Multi-Omics Analysis Reveals Aberrant Gut-Metabolome-Immune Network in Schizophrenia

Frontiers in Immunology

Feng Zhu²  Zai Yang³  Fengjie Gao³  Xiancang Ma³  Li Qian³  Qingyan Ma³  Xiaoyan He³  Wei Wang³  Yuan Gao³  Binbin Zhao³  Yajuan Fan³  Bin Yan⁴  Jian Yang⁴ 

[1] Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China;Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China;Clinical Research Center for Psychiatric Medicine of Shaanxi Province, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China;Clinical Research Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China;Department of Psychiatry, The First Afffliated Hospital of Xi’an Jiaotong University, Xi’an, China;

关键词: schizophrenia;    gut microbiota;    metabolism;    cytokines;    metagenomics;   

DOI  :  10.3389/fimmu.2022.812293

来源: DOAJ

【 摘 要 】

Schizophrenia (SCZ) is associated with several immune dysfunctions, including elevated levels of pro-inflammatory cytokines. Microorganisms and their metabolites have been found to regulate the immune system, and that intestinal microbiota is significantly disturbed in schizophrenic patients. To systematically investigate aberrant gut-metabolome-immune network in schizophrenia, we performed an integrative analysis of intestinal microbiota, serum metabolome, and serum inflammatory cytokines in 63 SCZ patients and 57 healthy controls using a multi-omics strategy. Eighteen differentially abundant metabolite clusters were altered in patients displayed higher cytokine levels, with a significant increase in pro-inflammatory metabolites and a significant decrease in anti-inflammatory metabolites (such as oleic acid and linolenic acid). The bacterial co-abundance groups in the gut displayed more numerous and stronger correlations with circulating metabolites than with cytokines. By integrating these data, we identified that certain bacteria might affect inflammatory cytokines by modulating host metabolites, such as amino acids and fatty acids. A random forest model was constructed based on omics data, and seven serum metabolites significantly associated with cytokines and α-diversity of intestinal microbiota were able to accurately distinguish the cases from the controls with an area under the receiver operating characteristic curve of 0.99. Our results indicated aberrant gut-metabolome-immune network in SCZ and gut microbiota may influence immune responses by regulating host metabolic processes. These findings suggest a mechanism by which microbial-derived metabolites regulated inflammatory cytokines and insights into the diagnosis and treatment of mental disorders from the microbial-immune system in the future.

【 授权许可】

Unknown