Propionate restores disturbed gut microbiota induced by methotrexate in Rheumatoid Arthritis: From clinic to experiments

Objective: Gut toxicity of methotrexate restricts its long-term clinical application in patients with rheumatoid arthritis (RA). However, the disturbed gut microbiota especially beneficial bacteria induced by methotrexate remain unclear, and the way to alleviate the disturbances is limited. The aim of present study was to elucidate the effects of methotrexate on gut microbiota in RA patients and collagen-induced-arthritis (CIA) rats, and to explore a way targeted for restoring gut microbiota. Methods: The gut microbiota including lactobacilli and bifidobacterial communities were analyzed by high-throughput sequencing of samples from RA patients and healthy controls (HCs), furthermore, propionate and butyrate were administrated to CIA rats to confirm the effects on gut microbiota. Results: The findings showed gut microbiota significantly altered, and bifidobacterial community was tolerant to methotrexate while lactobacilli community such as L. delbrueckii, L. manihotivorans and L. intestinalis species under-represented in RA samples. Propionate supplementation was significantly associated with the rebalance of gut microbiota especially lactobacilli species including L. acidophilus, L. intestinalis and L. amylovorus in CIA rats. Conclusion: Methotrexate disturbed gut microbiota and lactobacilli community in RA patients, and propionate supplementation contributed to normalize lactobacilli community in CIA rats. These findings suggested that propionate may be a potential alleviator for gut microbiota in RA patients treated with methotrexate