Cov xwm txheej tshwm sim ntawm lub plab-Brain Axis: Cov Kev Kho Mob Ntawm Tus Neeg Ua Yeeb Yam Tshiab Kefir tawm tsam Cov Kab Mob Neurodegenerative Part 2

Tau ntau xyoo lawm, peb tau pom nyob rau hauv cov qauv sib txawv ntawm kev kub siab uas lawv muaj qhov sib txawv: qhov tsis txaus ntseeg ntawm lub paj hlwb tsis zoo, kho los ntawm angiotensinII hauv cov hlab ntsha uas tswj cov ntshav ntim los ntawm paraventricular nucleus, subfornicalorgan, thiab hypothalamus [47,51,73. ].

Lub hypothalamus yog ib cheeb tsam tseem ceeb ntawm lub cev uas tswj hwm ntau yam kev ua haujlwm ntawm lub cev, suav nrog ntshav siab, lub plawv dhia, tshaib plab thiab satiety, thiab ntau dua. Nyob rau tib lub sijhawm, hypothalamus tseem ua lub luag haujlwm tseem ceeb hauv tib neeg kev paub thiab kev xav, cuam tshuam rau tib neeg lub siab thiab kev nco.

Lub hypothalamus tseem ceeb heev nyob rau hauv kev tswj ntawm cov ntshav khiav dynamics thiab ncig. Cov ntshav ncig hauv lub cev yog qhov tseem ceeb rau kev ua haujlwm ntawm lub cev, pab nws ua haujlwm zoo los ntawm kev nqa oxygen thiab cov as-ham rau txhua lub cell hauv lub cev. Lub hypothalamus tswj lub dilation thiab contraction ntawm ntau cov hlab ntsha los xyuas kom meej txaus cov ntshav txaus rau ntau qhov chaw thiab cov kabmob ntawm lub cev.

Tsis tas li ntawd, hypothalamus tuaj yeem cuam tshuam kev nco thiab mus ob peb vas. Kev tshawb fawb qhia tau hais tias kev ua haujlwm tsis zoo ntawm lub hypothalamus tuaj yeem ua rau kev paub tsis meej, nrog rau cov teeb meem nrog kev kawm, nco, thiab mloog. Los ntawm kev rov ua haujlwm ntawm hypothalamus, tib neeg txoj kev paub thiab kev txawj ntse tuaj yeem txhim kho thiab kev noj qab haus huv ntawm lub hlwb tuaj yeem txhawb nqa.

Yog li ntawd, peb yuav tsum ua tib zoo saib xyuas kev noj qab haus huv ntawm hypothalamus, nrog rau kev tswj hwm kev noj zaub mov zoo thiab kev ua neej nyob thiab tsis txhob muaj kev xav tsis zoo xws li kev ntxhov siab ntau dhau thiab kev ntxhov siab. Nyob rau tib lub sijhawm, tswj tus cwj pwm zoo, kev tawm dag zog, thiab txhim kho kev txawj ntse tuaj yeem txhim kho kev ua haujlwm ntawm hypothalamus thiab txhawb kev noj qab haus huv ntawm lub cev thiab lub hlwb. Nws tuaj yeem pom tias peb yuav tsum txhim kho kev nco, thiab Cistanche deserticola tuaj yeem txhim kho kev nco, vim Cistanche deserticola tseem tuaj yeem tswj hwm qhov sib npaug ntawm cov neurotransmitters, xws li nce qib ntawm acetylcholine thiab kev loj hlob. Cov khoom no tseem ceeb heev rau kev nco thiab kev kawm. Tsis tas li ntawd, Cistanche deserticola kuj tseem tuaj yeem txhim kho cov ntshav khiav thiab txhawb nqa cov pa oxygen, uas tuaj yeem ua kom lub hlwb tau txais cov as-ham txaus thiab lub zog, yog li txhim kho lub hlwb tseem ceeb thiab kev ua siab ntev.

Nyem paub ntxiv los txhim kho kev nco

Raws li kev sib tham saum toj no, peb tuaj yeem kwv yees tias ND thiab kab mob plawv tau txuas nrog microbiota-plab-hlwb axis, uas tuaj yeem yog qhov tshwm sim ntawm kev ua haujlwm tsis zoo ntawm vagal afferents thiab cov ntaub ntawv pov thawj.

Siv cov txheej txheem classicalpharmacological [73,81], peb lub chaw soj nstuam tau pom nyob rau hauv renovascularhypertension, SHR, thiab txawm nyob rau hauv cov qauv ntawm kev kub siab vim los ntawm cov blockade ntawm nitricoxide uas lub sympathetic paj hlwb yog lub ntsiab ua rau muaj kev kub ntxhov siab [82].

Hauv 2015, ob pawg kev tshawb fawb sib txawv tau pom qhov sib txuas ntawm lub plab dysbiosis thiab kub siab [83–85]. Nyob rau hauv lub xyoo tom ntej, ntau pab pawg (xws li peb tus kheej) tau mob siab rau rau lub elucidation ntawm no qhov teeb meem ntawm yuav ua li cas kev sib txuas lus ntawm gutmicrobiota thiab lub sympathetic paj hlwb tshwm sim.

Klippel thiab cov neeg koom tes [64] tau muab kev nkag siab tshiab rau hauv neural tswj ntshav siab thiab plawv dhia. Lawv pom tau hais tias kev tswj lub plawv vagal tonic uas ua rau Wistar-Kyoto (WKY) nas (kev tswj hwm ntawm SHR) yog overridden los ntawm kev ua siab ntev. Yog li ntawd, cov neeg mob hypertensive tshwm sim los qhia tib yam kev cuam tshuam ntawm neural uas ua rau muaj kev cuam tshuam vascular thiab nce ntshav siab mus rau aorta.

Cov kws sau ntawv kuj tau siv cov tshuaj kws tshuaj classical los tshawb xyuas hauv SHR ib qho kev koom tes ntawm cov txiaj ntsig zoo ntawm kefir ntawm lub hlwb-mediated reflex tswj ntshav siab.

Lawv pom muaj kev cuam tshuam ntawm vagal thiab sympathetic reflex tswj (baroreflex), uas tau txo qis los ntawm kev kho tsiaj nrog probiotic kefir rau 60 hnub [64]. Cov txiaj ntsig no kuj tau lees paub los ntawm kev soj ntsuam spectral ntawm kev ntsuas ntshav siab ncaj qha. Txhawb nqa peb qhov kev tshawb nrhiav hauv SHR, Toral, thiab al. [71] tau pom nyob rau hauv tib tus qauv uas muaj kev sib koom siab ua haujlwm txhawb nqa lub plab dysbiosis thiab txhawb nqa neuroinflammation, uas cuam tshuam rau kev tswj ntshav siab [71].

Ua ke, tonic thiab reflex lub hlwb tswj ntshav siab qhia tias probiotic kefir yog ib qho kev cog lus tsis yog tshuaj kho mob, yam tsawg kawg hauv thawj (SHR) thiab theem nrab (ob lub raum, ib qho clip (2K1C)) cov qauv kub siab.

Qhov muaj peev xwm siv tau ntawm txoj kev kho tshiab no tseem yuav tsum tau lees paub hauv kev soj ntsuam ntxiv. Interestingly, neuronal abnormalities, xws li dementia, AD, thiab obstructive sleepapnea, kuj yog tus cwj pwm los ntawm lub hlwb vascular anomalies, xws li ntshav-brain barrier (BBB) ​​cuam tshuam [40,85–87], uas zoo nkaus li muaj feem xyuam rau lub plab dysbiosis [ 86]. Probioticsupplementation tuaj yeem yog ib qho kev cog lus ntxiv rau kev tiv thaiv kev txhim kho ntawm cov kab mob plawv thiab ND (saib daim duab 3 thiab 4).

5. Cov Lus Qhia Txog Kev Tiv Thaiv Oxidative Stress

Nyob rau hauv 1985, thaum Sies thiab Cadenas tus yam ntxwv thawj zaug cov lus "oxidative kev nyuaj siab nyob rau hauv lub hlwb thiab lub cev", ob peb cov kws tshawb fawb los yog kws kho mob tau ntsuas qhov cuam tshuam tiag tiag ntawm tus neeg uas ua ntawv no nyob rau hauv chav kawm ntawm ntau lub NDs [88].

Tau ntau xyoo dhau los, qhov "dawb radicalchemistry" no tau nce siab dhau ntawm subfield ntawm biochemistry, mus txog kev sib koom tes loj hauv physiology, microbiology, pathology, thiab pharmacology. Txawm li cas los xij, nws twb paub lawm tias oxidative kev nyuaj siab yog ib qho tseem ceeb hauv kev tsim cov kab mob ntawm ob peb NDs los ntawm kev ua "lub voj voog phem" uas cuam tshuam rau kev laus [40,87].

Classically, lub ntiaj teb no tswvyim nyob rau hauv redox biology thiab / los yog kev kho mob cheeb tsam yog txhais raws li lub xeev ntawm imbalance ntawm oxidants thiab antioxidants (favoring oxidants) ua rau muaj kev cuam tshuam ntawm redox signaling, molecular puas [88,89], thiab o [90-92]. Cov ntaub ntawv tsis ntev los no qhia tau hais tias qhov redoxbalance no yog qhov tseem ceeb rau quartet "lub plab-hlwb-microbiota-cov kab mob", uas hloov pauv kev ntxhov siab uas cuam tshuam nrog kev ua txhaum ntawm txoj hnyuv plab thiab BBB [93,94].

Hauv seem no, peb sau cov ntaub ntawv tsis ntev los no uas qhia txog kev sib cuam tshuam zoo ntawm oxidative kev nyuaj siab thiab "lub ntiaj teb zoo kawg ntawm cov tub rog" sib ntaus kom muaj kev ncaj ncees ntawm lub plab-hlwb axis.Nws paub tias lub paj hlwb xav tau kev xav tau siab, txhawb nqa cov txheej txheem oxidative thiab ua kom tiav. Hauv cov neurons feem ntau raug ROS xws li superoxide anion (O2•−), hydrogen peroxide (H2O2), nitric oxide (NO) thiab lawv hloov mus ua cov oxidants muaj zog, xws li hydroxyl radical (•OH) thiab peroxynitrite ion (OONO•−) [ 40, 89, 95] ib.

Nyob rau tib lub sijhawm, ntau qhov kev tshawb fawb tau pom tias lub paj hlwb nthuav tawm qis qis ntawm cov enzymes antioxidant xws li superoxide dismutase (SOD) hauv cov neurons thiab glutathione / glutathione peroxidase (GSH / GPx) nyob hauv astrocytes, raws li nyuam qhuav hloov kho los ntawm peb thiab lwm tus [ 87,96–98], uas muaj feem cuam tshuam rau apoptosisby p53 signaling [99].

Yog li ntawd, cov txheej txheem no tshwm sim los pab txhawb rau qhov tsis muaj zog ntawm lub hauv nruab nrab paj hlwb, raws li elicited los ntawm oxidative kev nyuaj siab, thiab yog susceptible todegenerative txheej txheem. Tsis ntev los no, cov kev tshawb fawb tau qhia tias complex microbiota-hostcross-hais lus kuj tseem tuaj yeem ua lub luag haujlwm hloov pauv hauv oxidative kev nyuaj siab nyob rau hauv nruab nrab paj hlwb los ntawm kev ncaj thiab tsis ncaj (xws li lipopolysaccharides, amyloid proteins, orantibiotics) txoj hauv kev, uas tuaj yeem ncav cuag lub hlwb los ntawm kev ncig lossis lub paj hlwb vagus, activating microglia kom overproduce ROS [87,100].

Yog li, microbiota-gut-brain axis tau ua "qhib rooj vag" rau cov tswv yim kho tshiab rau ntau lub paj hlwb, raws li tau piav qhia nyob rau hauv cov tshooj tom ntej.Txawm hais tias lub cev tsis muaj oxidant raug feem ntau xav tau redox tswj thiab cell signaling, supraphysiological concentrations nyob rau hauv unspecific lub hom phiaj thiab ua rau lub cev tsis muaj oxidant. inhibition ntawm mitochondrial zog thiab kev hloov kho ntawm lipids, proteins, carbohydrates, thiab tsis tsawg tshaj plaws, kev puas tsuaj rau DNA [74,89,101–103].

Piv txwv li, lipidperoxidation tshwm sim los ntawm ROS culminates nyob rau hauv ib tug crescent poob ntawm daim nyias nyias fluidity nrog rau ib tug nce nyob rau hauv permeability rau Ca2+ thiab ib daim nyias nyias muaj peev xwm poob. Nyob rau tib lub sijhawm, cov ntaub ntawv tsis ntev los no tau pom tias nyob rau hauv cov xwm txheej tsis txaus ntseeg, cov kab mob epithelial ntawm lub plab tuaj yeem tsim cov theem pib ntawm ROS, uas ua rau muaj kev cuam tshuam ntawm lub plab thiab tiv thaiv kev tiv thaiv hauv nruab nrab ntawm lub paj hlwb [87].

Ntawm qhov tod tes, plab dysbiosis tuaj yeem yog ob qho laj thawj thiab qhov tshwm sim ntawm kev nce qib ntawm ROS nyob rau hauv lub hauv nruab nrab lub paj hlwb thiab thiaj li ua rau pro-oxidative thiab proinflammatory mechanisms, ua rau cov txheej txheem neurodegenerative [95,104,105].

Tam sim no, oxidative kev nyuaj siab yog tshawb fawb los ntawm ib txwm siv txoj kev tsis ncaj ncees thiab tseem tshawb nrhiav hauv cov kab mob neurodegenerative los ntawm kev ntsuas cov khoom ntawm lipid peroxidation (xws li malondialdehyde [106,107] thiab 4-hydroxynonenal [108]), cov khoom ntawm oxidized proteins (xws li, oxidation siab heev. Cov khoom lag luam protein (AOPP)) [40], thiab los ntawm "kev ntsuam xyuas lub hnub qub", cov cuab yeej siv tau zoo los ntsuas DNA tawg ntawm ib leeg-cell theem [101,103,109-111].

Tsis tas li ntawd, txoj kev tshawb nrhiav ncaj qha tau txais kev pom zoo los ntawm kev siv cov duab confocal thiab nyob-cell, ntws cytometry, thiab / lossis HPLC txoj kev (kom paub meej ntxiv, saib Dikalov li al., 2014 [112]), ua rau kev tshawb nrhiav ntawm qhov sib txawv ntawm kev koom tes ntawm O2. •−, H2O2 and •OH/OONO•-species [40,101–103,113–118]. Txij li cov kev ntsuam xyuas no qhia tau hais tias muaj kev ntsuam xyuas siab thiab qhov tseeb, cov kev tsis ncaj thiab ncaj qha yog cov cuab yeej ntxiv los tshawb xyuas cov tswv yim kho mob tiv thaiv kab mob neurodegenerative, raws li tau tham tom qab.

Hauv cov ntsiab lus, nyob rau hauv ib puas xyoo tau cim los ntawm kev kho tshuaj tsis ua haujlwm txawm tias tsis muaj qhov sib piv ntawm kev tshawb fawb, kev nkag siab txog kev paub txog ntau txoj hauv kev uas cov probiotics tuaj yeem ua lub luag haujlwm hauv kev tawm tsam NDs zoo li muaj txiaj ntsig zoo.

Muab lub luag haujlwm ntawm lub plab microbiota hauv kev noj qab haus huv thiab kev tiv thaiv kev tiv thaiv / kho lub peev xwm ntawm probiotics, qhov kev tshuaj xyuas no yuav tsom mus rau kev ua tiav cov tswv yim probiotic tiv thaiv cov kab mob tsis zoo xws li AD thiab PD thiab ND-epileptic mob uas tshwm sim raws li kev qaug dab peg.

6. Probiotics nyob rau hauv ND: Vim li cas thiaj yuav yog ib qho cuab yeej siv tau rau kev sib cuam tshuam tshuaj?

Cov kev tshawb fawb tshiab tau pom tias kev siv cov tshuaj probiotics tuaj yeem muab cov tswv yim nthuav tawm los tiv thaiv kev loj hlob ntawm ND, txo cov neuroinflammation [40,119–121], ameliorating gastrointestinal function [122,123], thiab diminishing plab leakiness [124,125].

Drugsdo tsis tsim ib qho txiaj ntsig tab sis hloov pauv kev ua haujlwm ntawm lub cev. Yog li ntawd, cov tswv yim siv probiotics, uas txhim kho kev ua haujlwm ntawm lub paj hlwb, tuaj yeem ua haujlwm zoo rau cov lus teb tshuaj los tswj thiab / lossis rov qab cov tshuaj cuam tshuam rau cov neeg mob feem ntau faib rau hauv pawg "refractory". Qee cov piv txwv ua tiav ntawm cov kab mob sib txawv ntawm cov kab mob neurodegenerative yuav qhia hauv qab no.

Hais txog AD, Akbari et al. (2016) [107] tau qhia (thawj zaug) tias kev noj cov kab mob sib kis uas muaj Lactobacillus acidophilus, Lactobacillus casei, Bifidobacteriumbifidum, thiab Lactobacillus fermentum (2 × 109colony forming units CFU/g rau txhua tus) txhim kho kev paub txog kev paub txog kev noj qab haus huv thiab kev ua haujlwm zoo. .

Txawm li cas los xij, ob xyoos tom qab, lwm txoj kev tshawb fawb los ntawm tib pab pawg tshawb fawb tau qhia txog qhov tsis sib haum xeeb ntawm cov neeg mob uas muaj dementia, uas tau raug lees paub los ntawm qee qhov kev txwv (ib qho teeb meem hauv hom kev sim no), xws li qee yam kev kawm, suav nrog cov neeg mob feem ntau hauv theem loj ntawm AD, qhov ntau npaum li cas thiab kev tsim cov kab mob probiotic, thiab ntau yam ntxiv rau lub sij hawm raug [126].

Txawm hais tias cov pov thawj tsiaj ua ntej txhawb nqa lub luag haujlwm tiv thaiv kev tiv thaiv ntawm probiotics ntawm kev paub txog kev ua haujlwm, tsis ntev los no meta-kev tshuaj ntsuam xyuas cov ntsiab lus AD yog qhov tsis sib haum xeeb, thiab ntxiv cov kev sim loj loj ntxiv nrog rau lub sijhawm ntev, kev sim randomized tseem xav tau [127].Qhov piv txwv thib ob yog hais txog cov neeg mob qaug dab peg.

Hmoov tsis zoo, cov tshuaj tiv thaiv kab mob vwm yog ib qho teeb meem cuam tshuam uas muaj ntau dua morbimortality thiab qis dua lub neej zoo dua li cov pej xeem [128]. Nyob rau hauv parallel, o yog ib qho tseem ceeb nyob rau hauv lub pathophysiology ntawm tib neeg qaug dab peg, thiab proinflammatory serum cytokines yog txuam nrog rau qhov hnyav thiab zaus ntawm qaug dab peg [128-130].

Txawm hais tias muaj ntau cov lus nug txog biomolecularmechanisms koom nrog tseem tsis tau teb, Gómez-Eguílaz li al., (2018) [128] tsis ntev los no tau soj ntsuam probiotic supplementation (Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus casei, Lactobacillus helveticillus, Lactobacillus, thiab Lactobacillus Streptococcus salivarius subsp. Thermophilus, CFU ~ 1011 rau txhua tus) tuaj yeem txo tus naj npawb ntawm qaug dab peg thiab txhim kho lub neej zoo ntawm cov neeg mob.

Interestingly, tsuas yog nyob rau hauv peb lub xyoos yog ib tug zoo tshwm sim ntawm probiotic supplementation qhia nyob rau hauv ib qho kev sim qauv ntawm qaug dab peg tshwm sim los ntawm pentylenetetrazole (PTZ) siv Lactobacillus rhamnosus, Lactobacillus reuteri, thiab Bifidobacterium infantis (CFU ~ 109 rau txhua tus, ntawm gavage rau 3 lub lis piam.) Tsis ntev los no, Kilinc et al. (2021) [132] corroborated antiepileptic nyhuv ntawm prebiotic + probiotic supplementation nyob rau hauv Wistar weaner nas (CFU ~ 109 muaj Bifidobacterium lactis, Bifidobacteriumbreve, Bifidobacterium longum, Bifidobacterium bifidum, Lactobacillus acidophilus, Lactobacillus acidophilus, Lactobacillus acidophilus Arius, Lactobacillus rhamnosus, Lactobacillus bulgaricus , Lactobacillus paracasei, Streptococcus thermophilus, Ascophyllum nodosum, thiab inulin), kuj muaj cov tshuaj tiv thaiv oxidative thiab alleviating neuroinflammation.

PD yog ib hom kab mob ntau yam uas tshwm sim los ntawm kev puas tsuaj hauv lub cev muaj zog ua haujlwm nrog kev poob ntawm dopaminergic neurons hauv substantia nigra [133-135]. Motorimpairment (tus cwj pwm los ntawm kev so tremors, postural instability, thiab cov leeg nqaij rigidity) thiab cov tsos mob uas tsis yog lub cev muaj zog (sensory cuam tshuam, olfactory tsis ua hauj lwm, mob, thiab gastrointestinal dysfunction) tau ntev tau lees paub raws li classical hallmarks ntawm PD [135-137].

Cov kev tshuaj xyuas tsis ntev los no tau qhia tias kev hloov kho ntawm microbiome thiab ntau lub peev xwm molecular mechanisms ntawm lub plab microbiota tau txuas nrog cov kab mob ntawm PD (saib [135,137,138]). Hauv xyoo 2011, thawj txoj kev tshawb fawb pom tau tias PD cov neeg mob nrog cem quav uas tau txais cov mis nyuj fermented uas muaj Lactobacillus casei Shirota rau 5 lub lis piam txhim kho cov quav sib xws thiab cov cwj pwm defecation [122].

Tsib xyoos tom qab, lwm txoj kev tshawb fawb siv probiotics (60 mg rau ib ntsiav tshuaj ntawm Lactobacillus acidophilus thiab Bifidobacteriuminfantis) rau 3 lub hlis kuj txo qhov mob plab thiab mob plab hauv cov neeg mob nrog PD [139].In 2019, randomized, ob-dig muag, tshuaj placebo-tswj tshuaj. Kev sim siv cov khoom siv probiotic (muaj Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus fermentum, thiab Lactobacillus reuteri) tau ua los soj ntsuam kev soj ntsuam (kev txav mus los) thiab biochemical (metabolic parameters) hauv cov neeg mob PD [140].

Interestingly, supplementation nrog cov khoom no rau 3 lub hlis ua rau muaj kev cuam tshuam rau malondialdehyde (MDA), ntshav glutathione (GSH) (txo oxidative kev nyuaj siab), insulin rhiab heev, thiab diminishedhigh-rhiab heev C-reactive protein (hs-CRP).

Txawm hais tias muaj peev xwm tshwm sim los kwv yees cov txiaj ntsig zoo ntawm probiotics hauv PD, cov txheej txheem tseem tsis meej, muaj ntau haiv neeg, thiab dav. Ntxiv mus, kev sim thiab / lossis cov pov thawj kho mob uas qhia tau tias cov txiaj ntsig ntawm PD tseem txwv, thiab xav tau kev tshawb fawb ntxiv rau kev pom zoo [ 137].Nws tau tsim muaj txiaj ntsig zoo tias levodopa (ntxiv rau carbidopa lossis benserazide), uas yog cov tshuaj hloov pauv hloov pauv, yog cov tshuaj siv tau zoo tshaj plaws los tswj cov tsos mob bradykinetics.

Txawm li cas los xij, nws paub tias qhov "on-off" lub cev muaj zog hloov pauv hauv cov neeg mob nrog PD yog nyob ntawm levodopa bioavailability, uas yog kev hloov pauv tsis ncaj ntawm cov amino acids thiab plab microbiota [121]. Tsis ntev los no, kev tshawb fawb los ntawm van Kessel et al.(2019) [141] tau qhia tias muaj ntau ntawm cov kab mob tyrosine decarboxylase nyob rau hauv cov hnyuv me me (xws li Enterococcus) tuaj yeem piav qhia txog kev siv tshuaj ntau ntxiv ntawm kev kho mob ntawm levodopa hauv PD cov neeg mob vim qhov kev puas tsuaj ntxov ntawm dopamine ntau dhau. sab nraum lub hlwb.

Probiotic supplementation tuaj yeem yog lub tswv yim nthuav los hloov cov plab hnyuv microbiotacomposition, txo cov kab mob hauv plab thiab lub hlwb, txo qis plab, tsis txhob kis kab mob, thiab txhim kho plab hnyuv [137,142].

Yog li, txiav txim siab tias kev ntxiv cov tshuaj probiotic hauv cov neeg mob neurological (xws li cov neeg mob refractory) tuaj yeem zam kev kho tsis ua haujlwm thiab txo cov tshuaj polypharmacy thiab / lossis toxicity (vim tsis tsim nyog hloov kho), kev sib cuam tshuam ntawm cov tshuaj probiotic yog ib txoj hauv kev pheej hmoo ntawm kev tshawb fawb thiab tuaj yeem muaj feem cuam tshuam rau cov neeg mob, lawv tsev neeg, thiab kev saib xyuas tib neeg.

7. Lub Symbiome thiab Pathobiome: Kev nkag siab tshiab ntawm lub plab hauv ND

Txawm hais tias lo lus "microbiome" feem ntau tau siv nyob rau hauv thaj chaw biomedical, nws yog ib qho tseem ceeb kom paub meej tias lo lus no tsis suav nrog eukaryotes, thaum lo lus "symbiome" piav qhia tag nrho cov khoom sib txuas, tsis suav nrog tus tswv [143].

Txij li thaum peb tshuaj xyuas, peb tab tom qhia qhov cuam tshuam ntawm prokaryotes hauv lub plab luminal tiv thaiv ND, lub sij hawm "microbiome" tuaj yeem siv thoob plaws hauv cov ntawv nyeem. Txawm li cas los xij, nws yuav tsum raug txiav txim siab tias probiotic kefir kuj muaj cov kab mob fungal xws li Kazachstania, Kluyveromyces, Naumovozyma [144], Saccharomyces cerevisiae, Kluyveromyces marxianus (yav tas los Candidakefyr) [145] thiab Candida albicans tsis tuaj yeem [7] Kev koom tes ntawm cov kab mob eukaryotic no nyob rau hauv cov kab mob neurodegenerative zuj zus.Ib yam nkaus, lo lus "pathobiome" yog hais txog cov kab mob sib koom ua ke (cov kab mob, prokaryotes, thiab eukaryotes) txuas nrog txo qis kev noj qab haus huv raws li kev cuam tshuam ntawm tus tswv tsev.

Tsis tas li ntawd, hauv qhov kev tshuaj xyuas no, peb qhov tseem ceeb yog ua kom pom qhov cuam tshuam ntawm prokaryotes ntawm dysbiosis. Yog li ntawd, muaj kev txaus siab rau kev tshawb fawb txog kev cuam tshuam ntawm cov kab mob hauv cov txheej txheem neurodegenerative, xws li herpes simplex virus type 1, cytomegalovirus, thiab varicella-zoster virus encephalomyelitis virus (saib [146–149]).

8. Keeb kwm luv luv thiab Biochemical Properties ntawm Kefir: Lub hauv paus rau kev tsim nyog ntxiv

Raws li kev lig kev cai, kefir nplej (saib daim duab 4) tau muab khoom plig los ntawm Allah rau tus Yaj Saub Mohammed, uas tau dhau mus rau Caucasians uas kis nws thoob ntiaj teb, hla nws tes-rau-tes [150].

Lub hauv paus chiv keeb ntawm cov mis nyuj fermented rov qab mus rau qub txeeg qub teg, feem ntau yuav yog thaum tib neeg pib siv cov mis nyuj hauv nws cov zaub mov. Caucasians pom tias cov mis nyuj tshiab nqa hauv hnab tawv nqaij (tsiaj tawv nqaij) tuaj yeem ua rau qee zaus ferment, ua rau cov dej fizzy [151] nws lub neej txee ntev dua li cov mis nyuj nyoos [152]. Phau Vajlugkub kuj piav txog ib yam khoom uas zoo ib yam li kefir, hu ua “manna”, uas yog cov khoom noj uas tau tsim muaj txuj ci tseem ceeb, tau muab los ntawm Vajtswv rau cov neeg Ixayees, coj los ntawm Mauxes, thaum nws nyob hauv suab puam mus rau thaj av uas tau cog lus tseg (Khiav Dim 16), uas justifies lub sij hawm "tus yaj saub haus dej" [153,154].

Kefir yog fermented mis nyuj tseem hu ua tibicos, "tus yaj saub Mohammed's grain", "Tibetan nceb", "yogurt nroj tsuag", "yogurt nceb", "kephir", "Kippur", "kefir", "snap on", "kepi" thiab", thiab "khib". Lub sij hawm muab los ntawm Turkish "keif", uas txhais tau hais tias "kev noj qab haus huv" lossis "zoo nyob" [100,153–155] .Nyob rau hauv qee qhov chaw ntawm lub ntiaj teb, kefir tseem tsis tau muaj cov khoom nrov.

Txawm li cas los xij, hauv Central Europe, Asia, thiab qee lub tebchaws Asmeskas, nws tau ua lag luam thiab ua rau ntawm cov khoom siv tes ua rau tus neeg noj [100,156] los ntawm fermentation ntawm ntau hom mis nyuj (saib Table 1).

Txawm li cas los xij, cov kua mis fermented no tau txais adherentsdue rau nws cov khoom ua haujlwm. Kefir yog cov kua mis fermented, qaub, me ntsis cawv ua los ntawm cov nplej uas muaj cov neeg nyob ruaj khov ntawm cov kab mob [7,157].

Cov txheej txheem fermentation ua rau muaj ntau yam sib txuas uas muab cov yam ntxwv tsw thiab aroma rau kefir, ntxiv rau bioactive tshuaj uas yog lub luag haujlwm rau nws cov khoom noj khoom haus [158]. Cov ntaub ntawv uas twb muaj lawm qhia txog cov txiaj ntsig kev noj qab haus huv vim yog kev noj haus kefir tsis tu ncua. Cov tebchaw no tau txuam nrog kefir's biologicalproperties, xws li immunomodulatory [159], antimicrobial [160,161], antitumor [162], anti-inflammatory [40,163], thiab antioxidant [7,14,40,63,101,115] zog.

Cov txiaj ntsig txhawb kev noj qab haus huv no cuam tshuam nrog kefir microorganisms, kev sib cuam tshuam ntawm lawv, thiab cov tshuaj bioactive uas tsim los ntawm fermentation ntawm mis nyuj [164].

Muaj kev sib koom ua ke ntawm cov poov xab, cov kab mob lactic acid, thiab cov kab mob acetic acid, ntawm lwm cov kab mob [100,151]. Txawm li cas los xij, cov microbial muaj pes tsawg leeg ntawm kefir tuaj yeem sib txawv raws li thaj tsam ntawm keeb kwm, lub sijhawm ntawm fermentation, hom substrate, thiab cov txheej txheem manipulations [7,165,166].

Cov tshuaj tiv thaiv thiab kho cov kab mob lactic acid tau kawm thaum pib ntawm lub xyoo pua xeem thaum Ilya Ivanovich Metchnikoff (leej txiv ntawm gerontology) tau nthuav tawm txoj kev xav ntawm kev ua neej ntev los ntawm kev noj cov mis nyuj fermented.

Txij thaum ntawd los, cov kws tshawb fawb tau txheeb xyuas cov kev soj ntsuam no, hais txog kev noj cov kab mob probiotic nrog kev hloov pauv ntawm cov kab mob hauv ntau yam kev sim [7,63,101].

Feem ntau cov kab mob sib cais los ntawm kefir nplej muaj xws li cov generaLactobacillus (L. casei, L. acidophilus, L. brevis, L. kefiri, L. plantarum, L. kefiranofaciens subsp.kefiranofaciens, L. kefiranofaciens subsp. kefirgranum, L. parakefir), Lactococcus (L. lactis subsp.lactis), Leuconostoc (L. mesenteroides), Acetobacter, Kluyveromyces (K. marxianus), Saccharomyces [7,165,166] thiab nws thiaj li muaj lwm yam genera teev saum toj no). Txawm hais tias qhov no microbiota yog nyob rau hauv symbiotic equilibrium, nws tsis tas li nyob tas mus li [7,191,192].

Cov txheej txheem ib txwm siv ntawm kefir tshwm sim ncaj qha los ntawm kev ntxiv 4% ntawm cov mis nyuj, zoo dua pasteurized los yog boiled, thiab tom qab ntawd txias rau 25 ◦C (chav kub) rau grain inoculation [7,9]. Tom qab lub sij hawm fermentation, uas txawv ntawm 18 mus rau 24 teev, nyob rau hauv chav tsev kub, cov nplej yog cais los ntawm fermented haus los ntawm filtration thiab tom qab siv rau inoculation nyob rau hauv ib tug tshiab substrate.

Cov lim xa mus rau lactic fermentation raug xa mus rau lub tub yees thiab nyob twj ywm rau 24 teev. Nyob rau theem no, cov poov xab yuav tsim cov cawv thiab CO2, ua rau cov khoom ua kom zoo dua qub [7,101,193] .Qhov muab ob npaug rau fermentation ntawm cov mis nyuj los ntawm cov kab mob thiab cov poov xab ua rau cov khoom noj uas muaj lactic, acetic, thiab glycolic acids, ethyl cawv, CO2, vitamin B12. , thiab polysaccharides, uas muab cov khoom tshwj xeeb rau kev hnov ​​​​mob [194].

Lub physicochemical muaj pes tsawg leeg ntawm kefir sib txawv nrog rau hom mis nyuj siv hauv fermentation. Ib txwm kefir muaj 89–90% (m / m) noo noo, 0.2% lipids, 3.0% protein, 6.0% carbohydrates, 0.7 % tshauv, thiab 1% cawv thiab lactic acid [195,196].

Txhawm rau txiav txim siab, cov yam ntxwv organoleptic ofkefir tuaj yeem yog vim nws cov khoom tseem ceeb kawg [197]. Piv txwv li, ethanol thiab CO2 imparta tshwj xeeb thiab txawv txawv aroma rau kefir [193]. Tsis tas li ntawd, lactic acid txhawb nqa me ntsis acidic thiab iab saj, thiab acetaldehyde muaj feem xyuam rau cov yam ntxwv tsw muaj mis nyuj [198].

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