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肠道菌群失调与抑郁症:对抗抑郁药初治的心境障碍患者肠道微生物群改变及功能通路的研究

Dysbiosis and depression: A study of gut microbiota alterations and functional pathways in antidepressant-naïve mood disorder patients.

作者信息

Lin Shih-Kai Kevin, Chen Hsi-Chung, Chen I-Ming, Hsu Cheng-Dien, Huang Ming-Chyi, Liu Chih-Min, Wu Shu-I, Chen Po-Yu, Chen Chun-Hsin, Kuo Po-Hsiu

机构信息

Department of Public Health & Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

School of Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.

出版信息

Transl Psychiatry. 2025 Aug 18;15(1):290. doi: 10.1038/s41398-025-03521-1.

DOI:10.1038/s41398-025-03521-1
PMID:40825932
Abstract

Depression, a common mood disorder, has been associated with gut microbiota alterations, though the underlying microbial mechanisms remain unclear. This study investigated potential gut microbiota biomarkers and functional pathways in 106 antidepressant-naïve depressive patients and 151 healthy controls, with careful of confounding factors. Stool samples were analyzed using 16S rRNA sequencing, revealing significantly lower alpha diversity and distinct beta diversity in depressive patients. Eleven taxa with differential abundance were identified, including Dialister and Lactococcus (decreased) and Hungatella, Sellimonas, and Lachnoclostridium (elevated), which may relate to gut inflammation and depressive symptom severity. Functional pathway analysis highlighted 36 altered pathways, including those involved in purine degradation, lipopolysaccharide biosynthesis, and amino acid metabolism. A random forest classification model built using the identified taxa achieved moderate accuracy (~0.72) in distinguishing depressive patients from controls. Additionally, we developed a novel Depression Dysbiosis Index (DDI), which positively correlated with depression severity and effectively differentiated between groups. The DDI was robust across analyses, emphasizing its potential clinical value. Future research should incorporate longitudinal designs, advanced sequencing techniques, and additional clinical factors to deepen our understanding of the gut-brain axis in depression and improve diagnostic and therapeutic strategies.

摘要

抑郁症是一种常见的情绪障碍,虽其潜在的微生物机制尚不清楚,但已发现与肠道微生物群改变有关。本研究在仔细考虑混杂因素的情况下,对106例未服用过抗抑郁药的抑郁症患者和151例健康对照者的潜在肠道微生物群生物标志物和功能途径进行了研究。使用16S rRNA测序分析粪便样本,结果显示抑郁症患者的α多样性显著降低,β多样性明显不同。鉴定出11个丰度有差异的分类群,包括戴阿利斯特菌属和乳球菌属(丰度降低)以及亨盖特菌属、塞尔利莫纳斯菌属和布劳特氏菌属(丰度升高),这些分类群可能与肠道炎症和抑郁症状严重程度有关。功能途径分析突出了36条改变的途径,包括参与嘌呤降解、脂多糖生物合成和氨基酸代谢的途径。使用鉴定出的分类群构建的随机森林分类模型在区分抑郁症患者和对照者方面达到了中等准确率(约0.72)。此外,我们开发了一种新的抑郁症生态失调指数(DDI),该指数与抑郁症严重程度呈正相关,并能有效区分不同组。DDI在各项分析中都很稳健,强调了其潜在的临床价值。未来的研究应纳入纵向设计、先进的测序技术和其他临床因素,以加深我们对抑郁症中肠-脑轴的理解,并改进诊断和治疗策略。

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本文引用的文献

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Exploring the intestinal ecosystem: from gut microbiota to associations with subtypes of inflammatory bowel disease.探索肠道生态系统:从肠道微生物群到与炎症性肠病亚型的关联。
Front Cell Infect Microbiol. 2024 Jan 4;13:1304858. doi: 10.3389/fcimb.2023.1304858. eCollection 2023.
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Unveiling the Connection between Microbiota and Depressive Disorder through Machine Learning.通过机器学习揭示微生物群与抑郁障碍之间的关系。
Int J Mol Sci. 2023 Nov 17;24(22):16459. doi: 10.3390/ijms242216459.
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Exploring the human gut microbiota targets in relation to the use of contemporary antidepressants.
探索与使用当代抗抑郁药相关的人类肠道微生物菌群靶标。
J Affect Disord. 2024 Jan 1;344:473-484. doi: 10.1016/j.jad.2023.10.016. Epub 2023 Oct 18.
4
Gut microbiota analyses of inflammatory bowel diseases from a representative Saudi population.沙特代表性人群炎症性肠病的肠道微生物组分析。
BMC Gastroenterol. 2023 Jul 28;23(1):258. doi: 10.1186/s12876-023-02904-2.
5
Insight into gut dysbiosis of patients with inflammatory bowel disease and ischemic colitis.炎症性肠病和缺血性结肠炎患者肠道菌群失调的研究
Front Microbiol. 2023 May 11;14:1174832. doi: 10.3389/fmicb.2023.1174832. eCollection 2023.
6
Suppressive Effects of on Depression through Regulating the Gut Microbiota and Metabolites in C57BL/6J Mice Induced by Ampicillin.通过调节氨苄青霉素诱导的C57BL/6J小鼠肠道微生物群和代谢产物对抑郁症的抑制作用。
Biomedicines. 2023 Apr 1;11(4):1068. doi: 10.3390/biomedicines11041068.
7
Depression and 24 gastrointestinal diseases: a Mendelian randomization study.抑郁与 24 种胃肠道疾病:一项孟德尔随机化研究。
Transl Psychiatry. 2023 May 4;13(1):146. doi: 10.1038/s41398-023-02459-6.
8
Changes of gut microbiota reflect the severity of major depressive disorder: a cross sectional study.肠道微生物群的变化反映了重度抑郁症的严重程度:一项横断面研究。
Transl Psychiatry. 2023 Apr 28;13(1):137. doi: 10.1038/s41398-023-02436-z.
9
The Firmicutes/Bacteroidetes Ratio as a Risk Factor of Breast Cancer.厚壁菌门与拟杆菌门的比例作为乳腺癌的一个风险因素
J Clin Med. 2023 Mar 13;12(6):2216. doi: 10.3390/jcm12062216.
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Lipopolysaccharide-binding protein expression is increased by stress and inhibits monoamine synthesis to promote depressive symptoms.脂多糖结合蛋白的表达受应激增加,并抑制单胺合成,从而促进抑郁症状。
Immunity. 2023 Mar 14;56(3):620-634.e11. doi: 10.1016/j.immuni.2023.02.002. Epub 2023 Feb 27.