Association Between Human Metabolomics and Rheumatoid Arthritis: A Systematic Review and Meta-analysis.

Objective: The underdiagnosis and inadequate treatment of rheumatoid arthritis (RA) can be attributed to the various clinical manifestations presented by patients. To address this concern, we conducted an extensive review and meta-analysis, focusing on RA-related metabolites.

Methods: A comprehensive literature search was conducted in PubMed, the Cochrane Library, Web of Science, and Embase to identify relevant studies published up to October 5, 2022. The quality of the included articles was evaluated and, subsequently, a meta-analysis was conducted using Review Manager software to analyze the association between metabolites and RA.

Results: Forty nine studies met the inclusion criteria for the systematic review, and six of these studies were meta-analyzed to evaluate the association between 28 reproducible metabolites and RA. The results indicated that, compared to controls, the levels of histidine (RoM = 0.83, 95% CI = 0.79-0.88, I = 0%), asparagine (RoM = 0.83, 95% CI = 0.75-0.91, I = 0%), methionine (RoM = 0.82, 95% CI = 0.69-0.98, I = 85%), and glycine (RoM = 0.81, 95% CI = 0.67-0.97, I = 68%) were significantly lower in RA patients, while hypoxanthine levels (RoM = 1.14, 95% CI = 1.09-1.19, I = 0%) were significantly higher.

Conclusion: This study identified histidine, methionine, asparagine, hypoxanthine, and glycine as significantly correlated with RA, thus offering the potential for the advancement of biomarker discovery and the elucidation of disease mechanisms in RA.