Investigating the role of gut microbiota in hemorrhagic stroke: Evidence from causal analysis

Abstract

BackgroundHemorrhagic stroke is potentially fatal and debilitating. Previous studies have indicated a potential correlation between gut microbiota and hemorrhagic stroke. MethodsWe conducted a two-sample Mendelian randomization (MR) study to assess the potential causal effects of gut microbiota on hemorrhagic stroke, including nontraumatic intracranial hemorrhage (ntICH), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). The inverse variance weighted (IVW) method was employed as the primary MR evaluation approach. Complementary methods of MR‒Egger, simple mode, weighted mode, and weighted median were utilized for validation. Heterogeneity and pleiotropy were assessed using Cochran's Q and MR‒Egger intercept tests. MR-PRESSO and leave-one-out analyses were employed to identify instrumental outliers. ResultsThe IVW estimates demonstrated significant causal associations between ntICH and taxa from two classes (Clostridia, Methanobacteria), one order (Methanobacteriales), two families (Clostridiales vadin BB60 group, Methanobacteriaceae), and two genera (Catenibacterium, unknown genus id. 1000000073) (P<0.05). Subgroup analyses revealed causal links between ICH and taxa from two classes (Clostridia, Methanobacteria), two orders (Methanobacteriales, Rhodospirillales), two families (Acidaminococcaceae, Methanobacteriaceae), and four genera (Butyricimonas, Catenibacterium, Lachnospiraceae UCG010, unknown genus id.2755) (P<0.05). Furthermore, for the SAH subgroup, we identified causal associations with taxa from one family (Rikenellaceae) and six genera (Alloprevotella, Enterorhabdus, Hungatella, Lachnoclostridium, Parabacteroides, Ruminococcus gauvreauii group) (P<0.05). These findings remained robust across all sensitivity tests. ConclusionsOur findings provide support for the causal effects of specific gut microbial taxa on hemorrhagic stroke and identify promising targets for its prevention and therapy. Further research is warranted to validate these associations.