首发重性抑郁症患者肠道菌群组成及与胃肠道症状的相关性

Gut microbiota in patients with first-episode major depressive disorder: composition and correlations with gastrointestinal symptoms

摘要:

【背景】重性抑郁症(major depressive disorder, MDD)是一种常见的重大精神疾病，MDD患者多伴有胃肠道症状，但很少有研究关注MDD患者胃肠道症状发生的机制。【目的】探索首发未治疗MDD患者肠道菌群的特征及其与炎症标志物和胃肠道症状的相关性，为MDD的治疗提供理论依据。【方法】募集符合入组和排除标准的91例首发未服药MDD患者和105名健康对照者(healthy controls, HCs)。采用16S rRNA基因测序技术和生物信息学分析评估粪便菌群组成。采用酶联免疫吸附试验(enzyme linked immunosorbent assay, ELISA)检测外周血高敏C反应蛋白(high-sensitivity C-reactive protein, hs-CRP)、白细胞介素-1β (interleukin-1β, IL-1β)、白细胞介素-6 (interleukin-6, IL-6)、白细胞介素-10 (interleukin-10, IL-10)和肿瘤坏死因子-α (tumor necrosis factor-α, TNF-α)；采用胃肠症状评定量表(gastrointestinal symptom rating scale, GSRS)和汉密尔顿抑郁量表(Hamilton depression scale, HAMD)分别评估胃肠道症状和抑郁症状的严重程度。【结果】所有MDD患者都伴有胃肠道症状，食欲下降、早饱感、恶心呕吐的发生率均高于70%。与HCs相比，MDD患者外周血中hs-CRP水平明显升高(P＜0.05)；两组受试者肠道菌群α多样性和β多样性存在明显差异(P＜0.05)。在属水平上，MDD组中地嗜皮菌属、异斯卡多维亚菌属、双歧杆菌属、布洛特菌属、钩丝菌属、红长菌属、马赛菌属、嗜血杆菌属、Candidatus Xiphinematobacter和Chthoniobacter的相对丰度较高，拟杆菌属、副拟杆菌属、SMB53、厌氧菌属、梭菌属、毛梭菌属、罗斯氏菌属、粪杆菌属、瘤胃球菌属、小杆菌属、考拉杆菌属和萨特氏菌属的相对丰度较低。相关性分析发现罗斯氏菌属、萨特氏菌属、副拟杆菌属的相对丰度与hs-CRP、HAMD-17总分、GSRS总分及GSRS部分条目呈负相关(P＜0.05)。【结论】MDD患者外周血hs-CRP升高，紊乱的肠道菌群与hs-CRP、抑郁症状和胃肠道症状密切相关。

Abstract:

[Background] Major depressive disorder (MDD) is a common major mental disorder and most MDD patients have gastrointestinal (GI) symptoms. However, little is known about the occurrence mechanisms of GI symptoms in MDD. [Objective] To explore the gut microbiota composition and its correlations with inflammation markers and GI symptoms in the patients with first-episode MDD, providing a theoretical basis for the treatment of MDD. [Methods] The participants included 91 first-episode, drug-naive MDD patients and 105 healthy controls (HCs). The 16S rRNA gene sequencing and bioinformatics tools were employed to reveal the composition of fecal microbiota. The levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-1 beta (IL-1β), IL-6, IL-10, and tumor necrosis factor-alpha (TNF-α) in the peripheral blood were measured via enzyme-linked immunosorbent assay (ELISA). Gastrointestinal symptom rating scale (GSRS) and Hamilton depression scale (HAMD) were used to evaluate the severity of GI symptoms and depression symptoms, respectively. [Results] All the MDD patients were accompanied by GI symptoms, and the incidence of anorexia, early satiety, nausea, and vomiting was higher than 70%. Compared with HCs, MDD patients had elevated level of hs-CRP and showed different alpha diversity and beta diversity of gut microbiota (P＜0.05). Linear discriminant analysis effect size (LEfSe) showed that MDD patients had higher relative abundance of Geodermatophilus, Alloscardovia, Bifidobacterium, Blautia, Leptothrix, Rubrivivax, Massilia, Haemophilus, Candidatus Xiphinematobacter, and Chthoniobacter and lower relative abundance of Bacteroides, Parabacteroides, SMB53, Anaerostipes, Clostridium, Lachnospira, Roseburia, Faecalibacterium, Ruminococcus, Dialister, Phascolarctobacterium, and Sutterella. Furthermore, the correlation analysis revealed that the relative abundance of Roseburia, Sutterella, and Parabacteroides were negatively correlated with hs-CRP, total score of HAMD-17, and the total score and some item scores of GSRS (P＜0.05). [Conclusion] This study demonstrates that compared with HCs, MDD patients showed elevated hs-CRP. The altered gut microbiota is closely associated with hs-CRP and depression and GI symptoms in MDD patients.