Dysregulation of Bile Acids, Lipids, and Nucleotides in Psoriatic Arthritis Revealed by Unbiased Profiling of Serum Metabolites

• Published in: Arthritis & rheumatology (Hoboken, N.J.) Vol. 75; no. 1; pp. 53 - 63
• Main Authors: Paine, Ananta, Brookes, Paul S., Bhattacharya, Soumyaroop, Li, Dongmei, De La Luz Garcia‐Hernandez, Maria, Tausk, Francisco, Ritchlin, Christopher
• Format: Journal Article
• Language: English
• Published: Boston, USA Wiley Periodicals, Inc 01.01.2023; Wiley Subscription Services, Inc
• Subjects: Amino Acids; Arthritis; Arthritis, Psoriatic - diagnosis; Bile; Bile acids; Bile Acids and Salts; Cell proliferation; Cross-Sectional Studies; Dysbacteriosis; Glutathione; Humans; Immune system; Inflammation; Leukotriene B4; Lipid metabolism; Lipids; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Metabolic disorders; Metabolism; Metabolites; Metabolomics; Microorganisms; Nucleotides; Psoriasis; Psoriatic arthritis; Purines; Pyrimidines; Skin diseases
• ISSN: 2326-5191; 2326-5205
• DOI: 10.1002/art.42288

Objective The transition from psoriasis to psoriatic arthritis (PsA) occurs in 20–30% of patients; however, the mechanisms underlying the emergence of musculoskeletal disease are not well understood. Metabolic disease is prevalent in psoriasis patients, but whether metabolic factors, other than obesity, increase arthritis risk in psoriasis patients is not known. This study was undertaken to investigate the link between metabolic changes and disease progression in psoriasis patients. Methods To characterize the metabolic alterations during the progression of arthritis in psoriasis patients, we analyzed cross‐sectional healthy controls and PsA samples and longitudinal psoriasis serum samples, before and after PsA onset. Nontargeted metabolomic profiling was performed using liquid chromatography mass spectrometry. Results We identified several serum metabolites that differed between PsA patients, psoriasis patients, and healthy controls. Differentially abundant bile acids, purines, pyrimidines, glutathione, lipids, and amino acid metabolites were noted in these 3 groups. We also noted differences between psoriasis patients who progressed and those who did not progress to PsA. Bile acid and butyrate levels were depressed in those who progressed to PsA compared to those who did not, and the level of inflammatory lipid mediators increased following PsA diagnosis. In particular, the combination of leukotriene B4 and glycoursodeoxycholic acid sulfate were sensitive and specific predictors of PsA progression. Conclusion We observed notable differences in bile acid, purine, lipid, and amino acid–derived metabolites, among the healthy controls, psoriasis patients, and PsA patients and identified changes during the transition from psoriasis to PsA. The decreased bile acid and butyrate levels and elevated guanine levels in psoriasis patients at risk for PsA were particularly striking and may reflect gut microbial dysbiosis and dysregulated hepatic metabolism, leading to altered proliferation of immune cells and enhanced cytokine expression.