Altered gut microbiota and mucosal immunity in patients with schizophrenia

• Published in: Brain, behavior, and immunity behavior, and immunity, 2020-03, Vol.85, p.120-127
• Main Authors: Xu, Ruihuan, Wu, Bingbing, Liang, Jingwen, He, Fusheng, Gu, Wen, Li, Kang, Luo, Yi, Chen, Jianxia, Gao, Yongbo, Wu, Ze, Wang, Yongqiang, Zhou, Wenhao, Wang, Mingbang
• Format: Article
• Language: English
• Subjects: 16S rRNA sequencing; Dysbiosis; Epitopes; Gastrointestinal Microbiome; Humans; IgA; Immunity, Mucosal; Microbial dysbiosis index; RNA, Ribosomal, 16S - genetics; Schizophrenia; Shotgun metagenomic sequencing
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2019.06.039

•Question Does the gut microbiota play a role in patients with schizophrenia through immune-mediated mechanisms?•Findings Reduced gut microbiota richnesses and altered gut microbiota-associated epitopes (MEs) were found in patients with schizophrenia. Nineteen gut microbiota taxonomies were associated with schizophrenia. Patients with schizophrenia exhibited high gut microbial dysbiosis (MD) index and were associated with high ME diversity and gut IgA levels. High gut Glutamate synthase (GOGAT) activity was found and associated with gut IgA levels. MD index, IgA, and GOGAT may be potential biomarkers for diagnosing schizophrenia.•Meaning These results suggest that schizophrenia may be associated with perturbation of gut immune function due to altered MEs, and regulating gut microbiota compositions and immunity may be a new approach to treating schizophrenia. 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.