Gut microbiome, and immune cells mediated effect on depression: A two-step, two-sample Mendelian randomization...

Area of Science:

• Genetics and Microbiology
• Immunology
• Psychiatry

Background:

• The gut microbiota (GM) is implicated in immune-related diseases and depression (Dep).
• The precise role of immune cells (ImC) in mediating the GM-Dep relationship remains unclear.

Purpose of the Study:

• To investigate if immune cells mediate the effect of the gut microbiota on depression.
• To identify and quantify the role of specific immune characteristics as potential mediators.

Main Methods:

• Utilized pooled genome-wide association study (GWAS) statistics for gut microbiota (n=7738) and immune cells (n=3757).
• Employed a mediated Mendelian randomization (MR) approach using depression data (n=47,696) to assess causal relationships.
• Investigated the mediating role of immune cells in the association between gut microbiota and depression.

Main Results:

• Genetically predicted gut microbiota showed significant correlations with both immune cells and depression.
• MR analysis identified five specific microbiomes, including Methionine biosynthesis III, with significant causal effects on depression.
• Five immune cell traits, such as T cell proportions and specific CD markers, were significantly associated with both GM and depression, with CD27 on peripheral blood plasma cells mediating 7.88% of the effect.

Conclusions:

• Gut microbiota plays a potential causal role in depression, mediated by immune cells.
• Findings elucidate the pathogenic mechanisms of GM in depression and highlight immune mediation risks.
• Suggests exploring immunologic intervention therapies for depression patients.