Evidence shows that gut microbiota may play important roles in schizophrenia pathogenesis via the "gut-brain" axis, but the mechanisms remain unclear. Here, eighty-four patients with schizophrenia and 84 sex- and age-matched healthy controls were enrolled. Shotgun metagenomic sequencing and 16S rRNA sequencing were performed, and the gut microbiota-associated epitopes (MEs) were predicted, which, together with IgA content, were used to determine the gut microbiota composition associated with gut immune status. Patients with schizophrenia had significantly reduced gut microbiota richnesses compared with those of the healthy controls, and the gut microbiota compositions clearly distinguished the patients with schizophrenia from the healthy controls. Based on two-stage metagenomic-wide association studies, nineteen gut microbiota taxonomies were associated with schizophrenia, and the microbial dysbiosis (MD) index was calculated based on the abundance of differential taxonomies. We found that MD index was positively correlated with MEs diversity and gut IgA levels, and negatively correlated with gut microbiota richness.. Glutamate synthase (GOGAT) was more active in the guts of patients with schizophrenia than in those of healthy controls, and high GOGAT activity was associated with altered gut microbiota taxonomies associated with gut IgA levels. Our results may imply a role of the microbiome in the etiology of schizophrenia and contribute to the development of microbiome targeted interventions for schizophrenia.

中文翻译：

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精神分裂症患者肠道菌群和粘膜免疫的改变

有证据表明，肠道微生物群可能通过“肠-脑”轴在精神分裂症的发病机制中发挥重要作用，但其机制尚不清楚。在这里，招募了 84 名精神分裂症患者和 84 名性别和年龄匹配的健康对照。进行鸟枪宏基因组测序和 16S rRNA 测序，并预测肠道微生物群相关表位 (ME)，与 IgA 含量一起用于确定与肠道免疫状态相关的肠道微生物群组成。与健康对照者相比，精神分裂症患者的肠道微生物群丰富度显着降低，肠道微生物群组成清楚地将精神分裂症患者与健康对照区分开来。基于两阶段宏基因组关联研究，19 种肠道微生物群分类法与精神分裂症有关，微生物失调 (MD) 指数是根据不同分类法的丰度计算得出的。我们发现MD指数与MEs多样性和肠道IgA水平呈正相关，与肠道微生物群丰富度呈负相关。精神分裂症患者肠道中的谷氨酸合酶（GOGAT）比健康对照组更活跃，高GOGAT活性与肠道 IgA 水平相关的肠道微生物群分类改变有关。我们的结果可能暗示微生物组在精神分裂症病因学中的作用，并有助于开发针对精神分裂症的微生物组靶向干预措施。微生物生态失调（MD）指数是根据不同分类法的丰度计算的。我们发现MD指数与MEs多样性和肠道IgA水平呈正相关，与肠道微生物群丰富度呈负相关。精神分裂症患者肠道中的谷氨酸合酶（GOGAT）比健康对照组更活跃，高GOGAT活性与肠道 IgA 水平相关的肠道微生物群分类改变有关。我们的结果可能暗示微生物组在精神分裂症病因学中的作用，并有助于开发针对精神分裂症的微生物组靶向干预措施。微生物生态失调（MD）指数是根据不同分类法的丰度计算的。我们发现MD指数与MEs多样性和肠道IgA水平呈正相关，与肠道微生物群丰富度呈负相关。精神分裂症患者肠道中的谷氨酸合酶（GOGAT）比健康对照组更活跃，高GOGAT活性与肠道 IgA 水平相关的肠道微生物群分类改变有关。我们的结果可能暗示微生物组在精神分裂症病因学中的作用，并有助于开发针对精神分裂症的微生物组靶向干预措施。谷氨酸合酶 (GOGAT) 在精神分裂症患者的肠道中比在健康对照组中更活跃，并且高 GOGAT 活性与肠道 IgA 水平相关的肠道微生物群分类改变有关。我们的结果可能暗示微生物组在精神分裂症病因学中的作用，并有助于开发针对精神分裂症的微生物组靶向干预措施。谷氨酸合酶 (GOGAT) 在精神分裂症患者的肠道中比在健康对照组中更活跃，并且高 GOGAT 活性与肠道 IgA 水平相关的肠道微生物群分类改变有关。我们的结果可能暗示微生物组在精神分裂症病因学中的作用，并有助于开发针对精神分裂症的微生物组靶向干预措施。