Dysregulation of Bile Acids, Lipids, and Nucleotides in Psoriatic Arthritis Revealed by Unbiased Profiling of Serum Metabolites.
Arthritis Rheumatol
; 75(1): 53-63, 2023 01.
Article
en En
| MEDLINE
| ID: mdl-35818333
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Psoriasis
/
Artritis Psoriásica
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Arthritis Rheumatol
Año:
2023
Tipo del documento:
Article