背景:许多研究报告了与健康个体相比,双相情感障碍(BD)和精神分裂症谱系障碍(SSD)的肠道微生物组变化,虽然,关于哪些特定细菌与这些疾病相关的共识有限.
方法:在本研究中,我们对103名荷兰BD/SSD患者和128名年龄匹配的健康对照进行了全面的宏基因组鸟枪测序分析,性别,体重指数和收入,在考虑饮食质量的同时,运输时间和技术混淆。为了评估调查结果的可复制性,我们使用了两个验证队列(总共n=203),包括来自具有不同宏基因组分离方案的不同人群的参与者。
结果:患者的肠道菌群具有显著不同的β-多样性,但与健康对照组相比,没有α多样性或神经活性潜能。最初,在患者中,有26种细菌分类群被鉴定为差异丰富。其中,在验证队列中重复了先前报道的蛛网膜菌属和Eggerthella属.采用CoDaCoRe学习算法,我们确定了两种特定于BD/SSD的细菌平衡,这表明受试者工作特征曲线下面积(AUC)在测试数据集中为0.77。这些平衡在验证队列中重复,并显示与精神症状和抗精神病药使用的严重程度呈正相关。最后,我们显示,克雷伯菌和肺炎克雷伯菌的相对丰度与抗精神病药物的使用,以及厌氧菌和锂的使用之间呈正相关.
结论:我们的研究结果表明,微生物平衡可能是识别BD/SSD特异性微生物特征的可重复方法,具有潜在的诊断和预后应用。值得注意的是,在BD/SSD中,衣原体和Eggerthella是常见的细菌。最后,我们的研究重申了先前建立的克雷伯菌属与抗精神病药物使用之间的联系,并确定了厌氧菌属与锂的使用之间的新关联.
BACKGROUND: Numerous studies report gut microbiome variations in bipolar disorder (BD) and schizophrenia spectrum disorders (SSD) compared to healthy individuals, though, there is limited consensus on which specific bacteria are associated with these disorders.
METHODS: In this study, we performed a comprehensive metagenomic shotgun sequencing analysis in 103 Dutch patients with BD/SSD and 128 healthy controls matched for age, sex, body mass index and income, while accounting for diet quality, transit time and technical confounders. To assess the replicability of the findings, we used two validation cohorts (total n = 203), including participants from a distinct population with a different metagenomic isolation protocol.
RESULTS: The gut microbiome of the patients had a significantly different β-diversity, but not α-diversity nor neuroactive potential compared to healthy controls. Initially, twenty-six bacterial taxa were identified as differentially abundant in patients. Among these, the previously reported genera Lachnoclostridium and Eggerthella were replicated in the validation cohorts. Employing the CoDaCoRe learning algorithm, we identified two bacterial balances specific to BD/SSD, which demonstrated an area under the receiver operating characteristic curve (AUC) of 0.77 in the test dataset. These balances were replicated in the validation cohorts and showed a positive association with the severity of psychiatric symptoms and antipsychotic use. Last, we showed a positive association between the relative abundance of Klebsiella and Klebsiella pneumoniae with antipsychotic use and between the Anaeromassilibacillus and lithium use.
CONCLUSIONS: Our findings suggest that microbial balances could be a reproducible method for identifying BD/SSD-specific microbial signatures, with potential diagnostic and prognostic applications. Notably, Lachnoclostridium and Eggerthella emerge as frequently occurring bacteria in BD/SSD. Last, our study reaffirms the previously established link between Klebsiella and antipsychotic medication use and identifies a novel association between Anaeromassilibacillus and lithium use.