Alteration of the cutaneous microbiome in psoriasis and potential role in Th17 polarization

Abstract

BackgroundPsoriasis impacts 1–3% of the world’s population and is characterized by hyper-proliferation of keratinocytes and increased inflammation. At the molecular level, psoriasis is commonly driven by a Th17 response, which serves as a major therapeutic target. Microbiome perturbations have been associated with several immune-mediated diseases such as atopic dermatitis, asthma, and multiple sclerosis. Although a few studies have investigated the association between the skin microbiome and psoriasis, conflicting results have been reported plausibly due to the lack of standardized sampling and profiling protocols, or to inherent microbial variability across human subjects and underpowered studies. To better understand the link between the cutaneous microbiota and psoriasis, we conducted an analysis of skin bacterial communities of 28 psoriasis patients and 26 healthy subjects, sampled at six body sites using a standardized protocol and higher sequencing depth compared to previous studies. Mouse studies were employed to examine dermal microbial-immune interactions of bacterial species identified from our study.ResultsSkin microbiome profiling based on sequencing the 16S rRNA V1–V3 variable region revealed significant differences between the psoriasis-associated and healthy skin microbiota. Comparing the overall community structures, psoriasis-associated microbiota displayed higher diversity and more heterogeneity compared to healthy skin bacterial communities. Specific microbial signatures were associated with psoriatic lesional, psoriatic non-lesional, and healthy skin. Specifically, relative enrichment of Staphylococcus aureus was strongly associated with both lesional and non-lesional psoriatic skin. In contrast, Staphylococcus epidermidis and Propionibacterium acnes were underrepresented in psoriatic lesions compared to healthy skin, especially on the arm, gluteal fold, and trunk. Employing a mouse model to further study the impact of cutaneous Staphylcoccus species on the skin T cell differentiation, we found that newborn mice colonized with Staphylococcus aureus demonstrated strong Th17 polarization, whereas mice colonized with Staphylococcus epidermidis or un-colonized controls showed no such response.ConclusionOur results suggest that microbial communities on psoriatic skin is substantially different from those on healthy skin. The psoriatic skin microbiome has increased diversity and reduced stability compared to the healthy skin microbiome. The loss of community stability and decrease in immunoregulatory bacteria such as Staphylococcus epidermidis and Propionibacterium acnes may lead to higher colonization with pathogens such as Staphylococcus aureus, which could exacerbate cutaneous inflammation along the Th17 axis.Electronic supplementary materialThe online version of this article (10.1186/s40168-018-0533-1) contains supplementary material, which is available to authorized users.

Combined culture and metagenomic analyses reveal significant shifts in the composition of the cutaneous microbiome in psoriasis

“…Moreover, in terms of 'signature' genera, increased amounts of Prevotella and Staphylococcus were significantly associated with lesional skin, whereas higher amounts of Anaerococcus and Propionibacterium were associated with nonlesional skin. This is at least partially consistent with Chang et al, 46 supporting further investigation of the extent to which Staphylococcus may promote T helper 17 cell polarization and psoriasis, while Propionibacterium may exert a protective role by outcompeting pathogenic bacteria, potentially via modulation of CD4 + T-cell responses. 47 Moreover, there was a tendency for treatment modality to influence the Actinobacteria-to-Firmicutes ratio, with the biologics exerting the largest effect.…”

The role of the microbiome in scalp hair follicle biology and disease

“…It has been demonstrated in a murine model that this type of bacteria triggers Th17 immune response, which is also overactive in patients with psoriasis. Therefore, a potential capability of S. aureus to influence psoriasis development is currently of interest …”

“…Especially, unsaturated free fatty acids can stimulate inflammation and epidermal hyperproliferation (1), but yeasts may further stimulate psoriasis flare‐ups by induction of cytokines release, complement activation and neutrophil recruitment (2) . S. aureus (blue) is often cultured from pustules and erosions in FD (3), but may also contribute to pro‐inflammatory or immunoregulatory environment in other diseases, for example by triggering Th17 immune response in psoriasis (4), more interdisciplinary research in such direction may reveal new mechanisms by which external microbiota in this specific anatomical niche influence skin microenvironment…”

Gut microbiota dysbiosis in a cohort of patients with psoriasis

“…19,20 The aetiology of psoriasis remains elusive but for decades it has been a wellknown fact that there is a relationship between streptococcal pharyngitis and a particular clinical form of psoriasis, so-called guttate psoriasis. 21 Recently, several studies have been conducted that focus on skin microbiome alterations and their connection with psoriasis [22][23][24][25][26][27] and atopic dermatitis, 28 although less attention has been focused on the potential role of gut microbiota dysbiosis in the pathogenesis of the disease. 29 Our hypothesis is that the intestinal microbiota dysbiosis may play a key role in the development of psoriatic disease due to an aberrant inflammatory response that can be connected with the skin.…”