Psoriasis is a chronic systemic inflammatory disease contributed by genetic, immunological, and environmental factors, with a prevalence rate of 2%–4% of the worldwide population (1). Thus far, psoriasis has no known cure, and innovative biological therapies are of great prospects. Emerging evidence supports the vital role of gut microbiota in psoriasis, and the relevant products such as probiotics have facilitated its treatment improvement, with an encouraging reduction in Psoriasis Area and Severity Index (PASI) and lower risk of relapse during follow-up (2, 3). In view of psoriasis being a skin disease, skin microbiota alternation may act more significantly to trigger or exacerbate psoriasis. Current research has put emphasis on the role of skin microbiome in immune-mediated inflammatory skin diseases, including atopic dermatitis, acne vulgaris, vitiligo, and systemic lupus erythematosus (4–8), yet there are certain blank regions in psoriasis. Even though the causal link between skin microbiome and psoriasis remains elusive, evolving knowledge supports its potential role interplaying on T helper cell 17 (Th17) in psoriatic patients, acting on inflammatory cells and cytokine pathways to induce immunity disorder on skin, confirmed by detection of plasma metabolism and bacterial metabolites (9). Furthermore, patients with psoriasis have higher risks of associated comorbidities, such as psoriasis arthritis (PSA), inflammatory bowel disease, periodontitis, cardiometabolic dysfunction, depression, and metabolic syndrome, which may be due to concurrent susceptible locus and aberrant impaired tolerance in response to microbiota (10–14). With the update of whole-genome shotgun (WGS) metagenomic sequencing (15), the assessment accuracy of bacterial species, community diversity, and gene prediction has been greatly optimized in trials. In the forthcoming period, specific skin microbiome signature might be a promising concept for the diagnostic, therapeutic, and preventive strategies for psoriasis. Novel therapeutic modalities that target or restore the altered skin microbiota are valuable adjuncts for the management of psoriasis and its comorbidities. This article describes the potential pathogenesis of psoriasis concerning how skin microbiota interplay with the host immune system, aiming at providing new insights regarding the immunopathogenesis of psoriasis. A good knowledge about their intrinsic and comprehensive interplay is certainly beneficial to form the basis of innovative treatment selection and may help revolutionize an unprecedented era of biologic therapies for psoriatic patients.

Given the concern that the efficacy of off-the-shelf treatment products for psoriasis is limited hitherto, fully understanding the pathogenesis of psoriasis remains a priority for future research. Microbiome research is very prevalent at present. Whether the skin dysbiosis consists in the primary etiological significance or is secondary to psoriasis (or both) has yet to be completely characterized. Moreover, no consensus microorganisms have been directly identified. The generally accepted viewpoint holds that the altered microbiota probably serves potentially as a trigger or exacerbator for psoriasis. This review summarizes the outcome of multiple preceding clinical trials relevant to the altered skin microbiome in psoriatic patients, with a primary focus on mechanisms underlying how they interplay with the host immune system.

The field of the psoriatic skin microbiome is relatively new, and there are few studies on the specific and novel therapies targeting skin microbiome, thus leaving us considerable room to excavate. The manipulation of skin microbiome for treatment efficacy that preliminary research mentioned mostly refers to the conventional therapeutic options such as topical or systemic antibiotics that reduce susceptible bacterial species. Additionally, narrow-band ultraviolet radiation (NB-UVB) and balneotherapy have been demonstrated to induce an alteration of lesional skin microbiota and the improvement of psoriatic progression (90, 91). On the other hand, there is a direct link between gut and skin microbiota (92). Human skin microbiome composition can also be modulated through manipulated therapy of the gut microbiome (93). Researchers hold that probiotics may exert immunomodulatory effects on skin and can strengthen its barrier function against hazardous flora (94). Navarro-López et al. (95) had performed probiotic therapy on 80 psoriatic patients, with PASI75 reaching 66.7% and lower risk of relapse during follow-up compared to placebo group. Moreover, skin microbiome transplantation to diseased skin has yet to be regarded as another possible approach (96). Given the aforementioned encouraging efficacy on blocking disease progression, it is expected that more skin microbiome-related intervention to alleviate or cure this dermatosis would be developed in future research. For example, transdermal drug delivery must produce a milder side effect profile than current systemic medications. Besides, complement therapeutics are under investigation to potentially modulate the skin microbiota and even treat psoriasis (97).

Unlike atopic dermatitis, it is more than likely that the potential pathogens of psoriasis involve multiple species. Much about the potential role of viruses in psoriatic inflammation remains unclear. In future research, the upmost challenge might be to identify the extent to which skin microbiome plays a role in psoriatic pathogenesis and be modulated, and we should also identify one or several microbes that exert predominant influence on psoriasis, therefore enhancing the accuracy of modulation. Nevertheless, the heterogeneous parameters including genetics, diet, treatment exclusion, and taxonomic levels probably render the results reported in clinical trials less authentic and comparable. Furthermore, even in a single specific trial, the site- and microenvironment-based matching between lesion and control samples might be absent. As discussed, the preliminary studies only elaborate the correlative relationship between skin microbiome and psoriatic state as a whole. In the forthcoming decades, further experimentation to validate their definite association, and performed on isolated microbes, presents a principal direction. For one thing, a new set of standardized analysis protocol, including study population, sampling and processing methodology, would be a useful first step to interpret microbiome data. For instance, healthy people who have a common living background with psoriatic patients ought to be enrolled in a control group to reduce the bias. For another, in terms of taxonomic levels, it is critical to apply strain-level rather than species-level resolution approaches to unravel the microbial signatures associated with psoriasis; particularly, there are still vast unprofiled and undetermined regions about cutaneous viruses. It is proposed that gene transcriptomics is a suitable predictor of disease severity. Nevertheless, there is another tough problem regarding whether the sequence reads in skin swabs could map to specific functional genomes, thus making microorganisms classifiable (98). It still remains difficult to identify the specific driven genes. A substantial number of large-scale prospective longitudinal clinical trials and proof-of-concept experiments in murine models are also required to trace the dynamics of microbial populations during the onset and progression of psoriasis, which may give some enlightenment to predictive approaches for therapeutic responses through particular transcriptomic and microbial biomarkers with disease severity.

Notably, it is hypothesized that skin microbiome composition is associated with the development of psoriatic comorbidities. Initial studies show that its reduced diversity, which may weaken the skin protective function to trigger an immune response, might be a signature for psoriatic patients with a higher risk to develop PSA. It also showed that antibiotics have the potential to reduce the risk of comorbidities in psoriatic patients (96, 99). Whether the skin microbiota is involved in its comorbidity association remains to be further explored. It is expected to develop preventative measures to intervene to halt the progression of PSA.

Taken together, endeavors should be made in seeking out the deeper association between skin microbiome and developing microbiota-related interventions to mitigate psoriasis, such as selective modulation of isolated microbiota via intraindividual or interindividual skin microbiota transplantation, facilitating gut–skin cross-talk via prebiotics, and manipulating microbial pathways by targeting microbial metabolites through pharmacologic inhibitors, and hence, eventually improving clinical outcomes of psoriatic patients. In addition, the characteristics of chronic inflammation, along with its relevant metabolic comorbidity, concurrently indicate the significance of metabolomics in psoriasis. The extent to which skin microbiota play a role in the pathogenesis in psoriasis and which it can be modulated is certainly a critical consideration, and the potential function of skin microbiota on regulating global metabolism in psoriasis is a promising field. Hopefully, microbiome-specific targeted treatments or even curative paradigms for this dermatosis will come true in the upcoming period.

Psoriasis is mediated by immunological and external factors as a commonly seen chronic dermatosis in the population. Given the previous findings, the existing immunopathogenesis for psoriatic inflammation mainly involves IL-23/Th17 axis, along with large amounts of cytokines and immunocytes. Also, skin microbiota could regulate the cutaneous immune tolerance. In psoriatic skin, it is observed that the microorganism composition has altered, which interplays with host innate and adaptive immunity and potentially constitutes the pathogenesis of psoriasis. Some treatments regarding modifying the skin microbiome have been manifested to yield certain efficacy in psoriasis, whereas this field is relatively new and there is a series of challenges existing in future research. It is expected that this potential pathogenesis could be verified and that novel therapeutics targeting the skin microbiome could be figured out to improve the clinical outcome of psoriatic patients.

This study was conceived and designed by YC. Screening of papers and data extraction were performed by XL and CO. Writing of the first draft of the article was performed by XL, CO, JZ, and JL. Tables and figure were prepared by XL, CO, FZ, and YZ. All authors contributed to the article and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.