A Mendelian randomization (MR) analysis found potential protective effects of Actinobacteria and Bifidobacteriaceae from the pathogenesis of major depressive disorder (MDD). These findings were published in the Journal of Affective Disorders.
Genome-wide association study (GWAS) results from a study of microbiota conducted using data from the international MiBioGen consortium and GWAS on MDD using data from the Psychiatric Genomics Consortium (PGC) were used in this study. Genetic data were sourced from a large association study comprising 24 international cohorts (n=18,340) and MDD data were sourced from a meta-analysis comprising 29 cohorts (cases n=135,458; controls n=344,901). This MR analysis considered a total of 211 taxa and their relationship with the pathogenesis of MDD.
Class Actinobacteria was negatively related with MDD (odds ratio [OR], 0.89; 95% CI, 0.87-0.9; P <.0001) with no directional horizontal pleiotropy (P =.08), horizontal pleiotropy (P =1), or heterogeneity (P =1).
Bifidobacteriaceae was also negatively related with MDD (OR, 0.89; 95% CI, 0.88-0.91; P <.0001) with no directional horizontal pleiotropy (P =.297), horizontal pleiotropy (P =1), or heterogeneity (P =1).
Bifidobacterium had similar effects (OR, 0.89; 95% CI, 0.88-0.91; P <.0001) with no directional horizontal pleiotropy (P =.201), horizontal pleiotropy (P =1), or heterogeneity (P =1).
Results from Ruminococcus were unclear, in which the main analysis indicated a negative relationship with MDD (OR, 0.88; 95% CI, 0.78-0.98; P =.024), but no effect was observed in further analyses (OR, 1.15; 95% CI, 0-359.77; P =.965).
Conversely, Streptococcaceae was positively associated with MDD (OR, 1.07; 95% CI, 1.01-1.14; P =.023), but was not significant in further analyses (OR, 1.42; 95% CI, 0.03-60.21; P =.857). Similarly, Streptococcus was significant in some analyses (OR, 2.59; 95% CI, 1.64-4.08; P =.0001) but not others (OR, 1.02; 95% CI, 0.99-1.05; P =.192).
The major limitation of this study was the inability of the investigators to correct for potential cofounders, such as medication use and diet.
Study authors concluded, “Our MR study showed that the Family Bifidobacteriaceae and its Genus Bifidobacterium had protective causal effects on MDD, which were consistent with previous studies. In addition, our study also demonstrated that the Actinobacteria and Ruminococcus might have a protective effect while Streptococcus might have anti-protective effects on MDD pathogenesis, but these findings warrant further examination owing to the unclear mechanisms.”
Chen M, Xie CR, Shi YZ, Tang TC, Zheng H. Gut microbiota and major depressive disorder: a bidirectional Mendelian randomization. J Affect Disord. 2022;316:187-193. doi:10.1016/j.jad.2022.08.012