Unveiling the Human Brain Virome in Brodmann Area 46: Novel Insights Into Dysbiosis and Its Association With Schizophrenia.

Unlabelled: Research suggests a potential role of the oral-neuro and gut-brain axes in schizophrenia, involving non-brain microbiomes such as salivary and gut microbiomes. However, the blood-brain barrier effectively prevents microorganism entry. Additionally, despite approximately 8% of the human genome consisting of and the established link between viral infections and schizophrenia, the presence of a resident virome (a viral component of the microbiome) in the brain and its association with mental disorders remain unexplored.

Methods: Whole-genome sequencing raw data from postmortem Brodmann Area 46 (BA46) tissue from 49 individuals (20 healthy controls [HCs], 29 with schizophrenia [SCZs]) obtained from the NCBI SRA database from BioProject: PRJNA422380.Virome profiles were retrieved using Metaphlan3, and viral signatures were identified using linear discriminant analysis effect size (LEfSe). Mann-Whitney tests and receiver operating characteristic curve validated the viral signatures.

Results: In BA46, 30 distinct species representing 9 phyla, 10 classes, 10 orders, 13 families, and 19 genera were identified. HCs exhibited greater alpha diversity, and there were significant differences in beta diversity between the groups. LEfSe analysis highlighted distinct viral levels, including , , , , , and in HCs, while and unknown virus showed higher levels in schizophrenia.

Conclusion: This is the first study to identify a human brain virome associated with schizophrenia in BA46. Brain virome dysbiosis may be associated with mental illness, and viral signatures may serve as biomarkers for the early detection of schizophrenia.