The correlation between gut metabolites and microbiota in patients with rheumatoid arthritis

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease that can cause cartilage and bone damage and lead to disability. The lack of early interventional therapy is closely associated with the increased disability rate of RA patients worldwide. This study aimed to investigate the role of fecal metabolisms and microbiomes in the pathogenesis of RA. Methods: A total of 46 RA patients and 9 healthy volunteers were enrolled in the study. Fecal samples were analyzed using microbiome (16S rRNA gene sequencing) and metabolomics (liquid chromatography-mass spectrometry, LC-MS) techniques. Cytokines are detected by the chemiluminescence immunoassay. These results were analyzed using bioinformatics, metabolomics, correlation analysis, and various other methods. Results: Significant differences were observed in the gut microbes and metabolites of RA patients compared to healthy controls (HC). The dominant intestinal flora in RA patients included Blautia, Oscillospira, and Coprococcus . Furthermore, multiple bacteria are associated with clinical indicators of RA. In particular, bile-philic bacteria were found to be significantly negatively correlated with IL-6, IL-10, and TNF-α. The predominant metabolites in the intestines of RA patients include Lysine-Proline peptides (Lys-Pro), Taurolithocholic Acid Sulfate, L-Leucine, etc, which are highly significantly correlated with clinical indicators and cytokines of RA, especially leucine, which may act through the mechanistic target of rapamycin (mTOR) signaling pathway. Conclusions: These findings provided substantial evidence indicating a novel interaction between the gut microbiome and metabolites, which contributed to clinical indicators and cytokines in RA patients, and L-leucine was identified as a potential diagnostic biomarker for RA progression.