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

Objectives: 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.

Methods: 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).

Results: 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.

Conclusions: 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.