The causal effects of gut microbiota on quantitative susceptibility mapping (QSM) and T2* imaging-derived phenotypes: insights from a Mendelian randomization study.

Background: Gut microbiota are associated with brain imaging-derived phenotypes (IDPs); however, the specific causal relationship between the gut microbiota and brain iron-related IDPs remains unclear. Thus, we sought to analyze the potential causal effects of gut microbiota on brain iron-related IDPs using Mendelian randomization (MR). Methods: We obtained the data of 196 gut microbiota from a genome-wide association study (GWAS) from the MiBioGen database, as well as the data of 18 quantitative susceptibility mapping (QSM) IDPs and 10 T2* IDPs from the United Kingdom Biobank (UKB). We then conducted one-way two-sample MR analyses to examine their causal interactions. To guarantee the robustness of the results, we performed two independent analysis processes by selecting statistically significant instrumental variables (IVs) with a distinct level of statistical strictness, and derived the intersection of these two analyses. Results: Our results showed that the genus Howardella was positively correlated with the median susceptibility in the right caudate [β: 0.0935, 95% confidence interval (CI): 0.0601, 0.1269, P Conclusions: This study found genetic evidence that gut microbiota dysbiosis has causal effects on brain iron-related IDPs. Our findings provide novel insights into the diagnosis and therapeutic management of central nervous system (CNS) diseases.