Bile acids act as signaling molecules that regulate immune homeostasis, including the differentiation of CD4⁺ T cells into distinct T cell subsets. The bile acid metabolite isoallolithocholic acid (isoalloLCA) enhances the differentiation of anti-inflammatory regulatory T cells (T_reg cells) by facilitating the formation of a permissive chromatin structure in the promoter region of the transcription factor forkhead box P3 (Foxp3). Here, we identify gut bacteria that synthesize isoalloLCA from 3-oxolithocholic acid and uncover a gene cluster responsible for the conversion in members of the abundant human gut bacterial phylum Bacteroidetes. We also show that the nuclear hormone receptor NR4A1 is required for the effect of isoalloLCA on T_reg cells. Moreover, the levels of isoalloLCA and its biosynthetic genes are significantly reduced in patients with inflammatory bowel diseases, suggesting that isoalloLCA and its bacterial producers may play a critical role in maintaining immune homeostasis in humans.

^{胆汁酸充当调节免疫稳态的信号分子，包括将 CD4 +} T 细胞分化为不同的 T 细胞亚群。胆汁酸代谢物异别石胆酸 (isoalloLCA)通过促进转录因子叉头盒 P3 ( Foxp3 ) 启动子区域中许可染色质结构的形成来增强抗炎调节 T 细胞 (T _reg细胞) 的分化。在这里，我们鉴定了从 3-氧代石胆酸合成 isoalloLCA 的肠道细菌，并发现了负责丰富的人类肠道细菌拟杆菌门成员转化的基因簇。_{我们还表明，isoalloLCA 对 T reg}细胞的作用需要核激素受体 NR4A1 。此外，炎症性肠病患者的isoalloLCA及其生物合成基因的水平显着降低，这表明isoalloLCA及其细菌生产者可能在维持人类免疫稳态中发挥关键作用。