Involvement of Gut Microbiota in the Development of Psoriasis Vulgaris

Abstract

Objectives: Psoriasis is a common chronic recurrent dermatitis. Accumulating observations show gut microbiota dysbiosis in psoriasis. We intend to further investigate the relationship between intestinal microbiota and psoriasis development. Design: We first performed an epidemiological investigation on differences of gastrointestinal discomfort symptoms between patients with psoriasis and general population. Then variation of gut microbiota in patients with psoriasis (un)treated with acitretin plus narrow-band ultraviolet B (NB-UVB) was analyzed by 16S rRNA sequencing. We last compared recovery status and vital cytokines (lesion and intestine) of mouse psoriasiform models, which were transplanted with fecal microbiota from patients with psoriasis or healthy controls. Results: (1) About 85.5% of patients with psoriasis vs. 58.1% of healthy controls presented with at least one gastrointestinal symptom. The prevalence of investigated symptoms (e.g., abdominal distension and constipation) were significantly higher in patients, compared with controls (p < 0.05). Passing flatus and constipation were significantly correlated with psoriasis (p < 0.05 in both cases). (2) The abundance of Ruminococcaceae family, Coprococcus_1 genus, and Blautia genus were decreased with psoriasis improvement (p < 0.05, respectively), which had been demonstrated significantly increased in psoriasis. (3) Mice receiving psoriatic microbes transplantation showed delayed recovery of psoriasiform dermatitis and less reduction of interleukin (IL)-17A than those receiving healthy microbiota or blank control (p < 0.05 and p < 0.01, respectively). Conclusion: Multiple evidence we provided here preliminarily demonstrates the involvement of gut microbiota in the different degree of psoriasis activity. The strategy based on overall microbial communities is expected to be a promising supplementary for long-term management of psoriasis.

Keywords: 16S rRNA sequencing; fecal microbiota transfer; gastrointestinal symptom; gut microbiota; psoriasis.

Figure 1

Study workflow. Epidemiological investigation on differences of gastrointestinal discomfort symptoms between patients with psoriasis and general population were first performed. Then variation of gut microbiota in patients with psoriasis (un)treated with acitretin plus NB-UVB was analyzed by 16S rRNA sequencing. Last, experiment with mouse psoriasiform models receiving fecal microbiota transplantation (FMT) was performed for crucial results validation. Visual observation and samples collection were performed at pre-FMT, day 0 after FMT (FMT-0d) and day 4 after FMT (FMT-4d). NB-UVB, narrow-band ultraviolet B.

Figure 2

Taxonomic composition of bacterial community in patients with psoriasis (un)treated with acitretin. (A) Non-metric Multidimensional Scaling (NMDS) analysis with unweighted UniFrac displayed that most of the untreated group were discriminated from the majority of Treated group samples. Each colored solid circle represents one sample. Solid circles that are closer together represent similar taxonomic composition. (B) The scores of linear discriminant analysis for the differentially abundant taxa. Significant bacterial differences at family level (C) and at genus level (D) between two groups were analyzed by MetaStat analysis.

Figure 3

Mice received fecal microbiota transplantation (FMT) from patients with psoriasis showed significantly delayed recovery of psoriasiform dermatitis. After daily application of imiquimod (IMQ) cream for 5 consecutive days, mice in the different groups were respectively transplanted with fecal microbiota from patients with psoriasis (PSO), healthy controls (NOR), or control of PBS (CON). (A) Phenotypic presentation of dorsal skin of mice in different group. (B) Scores of skin lesions were calculated by erythema plus scaling (a scale from zero to four, respectively). (C) H&E staining (scale bar 50 μm) of dorsal skin of mice from different group. (D) Epidermal thickness was indicated by number of epidermal cell layers. Colored symbols in (C,D) indicated mean score ± SD of five mice per group.

Figure 4

Analysis of IL-17A in mouse skin lesions of psoriasiform by immunofluorescence assay (scale bar 50 μm). (A) Mice received FMT of psoriatic fecal sample. (B) Mice received FMT of healthy fecal sample. (C) Control mice received oral gavage of PBS. Blue fluorescence represents DAPI; red fluorescence represents IL-17A. The borderline between epidermis and dermis was dotted using asterisks. (D) Numbers of red fluorescence were counted to analyze IL-17A expression. Colored symbols indicate mean number ± SD of five mice per group. (E–G) Are respectively enlarged local area of (A–C) at FMT_0d. DAPI, 4′,6-diamidino-2-phenylindole; FMT, fecal microbiota transplantation; PBS, phosphate-buffered saline.