肠道菌群通过调控Wnt信号通路介导产前甲基苯丙胺暴露诱导的焦虑与抑郁样行为

本文揭示了产前甲基苯丙胺（METH）暴露通过破坏子代肠道菌群平衡，诱发海马炎症并抑制神经发生，进而导致焦虑与抑郁样行为的重要机制。研究通过交叉哺育和菊粉补充实验证明菌群重塑可激活Wnt信号通路改善神经行为缺陷，为干预毒品跨代神经毒性提供了新靶点。

　　

研究亮点

• 产前METH暴露导致子代肠道菌群失调并伴随焦虑抑郁样行为

• 菌群紊乱与海马神经发生减少及炎症增加密切相关

• 交叉哺育实验证实母源菌群传播的关键作用

• 菊粉补充通过重塑菌群改善神经行为缺陷

• Wnt信号通路激活是菊粉干预的重要机制

结论

本研究证实产前甲基苯丙胺暴露会通过破坏子代肠道微生物群落平衡，引发海马区炎症反应并抑制神经干细胞增殖，最终导致焦虑与抑郁样行为表型。通过交叉哺育实验发现母源微生物传递在神经毒性中的关键作用，而补充益生元菊粉能有效重塑肠道菌群结构，激活经典Wnt/β-catenin信号通路，促进海马神经发生并改善行为异常。该研究不仅揭示了肠道微生物组在毒品跨代神经毒性中的核心媒介作用，更为临床干预提供了以菌群为靶点的治疗新策略。

Conclusion

Our findings demonstrate that prenatal METH exposure disrupts offspring gut microbial ecosystems, triggering hippocampal inflammation and suppressing neurogenesis, ultimately leading to anxiety- and depression-like phenotypes. Cross-fostering experiments reveal the critical role of maternal microbial transmission in mediating these neurodevelopmental deficits. Remarkably, inulin supplementation effectively restores gut microbiota homeostasis, activates canonical Wnt/β-catenin signaling, promotes hippocampal neurogenesis and ameliorates behavioral abnormalities. This study not only elucidates the pivotal role of gut microbiota in mediating intergenerational neurotoxicity of METH, but also provides novel microbiota-targeted therapeutic strategies for clinical intervention.