Irritable bowel syndrome with diarrhea (IBS-D) is a common and chronic gastrointestinal disorder that is characterized by abdominal discomfort and occasional diarrhea. The pathogenesis of IBS-D is thought to be related to a combination of factors, including psychological stress, abnormal muscle contractions, and inflammation and disorder of the gut microbiome. However, there is still a lack of comprehensive analysis of the logical regulatory correlation among these factors. In this study, we found that stress induced hyperproduction of xanthine and altered the abundance and metabolic characteristics of Lactobacillus murinus in the gut. Lactobacillus murinus-derived spermidine suppressed the basal expression of type I interferon (IFN)-α in plasmacytoid dendritic cells by inhibiting the K63-linked polyubiquitination of TRAF3. The reduction in IFN-α unrestricted the contractile function of colonic smooth muscle cells, resulting in an increase in bowel movement. Our findings provided a theoretical basis for the pathological mechanism of, and new drug targets for, stress-exposed IBS-D.

中文翻译：

---

压力通过亚精胺介导的 I 型干扰素下降引发腹泻性肠易激综合征


腹泻性肠易激综合征（IBS-D）是一种常见的慢性胃肠道疾病，其特征是腹部不适和偶尔腹泻。 IBS-D 的发病机制被认为与多种因素有关，包括心理压力、肌肉收缩异常以及肠道微生物群的炎症和紊乱。但目前还缺乏对这些因素之间逻辑调控关联性的全面分析。在这项研究中，我们发现压力会导致黄嘌呤的过度产生，并改变肠道中鼠乳杆菌的丰度和代谢特征。鼠乳杆菌衍生的亚精胺通过抑制 TRAF3 的 K63 连接的多聚泛素化来抑制浆细胞样树突状细胞中 I 型干扰素 (IFN)-α 的基础表达。 IFN-α 的减少不受结肠平滑肌细胞收缩功能的限制，导致排便增加。我们的研究结果为应激性IBS-D的病理机制和新的药物靶点提供了理论基础。