Assessing the joint effects of brain aging and gut microbiota on the risks of psychiatric disorders.

We aim to explore the potential interaction effects of brain aging and gut microbiota on the risks of sleep, anxiety and depression disorders. The genome-wide association study (GWAS) datasets of brain aging (N = 21,407) and gut microbiota (N = 3,890) were obtained from published studies. Individual level genotype and phenotype data of psychiatric traits (including sleep, anxiety and depression) were all from the UK Biobank (N = 107,947-374,505). We first calculated the polygenic risk scores (PRS) of 62 brain aging modes and 114 gut microbiota taxa as the instrumental variables, and then constructed linear and logistic regression analyses to systematically explore the potential interaction effects of brain aging and gut microbiota on psychiatric disorders. We observed the interaction effects of brain aging and gut microbiota on sleep, anxiety and depression disorders, such as Putamen/caudate T2* vs. Rhodospirillales (β = -0.012, P = 8.4 × 10-4) was negatively associated with chronotype, Fornix MD vs. Holdemanella (β = -0.007, P = 1.76 × 10-2) was negatively related to general anxiety disorder (GAD) scores, and White matter lesions vs. Acidaminococcaceae (β = 0.019, P = 1.29 × 10-3) was positively correlated with self-reported depression. Interestingly, Putamen volume vs. Intestinibacter was associated with all three psychiatric disorders, including chronotype (negative correlation), GAD scores (positive correlation) and self-reported depression (positive correlation). Our study results suggest the significant impacts of brain aging and gut microbiota on the development of sleep, anxiety and depression disorders, providing new clues for clarifying the pathogenesis of these disorders.