Differences in the gut microbiota and plasma metabolome of major depressive disorder patients with and without ischemic stroke

Abstract

Background Major depressive disorder (MDD) and ischemic stroke (IS) are prominent contributors to disease burden worldwide, and MDD has been recognized as a significant risk factor for IS in epidemiology studies; however, the specific mechanisms that explain the coexistence of MDD and IS have not been identified. Multiple studies have shown a strong association between the gut microbiota and both IS and MDD. We propose that the gut microbiota may play a role in the development of IS in individuals with MDD. This study aimed to investigate the mechanisms linking the gut microbiota and increased risk of IS development in patients with MDD. Methods We included 30 hospitalized individuals diagnosed with MDD with IS and 30 individuals diagnosed with MDD without IS using the matching method and used 16S rRNA gene sequencing and the nontarget metabolome to analyze the gut microbiota composition and plasma metabolic profiles of the included patients. Results MDD patients with IS and MDD patients without IS have different gut microbiota structures and plasma metabolic profiles. MDD patients with IS had more bacteria with lipopolysaccharide (LPS) structures and lacked bacteria that produce butyrate. Alloprevotella and Bacteroides massiliensis, along with their associated metabolites, facilitated precise differentiation between patients with and without IS. The area under the curve (AUC) for these bacteria was 0.998 (95% confidence interval: 0.992-1.000) and 0.992 (95% confidence interval: 0.978-1.000). Conclusions Compared with MDD patients without IS, patients with MDD who also had IS exhibited distinct changes in their gut microbiome and metabolite profiles. Changes in the gut microbiome are evident by an elevated abundance of bacteria with LPS structures and a reduced abundance of bacteria that produce butyrate. Additionally, the abundances of Alloprevotella and Bacteroides massiliensis, along with their related metabolites, strongly predict IS in patients with MDD.