Inflammatory bowel disease (IBD) mainly includes Crohn’s disease (CD) and ulcerative colitis (UC). Immune disorders play an essential role in the pathogenesis of these two IBDs, but the differences in the immune microenvironment of the colon and their underlying mechanisms remain poorly investigated. Here we examined the immunological features and metabolic microenvironment of untreated individuals with IBD by multiomics analyses. Modulation of CD-specific metabolites, particularly reduced selenium, can obviously shape type 1 T helper (Th1) cell differentiation, which is specifically enriched in CD. Selenium supplementation suppressed the symptoms and onset of CD and Th1 cell differentiation via selenoprotein W (SELW)-mediated cellular reactive oxygen species scavenging. SELW promoted purine salvage pathways and inhibited one-carbon metabolism by recruiting an E3 ubiquitin ligase, tripartite motif-containing protein 21, which controlled the stability of serine hydroxymethyltransferase 2. Our work highlights selenium as an essential regulator of T cell responses and potential therapeutic targets in CD.

炎症性肠病（IBD）主要包括克罗恩病（CD）和溃疡性结肠炎（UC）。免疫紊乱在这两种 IBD 的发病机制中起着至关重要的作用，但结肠免疫微环境的差异及其潜在机制仍然缺乏研究。在这里，我们通过多组学分析检查了未经治疗的 IBD 个体的免疫学特征和代谢微环境。CD 特异性代谢物的调节，特别是还原硒，可以明显地塑造 1 型 T 辅助 (Th1) 细胞分化，其在 CD 中特别富集。硒补充剂通过硒蛋白 W (SELW) 介导的细胞活性氧清除抑制了 CD 和 Th1 细胞分化的症状和发作。