(1) Background: A growing body of evidence highlights that intestinal dysbiosis is associated with the development of psoriasis. The gut–skin axis is the novel concept of the interaction between skin diseases and microbiome through inflammatory mediators, metabolites and the intestinal barrier. The objective of this study was to synthesize current data on the gut microbial composition in psoriasis. (2) Methods: We conducted a systematic review of studies investigating intestinal microbiome in psoriasis, using the PRISMA checklist. We searched MEDLINE, EMBASE, and Web of Science databases for relevant published articles (2000–2020). (3) Results: All of the 10 retrieved studies reported alterations in the gut microbiome in patients with psoriasis. Eight studies assessed alpha- and beta-diversity. Four of them reported a lack of change in alpha-diversity, but all confirmed significant changes in beta-diversity. At the phylum-level, at least two or more studies reported a lower relative abundance of Bacteroidetes, and higher Firmicutes in psoriasis patients versus healthy controls. (4) Conclusions: There is a significant association between alterations in gut microbial composition and psoriasis; however, there is high heterogeneity between studies. More unified methodological standards in large-scale studies are needed to understand microbiota’s contribution to psoriasis pathogenesis and its modulation as a potential therapeutic strategy.

Dysbiosis has been identified in many dermatological conditions (e.g., psoriasis, atopic dermatitis, systemic lupus erythematosus). One of the ways by which the microbiota affect homeostasis is through microbiota-derived molecules (metabolites). There are three main groups of metabolites: short-chain fatty acids (SCFAs), tryptophan metabolites, and amine derivatives including trimethylamine N-oxide (TMAO). Each group has its own uptake and specific receptors through which these metabolites can exert their systemic function. This review provides up-to-date knowledge about the impact that these groups of gut microbiota metabolites may have in dermatological conditions. Special attention is paid to the effect of microbial metabolites on the immune system, including changes in the profile of the immune cells and cytokine disbalance, which are characteristic of several dermatological diseases, especially psoriasis and atopic dermatitis. Targeting the production of microbiota metabolites may serve as a novel therapeutic approach in several immune-mediated dermatological diseases.

Alterations of intestinal microbiota play a significant role in the pathogenesis of psoriasis. Dysbiosis may cause disruption of the intestinal barrier, which contributes to immune activation by translocation of microbial antigens and metabolites. Intestinal fatty acid binding protein (I-FABP) serves as a biomarker of enterocyte damage. The aim of this study was to investigate clinical and metabolic factors affecting plasma concentration of I-FABP in patients with psoriasis. Eighty patients with psoriasis and 40 control subjects were enrolled in the study. Serum I-FABP (243.00 (108.88–787.10) vs. 114.38 (51.60–241.60) pg/ml, p < 0.001) and neutrophil to lymphocyte ratio (NLR; 2.59 (1.96–3.09) vs. 1.72 (1.36–47 2.11), p < 0.01) were significantly increased in patients with psoriasis compared to controls. A significant positive correlation was found between I-FABP and body mass index (BMI) (r = 0.82, p < 0.001), Psoriasis Area Severity Index (PASI) (r = 0.78, p < 0.001) and neutrophil to lymphocyte ratio (NLR) (r = 0.24, p < 0.001). Rising quartiles of I-FABP were associated with increasing values of BMI, PASI and NLR. The results of the logistic regression model confirmed an increased risk of higher disease severity with I-FABP concentration – odds ratio 3.34 per 100 pg/mL I-FABP increase. In conclusion, intestinal integrity in patients with psoriasis is affected by obesity, severity of the disease and systemic inflammation. The modulation of gut barrier may represent a new therapeutic approach for psoriasis.

Background: An increasing amount of evidence suggests an association between increased intestinal permeability and the pathogenesis of chronic inflammatory diseases. However, the clinical significance of gut barrier dysfunction in psoriasis remains to be established. Objective: To evaluate whether there are differences in disease activity, the severity of gastrointestinal symptoms and the blood concentration of bacterial metabolites in psoriatic patients with a normal and altered intestinal barrier. Patients and Methods: Gut barrier integrity was assessed with the serum concentrations of claudin-3, a modulator of intestinal tight junctions and an intestinal fatty acid-binding protein, a marker of enterocyte damage. Gastrointestinal symptoms were evaluated with a validated questionnaire. The concentration of trimethylamine N-oxide (TMAO), a gut microbiota-associated metabolite, was measured with high-performance liquid chromatography. Results: One hundred and fourteen patients with psoriasis were finally enrolled in the study – 68 with an altered gut barrier and 46 with a properly functioning intestinal barrier. Patients with an altered gut barrier showed a significantly higher score in the Gastrointestinal Symptom Rating Scale (3.20 vs 1.46, p< 0.001). Moreover, patients with psoriasis and a disrupted intestinal barrier demonstrated a higher disease activity (PASI: 19.7 vs 10.3, p< 0.001) and systemic inflammatory parameters (neutrophil-to-lymphocyte ratio: 2.86 vs 1.71, p< 0.001; C-reactive protein 3.76 vs 1.92; p< 0.05). The marker of bacterial translocation was significantly higher in psoriatic patients with damaged gut integrity (TMAO: 375.7± 51.9 vs 119.4± 27.5 ng/mL; p< 0.05). Conclusion: The altered gut barrier in psoriasis is associated with gastrointestinal symptoms, systemic inflammatory profile and the increased blood concentration of gut microbiota-derived metabolite – TMAO. Intestinal barrier modulation represents a new promising therapeutic approach.

Introduction Trimethylamine N-oxide (TMAO), a gut microbiota metabolite from dietary phosphatidylcholine, is involved in the pathogenesis of atherosclerosis and cardiovascular diseases. Psoriasis is associated with increased cardiovascular risk that is not captured by traditional biomarkers. The aim of the present study was to assess TMAO concentration in psoriasis and evaluate the relationship between TMAO and cardiovascular risk in psoriatic patients. Methods In 72 patients with psoriasis and 40 age- and sex-matched non-psoriatic controls, we evaluated fasting plasma TMAO, measured by high-performance liquid chromatography, and cardiovascular risk assessed by various scoring systems such as Framingham, QRISK2, AHA/ACC, and Reynolds risk scores. Results In patients with psoriasis, TMAO concentration was significantly higher than in the control group (195.68 [133.54–332.58] ng/ml versus 126.06 [84.29–156.88] ng/ml, respectively; p < 0.001). Plasma TMAO concentration was significantly correlated with age, total cholesterol, triglycerides, systolic and diastolic blood pressure. Furthermore, the receiver-operating characteristic (ROC) and multiple regression analysis showed that TMAO is an independent predictor of cardiovascular risk. Conclusion TMAO is a valuable candidate for biomarker and a translational link between dysbiosis and atherosclerosis in psoriasis.

Background: Systemic sclerosis (SSc) is a rare immune-mediated connective tissue disease characterized by fibrosis of the skin and internal organs, whose pathogenesis is not fully understood. Recent studies have revealed dysbiosis in patients with systemic sclerosis and have indicated the possible role of the microbiota and its metabolites in the pathogenesis of the disease. Trimethylamine N-oxide (TMAO) is a compound produced by dysbiotic microbiota observed at higher concentrations in several autoimmune diseases. Objective: To determine concentrations of the bacteria-derived metabolite TMAO in patients with systemic sclerosis and to assess possible correlation between TMAO and a specific manifestation of the disease. Patients and Methods: The study included 63 patients with SSc and 47 matched control subjects. The concentration of TMAO was measured with high-performance liquid chromatography. Results: Plasma TMAO level was significantly increased in patients with SSc (283.0 [188.5– 367.5] ng/mL versus 205.5 [101.0– 318.0] ng/mL; p < 0.01). An increased concentration of TMAO was observed in patients with concomitant interstitial lung disease (ILD) (302.0 ng/mL [212.0– 385.5] ng/mL versus 204.0 [135.5– 292.0] ng/mL; p < 0.01) and esophageal dysmotility (289.75 [213.75– 387.5] ng/mL versus 209.5 ng/mL [141.5– 315.0] ng/mL; p < 0.05) compared to patients without these complications. Furthermore, TMAO concentration exhibited significant correlation with markers of heart involvement (left ventricle ejection fraction, NT-proBNP), marker of ILD severity and Scleroderma Clinical Trials Consortium Damage Index. Conclusion: The concentration of TMAO, gut microbiota-associated metabolite, is increased in systemic sclerosis, particularly in patients with advanced organ involvement. This is the first study evaluating plasma TMAO in systemic sclerosis. Bacterial metabolites may be a link between dysbiosis and organ involvement in the course of the disease. Modulation of gut bacterial-derived metabolites may represent a new therapeutic approach in the management of systemic sclerosis.