Association of gut microbiota with cerebral cortical thickness: A Mendelian randomization study

Abstract

Background: The causal relationship between gut microbiota and cerebral cortex development remains unclear. We aimed to scrutinize the plausible causal impact of gut microbiota on cortical thickness via Mendelian randomization (MR) study.

Methods: Genome-wide association study (GWAS) data for 196 gut microbiota phenotypes (N = 18,340) were obtained as exposures, and GWAS data for cortical thickness-related traits (N = 51,665) were selected as outcomes. Inverse variance weighted was used as the main estimate method. A series of sensitivity analyses was used to test the robustness of the estimates including Cochran's Q test, MR-Egger intercept analysis, Steiger filtering, scatter plot funnel plot and leave-one-out analysis.

Results: Genetic prediction of high Bacillales (β = 0.005, P = 0.032) and Lactobacillales (β = 0.010, P = 0.012) abundance was associated with a potential increase in global cortical thickness. For specific functional brain subdivisions, genetically predicted order Lactobacillales would potentially increase the thickness of the fusiform (β = 0.014, P = 0.016) and supramarginal (β = 0.017, P = 0.003). Meanwhile, order Bacillales would increase the thickness of fusiform (β = 0.007, P = 0.039), insula (β = 0.011, P = 0.003), rostralanteriorcingulate (β = 0.014, P = 0.002) and supramarginal (β = 0.006, P = 0.043). No significant estimates of heterogeneity or pleiotropy were found.

Conclusions: Through MR studies, we discovered genetic prediction of the Lactobacillales and Bacillales orders potentially linked to cortical thickness, affirming gut microbiota may enhance brain structure. Genetically predicted supramarginal and fusiform may be potential targets.

Keywords: Cerebral cortex thickness; Genetic variants; Gut microbiota; Mendelian randomization.