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

• Published in: Joint, bone, spine : revue du rhumatisme bone, spine : revue du rhumatisme, 2022-11, Vol.89 (6), p.105438-105438, Article 105438
• Main Authors: Huang, Qian, Su, Jiang, Zhang, Weihua, Chang, Shengjia, Li, Silin, Zhou, Jun, Zhang, Jie, Li, Xue, Huang, Hong, Wang, Tingting, Jiang, Xuejun, Wu, Jianhong, Zhu, Jing, Zeng, Fanxin
• Format: Article
• Language: English
• Subjects: Arginine; Arthritis, Rheumatoid; Bacteria; Biomarkers; Bone destruction; Fungi; Humans; Metabolites; Rheumatoid arthritis; RNA, Ribosomal, 16S
• ISSN: 1297-319X; 1778-7254
• DOI: 10.1016/j.jbspin.2022.105438

•Seven metabolites were selected for classifying the BD(+) and BD(−) groups with moderate accuracy (AUC=0.71).•The changed 4 bacteria and 12 fungi yielded accuracy (AUC=0.74 and AUC=0.87, respectively) for the two groups.•Nontargeted LC-MS, 16S rRNA, and ITS highlighted a novel link among the metabolites, bacteria, and fungi. 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.