Multi-omics Analysis of the Biomarkers and Molecular Mechanism of Rheumatoid Arthritis With Bone Destruction

Abstract

ObjectivesOur study aimed to elucidate the role of metabolites, bacteria, and fungi in rheumatoid arthritis (RA) patients with bone destruction (BD(+)) and find some biomarkers to predicate bone progression of RA.MethodsWe conducted plasma metabolites of the 127 RA patients and 69 healthy control by using nontargeted liquid chromatography-mass spectrometry (LC-MS), and the gut bacteria and fungi were assessed by 16S rRNA and internal transcribed spacer (ITS).ResultsCompared with RA patients without bone destruction (BD(-)), some metabolites, bacteria, and fungi altered in BD(+). Sever metabolites were selected as key metabolites for classifying the BD(+) and BD(-) groups with moderate accuracy (AUC=0.71). Metabolites-groups, metabolites-metabolites, and metabolites-clinical factors had a certain correlation, and 7 metabolites were enriched in glycerophospholipid metabolism and L-arginine and proline metabolism pathways. The bacteria and fungi of the BD(+) group showed significant differences in composition and function compared with BD(-) group. The changed 4 bacteria and 12 fungi yielded accuracy (AUC=0.74 and AUC=0.87, respectively) for the two groups. Taken 7 metabolites, 4 bacteria and 12 fungi as a panel for AUC analysis, an improved AUC of 0.99 significantly discriminated the two groups. The changed metabolites, gut bacteria, and fungi may affected the pathway related to L-arginine.ConclusionsOur nontargeted LC-MS, 16S rRNA, and ITS highlight a novel link among the metabolites, bacteria, fungi, and pathology of BD(+), which contributed to our understanding of the role of metabolites, bacteria, and fungi in BD(+) aetiology and offers some novel biomarkers to predict the bone progression of RA.