Clinical Laboratory, Longgang Distric Central Hospital, Affliated to Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong 518116, China.
Shanghai Key Laboratory of Birth Defects, The Molecular Medical Center, Pediatrics Research Institute, Children's Hospital of Fudan University, National Center for Children's Health, Shanghai 201102, China.
Brain Behav Immun. 2020 Mar;85:120-127. doi: 10.1016/j.bbi.2019.06.039. Epub 2019 Jun 27.
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.
证据表明，肠道微生物群可能通过“肠-脑”轴在精神分裂症发病机制中发挥重要作用，但具体机制尚不清楚。在这里，我们招募了 84 名精神分裂症患者和 84 名性别和年龄匹配的健康对照者。进行了 shotgun 宏基因组测序和 16S rRNA 测序，并预测了与肠道微生物群相关的表位（MEs），这些表位与 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。与健康对照组相比，精神分裂症患者的肠道微生物丰富度明显降低，肠道微生物组成清楚地区分了精神分裂症患者和健康对照组。基于两阶段宏基因组关联研究，有 19 种肠道微生物分类群与精神分裂症相关，并且基于差异分类群的丰度计算了微生物失调（MD）指数。我们发现 MD 指数与 ME 多样性和肠道 IgA 水平呈正相关，与肠道微生物丰富度呈负相关。与健康对照组相比，精神分裂症患者的肠道中谷氨酸合酶（GOGAT）活性更高，而高 GOGAT 活性与与肠道 IgA 水平相关的肠道微生物分类群的改变有关。我们的研究结果可能暗示了微生物组在精神分裂症发病机制中的作用，并有助于开发针对精神分裂症的微生物组靶向干预措施。
