Gut microbiota and cognitive performance: A bidirectional two-sample Mendelian randomization

Previous studies have suggested a potential association between gut microbiota and neurological and psychiatric disorders. However, the causal relationship between gut microbiota and cognitive performance remains uncertain. A two-sample Mendelian randomization (MR) study used SNPs linked to gut microbiota (n = 18,340) and cognitive performance (n = 257,841) from recent GWAS data. Inverse-variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode were employed. Heterogeneity was assessed via Cochran's Q test for IVW. Results were shown with funnel plots. Outliers were detected through leave-one-out method. MR-PRESSO and MR-Egger intercept tests were conducted to address horizontal pleiotropy influence. Limited to European populations, generic level, and potential confounding factors. IVW analysis revealed detrimental effects on cognitive perfmance associated with the presence of genus Blautia (P = 0.013, 0.966[0.940–0.993]), Catenibacterium (P = 0.035, 0.977[0.956–0.998]), Oxalobacter (P = 0.043, and 0.979[0.960–0.999]). Roseburia (P < 0.001, 0.935[0.906–0.965]), in particular, remained strongly negatively associated with cognitive performance after Bonferroni correction. Conversely, families including Bacteroidaceae (P = 0.043,1.040[1.001–1.081]), Rikenellaceae (P = 0.047,1.026[1.000–1.053]), along with genera including Paraprevotella (P = 0.044, 1.020[1.001–1.039]), Ruminococcustques group (P = 0.016, 1.062[1.011–1.115]), Bacteroides (P = 0.043, 1.040[1.001–1.081]), Dialister (P = 0.027, 1.039[1.004–1.074]), Paraprevotella (P = 0.044, 1.020[1.001–1.039]) and RuminococcaceaeUCG003 (P = 0.007,1.040[1.011–1.070]) had a protective effect on cognitive perfmance. Our results suggest that interventions targeting specific gut microbiota may offer a promising avenue for improving cognitive function in diseased populations. The practical application of these findings has the potential to enhance cognitive performance, thereby improving overall quality of life.