From microbes to mind and actions: Uncovering the gut-brain connection in major depressive disorder and its implications for human health and lifestyle - presented by Maria Kardakova

From microbes to mind and actions: Uncovering the gut-brain connection in major depressive disorder and its implications for human health and lifestyle

Maria Kardakova

Maria Kardakova
From microbes to mind and actions: Uncovering the gut-brain connection in major depressive disorder and its implications for human health and lifestyle
Maria Kardakova
Maria Kardakova
University of Surrey

The gut microbiome, shaped by dietary choices, medication use, and host genetics, is emerging as a key determinant of physical and mental health. In this study, we explored the intricate links between the gut microbiome and major depressive disorder (MDD). Using a comprehensive dataset included 16S rRNA gene sequences from 7,472 individuals across Eastern and Western Europe, we employed a discovery-replication design followed by meta-analysis. Data processing and bioinformatics analyses were conducted using the QIIME2 platform.

In the discovery set, 544 individuals (12%) reported a clinical diagnosis of MDD, compared to 3,912 without. Similarly, in the replication set, 285 (12%) reported MDD, while 2,167 did not. We applied linear regression models and meta-analysis across the two datasets using MaAsLin2 and ANCOM-BC2, adjusting for geographic region, age, gender, and batch effects using bacterial relative abundance was the primary outcome. Meta-analysis across the datasets identified 22 taxa significantly associated with MDD (q<0.05) using MaAsLin2, with nine taxa: Romboutsia, Clostridium sensu stricto, Agathobacter, Bacteroides pectinophilus group, Flavonifractor, Coprococcus, Victivallis, Tyzzerella, and Bacteroides, - confirmed by ANCOM-BC2.

MR analysis using MiBioGen and depression GWAS data revealed no consistent causal relationships between bacterial taxa and MDD. However, mediation analyses showed that Bacteroides mediated 3–8% of single lifestyle effects and up to 61% of total effects on MDD, with notable contributions for healthy weight, physical activity, and diet. Specific taxa such as Bacteroides pectinophilus group, Victivallis, and Tyzzerella mediated 14–16%, 3–6%, and 4% of certain lifestyle effects, respectively. Additionally, a history of supplementation with Lactobacillus and Bifidobacteria probiotics was positively associated with MDD, indicating potential microbial alterations in individuals with depressive disorders. The integration of multiple bacterial taxa into a microbiome risk score outperformed single-taxon associations, achieving an AUC of 0.6 and demonstrating its potential to capture broader microbial patterns.

Our findings reveal consistent microbial signatures linked to MDD. Individuals with a history of MDD exhibited notably reduced microbiome alpha diversity but higher relative abundance of SCFA-producing bacteria. These results suggest that the gut microbiota may play a significant role in the pathophysiology of MDD and highlight the importance of microbial composition in understanding and potentially managing MDD.

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MVIF 36 - with keynote talk by Prof. Ruixin Liu
Microbiome Virtual International Forum
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M. Kardakova (2025, February 17), From microbes to mind and actions: Uncovering the gut-brain connection in major depressive disorder and its implications for human health and lifestyle
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Video length 06:43