The causal effects of gut microbiota on quantitative susceptibility mapping (QSM) and T2* imaging-derived phenotypes:...

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).

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.

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_{inverse variance weighting (IVW)}=4.00E-08]; the genus Dialister was positively correlated with the median susceptibility in the right accumbens (β: 0.0949, 95% CI: 0.0575, 0.1324, P_IVW=6.90E-07); the genus Butyricicoccus was positively associated with the median T2* in the left hippocampus with the additional deconfounding of the background field gradient (β: 0.1543, 95% CI: 0.0959, 0.2127, P_IVW=2.20E-07); the genus Desulfovibrio was positively related to the T2* white matter hyperintensity (WMH) IDP with WMH volume regressed out (β: 0.1168, 95% CI: 0.0697, 0.1639, P_IVW=1.20E-06). Notably, both the family Defluviitaleaceae (β: -0.1215, 95% CI: -0.1604, -0.0827, P_IVW=8.40E-10) and genus DefluviitaleaceaeUCG011 (β: -0.1142, 95% CI: -0.1614, -0.0670, P_IVW=2.10E-06) were negatively correlated with the median T2* in the right accumbens with the additional deconfounding of the background field gradient.

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.