Evaluating Causal Effects of Gut Microbiome on Bipolar Disorder

Background: Previous studies have shown that gut microbiome dysbiosis has pathogenic significance in the development of bipolar disorder (BD), but the direct causal relationship remains unclear. We aimed to investigate this potential correlation. Methods: Using a two-sample Mendelian randomization (TSMR) analysis, we examined the potential causal effects of gut microbiota on BD. Summary results for gut microbiota were derived from two large genome-wide association studies (GWAS) on gut microbiota: the MibioGen consortium (N = 18,340) and the Dutch Microbiome Project (N = 8208), as well as one GWAS summary result for BD (N = 413,466). Results: Our TSMR analysis revealed that the levels of 12 taxa were associated with a reduced risk of BD. These included the phylum Bacteroidetes, its class Bacteroidia, its order Bacteroidales, its species Parabacteroides johnsonii and Paraprevotella unclassified, and genus Faecalibacterium (OR: 0.85 ~ 0.96, p ≤ 0.043). Conversely, 11 gut bacterial taxa were linked to an increased risk of BD. These comprised the class Betaproteobacteria, its order Burkholderiales, and its family Sutterellaceae (OR: 1.06 ~ 1.25, p ≤ 0.049). Conclusions: Our study further identifies a genetic link between BD and gut microbiota. The causal effects of certain gut microbiota on BD may bring potential clinical benefits and provide a new paradigm for the prevention and treatment of BD.