Gut Microbiota, Disorders of Gut-Brain Interaction and Psychiatric Disorders: a Mendelian Randomization Study.

Abstract

Background: Observational studies suggest that there are associations among gut microbiota, disorders of gut-brain interaction (DGBIs) and psychiatric disorders. Therefore, the aim of this study was to use Mendelian randomization (MR) to systematically identify the causality of the associations among the abundances of several gut microbiota and the risk of developing DGBIs and psychiatric disorders.

Methods: Genetic data associated with gut microbiota, DGBIs, and psychiatric disorders were obtained from large-scale genome-wide association studies (GWASs). Inverse-variance weighting, MR-Egger, and weighted median methods were used to examine causal associations. The sensitivity analyses were conducted via the MR-Egger intercept test, Cochran's Q test, MR-pleiotropy residual sum and outlier (MR-PRESSO) test, leave-one-out analysis, and funnel plots. Reverse-MR analysis was performed to evaluate the possibility of reverse causation. Finally, we used MR mediation analysis to explore potential mediators of the causal associations among the abundances of gut microbiota and the risk of developing DGBIs and psychiatric disorders.

Results: Our MR analysis revealed 44 causal relationships between the abundances of several gut microbiota and the risk of developing DGBIs and 66 causal relationships between the abundances of several gut microbiota and the risk of developing psychiatric disorders. In addition, in the reverse-MR analysis, 15 causal relationships between the risk of developing DGBIs and the abundances of several gut microbiota and 47 causal relationships between the risk of developing psychiatric disorders and the abundances of several gut microbiota were explored. Our results showed that the abundances of some microbiota and their child taxa might be closely associated with the risk of developing certain diseases. Moreover, we observed one causal relationship between the risk of developing DGBIs and the risk of developing psychiatric disorders and 7 causal relationships between the risk of developing psychiatric disorders and the risk of developing DGBIs. Compared with the causal effect of the risk of developing DGBIs on the risk of developing psychiatric disorders, the risk of developing psychiatric disorders was more likely to causally influence the risk of developing DGBIs. Further sensitivity analyses reinforced the robustness of these results.

Conclusions: Our results indicate potential genetic predispositions linking gut microbiota, DGBIs, and psychiatric disorders. This information may be useful for providing new insights into the underlying pathophysiological modulators and treatment strategies for bidirectional dysregulation of brain-gut interactions.