Causal link between gut microbiome and schizophrenia: a Mendelian randomization study

Abstract

Objective 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. Methods 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). Results 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. Conclusion 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.