Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation leading to cartilage damage, as well as extra-articular manifestations [1]. The prevalence of RA was estimated as 460 per 100,000 of the global population [2], being more prevalent in developed countries [3]. Pathogenesis of RA involves a plethora of mechanisms including T- and B-cell activation, macrophage and dendritic cell infiltration, ultimately leading to overproduction of autoantibodies, as well as proinflammatory cytokines [4]. Activation of the complement system also contributes to RA pathogenesis through promotion of inflammation and cytotoxicity [5]. Autoimmune inflammation, driven by these mechanisms, result in joint damage with the release of the products of cartilage degradation, which are used as biomarkers in RA-induced cartilage injury [6]. Cartilage oligomeric matrix protein (COMP) is an extracellular glycoprotein found in the extracellular matrix of the cartilage [7], being used as a biomarker of cartilage damage in RA [8]. Moreover, it has been shown that COMP also contributes to RA pathogenesis [9] at least partially through modulation of complement system activation [10].

Risk factors for RA include both modifiable and non-modifiable factors like sex, age, and genetics [3]. Modifiable factors include environmental influences including exposure to infectious agents, environmental and occupational pollutant exposure, cigarette smoking, obesity, low socio-economic status, etc. [11]. Nutrition and intestinal health are also considered as important factors of RA risk [3].

Recent studies have shown that gut dysbiosis is tightly associated with RA development [12]. However, certain contradictions in taxonomic characteristics of gut microbiota in RA patients exist [13]. Alterations in gut microbiota contribute to RA pathogenesis through impaired gut barrier function, modulation of immune responses, and alterations in bacterial metabolite production [14]. Specifically, microbial metabolites including lipopolysaccharide (LPS) and trimethylamine-N-oxide promote inflammatory response, thus contributing to RA pathogenesis [15]. Environmental factors including nutrient intake induce such dysbiosis, mediating their role in RA risk [16]. Although recent findings show the association of gut microbiota with inflammatory biomarkers in RA [17], its relationship to cartilage damage biomarkers is insufficiently studied.

Trace elements play a significant role in cartilage physiology, and alterations of trace element and mineral metabolism are involved in development of RA [18]. Meta-analysis of epidemiological findings demonstrate that RA patients are characterized by lower serum Zn and Se levels, while having higher circulating Cu concentrations. However, data on the concentration of other trace elements are inconsistent [19]. In addition, serum Cu, Zn, and Fe levels are associated with disease severity [20]. It has been also demonstrated that circulating trace element levels significantly correlate with biomarkers of inflammation, including C-reactive protein [21] and prostaglandin E2 [22]. However, data on the potential association between trace element and mineral metabolism and cartilage damage biomarkers in RA are lacking.

Along with the understanding of the role of trace elements and gut microbiota in RA development, recent findings show a tight relationship between metabolism of essential trace elements [23] like Zn [24], Se [25], or Mn [26] and gut microbiota. Single studies show a tight association between altered trace element metabolism and taxonomic and metabolic characteristics of gut microbiota in patients with Crohn's disease [27], autism spectrum disorder [28], gestational diabetes mellitus [29], and infertility [30]. At the same time, data on the potential interplay between trace element metabolism and gut microbiota, as well as their relationship to cartilage damage in RA patients are lacking.

Therefore, the objective of the present study was to evaluate serum trace element and mineral levels as well as taxonomic characteristics of gut microbiota and their association with cartilage damage in patients with RA.