Gut Microbiota Influences Meningioma Pathogenesis via Circulating Metabolites: A Two-Sample Mendelian Randomization Study.

Background: Meningiomas are common solitary intracranial tumors without any apparent risk factors. In light of the growing interest in gut microbiome-brain tumor interactions, this investigation sought to explore potential links between intestinal microbial communities and meningioma pathogenesis, while also exploring the potential mediating role of specific metabolites.

Methods: To investigate potential causal links between intestinal microbial communities and meningioma development, we implemented a bidirectional two-sample Mendelian randomization (MR) approach examining 196 microbial taxa. Our analytical strategy incorporated a two-stage MR methodology to pinpoint potential mediating factors. Furthermore, we performed comprehensive mediation analyses to assess the degree to which particular metabolic intermediates might influence the observed microbiota-meningioma associations.

Results: Eight distinct microbial taxa exhibited potential causal associations with meningioma development. Among the identified taxa, genus Lachnoclostridium (odds ratio [OR]: 0.60; 95% confidence interval [CI]: 0.41, 0.89; p = 0.010) and class Lentisphaeria (OR: 0.73; 95% CI: 0.57, 0.95; p = 0.017) were suggestively associated with a reduced risk of meningioma, whereas family Oxalobacteraceae (OR: 1.28; 95% CI: 1.04, 1.58; p = 0.018) suggested a positive association with the risk of meningioma. An exploratory mediation analysis suggested that the relationships between genus Lachnoclostridium, class Lentisphaeria, and family Oxalobacteraceae and meningioma were mediated by the histidine to pyruvate ratio, hydroxymalonate, and 1-linoleoylglycerol. Each of these accounted for 10.65%, 10.78%, and 11.82%, respectively.

Conclusion: This investigation provides preliminary evidence that intestinal microbial communities play a contributory role in meningioma pathogenesis, with circulating metabolites potentially serving as key intermediaries in this microbiota-meningioma axis.