Gut viral metagenomics identifies viral signatures and their role in depression

Chen Xinyu¹Dahua Fan²Peiwen Zhang³Yongkai Cao^4,5*Meiqun Cao^5*

• ¹Graduate School, Guangxi University of Chinese Medicine, Guangxi, China
• ²Shunde Women and Children Hospital and Health Institute, Foshan, Guangdong Province, China
• ³Shandong Daizhuang Hospital, Jining, Shandong Province, China
• ⁴Shenzhen University, Shenzhen, China
• ⁵Institute of Translational Medicine, Shenzhen Second People's Hospital, Shenzhen, Guangdong Province, China

The gut microbiome has been implicated in the onset and progression of depression. Yet, the role of the gut virome in depression remains unexplored, and a diagnostic model has not been satisfactorily constructed. Herein, we analysed the gut virome profiles of 33 patients with depression and 29 healthy controls using bulk metagenome sequencing. A total of 45 differentially viral taxa were identified, among which four, s_Stenotrophomonas_virus_Pokken, g_Pokkenvirus, s_Dickeya_virus_AD1, and g_Alexandravirus, demonstrated strong diagnostic potential (AUCs > 0.8). These four viruses also exhibited strong correlations, suggesting they may constitute a synergistic ecological cluster. Function annotation revealed seven metabolic pathways with significant differences, including alanine, aspartate, and glutamate metabolism, branched-chain amino acid (BCAA) biosynthesis, and energy metabolism in patients with depression. This study identified four distinct viral signatures for depression and proposes novel viral biomarkers for its depression diagnosis, offering a robust diagnostic approach and new insights into pathological mechanisms of depression.