重性抑郁症患者的肠道菌群特征及与炎症因子的相关性

Characteristics of intestinal flora in patients with major depressive disorder and its correlation with inflammatory factors

目的探究重性抑郁症(major depressive disorder,MDD)患者肠道菌群特征,并分析其与炎症因子和汉密尔顿24项抑郁评定量表(Hamilton depression scale-24,HAMD-24))评分的相关性。方法研究共纳入符合纳入、排出标准的首发未治疗的MDD患者58例以及性别、年龄与之匹配的健康对照者(healthy controls,HCs)50例。采用HAMD-24评估所有受试者的抑郁症状严重程度,采用16S rRNA基因测序法评估肠道菌群的组成。使用酶联免疫吸附试验检测外周血中C反应蛋白(C-reactive protein,CRP)、白细胞介素-1β、白细胞介素-6及肿瘤坏死因子-α水平,采用Spearman相关性分析评估肠道菌群与炎症因子和HAMD-24评分的相关性。结果MDD组的CRP水平显著高于HC组(t=8.353,P<0.050)。Alpha多样性分析(Shannon指数、Simpson指数及Pielou指数)显示MDD组和HC组的肠道菌群差异有统计学意义(H=8.529、8.893、10.825,均P<0.050),beta多样性分析显示两组菌群分布差异有统计学意义(F=3.997,P<0.050)。进一步线性判别分析发现,在属水平上,MDD组的双歧杆菌属、布劳特菌属、粪球菌属、巨单胞菌属及Dorea相对丰度较高,HC组的拟杆菌属、粪杆菌属、罗氏菌属及小杆菌属相对丰度较高。Spearman相关性分析结果显示布劳特菌属和粪球菌属与CRP和HAMD-24评分呈正相关(r=0.258、0.284、0.235,0.262,均P<0.050),粪杆菌属和罗氏菌属与CRP呈负相关(r=−2.030、−0.221,均P<0.050)。结论MDD患者的肠道菌群发生改变,血浆CRP水平升高,且发生改变的肠道菌群与血浆CRP水平和HAMD-24评分密切相关。

Objective To explore the characteristics of intestinal flora in patients with major depressive disorder(MDD),and analyze its correlation with inflammatory factors and the score of the Hamilton depression scale-24(HAMD-24).Methods A total of 58 treatment-naïve first-episode MDD patients who met the inclusion criteria and 50 healthy genderand age-matched controls(HCs)were included.HAMD-24 was used to assess the severity of depressive symptoms,and 16S rRNA gene sequencing was used to assess the composition of intestinal flora.Enzyme linked immunosorbent assay was used to detect C-reactive protein(CRP),interleukin-1β,interleukin-6 and tumor necrosis factor-αin peripheral blood.Spearman correlation analysis was used to evaluate the correlation of intestinal flora with inflammatory factors and HAMD-24 score.Results The CRP level in MDD group was significantly higher than that in HC group(t=8.353,P<0.050).Alpha diversity analyses(Shannon index,Simpson index,Pielou index)showed that there were significant differences in intestinal flora between MDD group and HC group(H=8.529,H=8.893,H=10.825,all P<0.050),and beta diversity analyses showed that the difference in the distribution of intestinal flora between the two groups was statistically significant(F=3.997,P<0.050).Further linear discriminant analysis Effect Size analysis found that,at the genus level,the relative abundances of Bifidobacterium,Blautia,Coprococcus,Megamonas and Dorea were higher in MDD group,while those of Bacteroides,Faecalibacterium,Roseburia and Dialister were higher in HC group.Spearman correlation analysis showed that Blautia and Coprococcus were positively correlated with CRP and HAMD-24 score(r=0.258,r=0.284,r=0.235,r=0.262,P<0.050),while Faecalibacterium and Roseburia were negatively correlated with CRP(r=−2.030,r=−0.221,all P<0.050).Conclusion MDD patients have altered intestinal flora and increased plasma CRP level,and the altered intestinal flora is closely related to plasma CRP level and HAMD-24 score.