Some observational studies have shown that gut microbiome is significantly changed in patients with schizophrenia. We aim to identify the genetic causal link between gut microbiome and schizophrenia.

A two-sample Mendelian randomization (MR) study was used to evaluate the causal link between gut microbiome and schizophrenia with 28 gut microbiome-associated genetic instrumental variants chosen from recent MR reports and the largest schizophrenia genome-wide association studies (8-Apr-22 release).

Inverse variance weighted method showed that genetically increased Bacteroidales_S24-7 (per SD) resulted in increased risk of schizophrenia (OR = 1.110, 95% CI: [1.012–1.217], P = 0.027). Similarly, genetically increased Prevotellaceae promoted schizophrenia risk (OR = 1.124, 95% CI: [1.030–1.228], P = 0.009). However, genetically increased Lachnospiraceae reduced schizophrenia risk (OR = 0.878, 95% CI: [0.785–0.983], P = 0.023). In addition, schizophrenia risk was also suppressed by genetically increased Lactobacillaceae (OR = 0.878, 95% CI: [0.776–0.994], P = 0.040) and Verrucomicrobiaceae (OR = 0.860, 95% CI: [0.749–0.987], P = 0.032). Finally, we did not find any significant results in the causal association of other 23 gut microbiome with schizophrenia.

Our analysis suggests that genetically increased Bacteroidales_S24-7 and Prevotellaceae promotes schizophrenia risk, whereas genetically increased Lachnospiraceae, Lactobacillaceae, and Verrucomicrobiaceae reduces schizophrenia risk. Thus, regulation of the disturbed intestinal microbiota may represent a new therapeutic strategy for patients with schizophrenia.