Persistent gut microbiota alterations after ischemic stroke are modifiable by probiotic intervention

The gut-brain axis has emerged as a critical modulator in neurological diseases, including stroke. While acute post-stroke dysbiosis is well established, it remains unclear whether these alterations persist long-term and can be therapeutically modulated. This study addresses this gap through integrated metagenomic and metabolomic profiling in two independent clinical stroke cohorts, complemented by experimental models. Experimental stroke induced persistent changes in gut microbiota composition and altered short-chain fatty acid profiles. In patients, microbiota composition remained distinct from controls up to three months after ischemic stroke or transient ischemic attack (TIA), accompanied by persistent reductions in propionic and valeric acid and reduced abundance of Prevotella -associated microbial signatures. We performed a randomized, double-blind interventional trial (PRISE) testing a multispecies probiotic versus placebo, using household members as additional controls. Probiotic intervention led to microbiome compositional changes with increased abundance of beneficial taxa and significantly improved functional recovery. The tested probiotic strains showed anti-inflammatory and antioxidant effects in vitro. These findings suggest that targeted modulation of the microbiome represents a promising therapeutic avenue to improve chronic stroke recovery, warranting validation in larger Phase III clinical trials.