Viral metagenomics combined with metabolomics reveals the role of gut viruses in mouse model of depression.

Depression is a heterogeneous mental disorder that has been linked to disturbances in the gut microbiome. As an essential part of the gut microbiome, gut virome may play critical roles in disease progression and development. However, the relationship between the effect of gut virome on neurotransmitter metabolism and depression is unknown. We evaluated the alterations of gut virome and neurotransmitters in chronic restraint stress (CRS)-induced mouse model of depression based on viral metagenomics and LC-MS/MS metabolomics analyses. The results reveal that the gut virome profile of CRS group differed significantly from CON group. was the most abundant differential viral family in both groups, followed by , while was only enriched in CRS group of the top 100 differential viruses. The differential viruses that predicted to phage, phage and phage were enriched in CRS group. Furthermore, 12 differential neurotransmitters primarily involved in the tryptophan metabolism pathway were altered in depressive-like mice. Besides, tryptamine and 5-methoxytryptamine hydrochloride were strongly associated with differential viruses belonging to and . Our findings provide new insight into understanding the potential role of the gut virome and metabolites in depression.