Exploring the Hypothetical Role ofBacteroidesSpecies in Depression Progression: Insights from Metagenomic Analysis

Depression, a psychiatric disorder with significant morbidity and mortality, has a complex etiology. Recent advances in microbiome research have highlighted the potential role of gut microbiota in depression pathogenesis. This study utilized shotgun metagenomic sequencing to compare the fecal microbiota of 28 depression patients and 26 healthy individuals. Significant differences in gut microbiota composition were observed between the two groups. We generated 350 non-redundant high-quality metagenome-assembled Genomes (MAGs) by binning and conducted comparisons between the depression and control groups. Notably, we found that the MAGs enriched in people with depression mostly belonged to Bacte ndicating a close link between Bacteroides abundance and the development of depression, suggesting that Bacteroides might be a potential culprit for de roides , ipression. In the depression group, we found that the module of nitric oxide synthesis was remarkably enriched, and all Bacteroides MAGs were annotated to nitric oxide synthase, suggesting that increased levels of Bacteroides may contribute to elevated nitric oxide synthesis. Specifically, the mean relative abundance about the genomes of Bacteroides xylanisolvens , Bacteroides caccae , Bacteroides fragilis , Bacteroides stercoris and Bacteroides ovatus showed strong discriminatory power in distinguishing depressed patients from healthy individuals (AUC=0.834). This research shed light on the potential role of gut microbiota in depression and highlights specific metabolic pathways and microbial markers for further investigation. Improtance This research highlighted significant differences in the composition and function of gut microbiota between individuals with depression and healthy individuals, particularly the enrichment of Bacteroides MAGs in depression patients. The upregulation of the nitric oxide synthesis pathway associated with these MAGs belong to Bacteroides in the gut of depression patients had also been observed. The mean relative abundance of a specific set of Bacteroides MAGs had been identified, which could accurately classify individuals with depression from healthy individuals (AUC=0.834). Our results suggest the importance of exploring microbial markers as potential diagnostic and therapeutic targets in managing depression.