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Altered fecal metabolomics and potential biomarkers of psoriatic arthritis differing from rheumatoid arthritis

ABSTRACT: Psoriatic arthritis (PsA) is a chronic inflammatory joint disease, and the diagnosis is quite difficult due to the unavailability of reliable clinical markers. This study aimed to investigate the fecal metabolites in PsA by comparison with rheumatoid arthritis (RA), and to identify potential diagnostic biomarkers for PsA. The metabolic profiles of the fecal samples from 27 PsA and 29 RA patients as well as 36 healthy controls (HCs) were performed on ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). And differentially altered metabolites were screened and assessed using multivariate analysis for exploring the potential biomarkers of PsA. The results showed that 154 fecal metabolites were significantly altered in PsA patients when compared with HCs, and 45 metabolites were different when compared with RA patients. A total of 14 common differential metabolites could be defined as candidate biomarkers. Furthermore, a support vector machines (SVM) model was performed to distinguish PsA from RA patients and HCs, and 5 fecal metabolites, including α/β-turmerone, glycerol 1-hexadecanoate, dihydrosphingosine, pantothenic acid and glutamine, were determined as biomarkers for PsA. Through the metabolic pathways analysis, we found that the abnormality of amino acid metabolism, bile acid metabolism and lipid metabolism might contribute to the occurrence and development of PsA. In summary, our research provided ideas for the early diagnosis and treatment of PsA by identifying fecal biomarkers and analyzing metabolic pathways.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

SUBMITTER: Nan Wang

PROVIDER: MTBLS4206 | MetaboLights | 2022-02-23

REPOSITORIES: MetaboLights

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Project description:Rheumatoid arthritis (RA) is an inflammatory joint disorder that results in progressive joint damage when insufficiently treated. In order to prevent joint destruction and functional disability in RA, early diagnosis and initiation of appropriate treatment with Disease-Modifying Antirheumatic Drugs (DMARDs) is needed. However, in daily clinical practice, patients may initially display symptoms of arthritis that do not fulfil the classification criteria for a definite diagnosis of RA, or any other joint disease, a situation called “Undifferentiated Arthritis” (UA). Out of the patients with UA, 30 to 50% usually develop RA, and early identification of these remains a challenge. At the present time, although several risk factors associated with the development of RA have been identified (6-9), a model that reliably predicts the probability of evolution of UA into RA in individual patients is lacking. In order to better identify early RA patients, an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) collaboration recently developed new classification criteria. Although these criteria are more sensitive, the risk of over-diagnosis is an important issue to consider, especially in very early disease. In this context, the present study explores the feasibility of a molecular diagnosis of arthritis, based on the identification of disease-specific transcriptomic profiles in synovial biopsies from patients with arthritis according to the underlying condition. In a previous study, we performed global analyses of gene expression in synovial biopsies from patients with RA, Systemic Lupus Erythematosus (SLE) and Osteoarthritis (OA), using high-density oligonucleotide spotted microarrays. We found that the gene expression profiles are strikingly different according to the underlying condition. Thus, the majority of the genes up-regulated in SLE are type I Interferon-inducible genes, as compared with the up-regulation genes involved in T cell and B cell activation in RA, and in extracellular matrix homeostasis in OA. Based on these results, similar analyses were performed in synovial biopsies from patients with seronegative arthritis (SA) and microcrystalline arthritis (MIC), in order to identify disease-specific molecular signatures.

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Altered fecal metabolomics and potential biomarkers of psoriatic arthritis differing from rheumatoid arthritis

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