Strain-level structure of gut microbiome associated with the cognitive function in major depressive disorder

Background: Although the association between gut microbiota and the pathogenesis of major depressive disorder (MDD) has been well studied, it is unclear whether the gut microbiota affects cognitive function in patients with MDD. Based on a strain-level analysis, we explored the impact of gut microbiota on cognitive function in MDD and possible mechanisms. Methods We enrolled 57 patients with MDD and 30 healthy controls (HCs) in this study and used 16S rRNA gene sequencing analysis to determine gut microbial composition. Untargeted metabolite analyses were used to assess differences in metabolites between the two groups. A bespoke neuropsychological test suite was used to test the cognitive function of patients with MDD. Results We found that the richness and diversity of gut microbiota in patients with MDD was the same as that in HCs, but there were differences in the abundance of Bifidobacterium and Blautia . Compared with HCs, three strains (bin_31, bin_32, and bin_55) were significantly increased in patients with MDD base on the strain-level meta-analysis. We found time to complete the Stroop-C had a significant negative correlation with bin_31 and bin_32 (both P  < 0.05). Bin_55 had a significant negative correlation with time to complete the Stroop-C, time to complete the Stroop-CW, and repeated animal words in 60 seconds, but a significant positive correlation with correct answers in 120s on the Stroop-CW (all P  < 0.05). Co-occurrence network analysis showed that bin_31 had a significant negative correlation with Cer(d14:2(4E,6E)/22:0(2OH)) ( P  < 0.01). In addition, bin_55 had a significant positive correlation with Capsanthin 5,6-epoxide and a negative correlation with 5-Hepteneoylglycine, and bin_32 had a significant positive correlation with 6-Gingerol and Montecristin and negative correlation with 5-Hepteneoylglycine and 12-HETE-GABA (all P  < 0.05) Conclusions In the present study, we found a significant correlation between several strains of gut microbes (bin_31, bin_32, and bin_55) and cognitive function in patients with MDD. This provides a new basis for the treatment of MDD by intervening with the gut microbiome.