Inflammatory bowel diseases (IBDs), including Crohn’s disease and ulcerative colitis, are associated with dysbiosis of the gut microbiome. Emerging evidence suggests that small-molecule metabolites derived from bacterial breakdown of a variety of dietary nutrients confer a wide array of host benefits, including amelioration of inflammation in IBDs. Yet, in many cases, the molecular pathways targeted by these molecules remain unknown. Here, we describe roles for three metabolites—indole-3-ethanol, indole-3-pyruvate, and indole-3-aldehyde—which are derived from gut bacterial metabolism of the essential amino acid tryptophan, in regulating intestinal barrier function. We determined that these metabolites protect against increased gut permeability associated with a mouse model of colitis by maintaining the integrity of the apical junctional complex and its associated actin regulatory proteins, including myosin IIA and ezrin, and that these effects are dependent on the aryl hydrocarbon receptor. Our studies provide a deeper understanding of how gut microbial metabolites affect host defense mechanisms and identify candidate pathways for prophylactic and therapeutic treatments for IBDs.

包括克罗恩氏病和溃疡性结肠炎在内的炎症性肠病（IBD）与肠道微生物组营养不良有关。新兴证据表明，源自多种饮食营养成分的细菌分解产生的小分子代谢物可带来多种宿主益处，包括减轻IBD炎症。然而，在许多情况下，这些分子靶向的分子途径仍然未知。在这里，我们描述了三种代谢物（吲哚-3-乙醇，吲哚-3-丙酮酸盐和吲哚-3-醛）在调节肠道屏障功能中的作用，它们是必需氨基酸色氨酸的肠道细菌代谢产物。我们确定这些代谢产物可通过维持根尖连接复合物及其相关的肌动蛋白调节蛋白（包括肌球蛋白IIA和ezrin）的完整性来防止与结肠炎的小鼠模型相关的肠道通透性增加，并且这些作用取决于芳基烃受体。我们的研究提供了对肠道微生物代谢产物如何影响宿主防御机制的更深入了解，并确定了预防和治疗IBD的候选途径。