Comprehensive multi-omics analysis reveals the core role of glycerophospholipid metabolism in rheumatoid arthritis development
Abstract Objectives Rheumatoid arthritis (RA) is a chronic autoimmune disease with complex causes and recurrent attacks that can easily develop into chronic arthritis and eventually lead to joint deformity. Our study aims to elucidate potential mechanism among control, new-onset RA (NORA) and chroni...
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13075-023-03208-2 |
| _version_ | 1797388141722599424 |
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| author | Congcong Jian Lingli Wei Tong Wu Shilin Li Tingting Wang Jianghua Chen Shengjia Chang Jie Zhang Binhan He Jianhong Wu Jiang Su Jing Zhu Min Wu Yan Zhang Fanxin Zeng |
| author_facet | Congcong Jian Lingli Wei Tong Wu Shilin Li Tingting Wang Jianghua Chen Shengjia Chang Jie Zhang Binhan He Jianhong Wu Jiang Su Jing Zhu Min Wu Yan Zhang Fanxin Zeng |
| author_sort | Congcong Jian |
| collection | DOAJ |
| description | Abstract Objectives Rheumatoid arthritis (RA) is a chronic autoimmune disease with complex causes and recurrent attacks that can easily develop into chronic arthritis and eventually lead to joint deformity. Our study aims to elucidate potential mechanism among control, new-onset RA (NORA) and chronic RA (CRA) with multi-omics analysis. Methods A total of 113 RA patients and 75 controls were included in our study. Plasma and stool samples were obtained for 16S rRNA sequencing, internally transcribed spacer (ITS) sequencing and metabolomics analysis. And PBMCs were obtained for RNA sequencing. We used three models, logistic regression, least absolute shrinkage and selection operator (LASSO), and random forest, respectively, to distinguish NORA from CRA, and finally we validated model performance using an external cohort of 26 subjects. Results Our results demonstrated intestinal flora disturbance in RA development, with significantly increased abundance of Escherichia-Shigella and Proteobacteria in NORA. We also found that the diversity was significantly reduced in CRA compared to NORA through fungi analysis. Moreover, we identified 29 differential metabolites between NORA and CRA. Pathway enrichment analysis revealed significant dysregulation of glycerophospholipid metabolism and phenylalanine metabolism pathways in RA patients. Next, we identified 40 differentially expressed genes between NORA and CRA, which acetylcholinesterase (ACHE) was the core gene and significantly enriched in glycerophospholipid metabolism pathway. Correlation analysis showed a strong negatively correlation between glycerophosphocholine and inflammatory characteristics. Additionally, we applied three approaches to develop disease classifier models that were based on plasma metabolites and gut microbiota, which effectively distinguished between new-onset and chronic RA patients in both discovery cohort and external validation cohort. Conclusions These findings revealed that glycerophospholipid metabolism plays a crucial role in the development and progression of RA, providing new ideas for early clinical diagnosis and optimizing treatment strategies. |
| first_indexed | 2024-03-08T22:36:33Z |
| format | Article |
| id | doaj.art-8bbbd1653c134899b9e4f6e657052e0f |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-03-08T22:36:33Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-8bbbd1653c134899b9e4f6e657052e0f2023-12-17T12:25:57ZengBMCArthritis Research & Therapy1478-63622023-12-0125111410.1186/s13075-023-03208-2Comprehensive multi-omics analysis reveals the core role of glycerophospholipid metabolism in rheumatoid arthritis developmentCongcong Jian0Lingli Wei1Tong Wu2Shilin Li3Tingting Wang4Jianghua Chen5Shengjia Chang6Jie Zhang7Binhan He8Jianhong Wu9Jiang Su10Jing Zhu11Min Wu12Yan Zhang13Fanxin Zeng14School of Basic Medical Science, Chengdu University of Traditional Chinese MedicineDepartment of Rheumatology and Immunology, Dazhou Central HospitalDepartment of Rheumatology and Immunology, Sichuan Provincial People’s HospitalDepartment of Clinical Research Center, Dazhou Central HospitalDepartment of Rheumatology and Immunology, Dazhou Central HospitalInstitute of Basic Medicine and Forensic Medicine, North Sichuan Medical CollegeShantou University Medical College, Shantou UniversityDepartment of Clinical Research Center, Dazhou Central HospitalDepartment of Clinical Research Center, Dazhou Central HospitalDepartment of Rheumatology and Immunology, Dazhou Central HospitalDepartment of Rheumatology and Immunology, Sichuan Provincial People’s HospitalDepartment of Rheumatology and Immunology, Sichuan Provincial People’s HospitalHuaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan UniversityLung Cancer Center of West China Hospital, Sichuan UniversitySchool of Basic Medical Science, Chengdu University of Traditional Chinese MedicineAbstract Objectives Rheumatoid arthritis (RA) is a chronic autoimmune disease with complex causes and recurrent attacks that can easily develop into chronic arthritis and eventually lead to joint deformity. Our study aims to elucidate potential mechanism among control, new-onset RA (NORA) and chronic RA (CRA) with multi-omics analysis. Methods A total of 113 RA patients and 75 controls were included in our study. Plasma and stool samples were obtained for 16S rRNA sequencing, internally transcribed spacer (ITS) sequencing and metabolomics analysis. And PBMCs were obtained for RNA sequencing. We used three models, logistic regression, least absolute shrinkage and selection operator (LASSO), and random forest, respectively, to distinguish NORA from CRA, and finally we validated model performance using an external cohort of 26 subjects. Results Our results demonstrated intestinal flora disturbance in RA development, with significantly increased abundance of Escherichia-Shigella and Proteobacteria in NORA. We also found that the diversity was significantly reduced in CRA compared to NORA through fungi analysis. Moreover, we identified 29 differential metabolites between NORA and CRA. Pathway enrichment analysis revealed significant dysregulation of glycerophospholipid metabolism and phenylalanine metabolism pathways in RA patients. Next, we identified 40 differentially expressed genes between NORA and CRA, which acetylcholinesterase (ACHE) was the core gene and significantly enriched in glycerophospholipid metabolism pathway. Correlation analysis showed a strong negatively correlation between glycerophosphocholine and inflammatory characteristics. Additionally, we applied three approaches to develop disease classifier models that were based on plasma metabolites and gut microbiota, which effectively distinguished between new-onset and chronic RA patients in both discovery cohort and external validation cohort. Conclusions These findings revealed that glycerophospholipid metabolism plays a crucial role in the development and progression of RA, providing new ideas for early clinical diagnosis and optimizing treatment strategies.https://doi.org/10.1186/s13075-023-03208-2Rheumatoid arthritisMulti-omicsNew-onset RAChronic RA |
| spellingShingle | Congcong Jian Lingli Wei Tong Wu Shilin Li Tingting Wang Jianghua Chen Shengjia Chang Jie Zhang Binhan He Jianhong Wu Jiang Su Jing Zhu Min Wu Yan Zhang Fanxin Zeng Comprehensive multi-omics analysis reveals the core role of glycerophospholipid metabolism in rheumatoid arthritis development Arthritis Research & Therapy Rheumatoid arthritis Multi-omics New-onset RA Chronic RA |
| title | Comprehensive multi-omics analysis reveals the core role of glycerophospholipid metabolism in rheumatoid arthritis development |
| title_full | Comprehensive multi-omics analysis reveals the core role of glycerophospholipid metabolism in rheumatoid arthritis development |
| title_fullStr | Comprehensive multi-omics analysis reveals the core role of glycerophospholipid metabolism in rheumatoid arthritis development |
| title_full_unstemmed | Comprehensive multi-omics analysis reveals the core role of glycerophospholipid metabolism in rheumatoid arthritis development |
| title_short | Comprehensive multi-omics analysis reveals the core role of glycerophospholipid metabolism in rheumatoid arthritis development |
| title_sort | comprehensive multi omics analysis reveals the core role of glycerophospholipid metabolism in rheumatoid arthritis development |
| topic | Rheumatoid arthritis Multi-omics New-onset RA Chronic RA |
| url | https://doi.org/10.1186/s13075-023-03208-2 |
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