Abstract
Rising studies have consistently reported gut bacteriome alterations in schizophrenia (SCZ). However, little is known about the role of the gut virome on shaping the gut bacteriome in SCZ. Here in, we sequenced the fecal virome, bacteriome, and host peripheral metabolome in 49 SCZ patients and 49 health controls (HCs). We compared gut bacterial community composition and specific abundant bacteria in SCZ patients and HCs. Specific gut viruses and host peripheral metabolites co-occurring with differential bacteria were identified using Multiple co-inertia analysis (MCIA). Additionally, we construct a latent serial mediation model (SMM) to investigate the effect of the gut virome on SCZ through the bacteriome and host metabolic profile. SCZ patients exhibited decreased gut bacterial β-diversity compared to HCs, with eight differentially abundant bacteria, including coprobacillaceae, enterococcaceae etc. Gut viruses including Suoliviridae, Rountreeviridae, Intestiviridae etc. co-occur with these SCZ-related bacteria. We found that the viral-bacterial transkingdom correlations observed in HCs were dramatically lost in SCZ. The altered correlations profile observed in SCZ may impact microbiota-derived peripheral metabolites enriched in the bile acids pathway, eicosanoids pathway, and others, contributing to host immunity dysfunction and inflammation. The SMM model suggested potential causal chains between gut viruses and SCZ, indicating that the gut virome's effect on SCZ is significantly mediated by the bacteriome and metabolites. In conclusion, these findings provide a comprehensive prospective on the role of gut microbiota in the pathogenesis of SCZ. They reveal that SCZ patients harbor an abnormal bacteriome-virome ecology, shedding light on the potential development of microbial therapeutics.