The human gut microbiome plays an important role in the basic neurodevelopmental processes of the central nervous system and has been implicated in several neuropsychiatric disorders. However, the connection between the gut microbiome and the underlying pathogenesis of schizophrenia (SCZ) is poorly defined. Here we analyzed the faecal samples from 40 first-episode drug-naïve SCZ (FSCZ) patients, 85 chronically antipsychotic-treated SCZ (TSCZ) patients and 69 healthy controls (HCs) using 16S rRNA gene sequence to determine whether the alterations of the gut microbiome were associated with SCZ or antipsychotic treatment. In addition, we acquired the T1-weighted brain imaging data by using structural magnetic resonance imaging to test whether microbial composition correlated with structural brain signatures. Our analyses revealed low microbiome alpha-diversity indexes in TSCZ patients but not in FSCZ patients as compared to HCs. Importantly, both FSCZ and TSCZ patients had distinct changes in gut microbial composition at certain taxa including Christensenellaceae, Enterobacteriaceae, Pasteurellaceae, Turicibacteraceae at the family level and Escherichia at genus level as compared to HCs. We also found significant disturbances of gut microbial composition in TSCZ versus FSCZ patients (eg. Enterococcaceae and Lactobacillaceae). Most interestingly, our exploratory analyses found specific SCZ-associated microbiota to be correlated with the right middle frontal gyrus (rMFG) volume which was aberrant in SCZ patients. Our findings extend prior work and suggest a possible link between the gut microbiome and brain structure which may be implicated in the pathology of SCZ.

中文翻译：

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初次药物滥用和慢性药物性精神分裂症患者肠道微生物组的改变与局部脑容量相关。

人体肠道微生物组在中枢神经系统的基本神经发育过程中起着重要作用，并与多种神经精神疾病有关。但是，肠道微生物组与精神分裂症（SCZ）的潜在发病机制之间的联系定义不清。在这里，我们使用16S rRNA基因序列分析了40例首发首次药物治疗的SCZ（FSCZ）患者，85例经长期抗精神病药物治疗的SCZ（TSCZ）患者和69例健康对照（HCs）的粪便样本，以确定是否改变了肠道微生物组与SCZ或抗精神病药物治疗有关。此外，我们通过使用结构磁共振成像来测试微生物成分是否与结构性脑电信号相关，从而获得了T1加权脑成像数据。我们的分析显示，与HCs相比，TSCZ患者的微生物组α多样性指数低，而FSCZ患者的微生物群α多样性指数低。重要的是，与HCs相比，FSCZ和TSCZ患者在某些分类单元上的肠道微生物组成都有明显变化，包括克里斯滕菌科，肠杆菌科，巴斯德杆菌科，杜鹃花科和属大肠杆菌。我们还发现TSCZ与FSCZ患者的肠道微生物组成有明显紊乱（例如肠球菌科和乳杆菌科）。最有趣的是，我们的探索性分析发现，与SCZ相关的特定菌群与SCZ患者异常的右中额回（rMFG）量相关。