Relationships of oxidative stress, inflammation and gut microbiota with cognitive impairment in first-episode major depressive disorders: a pilot study in China
Objective Cognitive impairment runs through the entire course of major depressive disorder (MDD). However, the relationships between cognitive impairment and the gut microbiota (GM) and their predicted metabolic pathways as well as peripheral blood indicators remains unclear. We aimed to explore these relationships. Method Patients (n = 61) and healthy controls (HCs, n = 84) were enrolled. Our analyses were performed using data from the Hamilton Depression Scale, cognitive function (MATRICS™ Consensus Cognitive Battery [MCCB]), the GM and their predicted metabolic pathways, and peripheral blood indicators, including homocysteine (Hcy), superoxide dismutase (SOD), and C-reactive protein (CRP). Results In comparison with HCs, patients with MDD exhibited significant cognitive impairment, elevated SOD levels, enrichment of specific GM, and upregulation of microbial predicted metabolic pathways involving L-alanine, pyruvate, and salicortin. In patients with MDD, the salicortin biosynthesis pathway and pathways related to L-alanine metabolism were negatively correlated with the levels of Hcy and CRP, respectively, while the superpathway of de novo pyrimidine deoxyribonucleotide biosynthesis was positively correlated with the SOD levels. The abundance of Blautia_caecimuris and Dysosmobacter_sp._NSJ-60 was positively correlated with the scores for processing speed and attention/vigilance domain, while the abundance of Enterocloster_aldenensis was negatively correlated with the score for working memory. Moreover, the 6-gingerol analog biosynthesis pathway was negatively correlated with the score for processing speed. Conclusion Our research showed that the GM and their predicted metabolic pathways in patients with MDD were closely related to cognitive function and peripheral blood indicators, and that differences in these factors may manifest as oxidative stress and inflammation.