Comparison of gut microbiota compositions and corresponding genetic and metabolic features between guttate and plaque psoriasis by metagenomic sequencing.

BACKGROUND: Guttate psoriasis (GP) and psoriasis plaques (PP) are common subtypes of psoriasis. Previous studies have fully researched the association between psoriasis and gut microbiota. However, the differences in gut microbiota between GPs and PPs are still unknown. METHODS: Fecal samples were collected from 30 psoriatic patients (15 GP and 15 PP) and 15 healthy subjects. Metagenomic sequencing was then used to compare gut microbiota compositions and corresponding genetic and metabolic features between GP and PP. RESULTS: We found that the genus Megamonas was increased in PP and reduced in GP. The genus Eubacterium was increased in GP and decreased in PP. Ten KEGG pathway were significantly enriched in GP: bacterial secretion system, ribosome, sphingolipid signaling pathway, steroid hormone biosynthesis, complement and coagulation cascades, proteoglycans in cancer, FOXO signaling pathway, cGMP-PKG signaling pathway, insulin resistance, and Epstein-Barr virus infection. Ten metabolites were significantly differentially abundant between GP and PP. Among them, thiamine, biotin, butylamine, phenylethylamine, folic acid, 1,2-propanediol, and 4-aminobutyrate were enriched in PP and l-glutamate, l-glutamine, and propanoate were enriched in GP. CONCLUSIONS: These results provide a theoretical basis for the microbiome-guided stratification of patients with psoriasis.

Deciphering Gut Microbiota Dysbiosis and Corresponding Genetic and Metabolic Dysregulation in Psoriasis Patients Using Metagenomics Sequencing.

Background: Increasing evidence has shown that alterations in the intestinal microbiota play an important role in the pathogenesis of psoriasis. The existing relevant studies focus on 16S rRNA gene sequencing, but in-depth research on gene functions and comprehensive identification of microbiota is lacking. Objectives: To comprehensively identify characteristic gut microbial compositions, genetic functions and relative metabolites of patients with psoriasis and to reveal the potential pathogenesis of psoriasis. Methods: DNA was extracted from the faecal microbiota of 30 psoriatic patients and 15 healthy subjects, and metagenomics sequencing and bioinformatic analyses were performed. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database, cluster of orthologous groups (COG) annotations, and metabolic analyses were used to indicate relative target genes and pathways to reveal the pathogenesis of psoriasis. Results: Compared with healthy individuals, the gut microbiota of psoriasis patients displayed an alteration in microbial taxa distribution, but no significant difference in microbial diversity. A distinct gut microbial composition in patients with psoriasis was observed, with an increased abundance of the phyla Firmicutes, Actinobacteria and Verrucomicrobia and genera Faecalibacterium, Bacteroides, Bifidobacterium, Megamonas and Roseburia and a decreased abundance of the phyla Bacteroidetes, Euryarchaeota and Proteobacteria and genera Prevotella, Alistipes, and Eubacterium. A total of 134 COGs were predicted with functional analysis, and 15 KEGG pathways, including lipopolysaccharide (LPS) biosynthesis, WNT signaling, apoptosis, bacterial secretion system, and phosphotransferase system, were significantly enriched in psoriasis patients. Five metabolites, hydrogen sulfide (H2S), isovalerate, isobutyrate, hyaluronan and hemicellulose, were significantly dysregulated in the psoriatic cohort. The dysbiosis of gut microbiota, enriched pathways and dysregulated metabolites are relevant to immune and inflammatory response, apoptosis, the vascular endothelial growth factor (VEGF) signaling pathway, gut-brain axis and brain-skin axis that play important roles in the pathogenesis of psoriasis. Conclusions: A clear dysbiosis was displayed in the gut microbiota profile, genetic functions and relative metabolites of psoriasis patients. This study is beneficial for further understanding the inflammatory pathogenesis of psoriasis and could be used to develop microbiome-based predictions and therapeutic approaches.

Yangxue Jiedu Fang Ameliorates Psoriasis by Regulating Vascular Regression via Survivin/PI3K/Akt Pathway.

BACKGROUND: Psoriasis (PA) is a chronic autoimmune disease of the skin that adversely affects patients' quality of life. Yangxue Jiedu Fang (YXJD) has been used for decades to treat psoriasis in China. However, its antipsoriatic mechanisms are still poorly understood. In this study, we explored the effects of YXJD on angiogenesis and apoptosis of microvessels in PA, the underlying mechanisms in HUVEC cells transfected by Survivin overexpression plasmid and in a mouse model of imiquimod-induced psoriasis and the relationship between VEGF (vascular endothelial growth factor) and Survivin. METHODS: A BALB/c mouse model of imiquimod- (IMQ-) induced PA was established, and the mice were treated with YXJD. Cell viability was assessed by CCK8 assay. Apoptosis was detected by annexin V-FITC/PI double-staining and caspase-3 assays. The PI3K/Akt/ß-catenin pathway was analyzed by western blotting, ELISA, and immunochemical analysis. RESULTS: YXJD ameliorated symptoms and psoriasis area and severity index (PASI) scores and also reduced the number of microvessels, as determined by the microvessel density (MVD). The expression of apoptotic protein Survivin in endothelial cells, autophagy-related proteins p62, and angiogenic proteins VEGF was inhibited by YXJD, and the repressed expression of LC3II/I increased by YXJD. The proteins related to the PI3K/Akt pathway and ß-catenin expression and the nuclear entry of ß-catenin were reduced in IMQ-induced PA mice treated with YXJD. In HUVEC cells transfected by Survivin overexpression plasmid, we observed YXJD regulated the expression of Survivin, LC3II/I, and p62, VEGF, and PI3K/Akt pathway-relative proteins and the nuclear entry of ß-catenin. CONCLUSIONS: YXJD inhibited the expression of Survivin via PI3K/Akt pathway to adjust apoptosis, autophagy, and angiogenesis of microvessels and thus improve the vascular sustainability in psoriasis. YXJD may represent a new direction of drug research and development for immunomodulatory therapy for psoriasis.

Dysregulation of the gut-brain-skin axis and key overlapping inflammatory and immune mechanisms of psoriasis and depression.

The occurrence, progression and recurrence of psoriasis are thought to be related to mood and psychological disorders such as depression. Psoriasis can lead to depression, and depression, in turn, exacerbates psoriasis. No specific mechanism can explain the association between psoriasis and depression. The gut-brain-skin axis has been used to explain correlations among the gut microbiota, emotional states and systemic and skin inflammation, and this axis may be associated with overlapping mechanisms between psoriasis and depression. Therefore, in the context of the gut-brain-skin axis, we systematically summarized and comparatively analysed the inflammatory and immune mechanisms of psoriasis and depression and illustrated the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and the gut microbiota. This review provides a theoretical basis and new targets for the treatment of psoriasis and depression.

Plasma MicroRNA Expression Profiles in Psoriasis.

BACKGROUND: Psoriasis is an immune-mediated inflammatory chronic skin disease characterized by chronic inflammation in the dermis, parakeratosis, and excessive epidermal growth. MicroRNAs (miRNAs) are key regulators of immune responses. Although differential expression of miRNAs has been reported in certain inflammatory autoimmune diseases, their role in psoriasis has not been fully illuminated. Our aims were to confirm plasma miRNA expression signatures in psoriasis and to examine their potential influence on psoriasis pathogenesis. METHODS: A miRNome PCR array was used to analyse the plasma of psoriasis patients and healthy donors. We performed miRNA pathway enrichment and target gene network analyses on psoriasis plasma samples. RESULTS: We found several specific plasma miRNA signatures relevant to psoriasis. The miRNAs targeted pathways associated with psoriasis, such as the VEGF, MAPK, and WNT signaling pathways. Network analysis revealed pivotal deregulated plasma miRNAs and their relevant target genes and pathways regulating psoriasis pathogenesis. CONCLUSIONS: This study analysed the expression of plasma miRNAs and their target pathways, elucidating the pathogenesis of psoriasis; these results may be used to design novel therapeutic strategies and to identify diagnostic biomarkers for psoriasis.

Acupuncture combined with herbal medicine versus herbal medicine alone for plaque psoriasis: a systematic review protocol.

BACKGROUND: Psoriasis is a condition with a multifactorial etiopathogenesis worldwide, and plaque psoriasis, which is characterized by redness, thickness, and scaling, is the most common kind. Individuals living with psoriasis show low levels of life quality, and having fewer or less extensive lesions may improve spiritual and mental health. Therefore, our objective is to explore the effectiveness of acupuncture combined with herbal medicine for plaque psoriasis and to compare acupuncture combined with herbal medicine with herbal medicine alone. METHODS: Databases including PubMed, MEDLINE, the Cochrane Library, Excerpta Medica (EMBASE), the Chinese Biomedical Literature Database (CBM), the China National Knowledge Infrastructure Database (CNKI), the Wanfang database and the Chinese Scientific Journal Database (VIP database) will be searched from inception to March 2018. We will employ hand searches, and grey literature will also be obtained. Only randomized controlled trials evaluating acupuncture combined with herbal medicine to treat plaque psoriasis in adults will be assessed. The Psoriasis Area and Severity Index score (PASI score), the itching index, the life quality scores, and the anxiety index will be the outcome measures. Two independent reviewers will select the articles included, assess the risk of bias and extract data according to the inclusion criteria. A third reviewer will resolve disagreements. The purpose of this study will be to identify the effect of acupuncture combined with herbal medicine on the lesions (PASI score), symptoms (itching index, life quality scores) and mental status (anxiety index) of the patients. DISCUSSION: The meta-analysis will retrospectively examine current evidence regarding the effectiveness of the practice of acupuncture combined with herbal medicine to treat plaque psoriasis. This study may reveal, for the first time, an adjuvant therapy for psoriasis. TRIAL REGISTRATION: As the study is a systematic review protocol, trial registration will not be necessary. An article containing the results will be published in a peer-reviewed journal and disseminated through scientific conferences.