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.