Gut Microbiota and Psychiatric Disorders: A Two-Sample Mendelian Randomization Study.

Evidence supports the observational associations of gut microbiota with a variety of psychiatric disorders, but the causal nature of such associations remains obscure. Aiming to comprehensively investigate their causal relationship and to identify specific causal microbe taxa for psychiatric diseases, we conducted a two-sample Mendelian randomization (MR) analysis of gut microbiome with 15 psychiatric diseases. Specifically, the microbiome genome-wide association study (GWAS) in 18,473 individuals from the MiBioGen study was used as exposure sample, and the GWAS for 15 psychiatric diseases was used as outcome samples. One-hundred ninety bacterial taxa from six levels were available for analysis. At a multiple-testing corrected significance level (phylum < 5.56 × 10, class < 3.33 × 10, order < 2.63 × 10, family < 1.67 × 10, genus < 4.90 × 10, and species < 3.33 × 10), the following eight causal associations from seven bacterial features (one phylum + three classes + one order + one family + one species) were identified: family with autism spectrum disorder ( = 5.31 × 10), class with bipolar disorder ( = 1.53 × 10), class with schizophrenia ( = 1.33 × 10), class and order with Tourette syndrome ( = 2.51 × 10 and 2.51 × 10), phylum and class with extroversion ( = 8.22 × 10 and 1.09 × 10), and species with neuroticism ( = 8.92 × 10). Sensitivity analysis showed no evidence of reverse causality, pleiotropy, and heterogeneity. Our findings offered novel insights into the gut microbiota-mediated development mechanism of psychiatric disorders.