Most inflammatory bowel disease (IBD) patients are unable to maintain a lifelong remission. Developing a novel therapeutic strategy is urgently needed. In this study, we adopt a new strategy to attenuate colitis using the Escherichia coli Nissle 1917 probiotic strain to express a schistosome immunoregulatory protein (Sj16) in the gastrointestinal tract. The genetically engineered Nissle 1917 (EcN-Sj16) highly expressed Sj16 in the gastrointestinal tracts of dextran sulfate sodium-induced colitis mice and significantly attenuated the clinical activity of colitis mice. Mechanistically, EcN-Sj16 increased the intestinal microbiota diversity and selectively promoted the growth of Ruminococcaceae and therefore enhanced the butyrate production. Butyrate induced the expression of retinoic acid, which further attenuated the clinical activity of colitis mice by increasing Treg cells and decreasing Th17. Strikingly, retinoic acid inhibitor inhibited the therapeutic effects of EcN-Sj16 in colitis mice. These findings suggest that EcN-Sj16 represents a novel engineered probiotic that may be used to treat IBD.

中文翻译：

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分泌 Sj16 的工程益生菌通过瘤胃球菌科/丁酸盐/视黄酸轴改善结肠炎

大多数炎症性肠病（IBD）患者无法维持终生缓解。迫切需要开发一种新的治疗策略。在这项研究中，我们采用了一种新策略来减轻结肠炎，使用大肠杆菌Nissle 1917 益生菌菌株在胃肠道中表达血吸虫免疫调节蛋白 (Sj16)。基因工程Nissle 1917（EcN-Sj16）在葡聚糖硫酸钠诱导的结肠炎小鼠的胃肠道中高表达Sj16，并显着减弱结肠炎小鼠的临床活性。从机制上讲，EcN-Sj16 增加了肠道微生物群的多样性，并选择性地促进瘤胃球菌科的生长，从而提高了丁酸盐的产量。丁酸盐诱导视黄酸的表达，通过增加 Treg 细胞和减少 Th17 进一步减弱结肠炎小鼠的临床活性。引人注目的是，视黄酸抑制剂抑制了 EcN-Sj16 对结肠炎小鼠的治疗作用。这些发现表明 EcN-Sj16 代表了一种新型工程益生菌，可用于治疗 IBD。