Li Yi, Dai Jinhe, Wang Mengshu, Yan Chuming, Xiu Meihong, Qu Miao
Department of Neurology, Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, China.
Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China.
Int J Neurosci. 2025 Jul 16:1-18. doi: 10.1080/00207454.2025.2529238.
Microecological and metabolic disorders of the gut may be involved in the pathogenesis of generalized anxiety disorder (GAD), but clinical multi-omics evidence of this is lacking. Our study aimed to investigate characteristic alterations in the gut microbiota and plasma metabolome of patients with GAD and evaluate their clinical diagnostic value.
Ninety subjects (60 patients with GAD and 30 healthy volunteers) were included. We employed 16S rRNA gene sequencing to characterize the gut microbiota and targeted liquid chromatography-mass spectrometry to analyze plasma metabolomic profiles.
GAD was associated with increased abundances of , , and and decreased abundances of , , , and . Metabolomic analysis revealed 19 differential metabolites (upregulated in GAD: e.g. glutamic acid, cortisol; downregulated in GAD: e.g. γ-aminobutyric acid, serotonin). Enriched metabolic pathways included phenylalanine, tyrosine, and tryptophan biosynthesis; alanine, aspartate, and glutamate metabolism; and the biosynthesis of unsaturated fatty acids. Notably, microbiome-metabolome combined analysis revealed a significant correlation between intestinal flora disorders and changes in the plasma metabolic profile. The diagnostic model constructed based on the combined omics data exhibited excellent discriminatory efficacy, with areas under curve of 0.710, 0.986, and 0.997 for the microbiome, metabolome, and combined model, respectively.
This study revealed the characteristic gut microbiome-plasma metabolome covariation pattern of GAD and identified biomarker combinations with potential diagnostic value. The identified biomarker group provides new insights into the gut-brain axis mechanism of GAD, providing important theoretical support for clarifying the pathogenesis of GAD and developing precise diagnosis strategies.
肠道微生态和代谢紊乱可能参与广泛性焦虑障碍（GAD）的发病机制，但缺乏这方面的临床多组学证据。我们的研究旨在调查GAD患者肠道微生物群和血浆代谢组的特征性改变，并评估其临床诊断价值。
纳入90名受试者（60例GAD患者和30名健康志愿者）。我们采用16S rRNA基因测序来表征肠道微生物群，并采用靶向液相色谱-质谱分析法分析血浆代谢组学图谱。
GAD与[具体微生物名称1]、[具体微生物名称2]和[具体微生物名称3]丰度增加以及[具体微生物名称4]、[具体微生物名称5]、[具体微生物名称6]和[具体微生物名称7]丰度降低有关。代谢组学分析揭示了19种差异代谢物（在GAD中上调：如谷氨酸、皮质醇；在GAD中下调：如γ-氨基丁酸、血清素）。富集的代谢途径包括苯丙氨酸、酪氨酸和色氨酸生物合成；丙氨酸、天冬氨酸和谷氨酸代谢；以及不饱和脂肪酸的生物合成。值得注意的是，微生物组-代谢组联合分析揭示了肠道菌群紊乱与血浆代谢谱变化之间存在显著相关性。基于联合组学数据构建的诊断模型具有出色的鉴别效能，微生物组、代谢组和联合模型的曲线下面积分别为0.710、0.986和0.997。
本研究揭示了GAD独特的肠道微生物组-血浆代谢组协变模式，并确定了具有潜在诊断价值的生物标志物组合。所确定的生物标志物组为GAD的肠-脑轴机制提供了新见解，为阐明GAD的发病机制和制定精准诊断策略提供了重要的理论支持。
