A causal relationship between gut microbiota and subcortical brain structures contributes to the microbiota-gut-brain axis: a Mendelian randomization study

Abstract

A correlation between gut microbiota and brain structure, referring to as a component of the gut-brain axis, has been observed in observational studies. However, the causality of this relationship and its specific bacterial taxa remains uncertain. To reveal the causal effects of gut microbiota on subcortical brain volume, we applied Mendelian randomization (MR) studies in this study. Genome-wide association study data were obtained from the MiBioGen Consortium (n = 18,340) and the Enhancing Neuro Imaging Genetics through Meta-Analysis Consortium (n = 13,170). The primary estimate was obtained utilizing the inverse-variance weighted, while heterogeneity and pleiotropy were assessed using the Cochrane Q statistic, MR Pleiotropy RESidual Sum and Outlier, and MR-Egger intercept. Our findings provide strong evidence that a higher abundance of the genus Parasutterella is causally correlated with a decrease in intracranial volume (β = -30,921.33, 95% CI -46,671.78 to -15,170.88, P = 1.19 × 10-4), and the genus FamilyXIIIUCG001 is associated with a decrease in thalamus volume (β = -141.96, 95% CI: -214.81 to -69.12, P = 1.0× 10-4). This MR study offers novel perspectives on the intricate interplay between the gut microbiota and subcortical brain volume, thereby lending some support to the existence of the microbiota-gut-brain axis.

Keywords: Mendelian randomization; gut microbiota; microbiota–gut–brain axis; subcortical brain volume.