Bai Yu, Shu Chang, Zhang Shufang, Gui Gui, Zhang Rui, Yu Siye, Dong Chengzhen, Duan Rui, Ai Xu, Liu Ruijie, Shen Hexiao, Lv Yongling, Wang Gaohua
Department of Psychiatry, Institute of Neuropsychiatry, Renmin Hospital, Wuhan University, Wuhan city, Hubei Province, China.
Jingmen Central Hospital, Jingmen Central Hospital affiliated to Jingchu University of Technology, Hubei Clinical Medical Research Center for Functional Colorectal Diseases, Jingmen 44800, Hubei, China.
J Affect Disord. 2026 Jan 1;392:120141. doi: 10.1016/j.jad.2025.120141. Epub 2025 Aug 26.
Depression has become a leading global mental health disorder, with a rising prevalence of 15-20 % among adolescents. Emerging evidence suggests that adolescent depression may constitute a distinct subtype, differing clinically and neurobiologically from adult presentations. The gut microbiota's role in psychiatric disorders has garnered increasing attention, as dysbiosis may modulate behavior and mood via the microbiota-gut-brain axis, potentially contributing to depressive pathogenesis.
This study included 60 depressed and 64 healthy adolescents (aged 11-18). Fecal samples were immediately flash-frozen in liquid nitrogen after collection, stored at -80 °C within 30 min, and processed within 6 months to minimize DNA degradation. And microbial DNA was extracted using the HiPure Stool DNA Mini Kit. The V3-V4 hypervariable regions of the 16S rRNA gene were amplified via PCR with primers 341F (5'-CCTAYGGGRBGCASCAG-3') and 805R (5'-GACTACHVGGGTATCTAATCC-3'), followed by Illumina NovaSeq 6000 sequencing. PCR cycle optimization was performed via gradient testing (20-30 cycles), confirming 25 cycles as optimal to prevent chimera formation while maintaining amplicon yield. Bioinformatics pipelines included QIIME2 for quality filtering, DADA2 for ASV inference, and PICRUSt2 for functional prediction. Statistical analyses included t-tests, mediation analysis, and Linear discriminant analysis Effect Size (LEfSe).
Fifty percent of depressed adolescents originated from single-parent or grandparent-led households and exhibited reduced resilience scores alongside elevated adverse childhood experiences (ACEs). Gut microbiota analysis revealed significant compositional and functional dysbiosis in depressed youth, marked by depletion of beneficial taxa (e.g., Bifidobacterium, Faecalibacterium) and butyrate-producing species, alongside enrichment of pro-inflammatory genera (e.g., Escherichia-Shigella). Mediation analyses implicated ACEs as a potential driver of these microbial alterations.
This study reveals distinct gut microbiota profiles in adolescents with depression compared to healthy controls, offering mechanistic insights into how ACEs and microbial dysbiosis may contribute to depressive etiology.
抑郁症已成为全球主要的心理健康障碍，在青少年中的患病率呈上升趋势，为15%至20%。新出现的证据表明，青少年抑郁症可能构成一种独特的亚型，在临床和神经生物学上与成人表现不同。肠道微生物群在精神疾病中的作用日益受到关注，因为微生物失调可能通过微生物-肠道-脑轴调节行为和情绪，这可能是抑郁症发病机制的一个因素。
本研究纳入了60名抑郁青少年和64名健康青少年（年龄在11至18岁之间）。粪便样本在采集后立即在液氮中速冻，在30分钟内储存在-80°C，并在6个月内进行处理，以尽量减少DNA降解。使用HiPure粪便DNA微量提取试剂盒提取微生物DNA。通过PCR用引物341F（5'-CCTAYGGGRBGCASCAG-3'）和805R（5'-GACTACHVGGGTATCTAATCC-3'）扩增16S rRNA基因的V3-V4高变区，随后进行Illumina NovaSeq 6000测序。通过梯度测试（20-30个循环）进行PCR循环优化，确认25个循环为最佳循环数，以防止嵌合体形成，同时保持扩增子产量。生物信息学流程包括用于质量过滤的QIIME2、用于ASV推断的DADA2和用于功能预测的PICRUSt2。统计分析包括t检验、中介分析和线性判别分析效应大小（LEfSe）。
50%的抑郁青少年来自单亲或由祖父母主导的家庭，其复原力得分较低，同时童年不良经历（ACEs）增加。肠道微生物群分析显示，抑郁青少年存在明显的组成和功能失调，表现为有益菌群（如双歧杆菌、粪杆菌）和产丁酸物种的减少，以及促炎菌属（如大肠杆菌-志贺氏菌属）的富集。中介分析表明，ACEs是这些微生物改变的潜在驱动因素。
本研究揭示了与健康对照相比，抑郁青少年具有独特的肠道微生物群特征，为ACEs和微生物失调如何导致抑郁病因提供了机制性见解。
