Study Of The Protective Effects Of Bifidobacterium Breve CCFM683 On Psoriasis Vulgaris

Psoriasis,according to the different clinical phenotypes,is classified into various types,among which psoriasis vulgaris is the most common type.What we call“psoriasis”usually refers to psoriasis vulgaris,and it is characterized by epidermal thickening and scaling,and is periodic and repetitive.Allopathic remedies including corticosteroids,vitamin D analogs,methotrexate,and UV phototherapy may have side effects such as cutaneous atrophy,dyspigmentation,or bone marrow toxicity,thus limiting their application.Probiotics with accepted safety is used to treat psoriasis and considered substitute for allopathic remedies.Previous researches have confirmed the efficacy of probiotics on psoriasis treatment,however,the underlying machanisms and the minimum doses for probiotics to alleviate psoriasis remain unclear.Bifidobacterium breve CCFM683 was reported to regulate the microbiota,supress the activation of NF-κB,block the inflammatory cytokines,and modulate the gut microbiota,which made it possible for CCFM683 to ameliorate psoriasis.In the current study,the protective effects of B.breve CCFM683 on psoriasis and the underlying patterns were investigated,based on which the dose-repseponse efficacy was explored.The results are as follows:Firstly,the protective effects of B.breve CCFM683 on psoriasis was evaluated by the hisotogical score of the imiquimod-exposed psoriatic mice after administered with B.breve CCFM683.As a result,B.breve CCFM683 decreased the psoriasis area and severity index（PASI）to 76.12%of that in IMQ group,ameliorated the ear thickening,decreased the histological score,regulated the expression of the keratins and cornified envelope,and diminished the inflammatory cytokines thus ameliorating psoriasis.Additionally,heat-killed B.breve CCFM683 cell pellets made no influence on above symptoms,indicating that CCFM683ameliorated psoriasis by the metabolites of itself or/and the changed microbiota.Next,the metabolomic analysis,immunological methods and 16S r DNA sequencing were used to analyze the crutial metabolites,target,signaling pathway,and intestinal microbiota alteration that was responsible for the protective effect of B.breve CCFM683 on psoriasis.Our results showed that B.breve CCFM683 up-regulated the relative abundance of deoxycholic acid（DCA）-producing Lachnoclostridium,increased the concentration of DCA to 259.37 ng/mg.Additionly,CCFM683 activated farneside X receptor（FXR）,and inhibited NF-κB expression,which were possibly the crutial target and pathway to relieve skin inflammation and matain the skin barrier.Finally,B.breve CCFM683 at different doses were gavaged to psoriatic mice to analyze its dose-response efficacy.10⁹ and 10¹⁰ CFU/day CCFM683 significantly ameliorated psoriasis,while less than 10⁸ CFU/day CCFM683 made no influence.Additionally,the gavage dose of B.breve CCFM683 positively correlated with the psoriasis-relieving efficacy and the DCA concentration in both colon and serum.Through analyzing dose–effect curve,more than 10^8.42CFU/day was adequate to relieve psoriasis.