Transplantation of microbiota from drug-free patients with schizophrenia causes schizophrenia-like abnormal behaviors and dysregulated kynurenine metabolism in mice

Research output: Contribution to journalJournal articleResearchpeer-review

  • Feng Zhu
  • Ruijin Guo
  • Wei Wang
  • Yanmei Ju
  • Qi Wang
  • Qingyan Ma
  • Qiang Sun
  • Yajuan Fan
  • Yuying Xie
  • Zai Yang
  • Zhuye Jie
  • Binbin Zhao
  • Liang Xiao
  • Lin Yang
  • Tao Zhang
  • Bing Liu
  • Liyang Guo
  • Xiaoyan He
  • Yunchun Chen
  • Ce Chen
  • Chengge Gao
  • Xun Xu
  • Huanming Yang
  • Jian Wang
  • Yonghui Dang
  • Susanne Brix
  • Huijue Jia
  • Xiancang Ma

Accumulating evidence suggests that gut microbiota plays a role in the pathogenesis of schizophrenia via the microbiota–gut–brain axis. This study sought to investigate whether transplantation of fecal microbiota from drug-free patients with schizophrenia into specific pathogen-free mice could cause schizophrenia-like behavioral abnormalities. The results revealed that transplantation of fecal microbiota from schizophrenic patients into antibiotic-treated mice caused behavioral abnormalities such as psychomotor hyperactivity, impaired learning and memory in the recipient animals. These mice also showed elevation of the kynurenine–kynurenic acid pathway of tryptophan degradation in both periphery and brain, as well as increased basal extracellular dopamine in prefrontal cortex and 5-hydroxytryptamine in hippocampus, compared with their counterparts receiving feces from healthy controls. Furthermore, colonic luminal filtrates from the mice transplanted with patients’ fecal microbiota increased both kynurenic acid synthesis and kynurenine aminotransferase II activity in cultured hepatocytes and forebrain cortical slices. Sixty species of donor-derived bacteria showed significant difference between the mice colonized with the patients’ and the controls’ fecal microbiota, highlighting 78 differentially enriched functional modules including tryptophan biosynthesis function. In conclusion, our study suggests that the abnormalities in the composition of gut microbiota contribute to the pathogenesis of schizophrenia partially through the manipulation of tryptophan–kynurenine metabolism.

Original languageEnglish
JournalMolecular Psychiatry
Volume25
Issue number11
Pages (from-to)2905-2918
Number of pages14
ISSN1359-4184
DOIs
Publication statusPublished - 2020

ID: 228248005