Improving precision management of anxiety disorders: a Mendelian randomization study targeting specific gut microbiota and associated metabolites
- PMID: 38655090
- PMCID: PMC11035889
- DOI: 10.3389/fmicb.2024.1380912
Improving precision management of anxiety disorders: a Mendelian randomization study targeting specific gut microbiota and associated metabolites
Abstract
Background: There is growing evidence of associations between the gut microbiota and anxiety disorders, where changes in gut microbiotas may affect brain function and behavior via the microbiota-gut-brain axis. However, population-level studies offering a higher level of evidence for causality are lacking. Our aim was to investigate the specific gut microbiota and associated metabolites that are closely related to anxiety disorders to provide mechanistic insights and novel management perspectives for anxiety disorders.
Method: This study used summary-level data from publicly available Genome-Wide Association Studies (GWAS) for 119 bacterial genera and the phenotype "All anxiety disorders" to reveal the causal effects of gut microbiota on anxiety disorders and identify specific bacterial genera associated with anxiety disorders. A two-sample, bidirectional Mendelian randomization (MR) design was deployed, followed by comprehensive sensitivity analyses to validate the robustness of results. We further conducted multivariable MR (MVMR) analysis to investigate the potential impact of neurotransmitter-associated metabolites, bacteria-associated dietary patterns, drug use or alcohol consumption, and lifestyle factors such as smoking and physical activity on the observed associations.
Results: Bidirectional MR analysis identified three bacterial genera causally related to anxiety disorders: the genus Eubacterium nodatum group and genus Ruminococcaceae UCG011 were protective, while the genus Ruminococcaceae UCG011 was associated with an increased risk of anxiety disorders. Further MVMR suggested that a metabolite-dependent mechanism, primarily driven by tryptophan, tyrosine, phenylalanine, glycine and cortisol, which is consistent with previous research findings, probably played a significant role in mediating the effects of these bacterial genera to anxiety disorders. Furthermore, modifying dietary pattern such as salt, sugar and processed meat intake, and adjusting smoking state and physical activity levels, appears to be the effective approaches for targeting specific gut microbiota to manage anxiety disorders.
Conclusion: Our findings offer potential avenues for developing precise and effective management approaches for anxiety disorders by targeting specific gut microbiota and associated metabolites.
Keywords: Mendelian randomization; anxiety disorders; causal effects; gut microbiota and associated metabolites; management approaches.
Copyright © 2024 Xu, Qiu, Ma, Yu, Yang, Hu, Guo and Chen.
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Figures
Similar articles
-
Cross-talks between gut microbiota and tobacco smoking: a two-sample Mendelian randomization study.BMC Med. 2023 Apr 28;21(1):163. doi: 10.1186/s12916-023-02863-1. BMC Med. 2023. PMID: 37118782 Free PMC article.
-
Investigating causal associations among gut microbiota, metabolites and autoimmune hypothyroidism: a univariable and multivariable Mendelian randomization study.Front Immunol. 2024 Jan 4;14:1213159. doi: 10.3389/fimmu.2023.1213159. eCollection 2023. Front Immunol. 2024. PMID: 38239342 Free PMC article.
-
Causality Investigation between Gut Microbiota, Derived Metabolites, and Obstructive Sleep Apnea: A Bidirectional Mendelian Randomization Study.Nutrients. 2023 Oct 26;15(21):4544. doi: 10.3390/nu15214544. Nutrients. 2023. PMID: 37960197 Free PMC article.
-
Exploring the potential causal relationship between gut microbiota and heart failure: A two-sample mendelian randomization study combined with the geo database.Curr Probl Cardiol. 2024 Feb;49(2):102235. doi: 10.1016/j.cpcardiol.2023.102235. Epub 2023 Nov 30. Curr Probl Cardiol. 2024. PMID: 38040216 Review.
-
Causal relationship between gut microbiota and polycystic ovary syndrome: a literature review and Mendelian randomization study.Front Endocrinol (Lausanne). 2024 Feb 1;15:1280983. doi: 10.3389/fendo.2024.1280983. eCollection 2024. Front Endocrinol (Lausanne). 2024. PMID: 38362275 Free PMC article. Review.
References
-
- Biswas T., Scott J. G., Munir K., Renzaho A. M. N., Rawal L. B., Baxter J., et al. . (2020). Global variation in the prevalence of suicidal ideation, anxiety and their correlates among adolescents: a population based study of 82 countries. EClinicalMedicine 24:100395. doi: 10.1016/j.eclinm.2020.100395, PMID: - DOI - PMC - PubMed
Grants and funding
LinkOut - more resources
Full Text Sources