小柯机器人

中国药科大学郝海平等研究人员合作发现，心理压力诱导的微生物代谢物吲哚-3-乙酸酯会扰乱肠道细胞谱系的确立。该项研究成果于2024年1月23日在线发表在《细胞—代谢》杂志上。

研究人员描述了一种应激反应性大脑-肠道代谢轴，它损害了肠干细胞（ISC）的谱系确立。研究人员发现，心理压力触发的交感神经输出使肠道共生乳酸杆菌（Lactobacillus murinus）富集，增加了吲哚-3-乙酸酯（IAA）的产生，从而导致肠道分泌细胞的转移性丧失。细菌IAA破坏了ISC线粒体的生物能，从而以细胞内在的方式阻止了分泌谱系的形成。口服α-酮戊二酸能促进ISC的分化，并赋予其对应激触发的肠上皮损伤的恢复能力。

研究人员证实，精神抑郁患者的粪便IAA较高，并且与肠道功能紊乱相关。这些发现揭示了微生物介导的大脑-肠道通路，可以作为压力驱动的肠道-大脑合并症的治疗靶点。

研究人员表示，大脑和肠道错综复杂地联系在一起，并对各种刺激做出反应。压力诱导的脑肠交流与肠道疾病的发病和复发有关。将心理压力传递给肠道上皮细胞，导致肠道上皮细胞适应不良的机制仍然鲜为人知。

附：英文原文

Title: Psychological stress-induced microbial metabolite indole-3-acetate disrupts intestinal cell lineage commitment

Author: Wei Wei, Yali Liu, Yuanlong Hou, Shuqi Cao, Zhuo Chen, Youying Zhang, Xiaoying Cai, Qingyuan Yan, Ziguang Li, Yonggui Yuan, Guangji Wang, Xiao Zheng, Haiping Hao

Issue&Volume: 2024-01-23

Abstract: The brain and gut are intricately connected and respond to various stimuli. Stress-inducedbrain-gut communication is implicated in the pathogenesis and relapse of gut disorders.The mechanism that relays psychological stress to the intestinal epithelium, resultingin maladaptation, remains poorly understood. Here, we describe a stress-responsivebrain-to-gut metabolic axis that impairs intestinal stem cell (ISC) lineage commitment.Psychological stress-triggered sympathetic output enriches gut commensal Lactobacillus murinus, increasing the production of indole-3-acetate (IAA), which contributes to a transferrableloss of intestinal secretory cells. Bacterial IAA disrupts ISC mitochondrial bioenergeticsand thereby prevents secretory lineage commitment in a cell-intrinsic manner. Oralα-ketoglutarate supplementation bolsters ISC differentiation and confers resilienceto stress-triggered intestinal epithelial injury. We confirm that fecal IAA is higherin patients with mental distress and is correlated with gut dysfunction. These findingsuncover a microbe-mediated brain-gut pathway that could be therapeutically targetedfor stress-driven gut-brain comorbidities.

DOI: 10.1016/j.cmet.2023.12.026

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00477-1

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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