A causal role of the gut microbiome in schizophrenia

The gut-brain axis has been enthusiastically discussed in recent years. Gut bacteria are known to promote serotonin biosynthesis from colonic enterochromaffin cells1. Germ-free mice are also known to have impaired blood-brain barrier, which could be rescued by short-chain fatty acids2. However, there has been little evidence from human studies, not to mention a study that combined human cohorts with animal models. Here we provide metagenomic shotgun sequencing data for a typical psychiatric disease, schizophrenia, for which tens of thousands of samples have been characterized in genome-association studies (GWAS). Metagenome-wide association studies (MWAS) identified bacteria that differ between patients and controls, which was partially recapitulated in mice transplanted with the human faeces. We show that the schizophrenic gut microbiome was causally responsible for core symptoms such as psychomotor hyperactivity and impaired learning and memory, whereas non-specific symptoms such as anxiety were lost in the mice model. Our findings pave the road for better diagnosis as well as mechanistic understandings of this devastating disease.