Abstract Background Psoriasis is recognized as a systemic inflammatory disease associated with metabolic dysregulation. Understanding these metabolic changes may reveal biomarkers to elucidate disease mechanisms and predict comorbidities. While previous studies have identified psoriasis-associated metabolites, findings are often limited by sample sizes and lack validation. Objectives To identify circulating metabolites associated with psoriasis, including disease severity and psoriatic arthritis. Further, we investigated whether the metabolic signature was disease-specific compared to other immune-mediated inflammatory diseases (IMIDs). Methods We performed a cross-sectional analysis of 470,352 White/European individuals from the UK Biobank (n=453,428) and HUNT (n=16,924). Nuclear Magnetic Resonance spectroscopy was used to quantify metabolite levels, covering lipoprotein fractions and subfractions, fatty acids, and small-molecular metabolites. For each metabolite, we performed multivariable linear regression adjusting for age, sex, BMI, smoking status, and use of lipid-lowering medications. Results The metabolomic profile of psoriasis was largely consistent across the two populations. In the model adjusted for age and sex, 123 metabolic measures were associated with psoriasis. After full adjustment, only Glycoprotein acetyls (GlycA) remained associated with psoriasis (coefficient 95% CI: 0.09 0.07-0.11 in UK Biobank and 0.11 0.06-0.17 in HUNT). In HUNT, severe psoriasis exhibited more pronounced metabolic alterations compared to non-severe psoriasis. Across both populations, phenylalanine levels were highly elevated in psoriatic arthritis compared to cutaneous psoriasis (0.44 0.29-0.60 in UK Biobank and 0.47 0.28-0.67 in HUNT). In comparisons across IMIDs, atopic dermatitis and cutaneous-limited psoriasis exhibited milder metabolic alterations, and psoriasis in HUNT showed a distinct lipoprotein profile. Conclusions This large-scale study confirms metabolic alterations in individuals with psoriasis and highlights phenylalanine as a potential biomarker for joint involvement in psoriasis. The distinct metabolomic profile of psoriasis relative to other IMIDs suggests a potentially unique systemic profile. These findings offer a foundation for advancing biomarker research and mechanistic studies for psoriasis.
Arham et al. (Mon,) studied this question.