Multiomics analysis reveals aberrant tryptophan-kynurenine metabolism and immunity linked gut microbiota with cognitive impairment in major depressive disorder.

Abstract

Objective: Cognitive impairment occurs throughout the entire course of and affects the work and life of patients with major depressive disorder (MDD). The gut microbiota, kynurenine pathway (KP) and inflammatory response may have important roles in the mechanism of cognitive impairment in MDD patients. Consequently, our goal was to investigate the association among the gut microbiota, inflammation, KP, and cognition in MDD.

Method: We enrolled patients with MDD (N = 86) and healthy controls (HCs, N = 120) in this research. The study involved participant data regarding the levels of serum inflammatory factors (interleukin [IL]-1β, IL-4, IL-6, brain-derived neurotropic factor [BNDF], migration inhibitory factor [MIF], tumor necrosis factor [TNF]-α, vascular endothelial growth factor [VEGF]), gut microbiota and cognitive function (MCCB) were collected.

Results: Patients demonstrated poorer cognitive function. Gut microbiota, such as Bacteroide, Prevotella, Faecalibacterium and Parabacteroides between MDDs and HCs were significantly different. Moreover, in patients with MDD, we found that different microbiomes were related to cognition and that Acidaminococcus was positively correlated with multiple domains of cognition. Allisonella and Acidaminococcus were significantly positively correlated with BDNF and negatively correlated with MIF. Alloprevotella, Blautia, and Megamonas were positively correlated with kynurenine/tryptophan (KYN/TRP). Acidaminococcus was negatively correlated with 3-hydroxykynurenine (3-HK). BDNF levels was significantly positive correlated with kynurenic acid (KA) and quinolinic acid (QA).

Conclusion: The results of the present study suggest that the gut microbiota is associated with cognitive function, cytokine levels and KP metabolism in patients with MDD; however, the mechanism of the interaction between cognition and gut microbiota in MDD patients require further investigation.