Escherichia coli is an important model organism in microbiology and a prominent member of the human microbiota¹. Environmental isolates readily colonize the gastrointestinal tract of humans and other animals, and they can serve diverse probiotic, commensal and pathogenic roles in the host^2,3,4. Although certain strains have been associated with the severity of inflammatory bowel disease (IBD)^2,5, the diverse immunomodulatory phenotypes remain largely unknown at the molecular level. Here, we decode a previously unknown E. coli metabolic pathway that produces a family of hybrid pterin–phenylpyruvate conjugates, which we named the colipterins. The metabolites are upregulated by subinhibitory levels of the antifolate sulfamethoxazole, which is used to treat infections including in patients with IBD^6,7. The genes folX/M and aspC/tyrB involved in monapterin biosynthesis^8,9,10 and aromatic amino acid transamination,¹¹ respectively, were required to initiate the colipterin pathway. We show that the colipterins are antioxidants, harbour diverse immunological activities in primary human tissues, activate anti-inflammatory interleukin-10 and improve colitis symptoms in a colitis mouse model. Our study defines an antifolate stress response in E. coli and links its associated metabolites to a major immunological marker of IBD.

大肠杆菌是微生物学中的一种重要模式生物，也是人类微生物群¹的重要成员。环境分离物很容易在人类和其他动物的胃肠道中定殖，它们可以在宿主^{2,3,4 中}发挥多种益生菌、共生和致病作用。虽然某些菌株与炎症性肠病 (IBD) ^2,5的严重程度有关，但在分子水平上，不同的免疫调节表型在很大程度上仍然未知。在这里，我们解码了以前未知的大肠杆菌产生一系列杂合蝶呤-苯基丙酮酸缀合物的代谢途径，我们将其命名为 colipterins。代谢物被抗叶酸磺胺甲恶唑的亚抑制水平上调，磺胺甲恶唑用于治疗感染，包括 IBD ^6,7患者。基因folX / M和ASPC / tyrB参与生物合成monapterin ^8,9,10和芳香族氨基酸氨基转移，¹¹分别需要启动 colipterin 途径。我们表明，colipterins 是抗氧化剂，在原代人体组织中具有多种免疫活性，激活抗炎性白细胞介素 10 并改善结肠炎小鼠模型中的结肠炎症状。我们的研究定义了大肠杆菌中的抗叶酸应激反应，并将其相关代谢物与 IBD 的主要免疫学标志物联系起来。