在IBS-抑郁症并发症中针对MPO/LCN2/GMPPB轴:用于精确诊断和治疗的综合多omics和双向网络药理学
Shirui Li1, Feng Jiang1, Xiuyang Li1
1Department of Big Data in Health Science, and, Center for Clinical Big Data and Statistics, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzho, Zhejiang, China.
Computational biology and chemistry
|February 12, 2026
概括
这项研究揭示了关键基因 (MPO,LCN2,GMPPB) 关联刺激性肠综合征 (IBS) 和严重抑郁症 (MDD),这表明肠-大脑轴治疗的环境因素和自然化合物.
科学领域:
- 神经科学是一个神经科学.
- 胃肠病学 胃肠病学
- 精神病学是一个精神病学.
- 计算生物学 计算生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 刺激性肠综合征 (IBS) 和严重抑郁症 (MDD) 经常同时发生,这表明共享的肠-大脑轴失调.
- 现有研究面临临临床异质性和分散方法的挑战,阻碍了核心分子机制和治疗点的识别.
研究的目的:
- 阐明IBS-MDD共患病的共同分子机制.
- 确定IBS-MDD的新型诊断生物标志物和治疗点.
- 探索环境因素和自然化合物在调节肠-大脑轴上的作用.
主要方法:
- 综合分析流行病学数据 (查尔斯队列),多组织转录组学 (GEO数据集) 和机器学习.
- 构建和验证蛋白质与蛋白质相互作用 (PPI) 网络.
- 功能丰富分析,免疫解卷 (CIBERSORTx) 和双向药理学 (CTD,TCM网络药理学).
- 分子对接和短期分子动力学 (MD) 模拟用于结合性评估,以及ADME/Tox分析.
主要成果:
- 流行病学分析证实IBS和MDD之间存在双向风险.
- 转录组分析确定MPO,LCN2和GMPPB是与中性粒细胞激活,铁失调和糖化缺陷相关的核心并发性基因.
- 免疫分析显示了IBS与MDD的独特的组织特异性免疫细胞透模式.
- 药理学查确定了潜在的治疗化合物 (白醇,氨酸) 和致病剂 (双醇A,脂多糖),分子模拟支持与MPO和GMPPB结合.
结论:
- MPO,LCN2和GMPPB被提名为IBS-MDD并发症的关键诊断生物标志物和治疗标.
- 神经免疫内分泌交叉是IBS-MDD病变发生的一个关键因素.
- 环境毒素和自然化合物为肠-大脑轴干预提供了可行的策略.
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