Multi-omics analysis of biomarkers and molecular mechanism of rheumatoid arthritis with bone destruction

Our study aimed to elucidate the role of metabolites, bacteria, and fungi in rheumatoid arthritis (RA) patients with bone destruction (BD(+)) and identify some biomarkers to predicate bone progression of RA.Plasma metabolites of the 127 RA patients and 69 healthy controls were conducted by using nontargeted liquid chromatography-mass spectrometry (LC-MS). The gut bacteria and fungi were assessed by 16S rRNA and internal transcribed spacer (ITS).Compared with RA patients without bone destruction (BD(-)), some metabolites, bacteria, and fungi were altered in BD(+). Seven 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. Taking 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 affect the pathway related to L-arginine.Our nontargeted LC-MS, 16S rRNA, and ITS highlighted a novel link among the metabolites, bacteria, fungi, and pathology of BD(+), which could contribute to our understanding of the role of metabolites, bacteria, and fungi in BD(+) etiology and offered some novel biomarkers to predict the bone progression of RA.