Siv tau thiab kub-killed Probiotic hom txhim kho qhov ncauj tiv thaiv kab mob los ntawm kev txhawb nqa IgA concentration hauv lub qhov ncauj mucosa

Abstract

Qhov ncauj-qhov ntswg mucosal tiv thaiv kab mob ua lub luag haujlwm tseem ceeb hauv kev tiv thaiv lub cev tiv thaiv kab mob thiab kis kab mob. Cov khoom lag luam zoo probiotic tau siv los txhim kho tib neeg kev tiv thaiv kab mob thiab qhov ncauj noj qab haus huv. Hauv txoj kev tshawb no, peb tau txheeb xyuas cov txiaj ntsig zoo ntawm cov ntsiav tshuaj sib xyaw ua ke, suav nrog Lactobacillus salivarius subsp. salicinius AP -32, Bifdobacterium animalis subsp. lactis CP-9, thiab Lactobacillus paracasei ET-66, thiab cov ntsiav tshuaj kub-tua probiotic, suav nrog L. salivarius subsp. salicinius AP-32 thiab L. paracasei ET-66, ntawm kev tiv thaiv qhov ncauj ntawm 45 tus neeg noj qab haus huv. Cov neeg koom nrog tau muab faib ua qhov muaj txiaj ntsig zoo, probiotics tua hluav taws kub, thiab pab pawg placebo. Kev tswj hwm kev kho mob tau siv sijhawm li 4 lub lis piam. Cov qauv qaub ncaug tau sau rau lub lis piam 0, 2, 4, thiab 6, thiab Lactobacillus, Bifidobacterium, thiab Streptococcus mutans pejxeem thiab IgA concentration tau ntsuas. IgA concentrations thiab theem ntawm TGF-beta thiab IL-10 hauv PBMC hlwb raug ntsuas los ntawm txoj kev ELISA. Cov txiaj ntsig tau pom tias cov kua qaub IgA qib tau nce ntxiv rau kev tswj hwm ntawm ob qho tib si siv tau (119.30 ± 12.63%, ***P<0.001) and heat-killed (116.78±12.28%, ***P<0.001) probiotics for 4 weeks. Among three probiotic strains, AP-32 would effectively increase the levels of TGF-beta and IL-10 in PBMCs. The oral pathogen Streptococcus mutans was significantly reduced on viable probiotic tablet administration (49.60±31.01%, ***P<0.001). The in vitro antibacterial test confirmed that viable probiotics effectively limited the survival rate of oral pathogens. Thus, this clinical pilot study demonstrated that oral probiotic tablets both in viable form or heat-killed form could exert beneficial effects on oral immunity via IL-10, TGB-beta mediated IgA secretion. The effective dosage of viable probiotic content in the oral tablet was 109 CFUs/g and the heat-killed oral tablet was 1× 1010 cells/g.

cistanche ntxiv cov txiaj ntsig-nce kev tiv thaiv

Taw qhia

Lub qhov ncauj-qhov ntswg mucosa, lub rooj vag rau kev sib cuag inhaled antigens, yog lub frontline tiv thaiv ntawm tib neeg lub cev tiv thaiv kab mob [1, 2]. Feem ntau, cov kab mob pathogenic los yog cov kab mob nkag mus rau hauv lub qhov ncauj qhov ntswg los ntawm kev sib ntaus sib tua tiv thaiv kab mob hauv zos thiab kev noj qab haus huv microbiota [3]. Kev mob thiab cov tsos mob, suav nrog hnoos, mob caj pas, qhov ntswg, thiab kub taub hau, txhim kho vim lub cev tsis muaj zog tiv thaiv kab mob thiab kab mob kis tau [4]. Tsis tas li ntawd, immunoglobulin A (IgA) yog lub hauv paus tiv thaiv kab mob hauv cov qaub ncaug thiab tswj cov homeostasis ntawm qhov ncauj microbiota [5]. Ntau qhov kev tshawb fawb tau tshaj tawm txog lub peev xwm ntawm secretory IgA los tiv thaiv lub cev los ntawm kev kis kab mob los ntawm cov kab mob, nrog rau cov kab mob ua pa syncytial [6], rotavirus [7], thiab kab mob khaub thuas [7]. Secretory IgA ua haujlwm los tiv thaiv mucosal epithelia. Nicolas Millet et al. tshawb pom tias mucosal IgA tuaj yeem tiv thaiv commensal Candida albicans dysbiosis hauv qhov ncauj [8]. Nws kuj tseem tiv thaiv kev sib sau ntawm qhov ncauj kab mob Streptococcus mutans, uas ua rau cov quav hniav [9].

Tsis tas li ntawd, cov kws tshawb fawb tau tshawb pom tias qhov ncauj microbiota thiab nws cov metabolites tuaj yeem cuam tshuam kev tiv thaiv kab mob ntawm qhov ncauj [10]. Cov kev tshawb fawb yav dhau los tau qhia txog kev ua tau zoo ntawm probiotics hauv kev nce qib IgA hauv qhov ncauj mucosa [11]. Ericson et al. pom tau tias zom cov pos hniav uas muaj Lactobacillus reuteri tau koom nrog kev hloov kho lub cev tiv thaiv kab mob ntawm cov neeg noj qab haus huv los ntawm kev nce qib IgA ntawm salivary [12]. Hauv tib neeg, lub cev tiv thaiv kab mob cytokines TGF-beta thiab IL-10 muaj feem cuam tshuam rau kev tsim cov IgA [13].

Txawm li cas los xij, txawm hais tias qhov ncauj microbiota nce secretory IgA qib los ntawm cytokines TGF-beta thiab IL-10 tseem tsis paub meej. Tsis tas li ntawd, cov kab mob hauv qhov ncauj muaj xws li S. mutans, P. gingivalis, thiab F. nucleatum subsp. polymorphism thiab A. actinomycetemcomitans pom muaj kev sib raug zoo nrog cov kab mob periodontal thiab ua tsis taus pa [14]. Cov khoom lag luam Probiotic tuaj yeem yog lwm txoj kev kho mob rau cov kab mob hauv lub cev los ntawm inhibiting qhov ncauj kab mob Fusobacterium nucleatum, tab sis Porphyromonas gingivalis thiab Aggregatibacter actinomycetemcomitans tsis muaj qhov txo qis [15]. Probiotic supplementation tuaj yeem tiv thaiv kab mob kab mob [16]. Nws tau raug tshaj tawm tias hom tseem ceeb ntawm microbiota txwv txoj kev loj hlob ntawm cov kab mob Streptococcus pneumonia [17]. Yog li, tswj kom muaj kev sib npaug microbial ecosystem los ntawm kev siv cov kab mob probiotic tuaj yeem yog lwm txoj hauv kev los tswj kev tiv thaiv qhov ncauj thiab txhim kho qhov ncauj. Cov kev tshawb pom yav dhau los ntawm inhibition ntawm qhov ncauj kab mob los ntawm cov kab mob probiotic tau qhia tias Lactobacillus salivarius subsp. salicinius AP -32, Bifdobacterium animalis subsp. lactis CP-9, thiab Lactobacillus paracasei ET-66 siv tshuaj tua kab mob zoo heev hauv vitro; Txawm li cas los xij, tsis yog los ntawm kev nce qib H2O2 [18]. Cov tswv yim tseem ceeb rau cov kab mob probiotic los txwv qhov kev loj hlob ntawm qhov ncauj yog kev sib koom ua ke cov kab mob hauv qhov ncauj, tsim cov biosurfactants, hloov lub qhov ncauj ib puag ncig, thiab tsim cov tshuaj tua kab mob [19]. Tsis tas li ntawd, ib qho kev tshawb fawb hauv vitro tau pom tias L. salicinius AP-32 kho mob inflammatory cytokine [interleukin (IL)-8, IL-10] qhia hauv tib neeg epithelial hlwb [20]. Yog li ntawd, hauv txoj kev tshawb no, peb tau txheeb xyuas seb puas muaj cov tshuaj probiotic sib xyaw ua ke, suav nrog L. salivarius subsp. salicinius AP-32, B. animalis subsp. lactis CP-9, thiab L. paracasei ET-66, thiab cov ntsiav tshuaj tua hluav taws kub, suav nrog L. salivarius subsp. Salicinius AP-32 thiab L. paracasei ET-66, txhim kho kev tiv thaiv kab mob ntawm TGF-beta, IL-10 lossis nce qib ntawm salivary IgA concentration. Cov tshuaj tiv thaiv kab mob ua haujlwm ntawm cov khoom probiotic uptake hauv qhov ncauj kab noj hniav tau sim.

cistanche ntxiv cov txiaj ntsig-yuav ua li cas ntxiv dag zog rau lub cev

Nyem qhov no mus saib Cistanche Enhance Immunity khoom

【Nug ntxiv】 Email: cindy.xue@wecistanche.com / Whats App: 0086 18599088692 / Wechat: 18599088692

Khoom siv thiab cov txheej txheem

Cov neeg koom nrog

Nyob rau hauv tag nrho, 45 tus neeg koom nrog noj qab haus huv hnub nyoog 20-40 xyoo tau raug xaiv thiab muab faib ua peb pawg: cov ntsiav tshuaj probiotic qhov ncauj uas siv tau, cov tshuaj tua hluav taws kub tua probiotic qhov ncauj, thiab cov placebo pawg. Txhua pab pawg muaj 15 tus neeg koom. Cov neeg koom nrog haus luam yeeb thiab noj cov txiv ntseej tsis suav nrog. Cov ntsiav tshuaj ntawm qhov ncauj tau ua qhov muag tsis pom kev rau cov neeg koom. Txhua tus neeg koom nrog noj cov ntsiav tshuaj ntawm qhov ncauj peb zaug hauv ib hnub (thaum sawv ntxov, tav su, thiab yav tsaus ntuj) rau 4 lub lis piam. Cov qauv qaub ncaug (2 mL) tau sau los ntsuas IgA concentration thiab cov kab mob microorganism nyob rau lub lis piam 0, 2, 4, thiab 6. Cov ntaub ntawv pom zoo tau txais los ntawm txhua tus neeg koom nrog hauv txoj kev tshawb no. Cov txheej txheem tau pom zoo los ntawm Pawg Saib Xyuas Kev Tshawb Fawb ntawm Chung Shan Medical University, Taiwan (CS19052).

Siv tau Probiotic Oral Tablets

Cov ntsiav tshuaj uas siv tau probiotic qhov ncauj (1 g) muaj peb hom probiotic, L. salivarius subsp. salicinius AP-32, B. animalis subsp. lactis CP-9, thiab L. paracasei ET-66. Peb sib tov 0.01 g ntawm 1011 colony formation units (CFUs) ib leeg probiotic nyob rau hauv lub qhov ncauj ntsiav tshuaj. Txhua tus kab mob probiotic raug ntsuas nyob ib ncig ntawm 0.33 * 109CFUs / g. Tag nrho cov ntsiab lus probiotic nyob rau hauv lub qhov ncauj ntsiav tshuaj yog 109 colony CFUs / g. Kev siv ntau npaum li cas ntawm cov ntsiav tshuaj probiotic qhov ncauj tau ua raws li cov ntawv tshaj tawm yav dhau los [18]. Tag nrho cov kab mob probiotic tau txais los ntawm chav kuaj ntawm Biofag Biotech Co., Ltd. (Tainan, Taiwan). L. salivarius subsp. salicinius AP-32 raug cais tawm ntawm tib neeg lub plab noj qab haus huv thiab muab tso rau hauv Food Industry Research thiab Development Institute, Taiwan (ID: BCRC 910437) thiab ntawm Wuhan University, Tuam Tshoj (ID: CCTCC-M2011127); B. animalis subsp. lactic CP-9 raug cais los ntawm tib neeg cov kua mis noj qab haus huv thiab muab tso rau hauv Food Industry Research thiab Development Institute, Taiwan (ID: BCRC 910645) thiab hauv Wuhan University (ID: CCTCC-M2014588); L. paracasei ET-66 raug cais tawm ntawm tib neeg lub mis noj qab haus huv thiab muab tso rau hauv Food Industry Research thiab Development Institute, Taiwan (ID: BCRC 910753) thiab hauv Tuam Tshoj General Microbiological Culture Collection Center, Beijing, Suav teb (ID: CGMCC{ {22}}). Lactobacillus. salivarius subsp. salicinius AP-32 thiab L. paracasei ET-66 tau coj los ntawm de Man, Rogosa, thiab Sharpe (MRS) agar daim hlau (110,660, Merck, Darmstadt, Lub teb chaws Yelemees) thiab incubated nyob rau hauv facultative anaerobic mob ntawm 37 degree rau 48h. B. animalis subsp. Lactis CP-9 tau coj los ntawm MRS agar ntxiv nrog 0.05% cysteine ​​thiab anaerobically incubated ntawm 37 degree rau 48 teev. Kev suav cov cheeb tsam tau ua rau kev txheeb xyuas cov kab mob CFU tom qab culturing probiotic hom [18].

cistanche cog-nce kev tiv thaiv kab mob

Thaum tshav kub kub-killed Probiotic Oral ntsiav tshuaj

Cov tshuaj tua hluav taws kub-tua probiotic qhov ncauj (1 g) muaj cov inactivated L. salivarius subsp. salicinius AP-32 thiab L. paracasei ET-66. Cov kab mob uas siv tau tau raug coj los ua thiab incubated, raws li tau piav qhia dhau los. Tom qab ntawd, AP-32 thiab ET-66 tau inactivated los ntawm incubating cov kab mob nyob rau hauv MRS media ntawm 100 degree rau 1 h. Cov ntsiab lus probiotic nyob rau hauv lub qhov ncauj ntsiav tshuaj yog 1 × 1010 hlwb / g. Kev siv ntau npaum li cas ntawm cov tshuaj tua kab mob hauv qhov ncauj tau ua raws li yav dhau los luam tawm hauv vitro kuaj [11]. Tag nrho cov txheej txheem sim tau ua nyob rau hauv chav kuaj ntawm Biofag Biotech Co., Ltd. (Tainan, Taiwan).

Kev ntsuas ntawm Lactobacillus thiab Bifidobacterium Populations hauv Saliva Samples

Cov qauv qaub ncaug (2 mL) tau sau los ntawm txhua tus neeg tuaj koom ntawm Lub Limtiam 0, 2, 4, thiab 6. Cov qauv qaub ncaug (100 µL) tau muab serially diluted thiab ntxiv rau MRS daim hlau. Txhawm rau ntsuas Lactobacillus cov pejxeem, Lactobacillus tau coj mus kuaj thiab ua rau ntawm MRS agar daim hlau nyob rau hauv facultative anaerobic mob ntawm 37 degree rau 48 h. Txhawm rau ntsuas cov neeg Bifdobacterium, Bifdobacterium tau coj los ua kab mob thiab ua rau muaj kab mob anaerobically ntawm MRS agar ntxiv nrog 0.05% cysteine ​​ntawm 37 degree rau 48 teev. Kev suav cov cheeb tsam tau ua rau kev txheeb xyuas cov kab mob CFU tom qab culturing probiotic hom. Cov Lactobacillus thiab Bifidobacterium cov pejxeem tau normalized rau tus naj npawb ntawm cov neeg probiotic nyob rau lub lim tiam 0. Cov pejxeem tus nqi ntawm Lactobacillus thiab Bifidobacterium sau nyob rau lub lim tiam 0 yog suav tias yog 100%. Txoj kev sim ua raws li kev tshaj tawm yav dhau los [18].

Kev ntsuas ntawm IgA Concentration nyob rau hauv lub qhov ncauj mucosa

Cov qauv qaub ncaug (2 mL) tau sau los ntawm txhua tus neeg koom nrog lub lis piam 0, 2, 4, thiab 6 thiab khaws cia ntawm 20 degree . Cov IgA Tib Neeg Uncoated ELISA Cov Khoom Siv (Catalog # 88-50600-88; Invitrogen, Thermo Fisher Scientific, San Jose, CA, USA) tau siv los txheeb xyuas qhov IgA concentration. Ua ntej, peb coated anti-tib neeg IgA cov tshuaj tiv thaiv rau ntawm 96- zoo phaj. Salivary IgA tam sim no nyob rau hauv cov qauv lossis tus qauv tau ntxiv rau hauv microwell, thiab tom qab ntawd HRP-conjugated anti-tib neeg IgA cov tshuaj tiv thaiv tau ntxiv ntawm chav tsev kub rau 1 h. Pipetting TMB Substrate rau txhua qhov dej rau 30 feeb. Thaum kawg, IgA concertation tau ntsuas ntawm spectrophotometer ntawm 450 nm. Tag nrho cov txheej txheem sim tau ua nyob rau hauv triplicate, raws li cov neeg tsim khoom cov lus qhia. Qhov concentration npaum li cas ntawm IgA sau ntawm Lub Limtiam 0 tau suav tias yog 100%. Txoj kev sim ua raws li kev tshaj tawm yav dhau los [18].

cistanche tubulosa- txhim kho lub cev tiv thaiv kab mob

Kev ntsuas ntawm TGF-Beta thiab IL-10 Concentration hauv PBMC

Kev sim ntawm probiotic-induced nce ntawm TGF-beta thiab IL-10 qib tom qab kev kawm dhau los [20]. Lub peripheral ntshav mononuclear hlwb (PBMCs) tau txais los ntawm cov ntshav kuaj ntawm cov neeg pub noj qab haus huv (Tainan Blood Center, Taiwan Blood Services Foundation). Centrifuging tag nrho cov ntshav los ntawm Ficoll-Hypaque gradient (Pharmacia, Sweden), thiab lub teeb-density feem ntawm 42.5% -50% interface tau eluted. Noob 4 * 105 cell rho tawm PBMC hlwb nyob rau hauv 100 µl RPMI-1640 nrog 1% FBS (Sigma Chemical Co., St. Louis, MO, USA) rau txhua qhov dej ntawm 96 zoo daim hlau. Tom qab ntawd ntxiv 5 * 105 cfu / 20 µl probiotic kho rau txhua PBMCs noob tau zoo (cov cell: probiotic hom=1: 10). Cov kev tswj zoo tau ntxiv 10 µg/ml Phytohaemagglutinin (PHA) (Sigma-Aldrich, Munich, Lub teb chaws Yelemees) rau PBMCs noob qhov dej rau kev tsim TGF- , IL-10 feem [21]. Co-culturing probiotics nrog PBMCs rau 48 teev. Ntsuas supernatant uas muaj cytokines IL-10 thiab TGF- los ntawm enzyme-linked immunosorbent assay (ELISA) tsom xam (Thermo Scientific, Carlsbad, CA, USA). Txhua qhov kev sim tau ntsuas thiab ua raws li cov txheej txheem kev lag luam tsawg kawg hauv triplicate.

Kev ntsuam xyuas ntawm Antibacterial Function nyob rau hauv qhov ncauj kab noj hniav

Streptococcus mutans yog ib qho kev hem thawj rau kev noj qab haus huv ntawm qhov ncauj, uas ua rau cov hniav caries los ntawm kev tsim kab mob plague lossis biofilm [22]. Cov qauv Streptococcus mutans tau sau los ntawm cov swabs, uas peb tau sau cov S. mutans ntawm qhov supragingival ib feem, gingivae, thiab qhov ncauj mucosa, nyob rau lub lis piam 0, 2, 4, thiab 6. S. mutans tau khaws cia hauv tryptic. soy broth (TSB, 5 mL) ntxiv nrog 50% glycerol. S. mutans nruab nrab yog serially diluted thiab ntxiv rau Mitis Salivarius-Bacitracin Agar (MSBA, 0.2 U/mL) phaj, uas yog incubated ntawm 37 degree rau 2 d. Thaum kawg, tus naj npawb ntawm S. mutans cov cheeb tsam hauv txhua tus neeg koom nrog cov qauv raug suav los suav cov kab mob muaj sia nyob; qhov ciaj sia taus ntawm S. mutans sau ntawm Lub Limtiam 0 tau suav tias yog 100%. Txoj kev sim ua raws li kev tshaj tawm yav dhau los [18].

Nyob rau hauv Vitro Antibacterial Activity ntawm lub qhov ncauj ntsiav tshuaj

Oral tablets (1 g) that contained viable (AP-32, CP-9, and ET-66; > 109 CFUs) and heat-killed (AP-32 and ET-66,>1010 CFUs) cov kab mob probiotic tau yaj hauv TSB thiab lub paj hlwb infusion nruab nrab, feem, kom tau txais qhov kawg ntawm 0.1 g / mL. Tsuas yog qhov nruab nrab tau siv rau cov pab pawg dawb huv, thaum cov ntsiav tshuaj (1 g) tsis muaj cov tshuaj probiotics tau yaj hauv cov xov xwm ntsig txog rau pawg placebo. Tom qab ntawd, cov kab mob hauv qhov ncauj (106 CFUs) tau nkag mus rau hauv cov tshuaj ntsiav tshuaj thiab co-incubated ntawm 37 degree rau 2 (S. mutans) lossis 3 (Porphyromonas gingivalis, Fusobacterium nucleatum subsp. polymorphum, thiab Aggregatibacter actinomy cetemcomitans) d. Cov kab mob tau txais los ntawm BCRC. Tus nqi ntawm qhov ncauj kab mob inhibition (%) raug xam raws li hauv qab no: (CFUblank tswj-CFUexperimental pawg) / CFUblank tswj. Txoj kev sim ua raws li kev xeem luam tawm yav dhau los [11].

Kev txheeb cais

GraphPad Prism software tau siv rau kev txheeb xyuas cov txiaj ntsig ntawm ob-tailed t-test. Cov ntaub ntawv tau nthuav tawm raws li qhov piv txwv tus qauv sib txawv (SD) lossis qhov txhais tau tias ntawm cov txiaj ntsig ntawm ob lossis peb qhov kev sim ywj pheej. Kev txheeb cais qhov sib txawv tau suav tias yog qhov tseem ceeb ntawm P tus nqi<0.05.

Cov txiaj ntsig

Cov ntsiav tshuaj Probiotic nce Bifidobacterium Population nyob rau hauv lub qhov ncauj kab noj hniav

Cov pej xeem Bifidobacterium tau ruaj khov nyob rau hauv qhov ncauj kab noj hniav tom qab kev tswj hwm cov ntsiav tshuaj probiotic. Cov neeg kab mob tom qab kho tau zoo li qub los ntawm cov kab mob ua ntej kev kho mob (Population rate %=post-treatment CFU/pre-treatment CFU). Hauv pab pawg neeg probiotic siv tau, cov pej xeem tus nqi nce mus rau 244.14 ± 164.96% ntawm Lub Limtiam 2 (**P<0.01, Fig. 1a) and 438.41±308.58 at Week 4 (***P<0.001), compared to Week 0. The Bifidobacterium population rate remained high at Week 6 (no administration of viable probiotic tablets for 2 weeks after Week 4, 550.16±448.19%, ***P<0.001), compared to Week 0. The Bifidobacterium population number was significantly different between the viable probiotic and placebo groups at Week 6 (**P<0.01). In the heat-killed probiotic group, the Bifidobacterium population was increased at Weeks 2 (149.92±60.47%, **P<0.01) and 4 (199.87±148.64%, *P<0.05), but was decreased at Week 6 after administration of the heat-killed probiotic tablets was stopped for 2 weeks (182.98±163.73%, Fig. 1a).

Cov ntsiav tshuaj Probiotic nce cov neeg Lactobacillus hauv qhov ncauj kab noj hniav

Qhov kev hloov pauv ntawm cov neeg nyob hauv qhov ncauj Lactobacillus vim yog kev tswj hwm cov ntsiav tshuaj probiotic tau nthuav tawm cov qauv zoo ib yam li qhov ua raws li qhov kev hloov pauv ntawm qhov ncauj Bifidobacterium pejxeem. Cov kab mob cov kab mob tom qab kev kho mob tau normalized los ntawm cov kab mob ua ntej kev kho mob. Hauv pab pawg neeg probiotic siv tau, Lactobacillus cov pej xeem tau nce mus rau 447.74 ± 337.89% ntawm Lub Limtiam 2 (**P<0.01, Fig. 1b) and 982.27±726.66% at Week 4 (***P<0.001), compared to Week 0. The Lactobacillus population rate was higher at Week 6 (no administration of viable probiotic tablets for 2 weeks after Week 4, 727.57±539.76%, ***P<0.001) than at Week 0. The Lactobacillus population number was significantly different between the viable probiotic and placebo groups at Week 6 (***P<0.001). In the heat-killed probiotic group, the Lactobacillus population was increased at Weeks 2 (256.66±183.78%, **P<0.01) and 4 (312.85 ± 279.71%, *P < 0.05). Additionally, the Lactobacillus number remained but showed no significant difference at Week 6 after the administration of heat-killed probiotics was stopped for 2 weeks (208.00±199.50%, Fig. 1b).

Fig. 1 Kev Ntsuas ntawm Bifidobacterium cov neeg nyob rau ntawm qhov ncauj mucosal. V siv tau probiotic ntsiav tshuaj; H kub tua inactivated probiotic ntsiav tshuaj; C placebo ntsiav tshuaj (tswj); thiab LAB lactic acid bacteria. Kev sau thiab txheeb xyuas cov qauv ntawm cov qaub ncaug ntawm Lub Limtiam 0, 2, 4, thiab 6 tau ua. Cov ntaub ntawv tau nthuav tawm raws li qhov nruab nrab tus qauv sib txawv (SD). Ib qho ob-tailed t-test tau siv los txheeb xyuas qhov sib txawv ntawm cov lej. Kev txheeb xyuas qhov tseem ceeb tau cim nrog * P<0.05, **P<0.01, ***P<0.001. b Measurement of Lactobacillus populations on the oral mucosal surfaces. V viable probiotic tablets; H heat-killed inactivated probiotic tablets; C placebo tablets (control); and LAB lactic acid bacteria. Collection and analysis of salivary samples at Weeks 0, 2, 4, and 6 were performed. Data were presented as the mean standard deviation (SD). A two-tailed t-test was used to analyze statistical differences. Statistical significances were marked with *P<0.05, **P<0.01, ***P<0.001

Cov ntsiav tshuaj Probiotic uas muaj AP-32, ET-66, thiab CP-9 ua rau muaj kev nce siab ntawm IgA Concentration hauv qhov ncauj Mucosa

Raws li cov ntsiav tshuaj probiotic (ua tau los yog kub-tua) tau raug pov thawj kom nce qib Bifidobacterium thiab Lactobacillus nyob rau hauv lub qhov ncauj kab noj hniav, peb ntxiv soj ntsuam cov salivary IgA concentration hloov, uas tshwm sim vim uptake ntawm probiotic cov khoom. Cov qib IgA tom qab kev kho mob tau normalized los ntawm qib IgA ua ntej kev kho mob. Hauv pab pawg probiotic siv tau, salivary IgA concentration me ntsis nce mus rau 103.24 ± 8.10% ntawm Lub Limtiam 2 (Fig. 2) thiab 104.81 ± 13.26 ntawm Lub Limtiam 4, tab sis tsis muaj qhov sib txawv tseem ceeb hauv statistically. Txawm li cas los xij, salivary IgA concentration nyob rau hauv cov pab pawg neeg probiotic, piv rau hauv pawg placebo, tau nce mus rau 119.30 ± 12.63% ntawm Lub Limtiam 6 (tsis muaj kev tswj hwm cov ntsiav tshuaj probiotic siv tau rau 2 lub lis piam tom qab Lub Limtiam 4), piv rau Lub Limtiam 0 ( ***P<0.001). Furthermore, in the heat-killed probiotic group, the salivary IgA concentration was slightly increased at Weeks 2 (102.51± 7.20%) and 4 (104.35 ± 10.27%). The saliva IgA concentration was increased at Week 6 (116.78 ± 12.28%, ***P < 0.001, Fig. 2), compared to Week 0.

Cov kab mob muaj peev xwm nce IL-10 thiab TGF-Beta Qib hauv PBMCs

Kev tswj zoo ntawm 10 µg/ml Phytohaemagglutinin (PHA) tau ua tiav cov qib IL-10 (58.2 ± 7.9 pg/ml, ***P < 0.001, Fig. 3a) thiab TGF- (53.4 ± 8 pg/ml, ***P<0.001, Fig. 3b) in PBMCs by comparing to the negative control (PBMCs treated with medium only). Viable strains of CP-9, AP-32 and ET-66 signifcantly increased the levels of IL-10 in PBMCs to 84.2±9 pg/ml (***P<0.001, ##P<0.01), 303.1±170.9 pg/ml (*P<0.05, ##P<0.01) and 98.2±17.5 pg/ml (***P<0.01, ##P<0.01), respectively. Symbol *indicated a significant difference by comparing to the medium-treated control; symbol #indicated a significant difference by comparing to the PHA control (Fig. 3a). Besides, viable strains of CP-9, AP-32, and ET-66 significantly increased the levels of TGF-beta in PBMCs to 23.2 ± 4.7 pg/ml (***P < 0.001), 130.9 ± 16 pg/ ml (***P < 0.001, ###P < 0.001) and 31.4 ± 5.5 pg/ml (***P<0.01), respectively (Fig. 3b).

Daim duab 2 Immunoglobulin A (IgA) concentration nyob rau hauv cov qaub ncaug. V siv tau probiotic ntsiav tshuaj; H kub tua inactivated probiotic ntsiav tshuaj; C placebo ntsiav tshuaj (tswj); thiab LAB lactic acid bacteria. Kev sau thiab txheeb xyuas cov qauv ntawm cov qaub ncaug ntawm Lub Limtiam 0, 2, 4, thiab 6 tau ua. Cov ntaub ntawv tau nthuav tawm raws li qhov nruab nrab tus qauv sib txawv (SD). Ib qho ob-tailed t-test tau siv los txheeb xyuas qhov sib txawv ntawm cov lej. Kev txheeb cais

Cov ntsiav tshuaj Probiotic uas muaj AP-32, ET-66, thiab CP-9 txwv tsis pub muaj S. mutans Pej Xeem nyob rau hauv qaub ncaug

Kev nce qib Bifidobacterium thiab Lactobacillus cov pejxeem thiab nce salivary IgA concentration tuaj yeem pab txhawb kev tawm tsam cov kab mob hauv qhov ncauj. Hauv qhov kev sim tom ntej, peb tau sim qhov hloov pauv hauv qhov ncauj kab mob S. mutans cov pej xeem vim muaj kev cuam tshuam probiotic. Cov kab mob cov kab mob tom qab kev kho mob tau normalized los ntawm cov kab mob ua ntej kev kho mob. Nyob rau hauv pab pawg neeg probiotic siv tau, S. mutans cov pej xeem tau txo qis hauv lub lis piam 2 (53.55 ± 31.60%, ***P<0.001), 4 (49.60±31.01%, ***P<0.001), and 6 (55.19±42.72%, **P<0.01, Fig. 4). At week 6, S. mutans was significantly inhibited in the viable probiotic group (55.19±42.72%, ***P<0.001), compared to in the placebo group. Furthermore, in the heat-killed probiotic group, the S. mutans population was slightly decreased at Week 2 (85.81±49.87%) and significantly reduced at Week 4 (58.35 ± 33.17%, ***P<0.001). The S. mutans population level in the heat-killed probiotic group (202.81±167.99%) reverted to that in the placebo group (225.05±127.01%) at Week 6 (no administration of heat-killed probiotic tablets for 2 weeks from Week 4) (Fig. 4).

Fig. 3 Viable strains nce IL-10, thiab TGF-beta, qib hauv PBMCs. Qib ntawm IL-10 thiab b TGF-beta hauv PBMCs raug kuaj los ntawm kev kho cov kab mob probiotic. Ntxiv 5 * 105 cfu/20 µl siv tau hom CP-9, AP-32, thiab ET-66 rau PMBCs 10 µg/ml. Phytohaemagglutinin (PHA) tau siv los ua kev tswj xyuas zoo. Kev tswj tsis zoo yog PBMCs kho nrog RMPI-1640 nruab nrab nkaus xwb. Triplicate xeem tau ua. Cov ntaub ntawv tau nthuav tawm raws li qhov nruab nrab tus qauv sib txawv (SD). Ib qho ob-tailed t-test tau siv los txheeb xyuas qhov sib txawv ntawm cov lej. Cov ntsiab lus tseem ceeb tau cim nrog P<0.05, P<0.01, P<0.001. The symbol *indicated a significant difference by comparing to the medium-treated control; symbol #indicated significant difference by comparing to the PHA control

Fig. 4 Kev ntsuas cov kab mob Streptococcus mutans cov neeg nyob ntawm qhov ncauj mucosal. V siv tau probiotic ntsiav tshuaj; H kub tua inactivated probiotic ntsiav tshuaj; C placebo ntsiav tshuaj (tswj); thiab LAB lactic acid bacteria. Kev sau thiab txheeb xyuas cov qauv ntawm cov qaub ncaug ntawm Lub Limtiam 0, 2, 4, thiab 6 tau ua. Cov ntaub ntawv tau nthuav tawm raws li qhov nruab nrab tus qauv sib txawv (SD). Ib qho ob-tailed t-test tau siv los txheeb xyuas qhov sib txawv ntawm cov lej. Cov ntsiab lus tseem ceeb tau cim nrog * P<0.05, **P<0.01, ***P<0.001

Kev lees paub ntawm Kev Muaj Peev Xwm ntawm Probiotic ntsiav tshuaj txhawm rau txwv kev loj hlob ntawm qhov ncauj los ntawm Kev Ntsuas Hauv Vitro

Txoj kev tshawb fawb hauv vitro tau qhia tias cov ntsiav tshuaj probiotics ua tau zoo inhibited qhov ciaj sia ntawm cov kab mob hauv qhov ncauj (Fig. 5a). Cov kab mob cov kab mob tom qab kev kho mob tau normalized los ntawm cov kab mob ua ntej kev kho mob. Qhov ciaj sia taus ntawm S. mutans, P. gingivalis, F. nucleatum, thiab A. actinomy cetemcomitans nyob rau hauv cov pab pawg neeg probiotic, piv rau hauv pawg placebo, tau txo mus rau 4.23% (***P < 0 .001, placebo=91%), 8.64% (***P < 0.001, placebo=89%), 5.77% (**P<0.01, placebo=98%), and 6.23% (**P<0.01, placebo=87%), respectively. However, the heat-killed probiotic tablet exerted weaker antibacterial effects than the viable probiotic tablet (Fig. 5b). The survival rate of S. mutans, P. gingivalis, F. nucleatum, and A. antinomy cetemcomitans in the heat-killed probiotic group, compared to in the placebo group, was slightly decreased without statistical significance (82%, placebo=91%), significantly reduced to 53% (*P<0.05, placebo=89%), not inhibited (96.88%, placebo=98%), and significantly reduced to 80% (**P<0.01, placebo=87%), respectively.

Kev sib tham

Piv nrog rau pawg placebo, cov neeg nyob qhov ncauj ntawm Lactobacillus thiab Bifidobacterium yuav nce ntxiv los ntawm kev noj cov ntsiav tshuaj probiotics los yog cov ntsiav tshuaj tua hluav taws kub rau 4 lub lis piam. Tsis tas li ntawd, tus lej Lactobacillus thiab Bifidobacterium tseem nyob rau theem siab heev rau 2 lub lis piam tom qab ncua kev noj cov tshuaj probiotics uas siv tau (Fig. 1a thiab b). Ib yam li ntawd, Camila Casuccio Almeida et al. qhia tau hais tias plaub-lub lim tiam kev tswj hwm ntawm kev kho mob probiotic tuaj yeem ua rau muaj cov tsos mob ameliorate hauv cov neeg mob lactose-intolerant tsawg kawg yog 3 lub hlis tom qab tso tseg kev noj probiotic [23]. Txawm li cas los xij, qhov cuam tshuam tsis tu ncua ntawm probiotics hauv kev kho mob ntev yuav tsum tau soj ntsuam yav tom ntej. Tsis tas li ntawd, salivary IgA concentration tau nce ntxiv rau kev tswj hwm ntawm cov ntsiav tshuaj probiotics uas siv tau thiab kub-tua. Ob pawg neeg tua hluav taws kub thiab muaj peev xwm ua tau tau nce qib IgA los ntawm kev siv cov ntsiav tshuaj ntawm qhov ncauj rau 4 lub lis piam, tab sis tsis qhia qhov sib txawv ntawm cov placebo. Lub IgA concentration nyob rau hauv tshav kub-tua thiab siv tau cov pab pawg neeg probiotic pom ib qho tseem ceeb nce nyob rau lub lim tiam 6. Txawm li cas los, lub mechanism ntawm IgA nce tom qab tso tseg probiotic tswj rau 2 lub lis piam yuav tsum tau soj ntsuam ntxiv (Fig. 2) Braathen li al. tshaj tawm cov txiaj ntsig zoo sib xws ntawm lub luag haujlwm tiv thaiv kab mob ntawm cov kab mob probiotic hauv qhov ncauj [24]. Tsis tas li ntawd, cov kab mob probiotic tau tshaj tawm kom nce fecal IgA concentration ntau hauv cov noob thiab npua [25]. Txawm li cas los xij, kev tshawb fawb txog IgA-txo cov tsos mob hauv cov kab mob hauv cov hlab ntsws sab saud tseem tsis txaus. Cov ncauj lus kom ntxaws molecular mechanism ntawm inhibition thiab tiv thaiv kab mob ntsws sab sauv los ntawm cov kab mob probiotic CP-9, AP{19}}, thiab ET-66 tuaj yeem tshawb xyuas hauv kev tshawb fawb yav tom ntej. Hauv kev tshawb fawb tam sim no, cov kab mob siv tau CP-9, AP-32, thiab ET-66 yuav nce qib IL-10, thiab TFG-beta hauv PBMC hlwb. AP-32 tau pom muaj peev xwm ua tau zoo hauv kev nce IL-10, thiab TFG-beta hauv PBMCs los ntawm kev muab piv rau PHA zoo tswj (Daim duab 3a thiab b). Nws xav tias cov kab mob uas siv tau CP-9, AP-32, thiab ET-66 tuaj yeem ua rau B-cell secreting IL-10 thiab TFG-beta kom nce cov qaub ncaug IgA. Txawm li cas los xij, kev sib raug zoo ntawm salivary IL-10, TFG-beta, thiab salivary IgA yuav tsum tau kuaj ntxiv [26]. Tsis tas li ntawd, seb puas yog cov tshuaj tua kab mob tua hluav taws tau nce IgA los ntawm inducing IL-10 thiab TFG-beta tseem tsis paub meej. Ib qho kev kuaj hauv vitro qhia tau hais tias qhov kub-tua AP-32 txhawb nqa interferon- thiab IL-12p70 secretion thiab txo qis IL-13 qib [27]. Yog li, hauv qhov kev tshawb fawb soj ntsuam no, lub peev xwm ntawm probiotic CP-9, AP-32, thiab ET-66 hom kab mob thiab cua sov tua AP-32 thiab ET-66 Cov kab mob los tiv thaiv cov kab mob pathogenic hauv lub qhov ncauj tau raug lees paub ntxiv (Daim duab 4). Cov tshuaj probiotics uas muaj peev xwm ua tau zoo dua los tiv thaiv kab mob ntau dua li cov tshuaj tua kab mob los ntawm kev zais cov organic acids, antimicrobial peptides [28], exopolysaccharides (EPSs) [29] bacteriocins [30] (Fig. 5a thiab b). Cov khoom siv tshuaj tua kab mob ua haujlwm tau tsim los ntawm cov kab mob probiotic siv tau yuav tsum raug kuaj pom los ntawm kev ua haujlwm siab ua kua chromatography (HPLC) thiab kua chromatography (LC)-mass spectrometry yav tom ntej [31]. Nws tau tshaj tawm tias cov tshuaj tua hluav taws kub tua tau muaj qhov zoo ntawm cov probiotics uas siv tau tab sis tsis muaj qee yam kev txhawj xeeb txog kev nyab xeeb ntawm cov kab mob probiotic siv tau [32]. Txawm li cas los xij, cov tshuaj tiv thaiv kab mob ntawm cov kab mob tua hluav taws kub yuav tsum tau tshawb xyuas ntxiv.

Fig. 5 Kev lees paub ntawm lub peev xwm ntawm cov ntsiav tshuaj probiotic rau inhibit qhov ncauj kab mob loj hlob los ntawm kev kuaj hauv vitro. Lub peev xwm ntawm cov ntsiav tshuaj uas siv tau thiab kub-tua cov tshuaj tiv thaiv kab mob los tiv thaiv kev ciaj sia ntawm cov kab mob hauv qhov ncauj, suav nrog Streptococcus mutans, Porphyromonas gingivalis, Fusobacterium nucleatum, thiab Aggregatibacter actinomycetemcomitans, tau lees paub. Pab pawg dawb, nruab nrab nkaus xwb; pab pawg placebo, ntsiav tshuaj (1 g) tsis muaj cov tshuaj probiotics. Triplicate xeem tau ua. Cov ntaub ntawv tau nthuav tawm raws li qhov nruab nrab tus qauv sib txawv (SD). Ib qho ob-tailed t-test tau siv los txheeb xyuas qhov sib txawv ntawm cov lej. Cov ntsiab lus tseem ceeb tau cim nrog * P<0.05, **P<0.01, ***P<0.001

Xaus

Cov ntsiav tshuaj sib xyaw ua haujlwm tau zoo, suav nrog L. salivarius subsp. salicinius AP-32, B. animalis subsp. lactic CP-9, thiab L. paracasei ET-66, thiab cov kab mob tua hluav taws kub, suav nrog L. salivarius subsp. salicinius AP-32 thiab L. paracasei ET-66, tau siv lawv cov txiaj ntsig zoo los ntawm kev txhawb nqa lub qhov ncauj ntawm Lactobacillus thiab Bifdobacterium, txo S. mutans hauv qhov ncauj kab noj hniav, thiab ua kom qaub ncaug IgA concentration hauv cov neeg noj qab haus huv. Cov txiaj ntsig hauv vitro tau lees paub tias cov tshuaj probiotics ua tau zoo tiv thaiv kab mob hauv qhov ncauj, suav nrog S. mutans, P. gingivalis, thiab F. nucleatum subsp. polymorphism, thiab A. actinomycetemcomitans. Qhov ncauj-qhov ntswg mucosal tiv thaiv kab mob yog pem hauv ntej tiv thaiv kab mob invading, thiab qhov no tau dhau los ua qhov teeb meem tseem ceeb. Yog li, txoj kev tshawb no yuav muab lwm lub tswv yim (probiotic supplementation) los tswj lub qhov ncauj thiab kev noj qab haus huv ntawm qhov ncauj.

cistanche ntxiv cov txiaj ntsig-yuav ua li cas ntxiv dag zog rau lub cev

Cov ntaub ntawv

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