lembe ma pire tek: colitis, Ban-Lan-Gen granules, gut microbiota, short-chain fatty acids, GLP-1
Ulcerative colitis (UC) utiye two ma rii pi kare malac ma nyayu lyethu i ic man ic ma nen ku ic ma wok kare ku kare, remu ic, rwinyu pa pek, man ic ma rimo.1 I kare ma ukadhu, rwom pa UC ubedo ka medere in ngom ma con ubedo nok, ikinde China, ku rwom pa kwo pa Western ma ube medere. kelo peko madit ikum yot kum pa dhanu man etiye ku adwogi marac ikum kero pa jurutwo mi tic man kwo maber. Ma pire tek, thek pa UC podi ungeyere ngo, ento dhanu mapol giyio nia genetics, lembe mi kabedu, gut microbiota, man immune system gikonyo i dongo pa UC.3 Kadi kawoni, yath pa UC epe, man yath pa UC utiye i ot yat nyayu man gwoko remo, kony mi keyo pa ler, man dwoko piny dwogo pa two. Yath macon uketho i iye aminosalicylates, corticosteroids, immunosuppressants, man biologics. Ento, yath eni copo nwangu ngo adwogi maber pi adwogi marac migi matung tung.4 I kare ma ukadhu, lembe mapol ma jutimo unyutho nia yath macon mi China (MTC) utiye ku adwogi maber copo mi konyo ni jwigo UC ku toxicity ma nok, ma nyutho nia dongo pa yore manyen mi thieth pa TCM utiye yore maber mi thieth pa UC.5-7��
Banlangen Granules (BLG) ubedo yath macon pa ju China ma juyubu ku pii ma juwodho kud i lum pa Banlangen.8 Mi medo ikum tic pare mi juku two, BLG nyuthu tic mi jwigo two matung tung.9,10 Mi medo, glucosinolates (R,S-goitrin, progoitrin, man epiprobin man glucoside juyike junwango kud i pii pa Radix isatidis) man nucleosides (hypoxanthine, adenosine, uridine man guanosine) man indigo alkaloids calu indigo man indirubin.11,12 Somo mukadho onyuthu maber nia adenosine, uridine man indirubin nyutho tic ma tek mi juku cololitis i lei ma tung tung. Ento, lembe moko mbe ma jutimo pi ni ngiyo tic pa BLG i colitis. I lembe maeni, wa lubo tok gwoko pa BLG ikum dextran sodium sulfate (DSS)-induced chronic relapsing colitis in C57BL/6 mice man wanwango ni miyo BLG i dog dhanu uketho DSS-induced chronic relapsing colitis udok piny Twoyo, yore pare mi telo wic utiye ku winjiri ku loko pa gut microbiota man dwoko pa gut-derived glucagon-like peptide-1 (GLP-1) production.
BLG granules (sugar-free, NMPA-approved Z11020357; Beijing Tongrentang Technology Development Co., Ltd., Beijing, China; batch number: 20110966) juwilo kud i ot yath. DSS (Molecular Weight: 36,000–000,000) juwilo kud i ot yath MP Biologicals (Santa Ana, USA).Sulfasalazine (SASP) (≥ 98% purity), hematoxylin man eosin juwilu kud i Sigma-Aldrich (St. Louis, MO, USA).Mouse TNF-α, IL-1β man IL-6 luminex Elisa assay kits juwilu kud i R&D systemass (MNacetic, MNAcetic, USA). propionic acid, man butyric acid juwilo kud i Aladdin Industries (Shanghai, China).2-Ethylbutyric acid juwilu kud i Merck KGaA (Darmstadt, Germany).
6-8-week-old male C57BL/6 mice (body weight 18-22 g) was purchase from Beijing Wetahe Laboratory Animal Technology Co., Ltd. (Beijing, China) and standed in place of 22 ± 2 °C with 12 h light/ dark cycle were standard a racet a rodent access to drinking water with one rodent access to drinking water. yenga mi bedo i kabedu manyen. I ngeye jupoko oyo i ungu angwen: ungu mi gwoko, ungu mi DSS, ungu mi SASP-treated (200 mg/kg, oral) man ungu mi BLG-treated (1 g/kg, oral). Nindo 5, man pii ma leng pi nindu 7, nimakere ku somo mwa mukadho.18 Oyo i dul ma jutimo igi SASP man BLG jutimo igi SASP man BLG, kubang ceng nicaku i ceng 0. Nimakere ku lembe ma jutimo, wel pa BLG juketho i 1 g/kg. Ikinde marom, wel pa SASP juketho i 20 mg/kg lembe ma jugoro.4 Udul mi control man DSS model ginwangu dwong pa pii marom i kare mi temo.
Cal 1 BLG dwoko piny DSS-induced chronic relapsing colitis in mice.(A) Experimental design of chronic recurrent colitis and treatment, (B) aloka loka pa pek pa kum, (C) two ma wok (DAI) score, (D) colon length, (E) representative image of colon, (F) H&E staining Colon (10) (G) wel. Lembe ju nyuthu calu wel ± SEM (n = 6).##p < 0.01 nyo ###p < 0.001 vs dul ma juporo (Con); *p < 0.05 nyo **p < 0.01 nyo ***p < 0.001 vs DSS group.
Pek pa kum, bedo pa ic, man remo ma wok kud i ic jubedu ka goyo piny kubang ceng. Disease activity index (DAI) ungiyure ku rwom pa pek pa kum, bedo pa ic, man remo ma wok kud i ic calu ma jukoro con.19 I thum pa lembe ma jutimo, junego oyo zo man remo, ic man colon ju kwalo pi temo mange.
Colon tissue juyike ku formalin man juyike i paraffin. 5-micron sections juyike man juyike ku hematoxylin-eosin (H&E), man juyike man juyike calu ma jukoro con.19
RNA ceke pa adila pa ic juwodho ku Trizol reagent (Invitrogen, Carlsbad, CA), man cDNA juwodho ku reverse transcriptase (TaKaRa, Kusatsu, Shiga, Japan). Quantitative PCR jutimo ku tic ku real-time PCR system ku SYBR Green Master (Roche, Basel, Switzerland, Switzerland Get-Get transscripted genes ma jutiyo kudu i β). lembe juporo ku yore mi 2-ΔΔCT. Gene primer sequences nen i Table 1.
Poko cell pa ic pa oyo ma kwong'a man jutimo kudu tic calu ma jukoro con.20 I lembe ma nok, ic pa oyo ma oro migi 6-8 juwodhe i ngei thwol ku cervical dislocation, man juyabu, juyiko ku Hanks Balanced Salt Solution (HBSS, manangu calcium man magneum epe) i 50-mm. dul. I ngeye, jupoko adila ku 0.4 mg/mL collagenase XI (Sigma, Poole, UK) i DMEM man juyiko i 300 xg pi dakika 5 i lyethu mi ot. Resuspend pellet i DMEM (ma ju medo ku 10% fetal serum bovinenic, 10/00 units, man peillin 100 μg/mL streptomycin) i 37 °C man kadhu kud i nylon mesh (pore size ~250 μm). Aliquots pa colonic epithelial cells ju ketho gi i glass-bottom dishes man ju ketho gi ku acetic acid, propionic acid, butyric acid, man fecal extract pi sawa 37 °C 5% CO2.
Colon tissue ubedo homogenized ku PBS, man kadhiri pa cytokines IL-6, TNF-α man IL-1β in colon tissue ju nwango ku luminex ELISA assay kits (R&D systems, Minneapolis, MN, USA). ELISA kit (Bioswamp, Wuhan, China) nimakere ku cik pa ju ma yiku.
DNA zo kud i ic juwodho ku tic ku DNA extraction kit (Tiangen, China). Ber pa DNA man wel pa DNA jupimu i ratio pa 260 nm/280 nm man 260 nm/230 nm, kubang wadi. I ngeye, jutiyo ku DNA acel acel ma juwodho calu lanyuth, primers 338F (ACCCG) man GCAGGA86 (GGACTACHVGGGTWTCTAAT) jutiyo kudu pi medo V3-V4 mi 16S rRNA gene i kabedo matung tung. Jam piny ma juyubu ku PCR juyike ku QIAquick Gel Extraction Kit (QIAGEN, Germany), jupimu ku PCR mi kare mandha, man juporo ku IlluminaMiseq PE300 sequencing platform (FI, USA). nyang ikum bioinformatics, timo tic ku lembe ma jukwanu con.21,22 I lembe ma nok, ti ​​ku Cutadapt (V1.9.1) pi filter raw express files.OTUs jupoko gi ku UPARSE (version 7.0.1001) ku rwom ma rom pa 97%, man UCHIME jutiyo kudu pi kwanyu chimer sequence classification man community analysis. jutimo ku tic ku RDP classifier (http://rdp.cme.msu.edu/) malube ku SILVA ribosomal RNA gene database.
Kite ma short-chain fatty acids (acetic acid, propionic acid, man butyric acid) jupimu kudu calu ma juloko con ni Tao et al., ku aloka loka moku.23 I lembe ma nok, 100 mg pa ic juyike i 0.4 mL pa pii ma ionized, man 0.1 mL pa 0.1 mL pa 0.5 mL pa acid man sulfuric mL. 2-ethylbutyric acid (internal standard), man juyike man juyike i 4°C. Centrifuge i 12,000 rpm pi dakika 15 i C. The supernatant juwodho ku 0.5 mL pa ether man jubolo i GC pi nyang kudu. Pi nyang ikum gas chromatography (GC), juporo lanyuth ku tic ku GC-2010 Plus gas chromatograph (Shimadzu, Inc) ma juketho i deteon deteon. (FID). Poko piny utimere ku tic ku ZKAT-624 column, 30 m × 0.53 mm × 0.3 μm (Lanzhou Zhongke Antai Analytical Technology Co., Ltd., China). Lembe ju nwango ku tic ku GC solution software (Shimadzu, Inc.). Ratio pa poko ubedo nitrogen: 10, gas, man carrier ubedo nitrogen, man carrier ubedo 10, man carrier ubedo gas, man carrier ubedo nitrogen, man gas ma tingo 10: rwom pa pii ubedo 6 mL/min. Dwong pa yath ubedo 1 μL. Piny ma jucwalo ku jam neno ubedo 300°C. Lyethu pa oven ubedo 140°C pi dakika 13.5, man jumedo ni 250°C ku rwom pa 120°C/min; lyethu ubedo pi dakika abic.
Lembe nyuthu calu rwom ± lembe ma rac pa rwom (SEM). Lembe ma pire tek jupimu ku one-way ANOVA ma ulubre ku Duncan's multiple range test. GraphPad Prism 5.0 software (GraphPad Software Inc., San Diego, CA, USA) jutiyo kudu pi kwanu zo man p < 0.05 ju kwanu ni lembe ma pire tek.
Ung'eyo maber niya UC utiye two ma dwoko ic ma rwinyo ku remo ic, ic man rimo. Pieno, DSS-induced chronic relapsing colitis i oyo juyike pi ni pimo tic pa BLG (cal 1A). Ka juporo ku oyo i dul pa DSS ma rwinyo, pek pa DSS ubedo piny man pek migi nok DAI, man aloka loka eni udok cen ingey nindu 24 mi yath pa BLG (lanyut 1B ku C). Colon shortening ubedo lanyuth ma pire tek pa UC. Calu ma ju nyuthu i cal 1D ku E, colon lengths pa oyo ma ginwangu DSS udoko nok mandha, ento judwokogi piny ku yath pa BLG. I ngeye, jutimo histonic analysis pi pimo colon lyethu. H&E cal ma rangi ku pathological scores unyutho nia DSS ma jumiyo unyotho colonic architecture man ukelo nyoth pa crypt, ento yath pa BLG unyayu nyoth pa crypt man pathological scores (Figure 1F ku G). Mandha, gwok pa BLG i rwom pa 1 g/Kg ubedo marom ku rwom pa SASP20 mg/Kg. I acel, lembe ma junwango nyutho nia BLG tiyo maber i jwigo peko pa DSS-induced chronic relapsing colitis i oyo.
TNF-α, IL-1β man IL-6 gitiye lanyuth ma pire tek mi lyethu pa ic. Calu ma ju nyuthu i cal mir 2A, DSS ukelo dongo ma lee i gene expression pa TNF-α, IL-1β man IL-6 i ic ka juporo ku dul ma jucaku kudu. Miyo BLG copo dwoko aloka loka ma DSS-mediated eni, ma watiyo kudu pi nyang ikum rwom pa ELISA. cytokines ma kelo two TNF-α, IL-1β, man IL-6 i ic. Adwogi ne unyutho bende nia rwom pa TNF-α, IL-1β, man IL-6 i ic umedire lee i oyo ma jutiyo kudu ku DSS, ento BLG uketho rwom eni piny (lanyut 2B).
Cal mir 2 BLG juku nyuthu pa gene man yubu pa proinflammatory cytokines TNF-α, IL-1β man IL-6 i colon pa DSS-treated mice.(A) Colonic gene expression pa TNF-α, IL-1β man IL-6; (B) colonic protein levels of TNF-α, IL-1β and IL-6. Data are presented as mean ± SEM (n = 4–6).#p < 0.05 or ##p < 0.01 or ###p < 0.001 vs control (Con) group; *p < 0.05 nyo **p < 0.01 vs DSS group.
Dysbiosis mi ic ubedo piny ma pire tek in pathogenesis pa UC.24 Mi lubo tok ka BLG loko gut microbiota pa DSS-treated mice, 16S rRNA sequencing jutimo pi nyang ikum bacterial community mi gut contents. The Venn diagram nyutho nia dul adek eno gi poko 385 OTUs. I kare marom, dul acel acel ubedu ku tung tung (Figs. OTU). 3A).Man de, Chao1 index man Shannon index ma junyutho i cal 3B ku C unyutho nia dul pa gut microbiota udok piny in BLG-treated mice, calu Shannon index udok piny lee i BLG-treated group.Principal component analysis (PCA) man principal coordinate analysis (PCA) jutiyo kudu pi nyang ikum dul adek dul man unyutho nia kit pa oyo ma jutiyo kudu ku DSS ubedo tung tung ingey BLG (lanyut 3D ku E). Lembe eni nyutho nia BLG ubedo ku matoke madit ikum kit pa oyo ma DSS-induced colitis.
Cal 3 BLG loko tung tung pa gut microbiota i oyo ma DSS-induced colitis. (A) Venn diagram pa OTU, (B) Chao1 index, (C) Shannon's richness index, (D) Principal Component Analysis (PCA) score plot pa OTU, (E) OTU Principal Coordinate Analysis score (PCA) Cal. Lembe ju nyuthu calu rwom ± SEM (n = 6).**p < 0.01 vs DSS group.
Mi ngiyo aloka loka moku ikum microbiota mi ic, wa ngiyo kit ma microbiota mi ic utiye kudu i rwom zo. Calu ma ju nyuthu i cal mir 4A, phyla madit i ungu zo ubedo Firmicutes man Bacteroidetes, ma lubo Verrucomicrobia. Wel pa Firmicutes man Firmicutes/Bacteroidetes umedire lee i kind mon dul pa microbial pa DSS-treated mice ka juporo ku control mice, man aloka loka eni udok cen ingey BLG treatment. I andha, BLG treatment umedire lee dit wel pa Verrucobacterium i feces pa oyo ma DSS-induced colitis. I ot, fecal microbial communities jubedo ka tiyo ku Lachnoaspire, Muribaculaceae, Akkermansiaceae, Ruminococcaceae man Prevotellaceae (cal 4B). Ka juporo ku dul pa DSS, jwigo pa BLG umedire wel pa Akkermansiaceae, ento udwoko piny wel pa Lachnospiraceae man Ruminococcaceae. Notably, i rwom pa gen, ubedo microbical feocal. ma juketho i Lachnospira_NK4A136_group, Akkermansia man Prevotellaceae_UCG-001 (cal 4C). Lembe ma junwango eni nyutho bende nia yath pa BLG udwoko piny ma rac pa microbiota i dwokowang lembe pa DSS, ma nen ku dwoko piny pa Eubacterium_xylalanophilum_group, Ruminococcaceae_UCG-014, Intestinimonas man Oscillibacter, man mediri pa Akkermansia man Prevotellaceae_UCG-001.
Cal 4 BLG loko wel pa gut microbiota i DSS-induced colitis mice. (A) Abundance pa gut microbiota i rwom pa phylum; (B) Pol pa gut microbiota i ot; (C) Wel pa gut microbiota i rwom pa thek. Lembe majunyutho calu mean ± SEM (n = 6).#p < 0.05 nyo ###p < 0.001 vs control (Con) group; *p < 0.05 nyo **p < 0.01 nyo ***p < 0.001 vs DSS group.
Ka waparu nia short-chain fatty acids (SCFAs) gi ubedo metabolites madongo pa Akkermansia man Prevotellaceae_UCG-001, ma acetate, propionate man butyrate gibedo SCFAs madwong uloyu i lumen mi ic, 25-27 podi watiye i somo mwa. judwok piny lee i dul pa ju ma jutimo igi DSS, man BLG copo juku dwoko piny eni.
Cal 5. BLG medu kadhiri pa SCFAs i ic pa oyo ma DSS-induced colitis.(A) Acetic acid ma nwang i ic; (B) wel pa propionic acid i ic; (C) butyric acid content in feces. Data are presented as mean ± SEM (n = 6).#p < 0.05 or ##p < 0.01 vs control (Con) group; *p < 0.05 nyo **p < 0.01 vs DSS group.
Wa medo kwanu Pearson correlation coefficient ikind genus-level differential SCFA ku fecal microbiota. Calu ma ju nyuthu i cal mir 6, Akkermansia ubedu ku winjiri maber ku yiku pa propionic acid (Pearson = 0.4866) man butyric acid (Pearson = 0.6192 I tung tung, Enteromonas man Ocillocters ubedu marac). ma rwate ku yubu acetate, ku Pearson coefficients pa 0.4709 man 0.5104, kubang wadi. Kumeno bende, Ruminococcaceae_UCG-014 ubedu ku winjiri marac ku yubu pa propionic acid (Pearson = 0.4508) man butyric acid (Pearson = 0.4508), kubang acel acel.
Cal 6 Pearson correlation analysis ikind SCFAs ma tung tung ku colonic microbes. (A) Enteromonas ku acetic acid; (B) Concussion bacillus ku acetic acid; (C) Akkermansia vs propionic acid; (D) Ruminococcus_UCG-014 ku propionic acid; (E) Akkermansia ku butyric acid; (F) ) Ruminococcus _UCG-014 ku butyric acid.
Glucagon-like peptide-1 (GLP-1) utiye cell-type-specific post-translational product pa proglucagon (Gcg) ku kero mi jwigo wang.28 Calu ma ju nyuthu i cal mir 7, DSS ukelo dwoko piny pa Gcg mRNA. Colon man BLG ma jutiyo kudu copo dwoko piny pa DSS ma judwoko piny ka juporo ku ju ma jutiyo kudu (Fig. 1). 7A).I saa marom, kadhiri pa GLP-1 i rimo ubedo piny akeca ikind ju ma jutiyo ku DSS, man BLG copo juku dwoko piny eni (cal 7B). Calu short-chain fatty acids copo ketho GLP-1 wok kud i G-protein-coupled receptor 43 (GRP43) man GRP-protein-protein 43 (43) tic, wan bende wa ngiyo GPR41 ku GRP43 i colon pa oyo ma colitis man wanwango ni colonic mRNA expression pa GRP43 ku GPR41 ubedo piny mandha ingey DSS challenge, man BLG treatment copo konyo dwoko piny eni (lanyut 7C ku D).
Cal mir 7 BLG medu kadhiri pa GLP-1 i remo man Gcg, GPR41 man GRP43 mRNA i ic pa oyo ma jutiyo kudu ku DSS. (A) Gcg mRNA nyuthu i ic; (B) GLP-1 level in serum; (C) GPR41 mRNA nyuthu in ic; (D) GPR43 mRNA expression in colon tissue. Data are presented as mean ± SEM (n = 5–6).#p < 0.05 or ##p < 0.01 vs control (Con) group; *p < 0.05 vs DSS group.
Calu ma yath pa BLG copo medo kadhiri pa GLP-1 i rimo, colonic Gcg mRNA expression, man kadhiri pa SCFA i ic i DSS-treated mice, wa medo ngiyo acetate, propionate, man butyrate man bende kud i control (F-Con), DSS colitis (F-Con) -DSS) man BLG-treated colitis (F-Con) ma juwodho kud i GLP-GL-1 kud i cell mi ic pa oyo. Calu ma ju nyuthu i cal mir 8A, cell mi ic pa oyo ma jutiyo kudu ku 2 mM acetic acid, propionic acid, man butyric acid, kubang wadi, uketho GLP-1 uwok woko, ma rwate ku somo mukadho.29,30 Kumeno bende, FDS-Con, FBL, man FG-equivalent ( 0.25 g pa ic) uketho GLP-1 wok kud i cell pa ic pa oyo. Ma pire tek, wel pa GLP-1 ma juwodho kud i F-DSS-treated primary mouse colonic epithelial cells ubedo piny akeca ni pa F-Con man F-BLG-treated primary colonic mouse epithelial cells (Cal 8 B). Thiwe pa BLG udwoko SCFA-derived GLP-1 i ic.
Cal 8 BLG-derived SCFA stimulate GLP-1 release from primary murine colonic epithelial cells.(A) Acetic acid, propionic acid, and butyric acid stimulates release of GLP-1 from primary murine colonic epithelial cells; (B) fecal extracts F-Con, F-DSS man F-BLG stimulated primary murine colonic epithelial cells Amount of GLP-1 released.Aliquots of colonic epithelial cells were placed in glass-bottom petri dishes and treated with 2 mM acetic acid, propionic acid, propioric acid, but fecal extract, and F-Con F-DSS, man F-BLG (ma rom ku 0.25 g pa ic), kubang wadi. 2 sawa i 37°C, 5% CO2, kubang wadi. Wel pa GLP-1 ma juwodho kud i cell pa ic pa murine junwange ku ELISA. Lembe majunyutho calu mean ± SEM (n = 3).#p < 0.05 nyo ##p < 0.01 vs. blank nyo F-C; *p < 0.05 vs. F-DSS.
Lembe ma jugoro: Ace, acetic acid; Pro, propionic acid; ento, butyric acid; F-Con, piny ma juwodho kud i ic pa oyo; F-DSS, piny ma juwodho kud i ic pa oyo ma colitis; F-BLG, kud i BLG-treated colon Fecal extracts of inflammatory mice.
Juyike i dul pa yot kum mi ng'om zoo ni two ma nyai, UC ubedoko two ma rac i ng'om zoo; ento, yore maber mi nyang, juku, man mi cango two ne podi nok. Pieno, mitire pio pio mi sayu man mi yubu yore manyen mi cango two UC. Yath mi thek mi China utiye yore maber pilembe yath mi thek mi China mapol unyuthire ni tiyo maber i thek mi UC i kind dhanu mi UC, pi oro madwong man gin zo gitiye piny ma kwo man piny ma kwo ma nyayu peko i kum dhanu man lei.31,32 Somo eni umitu ni sayu yore maber man maber pa yath macon pa ju China pi thieth pa UC man ni sayu kite ma etiyo kudu. BLG ubedo yath pa ju China ma julwongo maber ma jutiyo kudu pi thieth pa two jonyo. yath macon pa ju China ma wok kud i piny marom ku BLG, nyutho tic maber i thieth pa UC i dhanu man lei.4,34 Ento, adwogi pa BLG ikum twoyo mi colitis man adwogi pare. I lembe maeni, adwogi mwa nyutho nia BLG dwoko piny DSS-induced inflammation colonic, ma rwate ku modulation pa ic microbiota man dwoko piny pa GLP-1 ma wok kud i ic.
Jung'eyo maber nia UC ungiyure ku kare ma dwogo cen ku kit two, calu ve rwinyu pa pek, ic ic, remo ma wok kud i ic, man ret ma lee i ic.35 Pieno, two ma dwoko ic ma rii pi kare malac jutimo ku miyo 1.8% DSS wang adek pi nindu abic, man ju madhu pii pi nindu abiro. 1B, dwoko piny pa pek pa kum man DAI scores unyutho bedo ber pa two ma nyai. Mice i dul ma jutiyo kudu ku BLG unyutho upshift recovery nicaku i ceng mir 8, ma ubedu tung tung ku ceng 24. Aloka loka marom de nenre i DAI score, ma nyutho bedo maber pa colitis man ret mi colitis. bor pa ic, ret pa ic, man nyuthu pa gene man yubu pa proinflammatory cytokines TNF-α, IL-1β, man IL-6 i ic pa ic de udoko ber ingey yath pa BLG. I acel, adwogi eni nyutho kamaleng ni BLG tiyo maber i yath pa colitis ma dwogo cen i ic.
BLG timo tic pare nenedi? Somo madwong mukadho onyuthu nia gut microbiota timo tic ma pire tek i pathogenesis pa UC, man microbiome-based man microbiome-targeted therapies uwok ni yore maber mi thieth pa UC. I somo ma kawoni, wanyutho nia BLG thieth ukelo aloka loka madit i gut composition gwoko pa BLG ikum two ma wok kud i DSS utiye ku winjiri ku loko pa gut microbiota. Neno eni urombo ku paru ma nia dwoko homeostasis pa gut microbiota ubedo yore madit mi nyang ikum tic pa TCM.36,37 Ma pire tek, Akkermansia utiye Gram-negative man strictly anaerobicus ma kwo i layer mi lacrium ic, ma nyayu mucins, wodhu propionic acid, nyayu tung tung pa goblet cell, man gwoko mucosa. tic pa bedo maleng.26 Lembe madwong ma jutimo i ot yath man lei nyutho nia Akkermansia utiye ku winjiri madit ku mucosa ma kume yot,38 man miyo Akkermansia spp. copo dwoko piny lyethu pa ic.39 Lembe mwa ma kawoni nyutho nia dwong pa Akkermansia umedire lee ingey yath pa BLG. Mi medo, Prevotellaceae_UCG-001 utiye bacteria ma nyayu SCFA.27 Somo madwong unyutho nia Prevotellaceae_UCG-001 nwangire i dwong pa ic pa lei colitis.40,41 Lembe mwa ma kawoni nyutho nia yath pa BLG copo medo lee dit wel pa Prevotellaceae_UCG-001 i ic pa oyo ma jutiyo kudu ku DSS. I tung tung, Oscillibacter ubedo mesophilic, ma timo ngo yamo.42 onyuthu nia wel pa Ocillibacter umedire lee i UCClibacter oyo man ubedu ku winjiri maber ku IL-6 man IL-1β man wel pa two.43,44 Ma pire tek, yath pa BLG udwoko piny wel pa Oscillibacter i ic pa oyo ma jutiyo kudu ku DSS. Ma pire tek, BLG-altered bacteria eni ubedu SCFA-produmer ma nyayu adwogi maber uloyu i somo mukadho. SCFAs ikum lyethu pa ic man gwoko leng pa ic.45,46 Lembe mwa ma kawoni nyutho nya SCFA acetate, propionate, man butyrate i DSS-treated feces umedire lee i BLG-treated mice. Ka jukwanu karacelu, lembe ma wanwango nyutho kamaleng ni BLG-treated DSS copo medo DSS SCFA-producing bacteria in mice with chronic relapsing colitis.
GLP-1 ubedo incretin ma juyubu i ileum man colon man etiyo tic ma pire tek i dwoko piny remo ma wok kud i ic man dwoko piny glucose mi rimo i ngei cam.47 Lembe ma jukoro nyutho nia dipeptidyl peptidase (DPP)-4, GLP-1 receptor agonist, man GLP-1 nanomedicine copo dwoko piny lyethu pa ic i As-15. jukoro i somo mukadho, SCFA ma lee ubedo ku winjiri ku plasma GLP-1 i dhanu man i oyo. 52 Lembe mwa ma kawoni nyutho nia ingey yath pa BLG, kadhiri pa GLP-1 i rimo man Gcg mRNA umedire lee. Kumeno bende, GLP-1 umedire lee i colonic cultures i ngei timo ku fecal extracts kud i BLG-treated colitis mice ka juporo ku stimulation ku fecal extracts kud i DSS-treated colitis mice. wodhu pa GLP-1?Gwen Tolhurst et al. onyuthu nia SCFA copo ketho GLP-1 wok kud i GRP43 man GPR41.29 Lembe mwa ma kawoni nyutho nia yath pa BLG medo mRNA pa GRP43 man GPR41 i colon pa oyo ma jutiyo kudu ku DSS. Lembe eni nyutho nia yath pa BLG copo dwoko SCFA-promoted GLP-1 production ni kadhu kud i GRP4444444441.
BLG ubedo yath ma juwilo pi kare malac (OTC) i China. Dose ma malu pa BLG i Kunming mice utiye 80g/Kg, man epe ku two ma rac ma juneno.53 Kawoni, dose ma juyero ni BLG (ma epe ku sukari) i dhanu utiye 9-15 g/day (wang 3 i ceng acel). Somu mwa unyutho ni BLG i 1g/DSS uketho chronic-collitic ubedo maber i oyo. Dose eni utiye kago ku dose pa BLG ma jutiyo kudu i ot yath. Somo mwa de unwangu niya tic pare utiye, kadi nok, ku aloka loka i gut microbiota, asaga SCFA-producing bacteria, calu Akkermansia man Prevotellaceae_UCG-001, mi dwoko gut-derived GLP-production. lembe mukende ma jubiparu kudu calu yore mi thek pa colitis. Ento, yore mandha ma etiyo kudu pi loko gut microbiota podi jubi ketho i tic ku microbiota-deficient mice man fecal bacterial transplantation.
Ace, acetic acid; ento, butyric acid; BLG, pandan; DSS, dextran sodium sulfate; DAI, lanyuth pa tic pa two; DPP, dipeptidyl peptidase; FID, jam neno lyethu pa mac; F-Con, jwigo piny ma juwodho kud i ic pa oyo; F-DSS, piny ma juwodho kud i ic pa DSS colitis mice; F-BLG, piny ma juwodho kud i BLG-treated colitis mice; GLP-1, glucagon-like peptide-1; Gcg, glucagon; gas chromatography, gas chromatography; GRP43, G protein-coupled receptor 43; GRP41, G protein-coupled receptor 41; H&E, hematoxylin-eosin; HBSS, Hanks' Balanced Salt Solution ; OTC, OTC; PCA, nyang ikum piny ma pire tek; PCoA, poko lembe ma pire tek; Pro, propionic acid; SASP, sulfasalazine; SCFA, short-chain fatty acids; Yath pa ju China, yath pa ju China macon; UC, ulcerative colitis.
Lembe mi temo zo juyiyu ku Komite mi kura pa lei mi Peking University Shenzhen-Hong Kong University of Science and Technology Medical Center (Shenzhen, China) nimakere ku cik mi kanisa man cik pa lei (namba mi kura pa lei A2020157).
Jugor ceke gitimo kony madit ikum paru man yiku, kwanu lembe, nyo nyang ikum lembe man gonyo lembe; ubedo ikind ju ma kyewo wil nyo loko lembe ma pire tek; uyio ni cwalu waraga ne i gazeti ma kawoni; i ajikine eyiyu wil ne pi wodhu; Bedo ku twero ikum lembe ceke mi tic.
Tic eni jukonye ku National Natural Science Foundation of China (81560676 man 81660479), tic ma pire tek pa Shenzhen University (86000000210), Shenzhen Science and Technology Innovation Committee Fund (JCYJ202103240938102010), man Medical Science Provincial Fund mi sayu lembe (A2020157 man A2020272), Guizhou Medical University Pharmacy Guizhou Province Funded by Key Laboratory (YWZJ2020-01) man Peking University Shenzhen Hospital (JCYJ2018009).
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