The brain and gut are intricately connected and respond to various stimuli. Stress-induced brain-gut communication is implicated in the pathogenesis and relapse of gut disorders. The mechanism that relays psychological stress to the intestinal epithelium, resulting in maladaptation, remains poorly understood. Here, we describe a stress-responsive brain-to-gut metabolic axis that impairs intestinal stem cell (ISC) lineage commitment. Psychological stress-triggered sympathetic output enriches gut commensal , increasing the production of indole-3-acetate (IAA), which contributes to a transferrable loss of intestinal secretory cells. Bacterial IAA disrupts ISC mitochondrial bioenergetics and thereby prevents secretory lineage commitment in a cell-intrinsic manner. Oral α-ketoglutarate supplementation bolsters ISC differentiation and confers resilience to stress-triggered intestinal epithelial injury. We confirm that fecal IAA is higher in patients with mental distress and is correlated with gut dysfunction. These findings uncover a microbe-mediated brain-gut pathway that could be therapeutically targeted for stress-driven gut-brain comorbidities.

中文翻译：

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心理应激诱导的微生物代谢物吲哚-3-乙酸酯破坏肠道细胞谱系定向

大脑和肠道错综复杂地连接在一起，并对各种刺激做出反应。压力引起的脑肠通讯与肠道疾病的发病机制和复发有关。将心理压力传递给肠上皮从而导致适应不良的机制仍然知之甚少。在这里，我们描述了一种应激反应性脑肠代谢轴，它会损害肠道干细胞（ISC）谱系定向。心理压力触发的交感神经输出丰富了肠道共生菌，增加了吲哚-3-乙酸酯（IAA）的产生，这导致肠道分泌细胞的可转移性损失。细菌 IAA 会破坏 ISC 线粒体生物能，从而以细胞固有的方式阻止分泌谱系的形成。口服 α-酮戊二酸补充剂可促进 ISC 分化，并赋予对应激触发的肠上皮损伤的恢复能力。我们证实，精神困扰患者的粪便 IAA 较高，并且与肠道功能障碍相关。这些发现揭示了微生物介导的脑-肠通路，可以作为治疗压力驱动的肠-脑合并症的目标。