A Study of Probiotics in Patients With Acute Ischemic Stroke (PRO-STROKE)

Ischemic stroke induces a rapid and sustained systemic inflammatory response that contributes to secondary brain injury, post-stroke complications, and long-term functional outcome. In addition to well-characterized neuroinflammatory mechanisms, increasing evidence indicates that stroke profoundly alters the gut microbiota through autonomic dysfunction, reduced intestinal motility, altered permeability, and frequent exposure to antibiotics and hospital-related stressors. This stroke-induced dysbiosis has been linked to systemic immune activation, impaired immune homeostasis, and increased susceptibility to infections, all of which negatively affect recovery after stroke.

Experimental studies have demonstrated that the composition and functional capacity of the gut microbiota influence ischemic brain injury and post-stroke inflammation. Alterations in microbial community structure can modulate peripheral immune responses, including myeloid cell activation and cytokine production, and affect levels of microbiota-derived metabolites such as short-chain fatty acids (SCFAs). SCFAs, including acetate, propionate, and butyrate, exert immunomodulatory effects by regulating innate and adaptive immune responses and maintaining intestinal barrier integrity. Reduced SCFA availability has been associated with enhanced systemic inflammation and adverse neurological outcomes in experimental stroke models.

Clinical observations further support the relevance of the gut-brain axis in stroke. Patients with acute ischemic stroke exhibit rapid changes in gut microbiome composition, reduced microbial diversity, and shifts in specific taxa that correlate with stroke severity, systemic inflammation, and functional outcome. However, whether targeted modulation of the gut microbiota after stroke can reproducibly alter microbial community structure and downstream biological processes in humans remains unclear. Existing clinical studies of probiotics and synbiotics have shown anti-inflammatory effects in various non-neurological conditions, but data from adequately powered randomized controlled trials in acute ischemic stroke are lacking.

The probiotic formulation OMNi-BiOTiC® SR-9 contains multiple well-characterized bacterial strains combined with a prebiotic matrix designed to support bacterial viability and metabolic activity. This formulation has demonstrated immunomodulatory properties and a favorable safety profile in previous clinical applications. Administered early after stroke, probiotic supplementation represents a low-risk, non-invasive strategy to counteract stroke-associated dysbiosis, stabilize gut microbial community structure, and potentially restore microbiota-derived metabolic and immune signaling.

Given the complexity and inter-individual variability of the human gut microbiome, global measures of microbial community composition, such as beta diversity, represent sensitive and biologically meaningful endpoints to capture probiotic-induced changes. Assessing microbiome beta diversity at 90 days allows sufficient time for microbial ecosystem restructuring and stabilization following acute stroke and hospitalization, while still reflecting effects initiated during the early post-stroke phase.

Therefore, this randomized, placebo-controlled phase 2 trial is designed to evaluate whether daily oral administration of OMNi-BiOTiC® SR-9 for 90 days can induce measurable changes in gut microbiome beta diversity in patients with acute ischemic stroke. Secondary objectives address clinical outcome, specific microbial taxa, and circulating SCFAs to provide complementary mechanistic insights and inform the design of future outcome-driven trials.