Causal associations between gut microbiota and regional cortical structure: a Mendelian randomization study

Maochao Zhou; Song Chen; Yan Chen; Chunhua Wang; Chunmei Chen

doi:10.3389/fnins.2023.1296145

Causal associations between gut microbiota and regional cortical structure: a Mendelian randomization study

Front Neurosci. 2023 Dec 22:17:1296145. doi: 10.3389/fnins.2023.1296145. eCollection 2023.

Authors

Maochao Zhou^#¹, Song Chen^#¹, Yan Chen¹, Chunhua Wang², Chunmei Chen¹

Affiliations

¹ Department of Neurosurgery, Fujian Medical University Union Hospital, Fuzhou, China.
² Fujian Institute of Neurosurgery, Fuzhou, China.

^# Contributed equally.

Abstract

Introduction: Observational studies have reported associations between gut microbiota composition and central nervous system diseases. However, the potential causal relationships and underlying mechanisms remain unclear. Here, we applied Mendelian randomization (MR) to investigate the causal effects of gut microbiota on cortical surface area (SA) and thickness (TH) in the brain.

Methods: We used genome-wide association study summary statistics of gut microbiota abundance in 18,340 individuals from the MiBioGen Consortium to identify genetic instruments for 196 gut microbial taxa. We then analyzed data from 56,761 individuals from the ENIGMA Consortium to examine associations of genetically predicted gut microbiota with alterations in cortical SA and TH globally and across 34 functional brain regions. Inverse-variance weighted analysis was used as the primary MR method, with MR Egger regression, MR-PRESSO, Cochran's Q test, and leave-one-out analysis to assess heterogeneity and pleiotropy.

Results: At the functional region level, genetically predicted higher abundance of class Mollicutes was associated with greater SA of the medial orbitofrontal cortex (β = 8.39 mm², 95% CI: 3.08-13.70 mm², p = 0.002), as was higher abundance of phylum Tenericutes (β = 8.39 mm², 95% CI: 3.08-13.70 mm², p = 0.002). Additionally, higher abundance of phylum Tenericutes was associated with greater SA of the lateral orbitofrontal cortex (β = 10.51 mm², 95% CI: 3.24-17.79 mm², p = 0.0046). No evidence of heterogeneity or pleiotropy was detected.

Conclusion: Specific gut microbiota may causally influence cortical structure in brain regions involved in neuropsychiatric disorders. The findings provide evidence for a gut-brain axis influencing cortical development, particularly in the orbitofrontal cortex during adolescence.

Keywords: Mendelian randomization study; brain cortical structure; gut microbiota; gut-brain axis; neuropsychiatric disorders.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by Fujian Provincial Clinical Key Specialty Construction Program of Neurosurgery (grant no. 05029002).