Dissecting the Association between Gut Microbiota and Brain Structure Change Rate: A Two-Sample Bidirectional Mendelian Randomization Study

The connection between the gut microbiota and brain structure changes is still unclear. We conducted a Mendelian randomization (MR) study to examine the bidirectional causality between the gut microbiota (211 taxa, including 131 genera, 35 families, 20 orders, 16 classes and 9 phyla; N = 18,340 individuals) and age-independent/dependent longitudinal changes in brain structure across the lifespan (N = 15,640 individuals aged 4~99 years). We identified causal associations between the gut microbiota and age-independent/dependent longitudinal changes in brain structure, such as family Peptostreptococcaceae with age-independent longitudinal changes of cortical gray matter (GM) volume and genus Faecalibacterium with age-independent average cortical thickness and cortical GM volume. Taking age-independent longitudinal changes in brain structure across the lifespan as exposures, there were causal relationships between the surface area and genus Lachnospiraceae. Our findings may serve as fundamentals for further research on the genetic mechanisms and biological treatment of complex traits and diseases associated with the gut microbiota and the brain structure change rate.