Gut dysbiosis is associated with difficult-to-treat rheumatoid arthritis
BackgroundDifficult-to-treat rheumatoid arthritis (D2T RA) refers to a subset of patients who fail to achieve adequate disease control after the use of two or more biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) with different mechanisms of action, while maintaini...
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2025-01-01
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| author | Patricia Ruiz-Limón Patricia Ruiz-Limón Patricia Ruiz-Limón Natalia Mena-Vázquez Natalia Mena-Vázquez Isabel Moreno-Indias Isabel Moreno-Indias Isabel Moreno-Indias Jose Manuel Lisbona-Montañez Jose Manuel Lisbona-Montañez Jose Manuel Lisbona-Montañez Arkaitz Mucientes Arkaitz Mucientes Sara Manrique-Arija Sara Manrique-Arija Sara Manrique-Arija Rocío Redondo-Rodriguez Rocío Redondo-Rodriguez Laura Cano-García Laura Cano-García Francisco J. Tinahones Francisco J. Tinahones Francisco J. Tinahones Francisco J. Tinahones Antonio Fernández-Nebro Antonio Fernández-Nebro Antonio Fernández-Nebro |
| author_facet | Patricia Ruiz-Limón Patricia Ruiz-Limón Patricia Ruiz-Limón Natalia Mena-Vázquez Natalia Mena-Vázquez Isabel Moreno-Indias Isabel Moreno-Indias Isabel Moreno-Indias Jose Manuel Lisbona-Montañez Jose Manuel Lisbona-Montañez Jose Manuel Lisbona-Montañez Arkaitz Mucientes Arkaitz Mucientes Sara Manrique-Arija Sara Manrique-Arija Sara Manrique-Arija Rocío Redondo-Rodriguez Rocío Redondo-Rodriguez Laura Cano-García Laura Cano-García Francisco J. Tinahones Francisco J. Tinahones Francisco J. Tinahones Francisco J. Tinahones Antonio Fernández-Nebro Antonio Fernández-Nebro Antonio Fernández-Nebro |
| author_sort | Patricia Ruiz-Limón |
| collection | DOAJ |
| description | BackgroundDifficult-to-treat rheumatoid arthritis (D2T RA) refers to a subset of patients who fail to achieve adequate disease control after the use of two or more biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) with different mechanisms of action, while maintaining active inflammatory disease. This presents a therapeutic challenge and highlights the need to explore contributing factors such as the potential role of the gut microbiota. Therefore, the aim of this study was to analyze the gut microbiota and inflammation in patients with D2T RA in comparison to patients with easy-to-treat RA (E2T RA).ObjectiveTo analyze the gut microbiota and inflammation in patients with D2T RA.MethodsWe performed an observational study of a prospective cohort between 2007 and 2011 and analyzed the gut microbiota. In 2022, we identified 2 extreme patient phenotypes: (1) D2T RA, which was defined as failure of ≥2 biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) (with different mechanisms of action) plus signs of active disease; and (2) easy-to-treat RA (E2T RA), i.e., stable disease managed with a single treatment. The gut microbiota was analyzed using 16S rRNA gene sequencing; bioinformatics analysis was performed using QIIME2, and its functionality was inferred through PICRUSt. We recorded data on clinical findings, inflammation, and cytokines. A Cox multivariate analysis was performed to identify factors related to D2T RA.ResultsThe study population comprised 39 patients: 13 (33%) with D2T RA and 26 (66%) with E2T RA. The families Lachnospiraceae and Pasteurellaceae, and their genera Coprococcus and Haemophilus were more abundant in E2T RA patients, while the genus Megasphaera was more abundant in D2T RA patients. The Firmicutes/Bacteroidetes ratio decreased in D2T RA patients. The metabolic profile of the gut microbiota was characterized by differences in Degradation/Utilization/Assimilation pathway and the Biosynthesis pathway. The factors associated with D2T RA were inflammatory activity according to DAS28-ESR (HR, 2.649; p = 0.013), prednisone (HR, 3.794; p = 0.008), and the Firmicutes/Bacteroidetes ratio (HR, 0.288; p = 0.033).ConclusionThe composition of the gut microbiota of patients with D2T RA differed from that of E2T RA patients, as did the metabolic pathways. |
| format | Article |
| id | doaj-art-b74b32e1a4a64281a1059b4fab1d6e6d |
| institution | Kabale University |
| issn | 2296-858X |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-b74b32e1a4a64281a1059b4fab1d6e6d2025-01-16T15:27:42ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-01-011110.3389/fmed.2024.14977561497756Gut dysbiosis is associated with difficult-to-treat rheumatoid arthritisPatricia Ruiz-Limón0Patricia Ruiz-Limón1Patricia Ruiz-Limón2Natalia Mena-Vázquez3Natalia Mena-Vázquez4Isabel Moreno-Indias5Isabel Moreno-Indias6Isabel Moreno-Indias7Jose Manuel Lisbona-Montañez8Jose Manuel Lisbona-Montañez9Jose Manuel Lisbona-Montañez10Arkaitz Mucientes11Arkaitz Mucientes12Sara Manrique-Arija13Sara Manrique-Arija14Sara Manrique-Arija15Rocío Redondo-Rodriguez16Rocío Redondo-Rodriguez17Laura Cano-García18Laura Cano-García19Francisco J. Tinahones20Francisco J. Tinahones21Francisco J. Tinahones22Francisco J. Tinahones23Antonio Fernández-Nebro24Antonio Fernández-Nebro25Antonio Fernández-Nebro26The Biomedical Research Institute of Malaga and Platform in Nanomedicine (IBIMA BIONAND Platform), Málaga, SpainUnidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Málaga, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, SpainThe Biomedical Research Institute of Malaga and Platform in Nanomedicine (IBIMA BIONAND Platform), Málaga, SpainUGC de Reumatología, Hospital Regional Universitario de Málaga, Málaga, SpainThe Biomedical Research Institute of Malaga and Platform in Nanomedicine (IBIMA BIONAND Platform), Málaga, SpainUnidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Málaga, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, SpainThe Biomedical Research Institute of Malaga and Platform in Nanomedicine (IBIMA BIONAND Platform), Málaga, SpainUGC de Reumatología, Hospital Regional Universitario de Málaga, Málaga, SpainDepartamento de Medicina. Universidad de Málaga, Málaga, SpainThe Biomedical Research Institute of Malaga and Platform in Nanomedicine (IBIMA BIONAND Platform), Málaga, SpainUGC de Reumatología, Hospital Regional Universitario de Málaga, Málaga, SpainThe Biomedical Research Institute of Malaga and Platform in Nanomedicine (IBIMA BIONAND Platform), Málaga, SpainUGC de Reumatología, Hospital Regional Universitario de Málaga, Málaga, SpainDepartamento de Medicina. Universidad de Málaga, Málaga, SpainThe Biomedical Research Institute of Malaga and Platform in Nanomedicine (IBIMA BIONAND Platform), Málaga, SpainUGC de Reumatología, Hospital Regional Universitario de Málaga, Málaga, SpainThe Biomedical Research Institute of Malaga and Platform in Nanomedicine (IBIMA BIONAND Platform), Málaga, SpainUGC de Reumatología, Hospital Regional Universitario de Málaga, Málaga, SpainThe Biomedical Research Institute of Malaga and Platform in Nanomedicine (IBIMA BIONAND Platform), Málaga, SpainUnidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Málaga, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, SpainDepartamento de Medicina. Universidad de Málaga, Málaga, SpainThe Biomedical Research Institute of Malaga and Platform in Nanomedicine (IBIMA BIONAND Platform), Málaga, SpainUGC de Reumatología, Hospital Regional Universitario de Málaga, Málaga, SpainDepartamento de Medicina. Universidad de Málaga, Málaga, SpainBackgroundDifficult-to-treat rheumatoid arthritis (D2T RA) refers to a subset of patients who fail to achieve adequate disease control after the use of two or more biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) with different mechanisms of action, while maintaining active inflammatory disease. This presents a therapeutic challenge and highlights the need to explore contributing factors such as the potential role of the gut microbiota. Therefore, the aim of this study was to analyze the gut microbiota and inflammation in patients with D2T RA in comparison to patients with easy-to-treat RA (E2T RA).ObjectiveTo analyze the gut microbiota and inflammation in patients with D2T RA.MethodsWe performed an observational study of a prospective cohort between 2007 and 2011 and analyzed the gut microbiota. In 2022, we identified 2 extreme patient phenotypes: (1) D2T RA, which was defined as failure of ≥2 biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) (with different mechanisms of action) plus signs of active disease; and (2) easy-to-treat RA (E2T RA), i.e., stable disease managed with a single treatment. The gut microbiota was analyzed using 16S rRNA gene sequencing; bioinformatics analysis was performed using QIIME2, and its functionality was inferred through PICRUSt. We recorded data on clinical findings, inflammation, and cytokines. A Cox multivariate analysis was performed to identify factors related to D2T RA.ResultsThe study population comprised 39 patients: 13 (33%) with D2T RA and 26 (66%) with E2T RA. The families Lachnospiraceae and Pasteurellaceae, and their genera Coprococcus and Haemophilus were more abundant in E2T RA patients, while the genus Megasphaera was more abundant in D2T RA patients. The Firmicutes/Bacteroidetes ratio decreased in D2T RA patients. The metabolic profile of the gut microbiota was characterized by differences in Degradation/Utilization/Assimilation pathway and the Biosynthesis pathway. The factors associated with D2T RA were inflammatory activity according to DAS28-ESR (HR, 2.649; p = 0.013), prednisone (HR, 3.794; p = 0.008), and the Firmicutes/Bacteroidetes ratio (HR, 0.288; p = 0.033).ConclusionThe composition of the gut microbiota of patients with D2T RA differed from that of E2T RA patients, as did the metabolic pathways.https://www.frontiersin.org/articles/10.3389/fmed.2024.1497756/fullrheumatoid arthritisgut microbiotadisease modifying antirheumatic drugsFirmicutes/Bacteroidetes ratioinflammation |
| spellingShingle | Patricia Ruiz-Limón Patricia Ruiz-Limón Patricia Ruiz-Limón Natalia Mena-Vázquez Natalia Mena-Vázquez Isabel Moreno-Indias Isabel Moreno-Indias Isabel Moreno-Indias Jose Manuel Lisbona-Montañez Jose Manuel Lisbona-Montañez Jose Manuel Lisbona-Montañez Arkaitz Mucientes Arkaitz Mucientes Sara Manrique-Arija Sara Manrique-Arija Sara Manrique-Arija Rocío Redondo-Rodriguez Rocío Redondo-Rodriguez Laura Cano-García Laura Cano-García Francisco J. Tinahones Francisco J. Tinahones Francisco J. Tinahones Francisco J. Tinahones Antonio Fernández-Nebro Antonio Fernández-Nebro Antonio Fernández-Nebro Gut dysbiosis is associated with difficult-to-treat rheumatoid arthritis Frontiers in Medicine rheumatoid arthritis gut microbiota disease modifying antirheumatic drugs Firmicutes/Bacteroidetes ratio inflammation |
| title | Gut dysbiosis is associated with difficult-to-treat rheumatoid arthritis |
| title_full | Gut dysbiosis is associated with difficult-to-treat rheumatoid arthritis |
| title_fullStr | Gut dysbiosis is associated with difficult-to-treat rheumatoid arthritis |
| title_full_unstemmed | Gut dysbiosis is associated with difficult-to-treat rheumatoid arthritis |
| title_short | Gut dysbiosis is associated with difficult-to-treat rheumatoid arthritis |
| title_sort | gut dysbiosis is associated with difficult to treat rheumatoid arthritis |
| topic | rheumatoid arthritis gut microbiota disease modifying antirheumatic drugs Firmicutes/Bacteroidetes ratio inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2024.1497756/full |
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