Effects And Mechanisms Of Probiotics On Alleviation Of Psoriasis Vulgaris

Psoriasis is an immune-mediated systemic skin disease that severely reduces patients' quality of life.According to different clinical phenotypes,psoriasis can be separated into many types,of which psoriasis vulgaris accounts for about 90% of all cases.So,psoriasis is usually referred to psoriasis vulgaris.One of the typical pathological features of psoriasis is the hyperproliferation of keratinocytes,and early research mainly focuses on it,while the current research focuses on immune disorders,such as the disorder of IL-23 / Th17 axis.Probiotics,as microorganisms that are beneficial to human health,have been reported for a long time on the regulation of immunity.The mechanism of action can be divided into the direct effect relying on its own components and metabolitesm,and the indirect effect by regulating the gut microbiota.Considering that psoriasis is mediated by immunity and probiotics have a regulatory effect on immunity,combined with the literature reports of supplementing probiotics to alleviate psoriasis,the purpose of this study is to screen probiotics with the potential to alleviate psoriasis through psoriasis like pathological model and explore the mechanism of action.The main conclusions are as follows:(1)Screening of probiotics for inhibiting hyperproliferation of keratinocytes which works on skin and exploring its mechanism.Since the hyperproliferation of keratinocytes is one of the typical pathological characteristics of psoriasis,the psoriasis-like cell model was constructed by using TNF-? to over proliferate HaCaT cells.The fermented supernatant of lactic acid bacteria and the solution containing the components of lactic acid bacteria were applied to this cell model,and the inhibition effect of the two on cell proliferation was compared.It was found that the effect of the former was significantly better than that of the latter.Therefore,it was believed that lactic acid bacteria mainly inhibited cell proliferation through the metabolites,rather than the components themselves.By comparing the inhibitory effects of 102 strains of lactic acid bacteria,two probiotics with the best inhibitory effects were screened out: Lacticaseibacillus paracasei CCFM1147 and Bifidobacterium animalis CCFM1148,and the inhibition rates were 52.7% and 53.6% respectively.Based on the transcriptome of the cell samples,the mechanism of the fermentation supernatant that worked was predicted,and the subsequent verification experiments confirmed that the inhibitory effect of CCFM1147 and CCFM1148 on the hyperproliferation of HaCaT cells was achieved by inhibiting the activation of NF-?B signaling pathway and downregulating the levels of inflammatory factors IL-6 and IL-8.From what has been discussed above,the metabolites of CCFM1147 and CCFM1148 have the potential to alleviate psoriasis by working on the lesion.(2)Screening of probiotics for inhibiting the release of inflammatory cytokines from IL-23/Th17 axis which works on gut and exploring its mechanism.The psoriasis-like animal model was constructed by IMQ.Since the IL-23/Th17 axis plays an important role in the pathogenesis of psoriasis,while IL-17 is one of the important inflammatory factors of the Il-23/Th17 axis,strains that could or could not reduce the level of Th17 or IL-17 in other animal pathological models were applied to this animal model.The results showed that Bifidobacterium breve CCFM1078(decreased IL-23,IL-22 and IL-17 levels by 20.3%,22.9% and 18.3%),Bifidobacterium adolescentis CCFM667(decreased IL-23 and IL-22 levels by 24.6% and 30.1%),Lacticaseibacillus paracasei CCFM1074(decreased IL-23 and IL-17 levels by 39.2% and 20.2%)and Limosilactobacillus reuteri CCFM1132(decreased IL-23 and IL-17 levels by 37.6% and 18.5%),which reduced the levels of IL-23/Th17 axis related inflammatory factors,did alleviate psoriasis in mice,while the strains which did not reduce the levels of IL-23/Th17 axis related inflammatory factors did not.The mechanism was to reduce the levels of Il-23/Th17 axis related inflammatory factor by promoting SCFAs production,so as to alleviate psoriasis.According to fecal genomics and serum metabolomics analysis,it was found that strains that alleviated psoriasis had a certain regulatory effect on the gut microbiota and metabolism of psoriasis-like mice.From what has been discussed above,CCFM1078,CCFM667,CCFM1074 and CCFM1132 have the potential to alleviate psoriasis by working on the gut.