【摘要】 目的：通过检测抗抑郁经典中药方剂交泰丸（JTW）对抑郁症患者肠道微生物群短链脂肪酸（SCFA）神经递质/免疫轴的影响，研究其抗抑郁机制。方法：在这项为期8周的多中心随机对照试验中，120名抑郁症患者接受了JTW、选择性5-羟色胺再摄取抑制剂（SSRIs）、JTW+SSRIs或未接受干预（健康对照组，n=30）。通过肠道微生物群谱分析（16S核糖体RNA[16Sr DNA]基因测序）、粪便SCFA定量（气相色谱-质谱联用技术[GC-MS]）以及血浆神经递质（5-羟色胺[5-HT]、去甲肾上腺素[NE]、多巴胺[DA]）和肠道屏障/炎症标志物（脂多糖[LPS]、可溶性闭锁带蛋白-1[s ZO-1]、高迁移率族蛋白B1[HMGB1]）的检测，在治疗前后进行了评估。使用相关分析法分析了神经递质、肠道菌群、短链脂肪酸和肠道屏障/炎症标志物之间的相关性。结果：JTW治疗，特别是与SSRIs联合使用时，通过减少拟杆菌门的丰度和增加厚壁菌门的丰度，显著调节了肠道微生物群的组成。它选择性地改善了SCFA代谢紊乱，特别是提高了粪便中支链脂肪酸的水平，包括异丁酸和异戊酸。这些变化伴随着血浆中5-HT和DA水平的升高，以及LPS和HMGB1水平的降低，表明肠道屏障完整性得到改善，全身炎症减轻。相关性分析显示，厚壁菌门的丰度与s ZO-1呈正相关，且微生物变化、代谢变化和神经递质改善之间存在整体协调性。结论：JTW可能通过多靶点调节微生物群-SCFA-神经递质/免疫轴来缓解抑郁症状，可能涉及恢复微生物组成、增加有益SCFA产生、改善肠道屏障功能、减少炎症和提高单胺类神经递质水平。当JTW与SSRIs联合使用时，观察到了协同效应，这为使用JTW通过微生物群导向的方法治疗抑郁症提供了机制基础。更多还原

【Abstract】 Objective:To investigate the antidepressant mechanism of Jiaotaiwan(JTW),a classic Traditional Chinese Medicine formula,by examining its effects on the gut microbiota short-chain fatty acid(SCFA) neurotransmitter/immune axis in patients with depression.Methods:In this 8-week multicenter randomized controlled trial,120 patients with depression were randomized to receive JTW,selective serotonin reuptake inhibitors(SSRIs),or JTW+SSRIs,and 30 healthy volunteers were enrolled as controls without intervention(healthy controls,n=30).Gut microbiota profiling(16S ribosomal RNA [16S rDNA] gene sequencing),fecal SCFA quantification(gas chromatography-mass spectrometry),and plasma levels of neurotransmitters(5-hydroxytryptamine [5-HT],norepinephrine [NE],dopamine [DA]) and gut barrier/inflammatory markers(lipopolysaccharide [LPS],soluble zonula occludens-1[sZO-1],high mobility group box 1 [HMGB1]) were assessed pre-and post-treatment.Correlations between brain gut peptides,gut flora,SCFAs,and gut barrier/inflammatory markers were analyzed using Spearman correlation analysis.Results:Treatment with JTW,particularly in combination with SSRIs,significantly modulated gut microbiota composition by reducing Bacteroidetes abundance and increasing Firmicutes.It selectively ameliorated SCFA metabolic disturbances,notably elevating fecal levels of branched-chain fatty acids,including isobutyric and isovaleric acids.These changes were accompanied by increased plasma levels of 5-HT and DA,and reduced levels of LPS and HMGB1,suggesting improved gut barrier integrity and attenuated systemic inflammation.Correlation analysis revealed a positive association between Firmicutes abundance and sZO-1levels,and overall coordination among microbial shifts,metabolic changes,and neurotransmitter improvements.Conclusion:JTW may alleviate depressive symptoms through multitarget modulation of the microbiota-SCFA-neurotransmitter/immune axis,potentially involving the restoration of microbial composition,enhanced beneficial SCFA production,improved intestinal barrier function,reduced inflammation,and elevated monoamine neurotransmitters.Synergistic effects were observed when JTW was combined with SSRIs,thereby providing a mechanistic basis for using JTW in microbiota-directed approaches for treating depression.更多还原