AUTHOR=Xu Ran , Liu Shuo , Li Lu-yi , Zhang Ying , Luo Guang-cheng , Fang Bo-qin , Wang Xin-jun TITLE=Causal effects of gut microbiota on the risk of bipolar disorder: a Mendelian randomization study JOURNAL=Frontiers in Microbiomes VOLUME=2 YEAR=2023 URL=https://www.frontiersin.org/journals/microbiomes/articles/10.3389/frmbi.2023.1249518 DOI=10.3389/frmbi.2023.1249518 ISSN=2813-4338 ABSTRACT=Background

Recent studies have suggested a possible association between gut microbiota and bipolar disorder (BD). However, observational studies are limited and there are variations between the gut microbiota taxa found in different studies. Therefore, we aimed to explore whether there is a causal relationship between gut microbiota and bipolar disorder at the genetic level and to reveal trends in the effect of influential gut microbiota on the development of bipolar disorder.

Methods

We conducted a Mendelian randomisation (MR) study of summary statistics from a genome-wide association study (GWAS) of gut microbiota and bipolar disorder. Inverse variance weighting (IVW) was used as the primary method of statistical analysis, while results from the MR-Egger method, weighted median, weighted mode, and MR multiplicity residuals and outliers (MR-PRESSO) tests were used for additional validation.Cochrane’s Q test, MR-Egger intercept test, and MR-PRESSO global test were used to test MR results for stability and reliability.

Result

We identified 13 gut microbial taxa causally associated with bipolar disorder. Betaproteobacteria, Acidaminococcaceae, Eubacterium xylanophilum group, Butyricimonas, Peptococcus, Prevotella 7, Roseburia, Terrisporobacter, Burkholderiales and Desulfovibrionales increased the risk of BD, whereas Candidatus Soleaferrea, Ruminiclostridium 5 and Victivallis decreased the risk of BD. The results of the MR analysis were shown to be reliable in the sensitivity analysis.

Conclusion

With the MR study, we analysed the causal relationship between 196 gut microbial taxa and bipolar disorder and also identified gut microbiota associated with the risk of developing bipolar disorder. Our findings provide new biomarkers and potential therapeutic targets for the prevention and treatment of BD.