| Psoriasis is a common chronic inflammatory disease in dermatology,of which the pathogenesis,diagnosis and treatment need further study.Based on the recent research progress on the relationship between intestinal microbiota and disease,this study discussed the changes of intestinal microbiota in patients with psoriasis and the possible related mechanisms.This paper consists of three parts.The first part focuses on the patients who were selected from the psoriasis inpatients at the Institute(Hospital)of Dermatology,Chinese Academy of Medical Science and Peking Union Medical College,P.R.China and the healthy volunteers living around.16S rRNA gene and ITS gene sequencing were used to analyze the characteristics of bacterial diversity and the composition of bacterial community.First of all,we sequenced the 16S rRNA corresponding DNA sequence of the fresh feces of 12 patients with psoriasis and evaluated the similarity between the intestinal microflora of different subtypes.It was found that the intestinal bacterial populations of psoriasis vulgaris and pustular psoriasis were not significantly different in different types of psoriasis under the similar evolutionary background.On this basis,the most common subtype psoriasis vulgaris were selected as the experimental object,22 patients with psoriasis vulgar is and 23 healthy volunteers with the similar living environment,age,sex ratio and BMI to detect the bacterial and fungal flora in their intestinal microbiome,and no difference were found in the ?diversity between the two groups,but the analysis of the beta diversity disease patients can be part of the separation,and the total bacterial abundance significantly reduced in patients with psoriasis;In patients with psoriasis,the main proportion of phylum level is relatively consistent,which are Firmicutes?Bacterioidetes?Proteobacteria?Actinobacteria.The composition of genus level of different samples is quite different.Through LEfSe analysis,some bacteria have significant differences in different levels that can be used as markers.In psoriasis,Firmicutes,Clostridiale,Clostridia,Erysipelotrichales,Erysipelotrichaceae were significantly increaced.The biomarkers higher in the healthy group were Epsilonproteobacteria,Campylobacterales,Campylobacteraceae,Campylobacter,Bacteroidales.In patients with psoriasis,hyperuricemia or not had no effect on the relative abundance of Firmicutes?bacteroidetes and the ratio of Firmicutes/bacteroi detes(F/B).Compared with bacteria,the intestinal fungi in patients with psoriasis showed significantly increased abundance and significantly reduced a diversity.The majority of patients with psoriasis could be separated from healthy people by ? diversity analysis;the main components of fungi in all people were Ascomycota,Basidiomycota,Zygomycotina,Neocallimastigomycota,but the relative abundance was quite different by analyzing in different levels,it was found that Saccharo myces significantly increased in psoriasis group,and the species significantly increased in healthy people included Zygomycota,Mucor,Thanatephorus,Malassezia and other fungi.In the second part,metagenome sequencing technology was used to sequence,assemble,predict and annotate 8 plaque psoriasis patients and 8 healthy control volunteers,and then compared data with microbia database and KEGG Pathway D atabase to analyze gene diversity,species and origin differences,and gene function.On one hand,the results of metagenome sequencing confirmed the decreasing trend of diversity in the intestinal microflora of patients with psoriasis.On the other hand,Gene Pathway Analysis revealed that the ascorbate and aldarate metabolism,lipopolysaccharide biosynthesis,proximal tubule bicarbonate reclamation and 10 other pathways was lower in the psoriasis cases than in the controls.AGE-RAGE signaling pathway in diabetic complications,ECM-receptor interaction,endocytosis elevated in the psoriasis group.Finally,the relative abundance of Firmicutes?Lachnoclostridium sp.YL32?Paenibacillaceae?Paenibacillus?Bacillus virus Shanette?Morbillivirus were selected as the diagnostic indexes of psoriasis vulgaris.Third part based on the resuls of psoriasis and healthy intestinal bacteria genera analysis of significant differences,set the co-culture modesl of Saccharomyces cereviscera with intestinal epithelial Coca-2 cells,clarify the influence of S.cereviscera on Coca-2 cells activity,and establish the co-culture modesl of S.cereviscera with THP-1 cells in vitro,further clarify the S.cereviscera strain effects on immune cells in the immune response.It was found that under the conditions of in vitro experiment,S.cereviscera did not cause the inflammatory response of Caco-2 cells,but the co-culture of high concentration of S.cereviscera with caco-2 cells for 24h could promote the death of caco-2 cells.The inflammatory response of THP-1 with S.cereviscera at different concentrations was bidirectional.S.cereviscera inhibited the mRNA expression of TLR2,TNF-? and IL-1? in the presence of Candida albicans and promote the expression of IL-10.The influence of S.cereviscera on the expression of IL-17 and CXCL1 mRNA in THP-1 cells was bidir ectional when co-culture with Calbicans.The expression of IL-17 and CXCL1 mRNA was inhibited at low concentration of S.cereviscera,while increased at high concentration.Intestinal microbiota of psoriasis patients significantly changes in structure and function,this study carried on comprehensive analysis of intestinal microbiome structure and function in patients with psoriasis,further reveals the changes of intestinal microbiome in patients with psoriasis,and the function of S.cereviscera for intestinal inflammation and the steady state has been carried on the preliminary exploration This study provides a theoretical basis for clinical diagnosis and treatment of psoriasis through intestinal microbiome. |
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