Gut microbiota causally affects longitudinal changes in brain structure: a large-scale mendelian randomization study

Several studies have shown that the gut microbiota is associated with the brain structure. However, the causal relationship between the gut microbiota and structural changes in the brain remains undetermined. Gut microbiota data from genome-wide association (GWAS) meta-analyses summarized by the MiBioGen consortium were used (n=13,266) and screened for instrumental variables. Data from the ENIGMA consortium's GWAS meta-analysis of morphological changes in the brain were summarized as outcomes (n=15, 640). The relationship between gut microbiota and longitudinal changes in brain structure was detected using random effects inverse variance weighting (IVW), MR-Egger, MR-Weighted Median, MR-Simple Mode, and MR-Weighted Mode, and sensitivity analysis was performed. IVW estimates showed that Verrucomicrobia (β=-18.15, 95%CI: -30.25 to -6.05, P=3.27E-03) significantly attenuated the longitudinal volume changes of the putamen, Firmicutes (β=10.77, 95%CI:3.30 to 18.25), P=4.73E-03), Cyanobacteria (β=7.68, 95%CI:2.46 to 12.90, P=3.93E-03) and Gastranaerophilales (β=9.54, 95%CI:4.41 to 14.68, P=2.69E-04) significantly increased the longitudinal volume variation of pallidum. Our mendelian randomization (MR) analysis showed a causal relationship between the gut microbiota and longitudinal changes in brain structure and supported the existence of a gut-brain axis. This study provides new insights into further mechanistic and clinical studies of microbiota-mediated neuropsychiatric disorders.