A Review of Metabolomic Profiling in Rheumatoid Arthritis: Bringing New Insights in Disease Pathogenesis, Treatment and Comorbidities

Abstract

Metabolomic analysis provides a wealth of information that can be predictive of distinctive phenotypes of pathogenic processes and has been applied to better understand disease development. Rheumatoid arthritis (RA) is an autoimmune disease with the establishment of chronic synovial inflammation that affects joints and peripheral tissues such as skeletal muscle and bone. There is a lack of useful disease biomarkers to track disease activity, drug response and follow-up in RA. In this review, we describe potential metabolic biomarkers that might be helpful in the study of RA pathogenesis, drug response and risk of comorbidities. TMAO (choline and trimethylamine oxide) and TCA (tricarboxylic acid) cycle products have been suggested to modulate metabolic profiles during the early stages of RA and are present systemically, which is a relevant characteristic for biomarkers. Moreover, the analysis of lipids such as cholesterol, FFAs and PUFAs may provide important information before disease onset to predict disease activity and treatment response. Regarding therapeutics, TNF inhibitors may increase the levels of tryptophan, valine, lysine, creatinine and alanine, whereas JAK/STAT inhibitors may modulate exclusively fatty acids. These observations indicate that different disease modifying antirheumatic drugs have specific metabolic profiles and can reveal differences between responders and non-responders. In terms of comorbidities, physical impairment represented by higher fatigue scores and muscle wasting has been associated with an increase in urea cycle, FFAs, tocopherols and BCAAs. In conclusion, synovial fluid, blood and urine samples from RA patients seem to provide critical information about the metabolic profile related to drug response, disease activity and comorbidities.

Urinary metabolomic biomarker candidates for skeletal muscle wasting in patients with rheumatoid arthritis

“…A recent review about metabolome analysis in RA patients published by our group described potential metabolic biomarkers that might be helpful in the study of RA pathogenesis, drug response and risk of comorbidities as cachexia and sarcopenia. As a conclusion presented, physical impairment represented by higher fatigue scores and muscle wasting has been associated with an increase in urea cycle, FFAs, tocopherols and BCAAs 43 . Our findings corroborate that isobutiric acid as an SCFAs can be involved in muscle degradation, beeing the ffirst study that correlates dimethyglicine and oxoisovalerate with muscle mass wasting.…”

“…As a conclusion presented, physical impairment represented by higher fatigue scores and muscle wasting has been associated with an increase in urea cycle, FFAs, tocopherols and BCAAs. 43 Our findings corroborate that isobutiric acid as an SCFAs can be involved in muscle degradation, beeing the ffirst study that correlates dimethyglicine and oxoisovalerate with muscle mass wasting.…”

The association between dietary intake of branched-chain amino acids and odds and severity of rheumatoid arthritis

“…The complexity of diet is probably another factor contributing to the contradictory ndings. The Diet combines numerous nutrients, which differ signi cantly between people and cultures [39].…”

Bacterial Metabolites: A Link between Gut Microbiota and Dermatological Diseases

“…The subjects characterized by high plasma TMAO levels have an elevated concentration of TNF, sTNF-R p75, and sTNF-R p55 [ 115 ]. Moreover, higher levels of TMAO in plasma are associated with overexpression of pro-inflammatory cytokines such as TNF, IL-6, and C-reactive protein, and decreased expression of anti-inflammatory cytokine IL-10 [ 15 , 116 , 117 , 118 , 119 ]. By induction of NLRP3 inflammasome activation, TMAO contributes to an increase in the levels of IL-1β and IL-18, which are crucial cytokines in various dermatological and rheumatological conditions [ 118 , 120 ].…”