评估托法西提尼布在炎症性肠病中对肠道微生物群的影响
Alessia Favaron1, Nannapat Sangfuang1, Laura E McCoubrey2
1UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.
托法西提尼酸盐是一种简氏激酶 (JAK) 抑制剂,在炎症性肠病 (IBD) 模型中没有显著改变肠道微生物群功能. 然而,它降低了炎症标志物,表明通过肠道代谢物中介的潜在抗炎作用.
科学领域:
- 胃肠道学和免疫学
- 微生物组研究 微生物组研究
- 药理学 药理学是指药理学的学科.
背景情况:
- 炎症性肠病 (IBD) 涉及肠道微生物群失调和表皮屏障功能受损.
- 托法西替尼酸盐 (一种Janus激酶 (JAK) 抑制剂) 已被批准用于IBD,但其对肠道微生物群的影响尚未完全理解.
研究的目的:
- 研究托法西提尼布对人类肠道微生物群组成,发酵和代谢活动的影响.
- 在IBD背景下评估托法西替尼对表皮免疫调节和屏障完整性的影响.
主要方法:
- 利用了一个短期的人类结肠模型 (ProDigest,BE) 与克罗恩病捐赠者的微生物群.
- 采用Caco-2/THP1共同培养系统来评估上皮质反应.
- 分析了微生物组成,发酵/代谢活性,以及治疗后的化学/细胞水平.
主要成果:
- 托法西替尼不显著改变微生物群组成或整体发酵/代谢活动.
- 该药物在特定的捐赠者中持续降低了促炎性化学因子 (CXCL10,MCP-1) 和IL-6.
- 证明了针对上皮细胞的向免疫调节作用.
结论:
- 托法西替尼对肠道微生物群功能的影响很小,但可能通过微生物群衍生代谢物产生抗炎作用.
- ProDigest模型是研究IBD中微生物组与药物相互作用的宝贵平台.
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