Wang Xin, Sun Chao, Yang Xinmeng, Xu Guixia, Pei Lijia, Tang Lin, Xu Shengqian, Xie Changhao
Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230000, China.
Department of Rheumatology and Immunology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233004, China.
Clin Rheumatol. 2025 May 29. doi: 10.1007/s10067-025-07467-z.
To explore the role of gut microbiota and plasma metabolites in the therapeutic mechanism of tofacitinib in ankylosing spondylitis (AS).
Ten AS patients and ten matched healthy controls (HC) were enrolled in this study. 16S rRNA sequencing and LC-MS profiling was conducted to investigate the gut microbiota and plasma metabolite before and after tofacitinib therapy. An AS mouse model was established to validate the effect of tofacitinib in vivo via H&E staining, western blot, and ELISA.
Tofacitinib improved clinical symptoms in AS patients. Microbiota analysis revealed Microbiota analysis revealed reduced α-diversity (ACE, Chao1) and altered community structure in AS patients compared to HC, which partially normalized post-treatment. LEfSe identified 84 taxa biomarkers; Barnesiella, Coprobacter, Lachnospira, and Lactobacillus tended to return to normal after tofacitinib treatment. Plasma metabolomics uncovered 3 key metabolies, including choline metabolism, glycerophospholipid metabolism, and phenylalanine metabolism. Spearman analysis revealed that the gut microbiota were closely related to the changes in differential plasma metabolites. Combinated tofacitinib and trichostatin therapy attenuated inflammation, restored metabolism caused by AS in mice in vivo.
AS patients suffer from dysbiosis of gut microbiota, and the mechanism of tofacitinib treatment of AS may be related to the modulation of gut microbiota and alteration of plasma metabolites. Key Points • Tofacitinib improves clinical symptoms in patients with AS. • Tofacitinib regulates gut microbiota in AS patients. • Tofacitinib regulates plasma metabolites in patients with AS. • Tofacitinib regulates the choline metabolism.
探讨肠道微生物群和血浆代谢物在托法替布治疗强直性脊柱炎（AS）的作用机制。
本研究纳入10例AS患者和10例匹配的健康对照（HC）。采用16S rRNA测序和液相色谱-质谱联用分析技术，研究托法替布治疗前后的肠道微生物群和血浆代谢物。建立AS小鼠模型，通过苏木精-伊红染色、蛋白质免疫印迹法和酶联免疫吸附测定法验证托法替布在体内的作用效果。
托法替布改善了AS患者的临床症状。微生物群分析显示，与HC相比，AS患者的α多样性（ACE、Chao1）降低，群落结构改变，治疗后部分恢复正常。线性判别分析效应大小（LEfSe）鉴定出84个分类生物标志物；托法替布治疗后，Barnesiella菌属、粪杆菌属、毛螺菌属和乳杆菌属趋于恢复正常。血浆代谢组学发现了3种关键代谢物，包括胆碱代谢、甘油磷脂代谢和苯丙氨酸代谢。Spearman分析显示，肠道微生物群与血浆差异代谢物的变化密切相关。托法替布与曲古抑菌素联合治疗可减轻炎症，恢复AS小鼠体内由疾病引起的代谢异常。
AS患者存在肠道微生物群失调，托法替布治疗AS的机制可能与调节肠道微生物群和改变血浆代谢物有关。要点 • 托法替布改善AS患者的临床症状。 • 托法替布调节AS患者的肠道微生物群。 • 托法替布调节AS患者的血浆代谢物。 • 托法替布调节胆碱代谢。
