Causal effect of the gut microbiota on the risk of psychiatric disorders and the mediating role of immunophenotypes

Abstract

Background: Growing evidence indicates a significant correlation between the gut microbiota, immune system, and psychiatric disorders. Nevertheless, the impacts and interactions of the gut microbiota and immunophenotypes on psychiatric disorders remain unclear. Methods: We utilized a bidirectional Mendelian randomization (MR) study to evaluate the causal associations among the gut microbiota, immunophenotypes, and psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), posttraumatic stress disorder (PTSD), schizophrenia (SCZ), and Tourette's syndrome (TS). The primary analysis was conducted using the inverse variance weighted (IVW) method, with several complementary sensitivity analyses being performed to ensure the reliability of the results. Results: Our study reveals significant causal relationships between 22 immunophenotypes, 15 types of gut microbiota, and various psychiatric disorders. We further sought to ascertain whether immunophenotypes act as intermediaries in the pathway from gut microbiota to psychiatric disorders. In particular, three immunophenotypes were identified that mediate the causal effects of different gut microbiota on ADHD. Additionally, one immunophenotype was detected to mediate the causal effects of gut microbiota on PTSD. Conclusions: Our study indicates that immunophenotypes partially mediate the pathway from the gut microbiota to psychiatric disorders.