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Gut Microbiota, Disorders of Gut-Brain Interaction and Psychiatric Disorders: a Mendelian Randomization Study
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.
Insights
This study used Mendelian randomization to investigate causal links between gut microbiota, gut-brain interaction disorders (DGBIs), and psychiatric disorders. Findings suggest genetic predispositions connecting these conditions, offering insights for future treatments.
Area of Science:
- Genetics
- Microbiology
- Psychiatry
- Gastroenterology
Background:
- Observational studies indicate associations between gut microbiota, disorders of gut-brain interaction (DGBIs), and psychiatric disorders.
- The complex interplay between the gut microbiome and brain function necessitates causal investigation.
Purpose of the Study:
- To systematically identify causal relationships between gut microbiota abundances and the risk of DGBIs and psychiatric disorders using Mendelian randomization (MR).
- To explore potential bidirectional causal links between DGBIs and psychiatric disorders.
- To investigate potential mediators in the gut-brain axis.
Main Methods:
- Utilized large-scale genome-wide association study (GWAS) data for gut microbiota, DGBIs, and psychiatric disorders.
- Employed inverse-variance weighting, MR-Egger, and weighted median methods for causal inference.
- Conducted sensitivity analyses (MR-Egger intercept, Cochran's Q, MR-PRESSO, leave-one-out, funnel plots) and reverse-MR analysis.
Main Results:
- Identified 44 causal relationships between gut microbiota and DGBIs, and 66 between gut microbiota and psychiatric disorders.
- Revealed bidirectional causal links between DGBIs and psychiatric disorders, with psychiatric disorders more likely to influence DGBIs.
- Sensitivity analyses confirmed the robustness of the findings.
Conclusions:
- The study suggests potential genetic predispositions linking gut microbiota, DGBIs, and psychiatric disorders.
- Findings provide novel insights into pathophysiological modulators for brain-gut interactions.
- Results may inform the development of targeted treatment strategies for these interconnected conditions.
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